Sample records for hormone-mediated stress hypersensitivity
Stress Hormones mediated by the Built Environment
Fich, Lars Brorson; Wallergård, Mattias; Hansen, Åse Marie
Due to the aging society, dementia is one of the major challenges to the health care systems all over the world. The growing number of patients, the long process and intensive need for care, especially in the later stages of the disease, make the growth in human as well as socioeconomic costs huge....... The development of design strategies for nursing homes and other health care facilities such as day care centers addressing the needs of dementia patients is therefore very important. The vast majority of dementia cases is Alzheimer's Disease, representing approximately 70% of all cases. Alzheimer's disease...... of the hippocampus' function in the stress system, as the lack of control of cortisol levels during stress can lead to further degradation of the hippocampus. We refer to a stress experiment suggesting that is possible through the built environment to influence the release of cortisol during stress. This again...
Converging, Synergistic Actions of Multiple Stress Hormones Mediate Enduring Memory Impairments after Acute Simultaneous Stresses.
Chen, Yuncai; Molet, Jenny; Lauterborn, Julie C; Trieu, Brian H; Bolton, Jessica L; Patterson, Katelin P; Gall, Christine M; Lynch, Gary; Baram, Tallie Z
Stress influences memory, an adaptive process crucial for survival. During stress, hippocampal synapses are bathed in a mixture of stress-released molecules, yet it is unknown whether or how these interact to mediate the effects of stress on memory. Here, we demonstrate novel synergistic actions of corticosterone and corticotropin-releasing hormone (CRH) on synaptic physiology and dendritic spine structure that mediate the profound effects of acute concurrent stresses on memory. Spatial memory in mice was impaired enduringly after acute concurrent stresses resulting from loss of synaptic potentiation associated with disrupted structure of synapse-bearing dendritic spines. Combined application of the stress hormones corticosterone and CRH recapitulated the physiological and structural defects provoked by acute stresses. Mechanistically, corticosterone and CRH, via their cognate receptors, acted synergistically on the spine-actin regulator RhoA, promoting its deactivation and degradation, respectively, and destabilizing spines. Accordingly, blocking the receptors of both hormones, but not each alone, rescued memory. Therefore, the synergistic actions of corticosterone and CRH at hippocampal synapses underlie memory impairments after concurrent and perhaps also single, severe acute stresses, with potential implications to spatial memory dysfunction in, for example, posttraumatic stress disorder. Stress influences memory, an adaptive process crucial for survival. During stress, adrenal corticosterone and hippocampal corticotropin-releasing hormone (CRH) permeate memory-forming hippocampal synapses, yet it is unknown whether (and how) these hormones interact to mediate effects of stress. Here, we demonstrate novel synergistic actions of corticosterone and CRH on hippocampal synaptic plasticity and spine structure that mediate the memory-disrupting effects of stress. Combined application of both hormones provoked synaptic function collapse and spine disruption
Elevated Plasma Corticosterone Decreases Yolk Testosterone and Progesterone in Chickens : Linking Maternal Stress and Hormone-Mediated Maternal Effects
Henriksen, Rie; Groothuis, Ton G.; Rettenbacher, Sophie; Bartell, Paul A.
Despite considerable research on hormone-mediated maternal effects in birds, the underlying physiology remains poorly understood. This study investigated a potential regulation mechanism for differential accumulation of gonadal hormones in bird eggs. Across vertebrates, glucocorticoids can suppress
Role of insular cortex in visceral hypersensitivity model in rats subjected to chronic stress.
Yi, LiSha; Sun, HuiHui; Ge, Chao; Chen, Ying; Peng, HaiXia; Jiang, YuanXi; Wu, Ping; Tang, YinHan; Meng, QingWei; Xu, ShuChang
Abnormal processing of visceral sensation at the level of the central nervous system has been proven to be important in the pathophysiologic mechanisms of stress related functional gastrointestinal disorders. However, the specific mechanism is still not clear. The insular cortex (IC) was considered as one important visceral sensory area. Moreover, the IC has been shown to be involved in various neuropsychiatric diseases such as panic disorders and post-traumatic stress disorder. However, whether the IC is important in psychological stress related visceral hypersensitivity has not been studied yet. In our study, through destruction of the bilateral IC, we explored whether the IC played a critical role in the formation of visceral hypersensitivity induced by chronic stress on rats. Chronic partial restraint stress was used to establish viscerally hypersensitive rat model. Bilateral IC lesions were generated by N-methyl-D-day (door) aspartate. After a recovery period of 7 days, 14-day consecutive restraint stress was performed. The visceromotor response to colorectal distension was monitored by recording electromyogram to measure rats׳ visceral sensitivity. We found that bilateral insular cortex lesion could markedly inhibit the formation of visceral hypersensitivity induced by chronic stress. The insular cortex plays a critical role in the pathophysiology of stress-related visceral hypersensitivity.
Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress
Full Text Available Background. Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1 is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs and the role of CHT1 in visceral hypersensitivity. Methods. Repetitive water avoidance stress (WAS was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD was determined, and the abdominal withdrawal reflex (AWR and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3, the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results. Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion. Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity.
Background Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1) is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs) and the role of CHT1 in visceral hypersensitivity. Methods Repetitive water avoidance stress (WAS) was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD) was determined, and the abdominal withdrawal reflex (AWR) and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3), the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity. PMID:29849603
Adrenergic β2-receptors mediates visceral hypersensitivity induced by heterotypic intermittent stress in rats.
Chunhua Zhang
Full Text Available Chronic visceral pain in patients with irritable bowel syndrome (IBS has been difficult to treat effectively partially because its pathophysiology is not fully understood. Recent studies show that norepinephrine (NE plays an important role in the development of visceral hypersensitivity. In this study, we designed to investigate the role of adrenergic signaling in visceral hypersensitivity induced by heterotypical intermittent stress (HIS. Abdominal withdrawal reflex scores (AWRs used as visceral sensitivity were determined by measuring the visceromoter responses to colorectal distension. Colon-specific dorsal root ganglia neurons (DRGs were labeled by injection of DiI into the colon wall and were acutely dissociated for whole-cell patch-clamp recordings. Blood plasma level of NE was measured using radioimmunoassay kits. The expression of β2-adrenoceptors was measured by western blotting. We showed that HIS-induced visceral hypersensitivity was attenuated by systemic administration of a β-adrenoceptor antagonist propranolol, in a dose-dependent manner, but not by a α-adrenoceptor antagonist phentolamine. Using specific β-adrenoceptor antagonists, HIS-induced visceral hypersensitivity was alleviated by β2 adrenoceptor antagonist but not by β1- or β3-adrenoceptor antagonist. Administration of a selective β2-adrenoceptor antagonist also normalized hyperexcitability of colon-innervating DRG neurons of HIS rats. Furthermore, administration of β-adrenoceptor antagonist suppressed sustained potassium current density (IK without any alteration of fast-inactivating potassium current density (IA. Conversely, administration of NE enhanced the neuronal excitability and produced visceral hypersensitivity in healthy control rats, and blocked by β2-adrenoceptor antagonists. In addition, HIS significantly enhanced the NE concentration in the blood plasma but did not change the expression of β2-adrenoceptor in DRGs and the muscularis externa of the
Sex differences in stress-induced visceral hypersensitivity following early life adversity: a two hit model.
Prusator, D K; Greenwood-Van Meerveld, B
Early life adversity (ELA) has been indicated as a risk factor for the development of stress axis dysfunction in adulthood, specifically in females. We previously showed that unpredictable ELA induces visceral hyperalgesia in adult female rats. It remains to be determined whether ELA alters visceral nociceptive responses to stress in adulthood. The current study tested the hypothesis that following ELA, exposure to an adulthood stressor, or second hit, serves as a risk factor for exaggerated stress-induced visceral hypersensitivity that is sex-specific. Following ELA, adult stress was induced via a single exposure (acute) or repetitive daily exposure, 1 h/day for 7 days (chronic), to water avoidance stress (WAS). Acute WAS increased pain behaviors in all adult female rats, however, females that experienced unpredictable ELA exhibited significantly more pain behaviors compared to those exposed to predictable ELA or controls. Following chronic WAS, all adult females exhibited increased pain responses, however, an exaggerated response was observed in rats exposed to unpredictable or predictable ELA compared to controls. Similarly, in adult male rats exposure to acute or chronic WAS increased pain behaviors, however, there were no differences in pain behaviors between ELA groups. This study highlights a novel consequence of ELA on stress-induced visceral nociception in adulthood that is sex-specific. More importantly, our study suggests that ELA not only serves as a risk factor for development of chronic pain in adulthood, but also serves as a predisposition for worsening of visceral pain following adult stress in female rats. © 2016 John Wiley & Sons Ltd.
Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception.
Cao, Jing; Wang, Po-Kai; Tiwari, Vinod; Liang, Lingli; Lutz, Brianna Marie; Shieh, Kun-Ruey; Zang, Wei-Dong; Kaufman, Andrew G; Bekker, Alex; Gao, Xiao-Qun; Tao, Yuan-Xiang
Chronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear. In this study, we showed that pre- or post-surgical exposure to immobilization 6Â h daily for three consecutive days did not change basal responses to mechanical, thermal, or cold stimuli or peak levels of incision-induced hypersensitivity to these stimuli; however, immobilization did prolong the duration of incision-induced hypersensitivity in both male and female rats. These phenomena were also observed in post-surgical exposure to forced swimming 25Â min daily for 3 consecutive days. Short-term stress induced by immobilization was demonstrated by an elevation in the level of serum corticosterone, an increase in swim immobility, and a decrease in sucrose consumption. Blocking this short-term stress via intrathecal administration of a selective glucocorticoid receptor antagonist, RU38486, or bilateral adrenalectomy significantly attenuated the prolongation of incision-induced hypersensitivity to mechanical, thermal, and cold stimuli. Our results indicate that short-term stress during the pre- or post-operative period delays postoperative pain recovery although it does not affect basal pain perception. Prevention of short-term stress may facilitate patients' recovery from postoperative pain.
Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats
Zhou, Yuan-Yuan; Wanner, Natalie J; Xiao, Ying; Shi, Xuan-Zheng; Jiang, Xing-Hong; Gu, Jian-Guo; Xu, Guang-Yin
AIM: To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture (EA) and whether EA effect was mediated by endogenous opiates. METHODS: Six to nine week-old male Sprague-Dawley rats were used in this study. Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress (HIS) protocol composed of 3 randomly stressors, which included cold restraint stress at 4 °C for 45 min, water avoidance stress for 60 min, and forced swimming stress for 20 min, in adult male rats. The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex (AWR) scores of colorectal distension at different distention pressures (20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg). AWR scores either 0, 1, 2, 3 or 4 were obtained by a blinded observer. EA or sham EA was performed at classical acupoint ST-36 (Zu-San-Li) or BL-43 (Gao-Huang) in both hindlimbs of rats for 30 min. Naloxone (NLX) or NLX methiodide (m-NLX) was administered intraperitoneally to HIS rats in some experiments. RESULTS: HIS rats displayed an increased sensitivity to colorectal distention, which started from 6 h (the first measurement), maintained for 24 h, and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures. The AWR scores before HIS were 0.6 ± 0.2, 1.3 ± 0.2, 1.9 ± 0.2 and 2.3 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. Six hours after termination of the last stressor, the AWR scores were 2.0 ± 0.1, 2.5 ± 0.1, 2.8 ± 0.2 and 3.5 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg: 2.0 ± 0.2 vs 0.7 ± 0.1, P = 4.23 711 E-4; AWRs at 40 mmHg: 2.6 ± 0.2 vs 1.5 ± 0.2, P
Copper hypersensitivity
Fage, Simon W; Faurschou, Annesofie; Thyssen, Jacob P
hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common...
Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain
Rachel D. Moloney
Full Text Available Glutamate, the main excitatory neurotransmitter in the central nervous system, exerts its effect through ionotropic and metabotropic receptors. Of these, group III mGlu receptors (mGlu 4, 6, 7, 8 are among the least studied due to a lack of pharmacological tools. mGlu7 receptors, the most highly conserved isoform, are abundantly distributed in the brain, especially in regions, such as the amygdala, known to be crucial for the emotional processing of painful stimuli. Visceral hypersensitivity is a poorly understood phenomenon manifesting as an increased sensitivity to visceral stimuli. Glutamate has long been associated with somatic pain processing leading us to postulate that crossover may exist between these two modalities. Moreover, stress has been shown to exacerbate visceral pain. ADX71743 is a novel, centrally penetrant, negative allosteric modulator of mGlu7 receptors. Thus, we used this tool to explore the possible involvement of this receptor in the mediation of visceral pain in a stress-sensitive model of visceral hypersensitivity, namely the Wistar Kyoto (WKY rat. ADX71743 reduced visceral hypersensitivity in the WKY rat as exhibited by increased visceral sensitivity threshold with concomitant reductions in total number of pain behaviours. Moreover, AD71743 increased total distance and distance travelled in the inner zone of the open field. These findings show, for what is to our knowledge, the first time, that mGlu7 receptor signalling plays a role in visceral pain processing. Thus, negative modulation of the mGlu7 receptor may be a plausible target for the amelioration of stress-induced visceral pain where there is a large unmet medical need.
Hypersensitivity vasculitis
Cutaneous small vessel vasculitis; Allergic vasculitis; Leukocytoclastic vasculitis ... Hypersensitivity vasculitis, or cutaneous small vessel vasculitis, is caused by: An allergic reaction to a drug or other foreign ...
Acute physical and psychological stress effects on visceral hypersensitivity in male rat: role of central nucleus of the amygdala
Hamideh Afzali
Full Text Available Objective: The aim of this study was to investigate the effects of acute physical and psychological stress and temporary central nucleus of the amygdala (CeA block on stress-induced visceral hypersensitivity. Methods: Forty two male Wistar rats were used in this study. Animals were divided into 7 groups (n = 6; 1 – Control, 2 – physical stress, 3 – psychological stress, 4 – sham, 5 – lidocaine, 6 – lidocaine + physical stress and 7 – lidocaine + psychological stress. Stress induction was done using a communication box. Results: Abdominal withdrawal reflex (AWR score was monitored one hour after stress exposure. AWR score significantly heightened at 20, 40 and 60 mmHg in the psychological stress group compared with control (p stress group compared with psychological stress with no tangible response on physical stress. Total stool weight was significantly increased in psychological stress group compared with control (0.72 ± 0.15, 0.1 ± 0.06 g (p stress compared to control group (0.16 ± 0.12, 0.1 ± 0.06 g (p stress followed the same results in psychological groups (0.18 ± 0.2, 0.72 ± 0.15 g (p stress group (0.25 ± 0.1, 0.16 ± 0.12 g (p stress could strongly affect visceral hypersensitivity. This effect is statistically comparable with physical stress. Temporary CeA block could also reduce visceral hypersensitivity post-acute psychological stress. Resumen: Objetivo: O objetivo desse estudo foi investigar os efeitos do estresse físico e psicológico agudo e bloqueio temporário do núcleo central da amídala (CeA na hipersensibilidade visceral induzida por estresse. MÃ
Peripheral a-helical CRF (9-41) does not reverse stress-induced mast cell dependent visceral hypersensitivity in maternally separated rats
van den Wijngaard, R. M.; Stanisor, O. I.; van Diest, S. A.; Welting, O.; Wouters, M. M.; de Jonge, W. J.; Boeckxstaens, G. E.
Background Acute stress-induced hypersensitivity to colorectal distention was shown to depend on corticotropin releasing factor (CRF)-induced mast cell degranulation. At present it remains unclear whether CRF also induces chronic poststress activation of these cells. Accordingly, the objective of
Towards the Identification of New Genes Involved in ABA-Dependent Abiotic Stresses Using Arabidopsis Suppressor Mutants of abh1 Hypersensitivity to ABA during Seed Germination
Iwona Szarejko
Full Text Available Abscisic acid plays a pivotal role in the abiotic stress response in plants. Although great progress has been achieved explaining the complexity of the stress and ABA signaling cascade, there are still many questions to answer. Mutants are a valuable tool in the identification of new genes or new alleles of already known genes and in elucidating their role in signaling pathways. We applied a suppressor mutation approach in order to find new components of ABA and abiotic stress signaling in Arabidopsis. Using the abh1 (ABA hypersensitive 1 insertional mutant as a parental line for EMS mutagenesis, we selected several mutants with suppressed hypersensitivity to ABA during seed germination. Here, we present the response to ABA and a wide range of abiotic stresses during the seed germination and young seedling development of two suppressor mutants—soa2 (suppressor of abh1 hypersensitivity to ABA 2 and soa3 (suppressor of abh1 hypersensitivity to ABA 3. Generally, both mutants displayed a suppression of the hypersensitivity of abh1 to ABA, NaCl and mannitol during germination. Both mutants showed a higher level of tolerance than Columbia-0 (Col-0—the parental line of abh1 in high concentrations of glucose. Additionally, soa2 exhibited better root growth than Col-0 in the presence of high ABA concentrations. soa2 and soa3 were drought tolerant and both had about 50% fewer stomata per mm2 than the wild-type but the same number as their parental line—abh1. Taking into account that suppressor mutants had the same genetic background as their parental line—abh1, it was necessary to backcross abh1 with Landsberg erecta four times for the map-based cloning approach. Mapping populations, derived from the cross of abh1 in the Landsberg erecta background with each suppressor mutant, were created. Map based cloning in order to identify the suppressor genes is in progress.
Dominant Repression by Arabidopsis Transcription Factor MYB44 Causes Oxidative Damage and Hypersensitivity to Abiotic Stress
Helene Persak
Full Text Available In any living species, stress adaptation is closely linked with major changes of the gene expression profile. As a substrate protein of the rapidly stress-induced mitogen-activated protein kinase MPK3, Arabidopsis transcription factor MYB44 likely acts at the front line of stress-induced re-programming. We recently characterized MYB44 as phosphorylation-dependent positive regulator of salt stress signaling. Molecular events downstream of MYB44 are largely unknown. Although MYB44 binds to the MBSII element in vitro, it has no discernible effect on MBSII-driven reporter gene expression in plant co-transfection assays. This may suggest limited abundance of a synergistic co-regulator. MYB44 carries a putative transcriptional repression (Ethylene responsive element binding factor-associated Amphiphilic Repression, EAR motif. We employed a dominant repressor strategy to gain insights into MYB44-conferred stress resistance. Overexpression of a MYB44-REP fusion markedly compromised salt and drought stress tolerance—the opposite was seen in MYB44 overexpression lines. MYB44-mediated resistance likely results from induction of tolerance-enhancing, rather than from repression of tolerance-diminishing factors. Salt stress-induced accumulation of destructive reactive oxygen species is efficiently prevented in transgenic MYB44, but accelerated in MYB44-REP lines. Furthermore, heterologous overexpression of MYB44-REP caused tissue collapse in Nicotiana. A mechanistic model of MAPK-MYB-mediated enhancement in the antioxidative capacity and stress tolerance is proposed. Genetic engineering of MYB44 variants with higher trans-activating capacity may be a means to further raise stress resistance in crops.
Addition of posttraumatic stress and sensory hypersensitivity more accurately estimates disability and pain than fear avoidance measures alone after whiplash injury.
Pedler, Ashley; Kamper, Steven J; Sterling, Michele
The fear avoidance model (FAM) has been proposed to explain the development of chronic disability in a variety of conditions including whiplash-associated disorders (WADs). The FAM does not account for symptoms of posttraumatic stress and sensory hypersensitivity, which are associated with poor recovery from whiplash injury. The aim of this study was to explore a model for the maintenance of pain and related disability in people with WAD including symptoms of PTSD, sensory hypersensitivity, and FAM components. The relationship between individual components in the model and disability and how these relationships changed over the first 12 weeks after injury were investigated. We performed a longitudinal study of 103 (74 female) patients with WAD. Measures of pain intensity, cold and mechanical pain thresholds, symptoms of posttraumatic stress, pain catastrophising, kinesiophobia, and fear of cervical spine movement were collected within 6 weeks of injury and at 12 weeks after injury. Mixed-model analysis using Neck Disability Index (NDI) scores and average 24-hour pain intensity as the dependent variables revealed that overall model fit was greatest when measures of fear of movement, posttraumatic stress, and sensory hypersensitivity were included. The interactive effects of time with catastrophising and time with fear of activity of the cervical spine were also included in the best model for disability. These results provide preliminary support for the addition of neurobiological and stress system components to the FAM to explain poor outcome in patients with WAD.
Hypersensitive tourists
Jensen, Martin Trandberg
This research note sets forth a new agendum for sensuous tourism scholarship. It departs in the neglected study of the embodied life of hypersensitive tourists, and argues that the ambiguousness of the sensuous be better understood. To contextualise this argument the following suggests that aller......This research note sets forth a new agendum for sensuous tourism scholarship. It departs in the neglected study of the embodied life of hypersensitive tourists, and argues that the ambiguousness of the sensuous be better understood. To contextualise this argument the following suggests...... that allergic tourists make up a contemporary and increasingly relevant empirical field through which to illuminate the dark sides of the sensuous. Finally, the note develops four analytical dimensions that structure critical sensuous scholarship....
Metronidazole hypersensitivity.
Knowles, S; Choudhury, T; Shear, N H
To report a case of a possible hypersensitivity reaction induced by metronidazole. An Asian woman with a history of recurrent vaginitis had previously developed localized erythema while on intravaginal metronidazole and nystatin. While receiving oral metronidazole for treatment of a current bacterial vaginosis, she developed chills, fever, generalized erythema, and a rash within 60 minutes of the first dose. Treatment with diphenhydramine was instituted. The following day while in the hospital, the patient's condition worsened; she experienced shortness of breath and increased edema of the extremities. Methylprednisolone was administered with diphenhydramine and her condition improved over the next 5 days. The patient's vaginitis was treated with gentian violet and she was discharged on a tapering dosage of prednisone. Metronidazole-induced cutaneous reactions and systemic hypersensitivity reactions are reviewed. Alternatives to metronidazole and other potential cross-reactive drugs are suggested for the treatment of recurrent vaginitis. Although the patient's initial reaction to metronidazole represented a rare event, written documentation and communication in the patient's native language may have prevented the subsequent severe hypersensitivity reaction.
Dermal fibroblasts in Hutchinson-Gilford progeria syndrome with the lamin A G608G mutation have dysmorphic nuclei and are hypersensitive to heat stress
Worman Howard J
Full Text Available Abstract Background Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670 is a rare sporadic disorder with an incidence of approximately 1 per 8 million live births. The phenotypic appearance consists of short stature, sculptured nose, alopecia, prominent scalp veins, small face, loss of subcutaneous fat, faint mid-facial cyanosis, and dystrophic nails. HGPS is caused by mutations in LMNA, the gene that encodes nuclear lamins A and C. The most common mutation in subjects with HGPS is a de novo single-base pair substitution, G608G (GGC>GGT, within exon 11 of LMNA. This creates an abnormal splice donor site, leading to expression of a truncated protein. Results We studied a new case of a 5 year-old girl with HGPS and found a heterozygous point mutation, G608G, in LMNA. Complementary DNA sequencing of RNA showed that this mutation resulted in the deletion of 50 amino acids in the carboxyl-terminal tail domain of prelamin A. We characterized a primary dermal fibroblast cell line derived from the subject's skin. These cells expressed the mutant protein and exhibited a normal growth rate at early passage in primary culture but showed alterations in nuclear morphology. Expression levels and overall distributions of nuclear lamins and emerin, an integral protein of the inner nuclear membrane, were not dramatically altered. Ultrastructural analysis of the nuclear envelope using electron microscopy showed that chromatin is in close association to the nuclear lamina, even in areas with abnormal nuclear envelope morphology. The fibroblasts were hypersensitive to heat shock, and demonstrated a delayed response to heat stress. Conclusion Dermal fibroblasts from a subject with HGPS expressing a mutant truncated lamin A have dysmorphic nuclei, hypersensitivity to heat shock, and delayed response to heat stress. This suggests that the mutant protein, even when expressed at low levels, causes defective cell stability, which may be responsible for phenotypic
Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception
Cao, Jing; Wang, Po-Kai; Tiwari, Vinod; Liang, Lingli; Lutz, Brianna Marie; Shieh, Kun-Ruey; Zang, Wei-Dong; Kaufman, Andrew G.; Bekker, Alex; Gao, Xiao-Qun; Tao, Yuan-Xiang
Background Chronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear. Results In this study, we showed that pre- or post-surgical expos...
Attenuation of pCREB and Egr1 expression in the insular and anterior cingulate cortices associated with enhancement of CFA-evoked mechanical hypersensitivity after repeated forced swim stress.
Imbe, Hiroki; Kimura, Akihisa
The perception and response to pain are severely impacted by exposure to stressors. In some animal models, stress increases pain sensitivity, which is termed stress-induced hyperalgesia (SIH). The insular cortex (IC) and anterior cingulate cortex (ACC), which are typically activated by noxious stimuli, affect pain perception through the descending pain modulatory system. In the present study, we examined the expression of phospho-cAMP response element-binding protein (pCREB) and early growth response 1 (Egr1) in the IC and ACC at 3h (the acute phase of peripheral tissue inflammation) after complete Freund's adjuvant (CFA) injection in naïve rats and rats preconditioned with forced swim stress (FS) to clarify the effect of FS, a stressor, on cortical cell activities in the rats showing SIH induced by FS. The CFA injection into the hindpaw induced mechanical hypersensitivity and increased the expression of the pCREB and Egr1 in the IC and ACC at 3h after the injection. FS (day 1, 10min; days 2-3, 20min) prior to the CFA injection enhanced the CFA-induced mechanical hypersensitivity and attenuated the increase in the expression of pCREB and Egr1 in the IC and ACC. These findings suggested that FS modulates the CFA injection-induced neuroplasticity in the IC and ACC to enhance the mechanical hypersensitivity. These findings are thought to signify stressor-induced dysfunction of the descending pain modulatory system. Copyright © 2017 Elsevier Inc. All rights reserved.
Teenagers' experiences of living with food hypersensitivity: a qualitative study.
MacKenzie, Heather; Roberts, Graham; van Laar, Darren; Dean, Taraneh
Teenagers are a high-risk group for food-hypersensitivity fatalities, engage in risk-taking behaviours and may experience impaired quality of life. Understanding their experience is important to inform their care. This study aimed to describe the lived experiences of teenagers with food hypersensitivity. Individual semi-structured interviews were conducted with 21 teenagers (13-18 yr) with food hypersensitivity to a variety of foods and analysed using a phenomenological approach. Teenagers described living with (or coming to know) food hypersensitivity (FHS) as a way of life but still found living with food hypersensitivity to be burdensome. A necessary part of living with food hypersensitivity was coping with associated burden; a variety of coping strategies were employed to this effect. Teenagers described ways in which the burden of living with food hypersensitivity was alleviated or exacerbated by others. Management of food hypersensitivity was based on an assessment of acceptable risk resulting in varying levels of precaution taking. Teenagers' understanding of their FHS and ability to cope with it needs to be regularly assessed. Educational support may be required to ensure they take an appropriate level of precautions to minimize the chance of future reactions while not over compromising their quality of life. Psychological support may be required to help them to utilize healthy adaptive strategies to cope with the stresses of living with FHS. This approach is also likely to facilitate the smooth handover of responsibility from parent to teenager.
Apolipoprotein A-II polymorphism: relationships to behavioural and hormonal mediators of obesity
Smith, CE; Ordovás, JM; Sánchez-Moreno, C; Lee, Y-C; Garaulet, M
Background The interaction between apolipoprotein A-II (APOA2) m265 genotype and saturated fat for obesity traits has been more extensively demonstrated than for any other locus, but behavioural and hormonal mechanisms underlying this relationship are unexplored. In this study, we evaluated relationships between APOA2 and obesity risk with particular focus on patterns of eating and ghrelin, a hormonal regulator of food intake. Design Cross-sectional study. Subjects Overweight and obese subjects (n = 1225) were evaluated at baseline in five weight loss clinics in southeastern Spain. Methods Behavioural data were assessed using a checklist of weight loss obstacles. Logistic regression models were fitted to estimate the risk of a specific behaviour associated with APOA2 genotype. Relationships between APOA2 genotype and saturated fat intakes for anthropometric traits and plasma ghrelin were evaluated by analysis of variance. To construct categorical variables to evaluate interactions, saturated fat intake was dichotomized into high and low according to the population median intake or as tertiles. Results Homozygous minor (CC) subjects were more likely to exhibit behaviours that impede weight loss ('Do you skip meals', odds ratio (OR) = 2.09, P=0.008) and less likely to exhibit the protective behaviour of 'Do you plan meals in advance' (OR = 0.64, P=0.034). Plasma ghrelin for CC subjects consuming low saturated fat was lower compared with (1) CC subjects consuming high saturated fat, (2) TT + TC carriers consuming low saturated fat and (3) TT+TC carriers consuming high saturated fat (all Pghrelin. Expansion of knowledge of APOA2 and obesity to include modulation of specific behaviours and hormonal mediators not only broadens understanding of gene–diet interactions, but also facilitates the pragmatic, future goal of developing dietary guidelines based on genotype. PMID:21386805
Altered gene synchrony suggests a combined hormone-mediated dysregulated state in major depression.
Chris Gaiteri
Full Text Available Coordinated gene transcript levels across tissues (denoted "gene synchrony" reflect converging influences of genetic, biochemical and environmental factors; hence they are informative of the biological state of an individual. So could brain gene synchrony also integrate the multiple factors engaged in neuropsychiatric disorders and reveal underlying pathologies? Using bootstrapped Pearson correlation for transcript levels for the same genes across distinct brain areas, we report robust gene transcript synchrony between the amygdala and cingulate cortex in the human postmortem brain of normal control subjects (n = 14; Control/Permutated data, p<0.000001. Coordinated expression was confirmed across distinct prefrontal cortex areas in a separate cohort (n = 19 subjects and affected different gene sets, potentially reflecting regional network- and function-dependent transcriptional programs. Genewise regional transcript coordination was independent of age-related changes and array technical parameters. Robust shifts in amygdala-cingulate gene synchrony were observed in subjects with major depressive disorder (MDD, denoted here "depression" (n = 14; MDD/Permutated data, p<0.000001, significantly affecting between 100 and 250 individual genes (10-30% false discovery rate. Biological networks and signal transduction pathways corresponding to the identified gene set suggested putative dysregulated functions for several hormone-type factors previously implicated in depression (insulin, interleukin-1, thyroid hormone, estradiol and glucocorticoids; p<0.01 for association with depression-related networks. In summary, we showed that coordinated gene expression across brain areas may represent a novel molecular probe for brain structure/function that is sensitive to disease condition, suggesting the presence of a distinct and integrated hormone-mediated corticolimbic homeostatic, although maladaptive and pathological, state in major depression.
Chronic hypersensitivity pneumonitis.
Pereira, Carlos Ac; Gimenez, Andréa; Kuranishi, Lilian; Storrer, Karin
Hypersensitivity pneumonitis (HSP) is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary.
Drug hypersensitivity syndrome
Rashmi Kumari
Full Text Available Drug hypersensitivity syndrome (DHS is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs, viz., phenytoin (PHT, carbamazepine (CBZ, phenobarbital (PB, lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.
Conifer Diterpene Resin Acids Disrupt Juvenile Hormone-Mediated Endocrine Regulation in the Indian Meal Moth Plodia interpunctella.
Oh, Hyun-Woo; Yun, Chan-Seok; Jeon, Jun Hyoung; Kim, Ji-Ae; Park, Doo-Sang; Ryu, Hyung Won; Oh, Sei-Ryang; Song, Hyuk-Hwan; Shin, Yunhee; Jung, Chan Sik; Shin, Sang Woon
Diterpene resin acids (DRAs) are important components of oleoresin and greatly contribute to the defense strategies of conifers against herbivorous insects. In the present study, we determined that DRAs function as insect juvenile hormone (JH) antagonists that interfere with the juvenile hormone-mediated binding of the JH receptor Methoprene-tolerant (Met) and steroid receptor coactivator (SRC). Using a yeast two-hybrid system transformed with Met and SRC from the Indian meal moth Plodia interpunctella, we tested the interfering activity of 3704 plant extracts against JH III-mediated Met-SRC binding. Plant extracts from conifers, especially members of the Pinaceae, exhibited strong interfering activity, and four active interfering DRAs (7α-dehydroabietic acid, 7-oxodehydroabietic acid, dehydroabietic acid, and sandaracopimaric acid) were isolated from roots of the Japanese pine Pinus densiflora. The four isolated DRAs, along with abietic acid, disrupted the juvenile hormone-mediated binding of P. interpunctella Met and SRC, although only 7-oxodehydroabietic acid disrupted larval development. These results demonstrate that DRAs may play a defensive role against herbivorous insects via insect endocrine-disrupting activity.
Food hypersensitivity by inhalation
Bahna Sami L
Full Text Available Abstract Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization.
Chronic hypersensitivity pneumonitis
Pereira CA
Full Text Available Carlos AC Pereira,1 Andréa Gimenez,2 Lilian Kuranishi,2 Karin Storrer 2 1Interstitial Lung Diseases Program, 2Pulmonology Postgraduate, Federal University of São Paulo, São Paulo, Brazil Abstract: Hypersensitivity pneumonitis (HSP is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. Keywords: interstitial lung diseases, extrinsic allergic alveolitis, diffuse lung disease, lung immune response, HRCT, farmers lung
Metal Hypersensitivity in Orthodontic Patients
Sandhya Maheshwari Sanjeev K
Full Text Available Orthodontic treatment of individuals with metal hypersensitivity is a matter of concern for the orthodontist. Orthodontic appliances contain metals like Nickel, Cobalt and Chromium etc. Metals may cause allergic reactions and are known as allergens. Reaction to these metals is due to biodegradation of metals in the oral cavity. This may lead to the formation of corrosion products and their exposure to the patient. Nickel is the most common metal to cause hypersensitivity reaction. Chromium ranks second among the metals, known to trigger allergic reactions. The adverse biological reactions to these metals may include hypersensitivity, dermatitis and asthma. In addition, a significant carcinogenic and mutagenic potential has been demonstrated. The orthodontist must be familiar with the best possible alternative treatment modalities to provide the safest, most effective care possible in these cases. The present article focuses on the issue of metal hypersensitivity and its management in orthodontic
RECQL4-deficient cells are hypersensitive to oxidative stress/damage: Insights for osteosarcoma prevalence and heterogeneity in Rothmund-Thomson syndrome
Werner, Sean R.; Prahalad, Agasanur K.; Yang Jieping; Hock, Janet M.
Rothmund-Thomson syndrome (RTS) is a heterogeneous disease, associated with increased prevalence of osteosarcoma in very young patients with a mutated RECQL4 gene. In this study, we tested the ability of RECQL4 deficient fibroblasts, derived from a RTS patient to recover from hydrogen peroxide (H 2 O 2 )-induced oxidative stress/damage. Immunoperoxidase staining for 8-oxo-deoxyguanosine (8-oxo-dG) formation in RTS and normal human fibroblasts were compared to assess DNA damage. We determined DNA synthesis, cell growth, cell cycle distribution, and viability in RTS and normal human fibroblasts before and after H 2 O 2 treatment. H 2 O 2 induces 8-oxo-dG formation in both RTS and normal fibroblasts. In normal human fibroblasts, RECQL4 was predominantly localized to cytoplasm; nuclear translocation and foci formation occurred in response to oxidant stimulation. After recovery from oxidant exposure, viable RTS fibroblasts showed irreversible growth arrest compared to normal fibroblasts. DNA synthesis decreased significantly in treated RTS cells, with concomitant reduction of cells in the S-phase. These results suggest that enhanced oxidant sensitivity in RECQL4 deficient fibroblasts derived from RTS patients could be attributed to abnormal DNA metabolism and proliferation failure. The ramifications of these findings on osteosarcoma prevalence and heterogeneity in RTS are discussed
The crucial role of cyclic GMP in the eclosion hormone mediated signal transduction in the silkworm metamorphoses.
Shibanaka, Y; Hayashi, H; Okada, N; Fujita, N
The signal transduction of the peptide, eclosion hormone, in the silkworm Bombyx mori appears to be mediated via the second messenger cyclic GMP throughout their life cycle. Injection of 8-bromo-cGMP induced the ecdysis behavior in pharate adults with similar latency to eclosion hormone-induced ecdysis; the moulting occurred 50-70 min after the injection. The potency of 8Br-cGMP was 10(2) fold higher than that of cGMP and the efficacy was increased by the co-injection of the phosphodiesterase inhibitor IBMX. On the other hand, in the silkworm pupal ecdysis the eclosion hormone and also 8Br-cGMP induced the moulting behavior in a dose-dependent manner. The adult development of the ability to respond to 8Br-cGMP took place concomitantly with the response to the eclosion hormone. Both the developmental time courses were shifted by a shift of light and dark cycles. Accordingly, the sensitivities to the peptide and cyclic nucleotide developed correspondently under the light and dark circadian rhythm. Thus throughout the silkworm life cycle, eclosion hormone is effective to trigger the ecdysis behavior and cGMP plays a crucial role as the second messenger in the eclosion hormone-mediated signal transduction.
355-nm hypersensitization of optical fibers
Canagasabey, A.; Canning, J.; Groothoff, N.
A study is presented on 355-nm hypersensitization of optical fibers. It is found that the intrinsic 244-nm photosensitivity of boron-codoped germanosilicate optical fibers is enhanced by 355-nm hypersensitization. Hypersensitization through standard polymer coating is also demonstrated.
Intestinal Fungal Dysbiosis Is Associated With Visceral Hypersensitivity in Patients With Irritable Bowel Syndrome and Rats.
Botschuijver, Sara; Roeselers, Guus; Levin, Evgeni; Jonkers, Daisy M; Welting, Olaf; Heinsbroek, Sigrid E M; de Weerd, Heleen H; Boekhout, Teun; Fornai, Matteo; Masclee, Ad A; Schuren, Frank H J; de Jonge, Wouter J; Seppen, Jurgen; van den Wijngaard, René M
Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in the activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in the development of IBS. We analyzed intestinal mycobiomes of patients with IBS and a rat model of visceral hypersensitivity. We used internal transcribed spacer 1-based metabarcoding to compare fecal mycobiomes of 18 healthy volunteers with those of 39 patients with IBS (with visceral hypersensitivity or normal levels of sensitivity). We also compared the mycobiomes of Long-Evans rats separated from their mothers (hypersensitive) with non-handled (normally sensitive) rats. We investigated whether fungi can cause visceral hypersensitivity using rats exposed to fungicide (fluconazole and nystatin). The functional relevance of the gut mycobiome was confirmed in fecal transplantation experiments: adult maternally separated rats were subjected to water avoidance stress (to induce visceral hypersensitivity), then given fungicide and donor cecum content via oral gavage. Other rats subjected to water avoidance stress were given soluble β-glucans, which antagonize C-type lectin domain family 7 member A (CLEC7A or DECTIN1) signaling via spleen-associated tyrosine kinase (SYK), a SYK inhibitor to reduce visceral hypersensitivity, or vehicle (control). The sensitivity of mast cells to fungi was tested with mesenteric windows (ex vivo) and the human mast cell line HMC-1. α diversity (Shannon index) and mycobiome signature (stability selection) of both groups of IBS patients differed from healthy volunteers, and the mycobiome signature of hypersensitive patients differed from that of normally sensitive patients. We observed mycobiome dysbiosis in rats that had been separated from their mothers compared with non-handled rats. Administration of fungicide to hypersensitive rats reduced their visceral hypersensitivity to normal
[Anticonvulsant hypersensitivity syndrome and lamotrigine-associated anticonvulsant hypersensitivity syndrome].
Taillia, H; Alla, P; Fournier, B; Bounolleau, P; Ouologem, M; Ricard, D; Sallansonnet-Froment, M; de Greslan, T; Renard, J-L
Anticonvulsant hypersensitivity syndrome (AHS) is defined by the association of high fever, cutaneous rash and multiorgan-system abnormalities (incidence, one in 1000 to one in 10,000 exposures). Fatal complications are described in 10%. This reaction usually develops 1 to 12 weeks after initiation of an aromatic anticonvulsant. Drug rash with eosinophilia and systemic symptoms (DRESS) can be discussed as differential diagnosis. Several hypotheses have been put forward to explain the pathogenesis of AHS. These include accumulation of toxic metabolites, antibody production and viral infection. The one based on toxic metabolites has found the greatest acceptance due to the fact that it can be proven by an in vitro test, the lymphocyte toxicity assay. In vivo, skin biopsies show characteristic findings of erythema multiform or typical leucocytoclastic angitis. The patch-test is positive in 80% of the cases. Lamotrigine-associated anticonvulsant hypersensitivity syndrome (LASH) is rare and was described in 1998. We report two new cases demonstrating the two particular configurations of apparition of LASH found in the 14 cases from the review of literature (Pubmed: anticonvulsant hypersensitivity syndrome - lamotrigine): high doses of lamotrigine (or lamotrigine in very young or old patients), and lamotrigine associated with another anti-epileptic (phenobarbital or sodium valproate). We discuss the links between DRESS after lamotrigine and LASH as illustrated in a new case.
Electromagnetic hypersensitivity: Fact or fiction?
Genuis, Stephen J.; Lipp, Christopher T.
As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home or workplace; others suggest that electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various organizations including the World Health Organization as well as some nation states are carefully exploring this clinical phenomenon in order to better explain the rising prevalence of non-specific, multi-system, often debilitating symptoms associated with non-ionizing EMR exposure. As well as an assortment of physiological complaints, patients diagnosed with EHS also report profound social and personal challenges, impairing their ability to function normally in society. This paper offers a review of the sparse literature on this perplexing condition and a discussion of the controversy surrounding the legitimacy of the EHS diagnosis. Recommendations are provided to assist health professionals in caring for individuals complaining of EHS. - Highlights: â–º Many people report symptoms when near devices emanating electromagnetic fields(EMF). â–º Electromagnetic hypersensitivity (EHS) research has generated conflicting outcomes. â–º Recent evidence suggests pathophysiological change in some individuals with EHS. â–º EHS patients consistently report profound social and personal challenges. â–º Clinicians need to be apprised of the EHS condition and potential interventions.
Climate hypersensitivity to solar forcing?
W. Soon
Full Text Available We compare the equilibrium climate responses of a quasi-dynamical energy balance model to radiative forcing by equivalent changes in CO2, solar total irradiance (Stot and solar UV (SUV. The response is largest in the SUV case, in which the imposed UV radiative forcing is preferentially absorbed in the layer above 250 mb, in contrast to the weak response from global-columnar radiative loading by increases in CO2 or Stot. The hypersensitive response of the climate system to solar UV forcing is caused by strongly coupled feedback involving vertical static stability, tropical thick cirrus ice clouds and stratospheric ozone. This mechanism offers a plausible explanation of the apparent hypersensitivity of climate to solar forcing, as suggested by analyses of recent climatic records. The model hypersensitivity strongly depends on climate parameters, especially cloud radiative properties, but is effective for arguably realistic values of these parameters. The proposed solar forcing mechanism should be further confirmed using other models (e.g., general circulation models that may better capture radiative and dynamical couplings of the troposphere and stratosphere.Key words: Meteorology and atmospheric dynamics (climatology · general or miscellaneous · Solar physics · astrophysics · and astronomy (ultraviolet emissions
The transcription factor Krüppel homolog 1 is linked to hormone mediated social organization in bees
Fan Yongliang
Full Text Available Abstract Background Regulation of worker behavior by dominant queens or workers is a hallmark of insect societies, but the underlying molecular mechanisms and their evolutionary conservation are not well understood. Honey bee and bumble bee colonies consist of a single reproductive queen and facultatively sterile workers. The queens' influences on the workers are mediated largely via inhibition of juvenile hormone titers, which affect division of labor in honey bees and worker reproduction in bumble bees. Studies in honey bees identified a transcription factor, Krüppel-homolog 1 (Kr-h1, whose expression in worker brains is significantly downregulated in the presence of a queen or queen pheromone and higher in forager bees, making this gene an ideal candidate for examining the evolutionary conservation of socially regulated pathways in Hymenoptera. Results In contrast to honey bees, bumble bees foragers do not have higher Kr-h1 levels relative to nurses: in one of three colonies levels were similar in nurses and foragers, and in two colonies levels were higher in nurses. Similarly to honey bees, brain Kr-h1 levels were significantly downregulated in the presence versus absence of a queen. Furthermore, in small queenless groups, Kr-h1 levels were downregulated in subordinate workers with undeveloped ovaries relative to dominant individuals with active ovaries. Brain Kr-h1 levels were upregulated by juvenile hormone treatment relative to a vehicle control. Finally, phylogenetic analysis indicates that KR-H1 orthologs are presence across insect orders. Though this protein is highly conserved between honey bees and bumble bees, there are significant differences between orthologs of insects from different orders. Conclusions Our results suggest that Kr-h1 is associated with juvenile hormone mediated regulation of reproduction in bumble bees. The expression of this transcription factor is inhibited by the queen and associated with endocrine mediated
Genuis, Stephen J., E-mail: sgenuis@ualberta.ca [University of Alberta (Canada); Lipp, Christopher T. [Faculty of Medicine at the University of Calgary (Canada)
As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home or workplace; others suggest that electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various organizations including the World Health Organization as well as some nation states are carefully exploring this clinical phenomenon in order to better explain the rising prevalence of non-specific, multi-system, often debilitating symptoms associated with non-ionizing EMR exposure. As well as an assortment of physiological complaints, patients diagnosed with EHS also report profound social and personal challenges, impairing their ability to function normally in society. This paper offers a review of the sparse literature on this perplexing condition and a discussion of the controversy surrounding the legitimacy of the EHS diagnosis. Recommendations are provided to assist health professionals in caring for individuals complaining of EHS. - Highlights: Black-Right-Pointing-Pointer Many people report symptoms when near devices emanating electromagnetic fields(EMF). Black-Right-Pointing-Pointer Electromagnetic hypersensitivity (EHS) research has generated conflicting outcomes. Black-Right-Pointing-Pointer Recent evidence suggests pathophysiological change in some individuals with EHS. Black-Right-Pointing-Pointer EHS patients consistently report profound social and personal challenges. Black-Right-Pointing-Pointer Clinicians need to be apprised of the EHS condition and potential interventions.
Amalgam Contact Hypersensitivity Lesion: An Unusual Presentation ...
Contact allergic reactions due to hypersensitivity to dental materials in professionals and ... Keywords: Amalgam, Amalgam contact hypersensitivity lesion, Lichenoid reaction, Oral mucosa ... was associated with mild burning sensation. The patient did ... OLLD in which oral and/or skin lesions appear in temporal association ...
Hypersensitivity pneumonitis: an immunopathology review.
Woda, Bruce A
Hypersensitivity pneumonitis (HSP) is an immunologically mediated alveolar and interstitial lung disease caused by repeated inhalation of organic dusts and some occupational agents. The pathogenesis of HSP is uncertain. A number of unexplained features of HSP remain, namely (1) why do so few exposed individuals develop clinical HSP, (2) what triggers an acute episode after prolonged periods of previous sensitization, and (3) what leads to disease progression. This article considers these issues and aims to discuss and clarify current concepts in pathogenesis. Pertinent literature review in conjunction with the author's personal interpretive opinion. Current data suggest that individuals with a T(H)1 dominant response are likely to develop clinical disease. There is also some evidence that genetic factors such as polymorphisms in the major histocompatibility complex, tumor necrosis factor alpha, and tissue inhibitor of metalloproteinase 3 are associated with the development of or resistance to the disease.
Hypersensitivity reactions in patients receiving hemodialysis.
Butani, Lavjay; Calogiuri, Gianfranco
To describe hypersensitivity reactions in patients receiving maintenance hemodialysis. PubMed search of articles published during the past 30 years with an emphasis on publications in the past decade. Case reports and review articles describing hypersensitivity reactions in the context of hemodialysis. Pharmacologic agents are the most common identifiable cause of hypersensitivity reactions in patients receiving hemodialysis. These include iron, erythropoietin, and heparin, which can cause anaphylactic or pseudoallergic reactions, and topical antibiotics and anesthetics, which lead to delayed-type hypersensitivity reactions. Many hypersensitivity reactions are triggered by complement activation and increased bradykinin resulting from contact system activation, especially in the context of angiotensin-converting enzyme inhibitor use. Several alternative pharmacologic preparations and dialyzer membranes are available, such that once an etiology for the reaction is established, recurrences can be prevented without affecting the quality of care provided to patients. Although hypersensitivity reactions are uncommon in patients receiving hemodialysis, they can be life-threatening. Moreover, considering the large prevalence of the end-stage renal disease population, the implications of such reactions are enormous. Most reactions are pseudoallergic and not mediated by immunoglobulin E. The multiplicity of potential exposures and the complexity of the environment to which patients on dialysis are exposed make it challenging to identify the precise cause of these reactions. Great diligence is needed to investigate hypersensitivity reactions to avoid recurrence in this high-risk population. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Hypersensitivity to contrast media and dyes.
Brockow, Knut; Sánchez-Borges, Mario
This article updates current knowledge on hypersensitivity reactions to diagnostic contrast media and dyes. After application of a single iodinated radiocontrast medium (RCM), gadolinium-based contrast medium, fluorescein, or a blue dye, a hypersensitivity reaction is not a common finding; however, because of the high and still increasing frequency of those procedures, patients who have experienced severe reactions are nevertheless frequently encountered in allergy departments. Evidence on allergologic testing and management is best for iodinated RCM, limited for blue dyes, and insufficient for fluorescein. Skin tests can be helpful in the diagnosis of patients with hypersensitivity reactions to these compounds. Copyright © 2014 Elsevier Inc. All rights reserved.
Cutaneous drug hypersensitivity : Immunological and genetic perspective
Kisalay Ghosh
Full Text Available Drug hypersensitivity is an unpredictable, immunologically mediated adverse reaction, clustered in a genetically predisposed individual. The role of "hapten concept" in immune sensitization has recently been contested by the "pharmacological interaction" hypothesis. After completion of the "human genome project" and with the availability of high-resolution genotyping, genetic susceptibility to hypersensitivity for certain drugs has been proved beyond doubt though the trend is ethnicity and phenotype dependent. Application of this newly acquired knowledge may reduce or abolish the morbidity and mortality associated with cutaneous drug hypersensitivity.
Immediate-type hypersensitivity to polyethylene glycols
Wenande, E; Garvey, L H
Polyethylene glycols (PEGs) or macrogols are polyether compounds widely used in medical and household products. Although generally considered biologically inert, cases of mild to life-threatening immediate-type PEG hypersensitivity are reported with increasing frequency. Nevertheless, awareness...
Classification and pathophysiology of radiocontrast media hypersensitivity.
Brockow, Knut; Ring, Johannes
Hypersensitivity reactions to radiocontrast media (RCM) are unpredictable and are a concern for radiologists and cardiologists. Immediate hypersensitivity reactions manifest as anaphylaxis, and an allergic IgE-mediated mechanism has been continuously discussed for decades. Non-immediate reactions clinically are exanthemas resembling other drug-induced non-immediate hypersensitivities. During the past years, evidence is increasing that some of these reactions may be immunological. Repeated reactions after re-exposure, positive skin tests, and presence of specific IgE antibodies as well as positive basophil activation tests in some cases, and positive lymphocyte transformation or lymphocyte activation tests in others, indicate that a subgroup of both immediate and non-immediate reactions are of an allergic origin, although many questions remain unanswered. Recently reported cases highlight that pharmacological premedication is not safe to prevent RCM hypersensitivity in patients with previous severe reactions. These insights may have important consequences. A large multicenter study on the value of skin tests in RCM hypersensitivity concluded that skin testing is a useful tool for diagnosis of RCM allergy. It may have a role for the selection of a safe product in previous reactors, although confirmatory validation data is still scarce. In vitro tests to search for RCM-specific cell activation still are in development. In conclusion, recent data indicate that RCM hypersensitivity may have an allergic mechanism and that allergological testing is useful and may indicate tolerability. Copyright 2010 S. Karger AG, Basel.
Incidence of hypersensitivity and anaphylaxis with sugammadex.
Min, K Chris; Woo, Tiffany; Assaid, Christopher; McCrea, Jacqueline; Gurner, Deborah M; Sisk, Christine McCrary; Adkinson, Franklin; Herring, W Joseph
To evaluate the incidence of hypersensitivity and anaphylaxis after administration of sugammadex. Retrospective analysis. Sugammadex clinical development program and post-marketing experience. Surgical patients and healthy volunteers who received sugammadex or placebo/comparator with anesthesia and/or neuromuscular blockade (NMB). Sugammadex administered as 2.0 mg/kg at reappearance of the second twitch, 4.0 mg/kg at 1-2 post-tetanic count, or 16.0 mg/kg at 3 min after rocuronium 1.2 mg/kg. Three analytical methods were used: 1) automated MedDRA queries; 2) searches of adverse events (AEs) consistent with treatment-related hypersensitivity reactions as diagnosed by the investigator; and 3) a retrospective adjudication of AEs suggestive of hypersensitivity by a blinded, independent adjudication committee (AC). In addition, a search of all post-marketing reports of events of hypersensitivity was performed, and events were retrospectively adjudicated by an independent AC. Anaphylaxis was determined according to Sampson Criterion 1. The pooled dataset included 3519 unique subjects who received sugammadex and 544 who received placebo. The automated MedDRA query method showed no apparent increase in hypersensitivity or anaphylaxis with sugammadex as compared to placebo or neostigmine. Similarly, there was a low overall incidence of AEs of treatment-related hypersensitivity (sugammadex and placebo or neostigmine. Finally, the retrospective adjudication of AEs suggestive of hypersensitivity showed a low incidence of hypersensitivity (0.56% and 0.21% for sugammadex 2 mg/kg and 4 mg/kg, respectively), with an incidence similar to subjects who received placebo (0.55%). There were no confirmed cases of anaphylaxis in the pooled studies. During post-marketing use, spontaneous reports of anaphylaxis occurred with approximately 0.01% of sugammadex doses. Subjects who received sugammadex with general anesthesia and/or NMB had a low overall incidence of
Entomologic evaluation of insect hypersensitivity in horses.
Greiner, E C
Potential methods of incriminating insects as the cause of insect hypersensitivity are presented. A listing of the biting midges known to attack horses in North America is presented also. An example of how species may be determined to be the cause of the hypersensitivity is given using data from a recent study in Florida. Light trap collections indicated the temporal and geographic distribution of potential contributing species and collections made by vacuuming horses further delineated species by proving they feed on horses and the correct locations on the horses to match lesion distribution. Culicoides hypersensitivity in horses in Florida seems to be caused by a series of species active and feeding on the horses at different times of the year.
Drug hypersensitivity in clonal mast cell disorders
Bonadonna, P; Pagani, M; Aberer, W
and severity of immediate hypersensitivity reactions. Mastocytosis in adults is associated with a history of anaphylaxis in 22-49%. Fatal anaphylaxis has been described particularly following hymenoptera stings, but also occasionally after the intake of drugs such as nonsteroidal anti-inflammatory drugs......, opioids and drugs in the perioperative setting. However, data on the frequency of drug hypersensitivity in mastocytosis and vice versa are scarce and evidence for an association appears to be limited. Nevertheless, clonal MC disorders should be ruled out in cases of severe anaphylaxis: basal serum...... tryptase determination, physical examination for cutaneous mastocytosis lesions, and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC...
Hypersensitivity Reactions from Excipients in Systemic Glucocorticoid Formulations
Calogiuri, Gianfranco; Garvey, Lene H; Romita, Paolo
Glucocorticoids are the most widely used drugs for the treatment of hypersensitivity, however these drugs themselves and the excipients contained in commercial corticosteroid formulations are able to induce severe immediate-type hypersensitivity reactions. Reactions involving excipients have been...
Transcriptome Analysis of Capsicum Chlorosis Virus-Induced Hypersensitive Resistance Response in Bell Capsicum.
Widana Gamage, Shirani M K; McGrath, Desmond J; Persley, Denis M; Dietzgen, Ralf G
Capsicum chlorosis virus (CaCV) is an emerging pathogen of capsicum, tomato and peanut crops in Australia and South-East Asia. Commercial capsicum cultivars with CaCV resistance are not yet available, but CaCV resistance identified in Capsicum chinense is being introgressed into commercial Bell capsicum. However, our knowledge of the molecular mechanisms leading to the resistance response to CaCV infection is limited. Therefore, transcriptome and expression profiling data provide an important resource to better understand CaCV resistance mechanisms. We assembled capsicum transcriptomes and analysed gene expression using Illumina HiSeq platform combined with a tag-based digital gene expression system. Total RNA extracted from CaCV/mock inoculated CaCV resistant (R) and susceptible (S) capsicum at the time point when R line showed a strong hypersensitive response to CaCV infection was used in transcriptome assembly. Gene expression profiles of R and S capsicum in CaCV- and buffer-inoculated conditions were compared. None of the genes were differentially expressed (DE) between R and S cultivars when mock-inoculated, while 2484 genes were DE when inoculated with CaCV. Functional classification revealed that the most highly up-regulated DE genes in R capsicum included pathogenesis-related genes, cell death-associated genes, genes associated with hormone-mediated signalling pathways and genes encoding enzymes involved in synthesis of defense-related secondary metabolites. We selected 15 genes to confirm DE expression levels by real-time quantitative PCR. DE transcript profiling data provided comprehensive gene expression information to gain an understanding of the underlying CaCV resistance mechanisms. Further, we identified candidate CaCV resistance genes in the CaCV-resistant C. annuum x C. chinense breeding line. This knowledge will be useful in future for fine mapping of the CaCV resistance locus and potential genetic engineering of resistance into Ca
The Role of Esophageal Hypersensitivity in Functional Heartburn.
Kondo, Takashi; Miwa, Hiroto
Functional heartburn (FH) is defined as a functional esophageal disorder characterized by symptoms of chronic heartburn with no apparent correlation to acid or nonacid reflux. In addition, its symptoms persist despite the lack of organic abnormalities or inflammation, esophageal motility disorders, or metabolic disorders. Although conditions presenting with esophageal symptoms without endoscopic abnormalities were previously categorized as nonerosive reflux disease, such conditions are now classified into 3 categories under Rome IV criteria: nonerosive reflux disease, reflux hypersensitivity, and FH. Although many aspects of FH remain unclear, its onset mechanism is considered to be strongly associated with peripheral or central sensitization, given the fact that its symptoms seem to be unrelated to gastroesophageal reflux. In addition, the cause of such hypersensitivity is an interesting topic in itself, and psychological factors, such as stress followed by increasing esophageal permeability are gaining attention as factors that can potentially influence this condition. There is a great unmet clinical need for therapeutic drugs that can be used to treat FH, and the development of novel drugs, diagnostic tests and biomarkers is eagerly awaited.
Dentine hypersensitivity: real or imagined | Gbadebo | Nigerian ...
Background: Dentine hypersensitivity is a common presentation of cause of pain and or discomfort with mastication which has been shown to affect the quality of life of the affected individual. It is also a common cause of presentation at the dental clinics. However, the cause, diagnosis and possible management to give relief ...
Tuberculous Lymphadenitis: Skin Delayed-Type Hypersensitivity ...
Tuberculous Lymphadenitis: Skin Delayed-Type Hypersensitivity Reaction and Cellular Immune Responses. ... The tuberculin skin test (TST) and peripheral blood mono-nuclear cells (PBMCs) culture were conducted using PPD. The cytokines were measured using commercial kits. Results: The mean TST was 24.6 ±8.0 ...
Investigation of Seminal Plasma Hypersensitivity Reactions
diseases, chronic vaginal candidiasis ); 3) establish the prevalence of BSS and localized/systemic seminal plasma protein hypersensitivity among the GW...of further investigation as our population grows. Subsequent pharmacologic treatment of this female for chronic vaginal candidiasis with an...partner.2Ř Subsequently, women experiencing localized vaginal inflammation, characterized by burning and pain and occurring immediately after contact
Severe Hyperacusis, Photophobia, and Skin Hypersensitivity
Alessandra Barbara Fioretti
Full Text Available We report a case of a patient with severe hyperacusis, photophobia, and skin hypersensitivity. The patient was initially treated with sound therapy and medical therapy for 4 months and successfully with a selective serotonin reuptake inhibitor (SSRI and cognitive behavioral therapy which improved her mood and the tolerance for sounds and light.
Digital gene expression analysis of male and female bud transition in Metasequoia reveals high activity of MADS-box transcription factors and hormone-mediated sugar pathways.
Zhao, Ying; Liang, Haiying; Li, Lan; Tang, Sha; Han, Xiao; Wang, Congpeng; Xia, Xinli; Yin, Weilun
Metasequoia glyptostroboides is a famous redwood tree of ecological and economic importance, and requires more than 20 years of juvenile-to-adult transition before producing female and male cones. Previously, we induced reproductive buds using a hormone solution in juvenile Metasequoia trees as young as 5-to-7 years old. In the current study, hormone-treated shoots found in female and male buds were used to identify candidate genes involved in reproductive bud transition in Metasequoia. Samples from hormone-treated cone reproductive shoots and naturally occurring non-cone setting shoots were analyzed using 24 digital gene expression (DGE) tag profiles using Illumina, generating a total of 69,520 putative transcripts. Next, 32 differentially and specifically expressed transcripts were determined using quantitative real-time polymerase chain reaction, including the upregulation of MADS-box transcription factors involved in male bud transition and flowering time control proteins involved in female bud transition. These differentially expressed transcripts were associated with 243 KEGG pathways. Among the significantly changed pathways, sugar pathways were mediated by hormone signals during the vegetative-to-reproductive phase transition, including glycolysis/gluconeogenesis and sucrose and starch metabolism pathways. Key enzymes were identified in these pathways, including alcohol dehydrogenase (NAD) and glutathione dehydrogenase for the glycolysis/gluconeogenesis pathway, and glucanphosphorylase for sucrose and starch metabolism pathways. Our results increase our understanding of the reproductive bud transition in gymnosperms. In addition, these studies on hormone-mediated sugar pathways increase our understanding of the relationship between sugar and hormone signaling during female and male bud initiation in Metasequoia.
Digital gene expression analysis of male and female bud transition in Metasequoia reveals high activity of MADS-box transcription factors and hormone-mediated sugar pathways
Ying eZhao
Full Text Available Metasequoiaglyptostroboidies is a famous redwood tree of ecological and economic importance, and requires more than 20 years of juvenile-to-adult transition before producing female and male cones. Previously, we induced reproductive buds using a hormone solution in juvenile Metasequoia trees as young as5-to-7years old. In the current study, hormone-treated shoots found in female and male buds were used to identify candidate genes involved in reproductive bud transition in Metasequoia. Samples from hormone-treated cone reproductive shoots and naturally occurring non-cone setting shoots were analyzed using 24 digital gene expression (DGE tag profiles using Illumina, generating a total of 69,520 putative transcripts. Next, 32 differentially and specifically expressed transcripts were determined using quantitative real-time polymerase chain reaction, including the upregulation of MADS-box transcription factors involved in male bud transition and flowering time control proteins involved in female bud transition. These differentially expressed transcripts were associated with 243 KEGG pathways. Among the significantly changed pathways, sugar pathways were mediated by hormone signals during the vegetative-to-reproductive phase transition, including glycolysis/gluconeogenesis and sucrose and starch metabolism pathways. Key enzymes were identified in these pathways, including alcohol dehydrogenase (NAD and glutathione dehydrogenase for the glycolysis/gluconeogenesis pathway, and glucanphosphorylase for sucrose and starch metabolism pathways. Our results increase our understanding of the reproductive bud transition in gymnosperms. In addition, these studies on hormone-mediated sugar pathways increase our understanding of the relationship between sugar and hormone signaling during female and male bud initiation in Metasequoia.
Case of immediate hypersensitivity to beer.
Inoue, Tomoko; Yagami, Akiko; Shimojo, Naoshi; Hara, Kazuhiro; Nakamura, Masashi; Matsunaga, Kayoko
We report here a case of immediate hypersensitivity to beer, in which a female patient developed angioedema of the eyelids shortly after consuming beer. In skin prick tests, the patient showed positive reactions to the base ingredients of beer, particularly malt and barley. The specific serum immunoglobulin E antibodies against barley and malt displayed weakly positive reactivity. To identify the immunoreactive antigens, malt and barley proteins were separated by 2-D polyacrylamide gel electrophoresis and immunoreacted with the patient's serum. The results of mass spectrometric analysis revealed that the main antigen was a protein with similarity to protein z-type serpin. Notably, the identified antigen had a molecular weight of 20-25 kDa, which is markedly smaller than that previously reported for protein Z4 (44 kDa). Taken together, these analyses indicate that a possible new antigen which belongs to the protein Z family elicits immediate hypersensitivity to beer. © 2015 Japanese Dermatological Association.
7th drug hypersensitivity meeting: part one
Carr, Daniel F.; Chung, Wen-Hung; Jenkiins, Rosalind E.; Chaponda, Mas; Nwikue, Gospel; Cornejo Castro, Elena M.; Antoine, Daniel J.; Pirmohamed, Munir; Wuillemin, Natascha; Dina, Dolores; Eriksson, Klara K.; Yerly, Daniel; Pavlos, Rebecca; Mckinnin, Elizabeth; Ostrov, David
Table of contents Oral Abstracts O1 Functionally distinct HMGB1 isoforms correlate with physiological processes in drug-induced SJS/TEN Daniel F. Carr, Wen-Hung Chung, Rosalind E. Jenkiins, Mas Chaponda, Gospel Nwikue, Elena M. Cornejo Castro, Daniel J. Antoine, Munir Pirmohamed O2 Hypersensitivity reactions to beta-lactams, does the t cell recognition pattern influence the clinical picture? Natascha Wuillemin, Dolores Dina, Klara K. Eriksson, Daniel Yerly O3 Specific binding characteristics ...
Dentin Hypersensitivity: Recent Concepts in Management
Vijay Mantri
Full Text Available Tooth sensitivity is a very common clinical presentation which can cause considerable concern for patients. Dentin hypersensitivity (DH is characterized by short sharp pain arising from exposed dentin in response to stimuli. The most widely accepted theory of how the pain occurs is Brannstrom′s hydrodynamic theory, fluid movement within the dentinal tubules. The condition generally involves the facial surfaces of teeth near the cervical aspect and is very common in premolars and canines. This condition is frequently encountered by dentists, periodontists, hygienists and dental therapists. Some dental professionals lack confidence in treating DH. The management of this condition requires a good understanding of the complexity of the problem, as well as the variety of treatments available. This review considers the etiopathogenesis, incidence, diagnosis, prevention and management of dentinal hypersensitivity. DH is diagnosed after elimination of other possible causes of the pain. Any treatment plan for DH should include identifying and eliminating predisposing etiologic factors. Professionals should appreciate the role causative factors play in localizing and initiating hypersensitive lesions. It is important to identify these factors so that prevention can be included in the treatment plan. Treatments can be self-administered by the patient at home or be applied by a dental professional in the dental office. At-home methods tend to be simple and inexpensive and can treat simultaneously generalized DH affecting many teeth Desensitizing treatment should be delivered systematically, beginning with prevention and at-home treatments. The latter may be supplemented with in-office modalities.
... can be life-saving. But chronic stress can cause both physical and mental harm. There are at least three different types of stress: Routine stress related to the pressures of work, family, and other daily responsibilities Stress brought about ...
Carboplatin hypersensitivity: evaluation and successful desensitization protocol.
Bruchim, Ilan; Goldberg, Arnon; Fishman, Ami; Confino-Cohen, Ronit
Carboplatin-induced immediate hypersensitivity reactions are relatively common among patients with gynecological malignancies. Once this occurs, the patient might be at risk for future carboplatin-induced reactions. This study evaluated the efficacy of allergic consultation, carboplatin skin testing and desensitization as a single intervention strategy in this population. Patients with a well-documented immediate reaction to carboplatin were offered allergy consultation, carboplatin skin testing and a desensitization plan in a single visit between scheduled chemotherapy sessions. Fifty-five patients with an immediate reaction were evaluated. After allergist assessment, 44 (89%) of 49 patients skin tested had a positive result. A total of 207 carboplatin desensitization cycles were administered to 49 women. Among them, 10 patients had a mild immediate hypersensitivity reaction during desensitization. Five patients subsequently tolerated carboplatin administered in the prolonged desensitization protocol. In the data presented, we propose a strategy that is both cost effective and very convenient for the patient. The diagnostic procedure, including allergist consultation and skin test, can be completed in less than 2 h. In most cases where carboplatin is indispensable, desensitization can be administered without overnight hospitalization.
Development of mechanical hypersensitivity in rats during heroin and ethanol dependence: alleviation by CRF� receptor antagonism.
Edwards, Scott; Vendruscolo, Leandro F; Schlosburg, Joel E; Misra, Kaushik K; Wee, Sunmee; Park, Paula E; Schulteis, Gery; Koob, George F
Animal models of drug dependence have described both reductions in brain reward processes and potentiation of stress-like (or anti-reward) mechanisms, including a recruitment of corticotropin-releasing factor (CRF) signaling. Accordingly, chronic exposure to opiates often leads to the development of mechanical hypersensitivity. We measured paw withdrawal thresholds (PWTs) in male Wistar rats allowed limited (short access group: ShA) or extended (long access group: LgA) access to heroin or cocaine self-administration, or in rats made dependent on ethanol via ethanol vapor exposure (ethanol-dependent group). In heroin self-administering animals, after transition to LgA conditions, thresholds were reduced to around 50% of levels observed at baseline, and were also significantly lower than thresholds measured in animals remaining on the ShA schedule. In contrast, thresholds in animals self-administering cocaine under either ShA (1 h) or LgA (6 h) conditions were unaltered. Similar to heroin LgA rats, ethanol-dependent rats also developed mechanical hypersensitivity after eight weeks of ethanol vapor exposure compared to non-dependent animals. Systemic administration of the CRF1R antagonist MPZP significantly alleviated the hypersensitivity observed in rats dependent on heroin or ethanol. The emergence of mechanical hypersensitivity with heroin and ethanol dependence may thus represent one critical drug-associated negative emotional state driving dependence on these substances. These results also suggest a recruitment of CRF-regulated nociceptive pathways associated with escalation of intake and dependence. A greater understanding of relationships between chronic drug exposure and pain-related states may provide insight into mechanisms underlying the transition to drug addiction, as well as reveal new treatment opportunities. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.
An unusual oral habit presenting as Dentin Hypersensitivity | Afolabi ...
We present the case of a 30-year-old man with an unusual oral habit- office pin chewing and filing of the front tooth which resulted in dentine hypersensitivity. Clinical relevance: The role of daily oral habits and techniques of cessation were suggested in the management of dentine hypersensitivity. Keywords: Unusual oral ...
Association between Severity of Tooth Wear and Dentinal Hypersensitivity
Ashok Ayer
Full Text Available Background & Objectives: Tooth wear (attrition, abrasion, erosion, and abfraction is perceived globally as ever increasing problem. Several outcome of the tooth wear are hypersensitivity, esthetic problems, functional impairment, annoyance to the patient, and fracture of the tooth. Among these, the measurable and more commonly reported outcome is hypersensitivity to stimuli. Although dentin hypersensitivity is a common clinical condition and is generally reported by the patient after experiencing a sharp, short pain caused by one of the several different external stimuli, it is often inadequately understood. None of the scientific literature available till date attempted to establish the relationship between tooth wear and dentin hypersensitivity which could be a key factor in monitoring those patients. The aim of the study was to estimate the association between severity of teeth wear and sensitivity in the patients with reported dentinal hypersensitivity.Materials & Methods: Fifty patients with dentin hypersensitivity were investigated for tooth wear. Tooth wear measured using exact tooth wear index and level of sensitivity to stimuli was recorded using a numerical rating scale. Results: Enamel wear at cervical region of teeth showed a positive correlation (p=.010, similarly, dentin wear at cervical region of teeth showed positive correlation and significant association (p<.001 with dentinal hypersensitivity.Conclusion: The observation supports a significant association between severities of tooth surface wear and dentinal hypersensitivity.
Clinical efficacy of toothpaste containing potassium citrate in treating dentin hypersensitivity
Shih-Ya Shen
Conclusion: The prevalence of dentin hypersensitivity in this study was 38%. The use of desensitizing toothpaste containing potassium citrate with oral hygiene instruction can effectively reduce dentin hypersensitivity.
Improved reactive nanoparticles to treat dentin hypersensitivity.
Toledano-Osorio, Manuel; Osorio, Estrella; Aguilera, Fátima S; Luis Medina-Castillo, Antonio; Toledano, Manuel; Osorio, Raquel
The aim of this study was to evaluate the effectiveness of different nanoparticles-based solutions for dentin permeability reduction and to determine the viscoelastic performance of cervical dentin after their application. Four experimental nanoparticle solutions based on zinc, calcium or doxycycline-loaded polymeric nanoparticles (NPs) were applied on citric acid etched dentin, to facilitate the occlusion and the reduction of the fluid flow at the dentinal tubules. After 24 h and 7 d of storage, cervical dentin was evaluated for fluid filtration. Field emission scanning electron microscopy, energy dispersive analysis, AFM and Nano-DMA analysis were also performed. Complex, storage, loss modulus and tan delta (δ) were assessed. Doxycycline-loaded NPs impaired tubule occlusion and fluid flow reduction trough dentin. Tubules were 100% occluded in dentin treated with calcium-loaded NPs or zinc-loaded NPs, analyzed at 7 d. Dentin treated with both zinc-NPs and calcium-NPs attained the highest reduction of dentinal fluid flow. Moreover, when treating dentin with zinc-NPs, complex modulus values attained at intertubular and peritubular dentin were higher than those obtained after applying calcium-NPs. Zinc-NPs are then supposed to fasten active dentin remodeling, with increased maturity and high mechanical properties. Zinc-based nanoparticles are then proposed for effective dentin remineralization and tubular occlusion. Further research to finally prove for clinical benefits in patients with dentin hypersensitivity using Zn-doped nanoparticles is encouraged. Erosion from acids provokes dentin hypersensitivity (DH) which presents with intense pain of short duration. Open dentinal tubules and demineralization favor DH. Nanogels based on Ca-nanoparticles and Zn-nanoparticles produced an efficient reduction of fluid flow. Dentinal tubules were filled by precipitation of induced calcium-phosphate deposits. When treating dentin with Zn-nanoparticles, complex modulus
Hypersensitivity to pain in congenital blindness
Slimani, Hocine; Danti, Sabrina; Ricciardi, Emiliano
Vision is important for avoiding encounters with objects in the environment that may imperil physical integrity. We tested whether, in the absence of vision, a lower pain threshold would arise from an adaptive shift to other sensory channels. We therefore measured heat and cold pain thresholds an...... that blind subjects are more attentive to signals of external threats. These findings indicate that the absence of vision from birth induces a hypersensitivity to painful stimuli, lending new support to a model of sensory integration of vision and pain processing......., congenitally blind subjects have lower heat pain thresholds, rate suprathreshold heat pain stimuli as more painful, and have increased sensitivity for cold pain stimuli. Thresholds for nonpainful thermal stimulation did not differ between groups. The results of the pain questionnaires further indicated...
Respiratory hypersensitivity reactions to NSAIDs in Europe
Makowska, J S; Burney, P; Jarvis, D
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper...... and lower respiratory tract disorders. METHODS: The GA(2) LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled...... prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants...
A bi-functional xyloglucan galactosyltransferase is an indispensable salt stress tolerance determinant in arabidop
Li, Wenbo; Guan, Qingmei; Wang, Zhenyu; Wang, Yingdian; Zhu, Jianhua
Salinity is an abiotic stress that substantially limits crop production worldwide. To identify salt stress tolerance determinants, we screened for Arabidopsis mutants that are hypersensitive to salt stress and designated these mutants as short root
Jasmonic acid signaling modulates ozone-induced hypersensitive cell death.
Rao, M V; Lee, H; Creelman, R A; Mullet, J E; Davis, K R
Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent signaling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O(3)) exposure activates a hypersensitive response (HR)-like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling in influencing O(3)-induced cell death. Expression of salicylate hydroxylase (NahG) in Cvi-0 reduced O(3)-induced cell death. Methyl jasmonate (Me-JA) pretreatment of Cvi-0 decreased O(3)-induced H(2)O(2) content and SA concentrations and completely abolished O(3)-induced cell death. Cvi-0 synthesized as much JA as did Col-0 in response to O(3) exposure but exhibited much less sensitivity to exogenous Me-JA. Analyses of the responses to O(3) of the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic relationship between JA- and SA-signaling pathways in controlling the magnitude of O(3)-induced HR-like cell death.
Dilemma in the Diagnosis of Povidone-Iodine Hypersensitivity
Patil N
Full Text Available Povidone-iodine is a commonly used antiseptic solution in surgical practice. Almost every patient who needs a minor or a major surgical procedure (sometimes, a medical procedure too gets exposed to this antiseptic. Even though the use of this antiseptic is widespread, the number of cases reporting hypersensitivity to it is meagre. This case report highlights a case of povidone-iodine – induced hypersensitivity, which presented a great difficulty in diagnosis, due to the usage of other drugs that could have been more likely causes for this hypersensitivity.
Outpatient desensitization in selected patients with platinum hypersensitivity reactions.
O'Malley, David M; Vetter, Monica Hagan; Cohn, David E; Khan, Ambar; Hays, John L
Platinum-based chemotherapies are a standard treatment for both initial and recurrent gynecologic cancers. Given this widespread use, it is important to be aware of the features of platinum hypersensitivity reactions and the subsequent treatment of these reactions. There is also increasing interest in the development of desensitization protocols to allow patients with a history of platinum hypersensitivity to receive further platinum based therapy. In this review, we describe the management of platinum hypersensitivity reactions and the desensitization protocols utilized at our institution. We also describe the clinical categorizations utilized to triage patients to appropriate desensitization protocols. Copyright © 2017 Elsevier Inc. All rights reserved.
Disturbances of motility and visceral hypersensitivity in irritable bowel syndrome: biological markers or epiphenomenon.
Quigley, Eamonn M M
Motility and visceral hypersentitivity are regarded as the primary mechanisms of symptom development in irritable bowel syndrome(IBS). While a variety of motor abnormalities have been described throughout the gastrointestinal tract in IBS, their specificity and relationship to symptoms remain unclear. Visceral hypersensitivity is ubiquitous in functional gastrointestinal disease and is especially common in IBS. Again, however, its specificity for IBS has been questioned. Many factors, including stress and psychopathology,complicate the interpretation of these phenomena and new re-search suggests that mucosal inflammation and luminal factors may be more fundamental to the etiology of this common disorder.
Progressive anticonvulsant hypersensitivity syndrome associated with change of drug product
Sabroe, T.P.; Sabers, A.
This report describes the laboratory and physical manifestations of lamotrigine-like toxicity in a young man with refractory epilepsy receiving lamotrigine presenting as anticonvulsant hypersensitivity syndrome (AHS) associated with an abrupt change of drug product Udgivelsesdato: 2008/6...
The radiation hypersensitivity of cells at mitosis.
Stobbe, C C; Park, S J; Chapman, J D
Mitotic cells are hypersensitive to ionizing radiation, exhibiting single-hit inactivation coefficients near to those of repair deficient cell lines and lymphocytes. To elucidate possible mechanisms for this hypersensitivity, the kinetics of oxygen radiosensitization, the proportion of indirect effect by OH radicals and the kinetics of radiation-induced DNA strand breakage in the chromatin of mitotic cells were investigated. Synchronized populations of >90% mitotic HT-29 cells were obtained by the mitotic shake-off method. Cells were irradiated at indirect effect of OH radicals was investigated with the radical scavenger, DMSO. DNA strand breakage was measured by the comet assay. Mitotic HT-29 cell inactivation is well described by a single-hit inactivation coefficient (alpha) of 1.14 +/- 0.06 Gy(-1). The oxygen enhancement ratio of mitotic cells (at 10% survival) was found to be approximately 2.0, significantly lower than the value of 2.8 measured for interphase (asynchronous) cells. More than 60% of mitotic cell killing was eliminated when the media contained 2 M DMSO, indicating that indirect effect is as important in the killing of mitotic cells as it is for interphase cells. The chromatin in mitotic cells was found to be ~2.8 times more sensitive to radiation-induced DNA single-strand breakage than the chromatin of interphase cells. The alpha-inactivation coefficient of mitotic HT-29 cells was ~30 times larger than that of interphase cells. Mitotic cell chromatin appears to contain intrinsic DNA breaks that are not lethal. In addition, chromatin in mitotic cells was found to be more susceptible to radiation-induced DNA strand-breakage than the dispersed chromatin of interphase cells. How the enhanced production of these simple DNA lesions (that are usually reparable) translates into the lethal (non-reparable) events associated with alpha-inactivation is not known. The compaction/dispersion status of DNA throughout the cell cycle appears to be an important
A Rare Diabetic Autonomic Neuropathy: Carotid Sinus Hypersensitivity
Full Text Available Carotid sinus hypersensitivity is a common cause of fainting and falls in the elderly, and can be diagnosed by carotid sinus massage. We present a 67-year-old diabetic man who was admitted with hyperglycemia. During thyroid examination, clouding of consciousness occurred with unilateral palpation. Asystole was documented for 4.8 seconds and suspected for 7 seconds upon carotid sinus massage. A cardioverter defibrillator was implanted. Carotid sinus hypersensitivity should be kept in mind when examining diabetic patients.
Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update
Sánchez-Borges, Mario; Caballero-Fonseca, Fernan; Capriles-Hulett, Arnaldo; González-Aveledo, Luis
After beta lactam antibiotics, hypersensitivity reactions to nonsteroidal antiinflammatory drugs are the second cause of hypersensitivity to drugs. Acute manifestations affect the respiratory tract (aspirin exacerbated respiratory disease), the skin (urticaria and angioedema), or are generalized (anaphylaxis). Correct diagnosis and treatment in order to prevent unnecessary morbidity and the potential risk of death from these severe reactions, and to provide proper medical advice on future dru...
An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity
Chun-Bing Chen
Full Text Available Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS/drug-induced hypersensitivity syndrome (DIHS, or Stevens–Johnson syndrome (SJS/toxic epidermal necrolysis (TEN. Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs. The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity.
Abe, Riichiro; Pan, Ren-You; Wang, Chuang-Wei
Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR) molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity. PMID:29651444
Desensitization for Drug Hypersensitivity to Chemotherapy and Monoclonal Antibodies.
Bonamichi-Santos, Rafael; Castells, Mariana
Chemotherapies drugs and monoclonal antibodies are key components of the treatment of cancer patients and patients with chronic inflammatory conditions to provide increase in life expectancy and quality of life. Their increased use has lead to an increase in drugs hypersensitivity reactions (DHR) worldwide. DHR to those agents prevented their use and promoted the use of second line therapies to protect patients' hypersensitive reactions and anaphylaxis. Second line medications may not fully address the patients' medical condition and it is desirable to keep patients on first line therapy. Drug hypersensitivity symptoms can range from mild cutaneous reactions to life-threatening anaphylaxis. Rapid drug desensitization (RDD) is a novel approach to the management of drug hypersensitivity reactions which are IgE and non-IgE mediated. Through the diferent desensitization protocols patients can receive the full dose of the medications that they have presented a hypersensitive reaction and been protected against anaphylaxis. This review looks at the current literature on hypersensitivity reactions (HSR) to chemotherapy drugs and monoclonal antibodies and the potential use of RDD for their management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
... taking care of an aging parent. With mental stress, the body pumps out hormones to no avail. Neither fighting ... with type 1 diabetes. This difference makes sense. Stress blocks the body from releasing insulin in people with type 2 ...
Nonimmediate hypersensitivity reactions to iodinated contrast media.
Gómez, Enrique; Ariza, Adriana; Blanca-López, Natalia; Torres, Maria J
To provide a detailed analysis of the latest findings on the mechanisms underlying the nonimmediate reactions to iodinated contrast media and comment on the recent advances in diagnosis, focusing on the roles of the skin test, drug provocation test (DPT), and lymphocyte transformation test (LTT). Several studies have reported new findings supporting an important role for T-lymphocytes in the nonimmediate reactions to iodinated contrast media. The LTT has been used as an in-vitro tool for diagnosis, but with variable results. However, the inclusion of autologous monocyte-derived dendritic cells as professional antigen-presenting cells has improved the sensitivity of this test. Regarding in-vivo diagnosis, although skin testing has been routine, it has now been shown that its sensitivity and negative predictive value are low. Recent studies have demonstrated that the DPT is a well tolerated and useful procedure that is necessary to confirm the diagnosis of nonimmediate hypersensitivity reactions to iodinated contrast media. Nonimmediate reactions to contrast media are usually T-cell mediated. Diagnosis is based on skin testing, although its sensitivity and negative predictive value are not optimal. Consequently, drug provocation testing is often needed to confirm the diagnosis and also to seek alternative contrast media that can be tolerated.
Severe dapsone hypersensitivity syndrome in a child
So Yoon Choi
Full Text Available Dapsone (4,4'-diaminodiphenylsulfone, DDS, a potent anti-inflammatory agent, is widely used in the treatment of leprosy and several chronic inflammatory skin diseases. Dapsone therapy rarely results in development of dapsone hypersensitivity syndrome, which is characterized by fever, hepatitis, generalized exfoliative dermatitis, and lymphadenopathy. Here, we describe the case of an 11-year-old Korean boy who initially presented with high fever, a morbilliform skin rash, generalized lymphadenopathy, hepatosplenomegaly, and leukopenia after 6 weeks of dapsone intake. Subsequently, he exhibited cholecystitis, gingivitis, colitis, sepsis, aseptic meningitis, disseminated intravascular coagulation, syndrome of inappropriate antidiuretic hormone secretion, pneumonia, pleural effusions, peritonitis, bronchiectatic changes, exfoliative dermatitis, and acute renal failure. After 2 months of supportive therapy, and prednisolone and antibiotic administration, most of the systemic symptoms resolved, with the exception of exfoliative dermatitis and erythema, which ameliorated over the following 4 months. Agranulocytosis, atypical lymphocytosis, aseptic meningitis, and bronchiectatic changes along with prolonged systemic symptoms with exfoliative dermatitis were the most peculiar features of the present case.
Hazards of the 'hard cash': hypersensitivity pneumonitis.
Kupeli, Elif; Karnak, Demet; Sak, Serpil Dizbay; Kayacan, Oya
Hypersensitivity pneumonitis (HP) is a nonimmunoglobulin E-related immune-mediated parenchymal lung disease. A 45-year-old woman who was a lifelong nonsmoker with a six-month history of frequent episodes of cough and dyspnea was admitted to hospital. She had been working as a money counter for 20 years at a central bank. Bibasilar crackles on lung auscultation, ground-glass opacities and a mosaic pattern on high-resolution computed tomography, restrictive abnormality on pulmonary function tests and mild hypoxemia were the prominent findings. Bronchoalveolar lavage fluid analysis revealed a predominance of CD4-positive T cells, and she tested positive on her natural challenge test. She was diagnosed with subacute HP based on established criteria. She was advised to discontinue counting fresh banknotes. Prednisolone was commenced, then tapered to discontinue in the ensuing six months. Clinical and radiological improvement was achieved within two months. To the authors' knowledge, the present report is the first to describe 'hard cash HP', possibly caused by chipping dust or printing dye.
Visceral pain hypersensitivity in functional gastrointestinal disorders.
Farmer, A D; Aziz, Q
Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders whose diagnostic criteria are symptom based in the absence of a demonstrable structural or biochemical abnormality. Chronic abdominal pain or discomfort is a defining characteristic of these disorders and a proportion of patients may display heightened pain sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity (VPH). We examined the most recent literature in order to concisely review the evidence for some of the most important recent advances in the putative mechanisms concerned in the pathophysiology of VPH. VPH may occur due to anomalies at any level of the visceral nociceptive neuraxis. Important peripheral and central mechanisms of sensitization that have been postulated include a wide range of ion channels, neurotransmitter receptors and trophic factors. Data from functional brain imaging studies have also provided evidence for aberrant central pain processing in cortical and subcortical regions. In addition, descending modulation of visceral nociceptive pathways by the autonomic nervous system, hypothalamo-pituitary-adrenal axis and psychological factors have all been implicated in the generation of VPH. Particular areas of controversy have included the development of efficacious treatment of VPH. Therapies have been slow to emerge, mainly due to concerns regarding safety. The burgeoning field of genome wide association studies may provide further evidence for the pleiotropic genetic basis of VPH development. Tangible progress will only be made in the treatment of VPH when we begin to individually characterize patients with FGIDs based on their clinical phenotype, genetics and visceral nociceptive physiology.
Gelofen Induced Hypersensitivity: A Rare Case Report
M. Nikkhah Rankohie
Full Text Available Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs are drugs commonly pre-scribed in dental practice for the management of pain and swelling. But, rarely hypersensitiv-ity reactions are reported. Case Report: A 28 year old woman underwent periodontal plastic surgery (gingival graft. Postoperative analgesics (400 mg Gelofen ,oral and antibiotics were administrated for the patient. Three hours after discharge of patient, she complained of redness, itching , rapid swelling of her eyes in 10 minutes, and watery eye discharge 1 hour after taking the drugs. She was treated with 8mg/2ml mg Dexamethasone IM at the dental department and with Hy-drocortisone 100mg/ml IM and antihistamine drugs at the hospital. Conclusion: There are no published protocols and sensitivity and specifity of skin pick testing and patch testing for Gelofen. So avoidance of re-exposure is the best management strategy. The use of Cox-2 specific medications would be a proper alternative for pain relief. (Sci J Hamadan Univ Med Sci 2016; 23 (2:179-183
Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.
Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H
Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. © 2015 The Authors. European Journal of Neuroscience published by Federation of
Hypersensitivity myocarditis associated with ephedra use.
Zaacks, S M; Klein, L; Tan, C D; Rodriguez, E R; Leikin, J B
Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.
Hypersensitivity pneumonitis: a complex lung disease.
Riario Sforza, Gian Galeazzo; Marinou, Androula
Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a respiratory syndrome involving the lung parenchyma and specifically the alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic reaction. Such reaction is secondary to a repeated and prolonged inhalation of different types of organic dusts or other substances to which the patient is sensitized and hyper responsive, primarily consisting of organic dusts of animal or vegetable origin, more rarely from chemicals. The prevalence of HP is difficult to evaluate because of uncertainties in detection and misdiagnosis and lacking of widely accepted diagnostic criteria, and varies considerably depending on disease definition, diagnostic methods, exposure modalities, geographical conditions, agricultural and industrial practices, and host risk factors. HP can be caused by multiple agents that are present in work places and in the home, such as microbes, animal and plant proteins, organic and inorganic chemicals. The number of environment, settings and causative agents is increasing over time. From the clinical point of view HP can be divided in acute/subacute and chronic, depending on the intensity and frequency of exposure to causative antigens. The mainstay in managing HP is the avoidance of the causative antigen, though the complete removal is not always possible due to the difficulties to identify the agent or because its avoidance may lead to major changes in life style or occupational settings. HP is a complex syndrome that needs urgently for more stringent and selective diagnostic criteria and validation, including wider panels of IgG, and a closer collaboration with occupational physicians, as part of a multidisciplinary expertise.
Hypersensitivity to thrombin of platelets from hypercholesterolemic rats
Winocour, P.D.; Rand, M.L.; Kinlough-Rathbone, R.L.; Mustard, J.F.
Hypersensitivity of platelets to thrombin has been associated with hypercholesterolemia. The authors have examined the mechanisms involved in this hypersensitivity. Rats were given diets rich in milk fat and containing added cholesterol and taurocholate to produce hypercholesterolemia (HC) (262 +/- 25 mg%) or added sitosterol as a normocholesterolemic control (NC) (89 +/- 6 mg%). Washed platelets were prelabelled with 14 C-serotonin. In the presence of acetylsalicyclic acid (ASA) (to inhibit thromboxane A 2 (TXA 2 ) formation) and creatine phosphate/creatine phosphokinase (CP/CPK) (to remove released ADP), HC platelets aggregated more (26 +/- 1%) and released more 14 C (9.1 +/- 2.0%) than NC platelets (aggregation: 0%, p 14 C release: 1.5 +/- 0.5%, p 2 formation is involved in the hypersensitivity of HC platelets to thrombin. Total binding of 125 I-thrombin to HC platelets was less than that to NC platelets but HC platelets were smaller and had less protein than NC platelets; the thrombin binding per mg platelet protein was the same for HC and NC platelets, indicating that hypersensitivity to thrombin of HC platelets does not result from increased thrombin binding. Thus, hypersensitivity of HC platelets to thrombin is not due to TXA 2 formation, the action of released ADP or increased thrombin binding
Asthma and chemical hypersensitivity: prevalence, etiology, and age of onset.
Caress, S M; Steinemann, A C
This study investigates asthma's national prevalence and potential overlap with chemical hypersensitivity. It also examines asthma's etiology, age of onset, and demographic characteristics. Data were collected from a geographically weighted random sample of the continental U.S. (1058 cases), in four seasonal cohorts (2005-2006). The study found that 12.9% of the sample report asthma, 11.6% report chemical hypersensitivity, and 31.4% of those with asthma report chemical hypersensitivity. Among asthmatics, 38% report irritation from scented products, 37.2% report health problems from air fresheners, and 13.6% report their asthma was caused by toxic exposure. Asthma cases affected each racial/ethic group in roughly the same proportion, with nearly 50% classified as childhood onset.
Multinational experience with hypersensitivity drug reactions in Latin America.
Jares, Edgardo José; Sánchez-Borges, Mario; Cardona-Villa, Ricardo; Ensina, Luis Felipe; Arias-Cruz, Alfredo; Gómez, Maximiliano; Barayazarra, Susana; Bernstein, Jonathan A; Serrano, Carlos D; Cuello, Mabel Noemi; Morfin-Maciel, Blanca María; De Falco, Alicia; Cherrez-Ojeda, Iván
Epidemiologic drug allergy data from Latin America are scarce, and there are no studies on specific procedures focusing on this topic in Latin America. To assess the clinical characteristics and management of hypersensitivity drug reactions in different Latin American countries. An European Network of Drug Allergy questionnaire survey was implemented in 22 allergy units in 11 Latin American countries to report on consecutive patients who presented with a suspected hypersensitivity drug reaction. Each unit used its own protocols to investigate patients. Included were 868 hypersensitivity drug reactions in 862 patients (71% of adults and elderly patients were women and 51% of children were girls, P = .0001). Children presented with less severe reactions than adults and elderly patients (P Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
FOOD HYPERSENSITIVITY AND PRODUCTS OF ANIMAL ORIGIN RESOURCES
A. B. Lisitsyn
Full Text Available The number of people with food hypersensitivity, namely food intolerance and food allergies, grows every year. Food intolerance is classified into following types: enzymopathy; leaky gut syndrome; psychogenic food intolerance; detoxification insufficiency and true food intolerance. Food allergens mainly are glycoproteins, haptensor polypeptides. Most cases of food allergy are IgE-mediated allergic reactions. Recent discoveries in medicine, detailing and classification of food hypersensitivity require further researches to develop modern techniques and product recipes with specified propertiesfor consumers with food hypersensitivity. Existing technologies are based on the elimination and or reduction of the content of the allergenic substance in food. The article provides an overview of causes of food intolerance and food allergy, legislative background, a list of food allergens and methods of control, market profile of hypoallergenic produce and scientific approaches to creating hypoallergenic food products based on raw materials of animal origin.
[Adaptive desensitization for acetylsalicylic acid hypersensitivity: A success story?].
Mühlmeier, G; Hausch, R; Maier, H
Adaptive desensitization still remains the only causative therapy for acetylsalicylic acid (ASA) hypersensitivity and is carried out nearly worldwide. To date there are hardly any data available on disease development under current desensitization therapy and longitudinal data in particular are missing. Out of a large collective of patients with proven hypersensitivity to ASA, 194 patients with initiated desensitization treatment were observed for periods up to 5 years (average 32 months). Patients with immediate reactions to systemic challenge tests revealed a response rate of 77% after 12 months of therapy. In this period 12% reached complete remission, 38% showed a clear reduction in symptoms, 32% reached partial remission, 13% remained unchanged and 5% suffered from disease progression. Adaptive desensitization therapy for hypersensitivity to ASA has been shown to be an effective causative therapy and chronic hyperplastic sinusitis as well as bronchial asthma could be improved. For the determination of maintenance dosages and required time periods more data are needed.
Metal hypersensitivity after knee arthroplasty: fact or fiction?
Innocenti, Massimo; Vieri, Berti; Melani, Tommaso; Paoli, Tommaso; Carulli, Christian
Hypersensitivity to metals in the general population has an incidence of about 15%, and in rising also for the higher number of joint replacements in the last decades. Total Knee Arthroplasty (TKA) represents the most performed orthopaedic procedure during last years, and it seems to be particularly associated with sensitization after surgery. On the other hand, there is a rising amount of patients with painful but well implanted and functioning TKAs: in certain cases, after the exclusion of the most frequent causes of failure, a condition of hypersensitivity may be found, and a revision with anallergic implants is mandatory. The present study is a review of the potential problems related to hypersensitivity in TKA, its possible diagnostic procedures, and the surgical options to date available. Medical history, patch testing, and other specific laboratory assays are useful to assess a status of metals hypersensitivity before surgery in subjects undergoing a knee replacement, or even after TKA in patients complaining pain in otherwise well implanted and aligned prostheses. However, few groups worlwide deal with such condition, and all proposed diagnostic protocols may be considered still today conjectural. On the other hand, these represent the most updated knowledge of this condition, and may be useful for both the patient and the orthopaedic surgeon. Once assessed a possible or ascertained allergy to metals, several options are available for primary andr revision knee surgery, in order to avoid the risk of hypersensitivity. A review of the recent publications on this topic and an overview of the related aspects has been made to understand a condition to date considered negligible. Hypersensitivity to metals has not to be nowadays considered a "fiction", but rather a possible preoperative risk or a postoperative cause of failure of TKA. Crucial is the information of patients and the medical history, associated in suspect cases to laboratory testings. Today in the
Efficacy of two commercially available dentifrices in reducing dentinal hypersensitivity
Prasad KVV
Full Text Available Objective: A parallel design clinical study evaluated reduction in hypersensitivity after brushing for 12 weeks with Anchor toothpaste (containing potassium citrate, zinc citrate, triclosan and sodium monofluorophosphate (test and Colgate Total (sodium fluoride, silica, triclosan and copolymer (control dentifrices. Materials and Methods: Sixty adults with sensitivity to hot and cold stimulus in at least two tooth surfaces were stratified at the baseline examination by tactile, hot and cold stimuli scores in two balanced groups. Subjects were randomly allocated the test and control dentifrices and evaluated after 6 and 12 weeks of dentifrice use for hypersensitivity. Results: The two teeth that were selected in each patient were designated as two different sets. The 12 th -week scores as compared to baseline scores for tactile, heat and cold tests in the test group showed a reduction in tooth hypersensitivity by 36.67% (P < 0.01, 20.35% (P < 0.01 and 53.64 % (P < 0.01, respectively, in the first set of teeth and 43.75% (P < 0.01, 24.48% (P < 0.01 and 59.78% (P < 0.01, respectively, in the second set of teeth. The 12 th -week scores as compared to baseline scores for tactile, heat and cold tests in the control group showed a reduction in tooth hypersensitivity by 42.86% (P < 0.01, 13.02% (P < 0.01 and 45.14% (P < 0.01, respectively, in the first set of teeth and 40% (P < 0.01, 16.59% (P < 0.01 and 44.16% (P < 0.01, respectively, in the second set of teeth. Conclusions: Both the products reduced dentinal hypersensitivity in the study subjects at the end of the 12-week period. However, there was no statistically significant difference in reduction in hypersensitivity between the two products.
Corticosteroid hypersensitivity studies in a skin allergy clinic.
Berbegal, L; DeLeon, F J; Silvestre, J F
Corticosteroids can cause hypersensitivity reactions, particularly delayed-type allergic reactions. A new classification system for testing hypersensitivity to corticosteroids distributes the drugs into 3 groups according to molecular structure; patients are classified according to whether they are allergic to agents in 1 or more of the groups. We aimed to describe the clinical characteristics of corticosteroid-allergic patients treated at our clinic and apply the new classification system to them; we also compared these patients' characteristics to those of others treated at our clinic. Retrospective study of cases of delayed-type corticosteroid hypersensitivity treated in the skin allergy clinic of a tertiary level hospital over an 11-year period. We reviewed the records of 2857 patients, finding 33 with at least one positive patch test result showing corticosteroid hypersensitivity. Atopic dermatitis and hand involvement were less common in our corticosteroid-allergic patients. All were allergic to a group 1 corticosteroid (most often, budesonide, the culprit in 87.9%). Testing with a specific corticosteroid series revealed that 14 (42.4%) were also allergic to corticosteroids in group 2 and/or group 3. None were allergic exclusively to group 2 or group 3 agents. Twenty-one patients were exposed to a corticosteroid cream from a group their patch test results indicated allergy to; 13 of them (61.9%) did not develop a hypersensitivity reaction. The Spanish standard series only contains group 1 corticosteroids. In the interest of improving allergy management, we recommend testing with a specific corticosteroid series and a patient's own creams whenever patch testing with a standard series reveals a hypersensitivity reaction to corticosteroids. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.
Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs)
Nissen, Christoffer V; Bindslev-Jensen, Carsten; Mørtz, Charlotte G
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are reported to be the second most common cause of drug hypersensitivity. In 2011, experts from the EAACI/ENDA group and GA(2)LEN proposed a new classification system for NSAID hypersensitivity. The aim of this study was to classify...... responders reacted to non-pyrazolone drugs. Only one patient could not be classified according to the EAACI/ENDA system. An overlap between respiratory and cutaneous symptoms was found in 15/39 (38%) of patients. CONCLUSIONS: All but one of our patients could be classified according to the EAACI...
Cutaneous and systemic hypersensitivity reactions to metallic implants
Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C
Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous....... However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis...
Functional dyspepsia: The role of visceral hypersensitivity in its pathogenesis
John Keohane; Eamonn M M Quigley
Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists.It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process.The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review,we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.
Functional dyspepsia: the role of visceral hypersensitivity in its pathogenesis.
Keohane, John
Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.
Association of HLA genotypes with phenobarbital hypersensitivity in children.
Manuyakorn, Wiparat; Mahasirimongkol, Surakameth; Likkasittipan, Plernpit; Kamchaisatian, Wasu; Wattanapokayakit, Sukanya; Inunchot, Wimala; Visudtibhan, Anannit; Wichukchinda, Nuanjun; Benjaponpitak, Suwat
Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes (MPs) to severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drug hypersensitivity has been demonstrated to be associated with variations in the HLA genotypes. This study was to investigate the association between the variations of HLA genotypes and phenobarbital hypersensitivity in Thai children. The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included SCARs and MPs. The control patients were Thai children of a corresponding age who had taken phenobarbital for at least 12 weeks without any hypersensitivity reaction. Blood samples were collected for HLA genotyping by using a reverse-sequence-specific oligonucleotide (SSO) probes method. The carrier rates of HLA alleles were compared between 47 cases (27 SCARs and 20 MPs) and 54 controls. The carrier rates of HLA-A*01:01 and HLA-B*13:01 were significantly higher in the phenobarbital-induced SCARs than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [OR] 11.66, 95% confidence interval [CI] 1.21-578.19; 37.04% vs. 11.11%, p = 0.009, OR 4.60, 95%CI 1.29-17.98). There was a trend of a higher carrier rate of HLA-C*06:02 in the phenobarbital-induced SCARs when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, OR 3.31, 95% CI 0.88-13.31). In contrast to the phenobarbital-induced SCARs, only the HLA-A*01:01 carrier rate in the phenobarbital-induced MPs was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, OR 12.69, 95% CI 1.15-661.62). An association between phenobarbital hypersensitivity and HLA-A*01:01 and HLA-B*13:01 has been demonstrated in Thai children
Keller, Hanne Dauer
Kapitlet handler om stress som følelse, og det trækker primært på de få kvalitative undersøgelser, der er lavet af stressforløb.......Kapitlet handler om stress som følelse, og det trækker primært på de få kvalitative undersøgelser, der er lavet af stressforløb....
Stress !!!
Fledderus, M.
Twee op de vijf UT-studenten hebben last van ernstige studiestress, zo erg zelfs dat het ze in hun privéleven belemmert. Die cijfers komen overeen met het landelijk beeld van stress onder studenten. Samen met 14 andere universiteits- en hogeschoolbladen enquêteerde UT Nieuws bijna 5500 studenten. Opvallend is dat mannelijke studenten uit Twente zich veel minder druk lijken te maken over hun studie. Onder vrouwen ligt de stress juist erg hoog ten opzichte van het landelijk gemiddelde.
Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands
Schurink, A.; Wolc, A.; Ducro, B.J.; Frankena, K.; Garrick, D.J.; Dekkers, J.C.M.; Arendonk, van J.A.M.
Background: Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite
Agrobacterium -induced hypersensitive necrotic reaction in plant cells
High necrosis and poor survival rate of target plant tissues are some of the major factors that affect the efficiency of Agrobacterium-mediated T-DNA transfer into plant cells. These factors may be the result of, or linked to, hypersensitive defense reaction in plants to Agrobacterium infection, which may involve the recognition ...
Incidence of abacavir hypersensitivity reactions in euroSIDA
Bannister, Wendy P; Friis-Møller, Nina; Mocroft, Amanda
BACKGROUND: The aim of the study was to investigate the incidence of abacavir-related hypersensitivity reaction (HSR) and associated deaths in EuroSIDA HIV-1-infected patients. METHODS: Poisson regression models were developed to compare incidence of abacavir discontinuation according to the line...
Auditory Hypersensitivity in Children with Autism Spectrum Disorders
Lucker, Jay R.
A review of records was completed to determine whether children with auditory hypersensitivities have difficulty tolerating loud sounds due to auditory-system factors or some other factors not directly involving the auditory system. Records of 150 children identified as not meeting autism spectrum disorders (ASD) criteria and another 50 meeting…
Culicoides species attracted to horses with and without insect hypersensitivity
Rijt, van der R.; Boom, van den R.; Jongema, Y.; Sloet van Oldruitenborgh-Oosterbaan, M.M.
The aims of this study were to determine (1) which species of Culicoides is most commonly attracted to horses, (2) whether horses suffering insect hypersensitivity attract more Culicoides spp. than unaffected horses, and (3) the times when Culicoides spp. are most active. Horses affected by insect
Trichloroethylene hypersensitivity syndrome: a disease of fatal outcome.
Jung, Hyun Gul; Kim, Hyung Hun; Song, Bong Gun; Kim, Eun Jin
Trichloroethylene is commonly used as an industrial solvent and degreasing agent. The clinical features of acute and chronic intoxication with trichloroethylene are well-known and have been described in many reports, but hypersensitivity syndrome caused by trichloroethylene is rarely encountered. For managing patients with trichloroethylene hypersensitivity syndrome, avoiding trichloroethylene and initiating glucocorticoid have been generally accepted. Generally, glucocorticoid had been tapered as trichloroethylene hypersensitivity syndrome had ameliorated. However, we encountered a typical case of trichloroethylene hypersensitivity syndrome refractory to high dose glucocorticoid treatment. A 54-year-old Korean man developed jaundice, fever, red sore eyes, and generalized erythematous maculopapular rashes. A detailed history revealed occupational exposure to trichloroethylene. After starting intravenous methylprednisolone, his clinical condition improved remarkably, but we could not reduce prednisolone because his liver enzyme and total bilirubin began to rise within 2 days after reducing prednisolone under 60 mg/day. We recommended an extended admission for complete recovery, but the patient decided to leave the hospital against medical advice. The patient visited the emergency department due to pneumonia and developed asystole, which did not respond to resuscitation.
Cyproterone acetate in the treatment of oestrogen hypersensitivity vulvovaginitis.
Nguyen, Yvonne; Bradford, Jennifer; Fischer, Gayle
Oestrogen hypersensitivity vulvovaginitis is a rare chronic cyclical vulvovaginitis responsive to oestrogen suppression or antagonism. We present a case series of 16 patients with refractory cyclical vulvovaginitis, all of whom responded to oestrogen suppression with cyproterone acetate. © 2017 The Australasian College of Dermatologists.
Twee op de vijf UT-studenten hebben last van ernstige studiestress, zo erg zelfs dat het ze in hun privéleven belemmert. Die cijfers komen overeen met het landelijk beeld van stress onder studenten. Samen met 14 andere universiteits- en hogeschoolbladen enquêteerde UT Nieuws bijna 5500 studenten.
Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome - Is There a Clinical Relevance?
Jan Manousek
Full Text Available Takotsubo syndrome (TS is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA®.A total of 24 patients (23 women, 1 man with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA®; a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79% had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis. Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003; the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029.Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity to metals (mercury in particular evaluated by LTT-MELISA®. We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients.
Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome – Is There a Clinical Relevance?
Manousek, Jan; Stejskal, Vera; Kubena, Petr; Jarkovsky, Jiri; Nemec, Petr; Lokaj, Petr; Dostalova, Ludmila; Zadakova, Andrea; Pavlusova, Marie; Benesova, Klara; Kala, Petr; Miklik, Roman; Spinar, Jindrich; Parenica, Jiri
Objective Takotsubo syndrome (TS) is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA®. Methodology, Results A total of 24 patients (23 women, 1 man) with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA®); a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79%) had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis). Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003); the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029). Conclusion Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity to metals (mercury in particular) evaluated by LTT-MELISA®. We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients. PMID:27824862
Chambers, David W
We all experience stress as a regular, and sometimes damaging and sometimes useful, part of our daily lives. In our normal ups and downs, we have our share of exhaustion, despondency, and outrage--matched with their corresponding positive moods. But burnout and workaholism are different. They are chronic, dysfunctional, self-reinforcing, life-shortening habits. Dentists, nurses, teachers, ministers, social workers, and entertainers are especially susceptible to burnout; not because they are hard-working professionals (they tend to be), but because they are caring perfectionists who share control for the success of what they do with others and perform under the scrutiny of their colleagues (they tend to). Workaholics are also trapped in self-sealing cycles, but the elements are ever-receding visions of control and using constant activity as a barrier against facing reality. This essay explores the symptoms, mechanisms, causes, and successful coping strategies for burnout and workaholism. It also takes a look at the general stress response on the physiological level and at some of the damage American society inflicts on itself.
Cow's milk protein allergy and other food hypersensitivities in infants.
Venter, Carina
Food hypersensitivity (FHS) is the umbrella term used to describe both food allergy, which involves the immune system, and food intolerances, which do not. It is therefore important that the diagnosis is made by a specialist health care professional such as a paediatrician or allergist. Some experienced dietitians and health visitors may be able to assist in making a diagnosis. The diagnostic work-up includes a medical history and blood tests/skin tests (where applicable). A food and symptom diary followed by a special test diet to identify the foods causing the infant's symptoms may also be needed. Once a diagnosis is made, dietary advice should be given to eliminate or reduce the intake of the offending foods. For cow's milk hypersensitivity in infants, this will include choosing the most appropriate specialised infant formula.
ATM status of the clinically radio-hypersensitive
Clarke, R. A.; Hasnain, H.; Goozee, G.; Alvandi, R.; Miller, A.; Kearsley, J.H.; Farrell, A.; Bittell, G.; Chen, P.; Lavin, M.
The aim of this study was to characterise the response to ionising radiation of normal tissues from patients that display early and acute hypersensitivity to radiotherapy. Methods include cell proliferation assay using MTT, induced chromosomal aberration testing, cell cycle response to radiation via FACs, mutation analysis of Ataxia Telangiectasia (AT) gene, p53 and AT Western analysis. It is now well appreciated that standard clinical doses (1.8-2 Gy per fraction per day) produce predictable acute and late toxicity in most patients. Occasionally, however, the standard clinical dose produces acute and late toxicity which can exceed the norm both in their extent and timing. The study confirmed the innate cellular radiosensitivity of the clinically radio-hypersensitive patients. No indication of AT gene mutations was found
Hypersensitivity to mosquito bite manifested as Skeeter syndrome
Rafael Pérez-Vanzzini
Full Text Available The reactions to mosquito bites are immunological reactions with involvement of IgE, IgG and T cells mediated hypersensitivity. These reactions are common and range from small local reactions, large local reactions to systemic allergic reactions. Skeeter syndrome is defined as a large local induced inflammatory reaction to mosquito bite and sometimes accompanied by systemic symptoms such as fever and vomiting. Diagnosis is based on clinical history and physical examination, supported by the identification of specific IgE by skin testing. Treatment includes prevention, antihistamines and steroids in some cases. Specific immunotherapy still requires further study. This paper reports two cases of patients with hypersensitivity reactions to mosquito bites, which were evaluated in our center presenting positive skin tests.
The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders.
Farmer, Adam D; Ruffle, James K; Aziz, Qasim
The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.
Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.
Ding, Hao; Liu, Xiao-Chang; Mei, Qiao; Xu, Jian-Ming; Hu, Xiang-Yang; Hu, Jing
Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.
The Prevalence of food hypersensitivity in young adults
Østerballe, Morten; Mørtz, Charlotte G; Hansen, Tine Kjær
by questionnaire, skin prick test (SPT) and histamin release (HR) followed by oral challenge to the most common allergenic foods. FHS was divided into primary and secondary FHS. Primary FHS was defined as being independent of pollen sensitization, whereas secondary FHS was defined as reactions to pollen related......Osterballe M, Mortz CG, Hansen TK, Andersen KE, Bindslev-Jensen C. The Prevalence of food hypersensitivity in young adults. Pediatr Allergy Immunol 2009. (c) 2009 The Authors Journal compilation (c) 2009 John Wiley & Sons A/SA rising prevalence of food hypersensitivity (FHS) and severe allergic...... reactions to foods have been reported in the last decade. However, little is known on the prevalence in young adults. This study estimated the prevalence of FHS to the most common allergenic foods in an unselected population of young adults. We investigated a cohort of 1272 young adults 22 years of age...
Old, new and hidden causes of perioperative hypersensitivity
Garvey, Lene Heise
intravenously such as neuromuscular blocking agents (NMBA), induction agents and antibiotics have traditionally been reported to be implicated most commonly. It has recently become apparent that there are geographical differences in sensitization patterns related to variation in exposures, referral patterns...... and performance and interpretation of investigations. Differences in sensitization to NMBAs are partly explained by cross sensitization to pholcodine, an ingredient in cough-medicines available in some countries. While NMBAs are the most common causes of perioperative hypersensitivity in some countries, this may...... in causes of perioperative hypersensitivity emerging over time and to increase awareness about the "hidden allergens� in the perioperative setting. Some practical advice on how to approach the patient testing negative on all initial investigations is also included....
[Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].
Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P
Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.
Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions.
Böhm, Ruwen; Cascorbi, Ingolf
Adverse drug reactions adverse drug reaction (ADR) occur in approximately 17% of patients. Avoiding ADR is thus mandatory from both an ethical and an economic point of view. Whereas, pharmacogenetics changes of the pharmacokinetics may contribute to the explanation of some type A reactions, strong relationships of genetic markers has also been shown for drug hypersensitivity belonging to type B reactions. We present the classifications of ADR, discuss genetic influences and focus on delayed-onset hypersensitivity reactions, i.e., drug-induced liver injury, drug-induced agranulocytosis, and severe cutaneous ADR. A guidance how to read and interpret the contingency table is provided as well as an algorithm whether and how a test for a pharmacogenetic biomarker should be conducted.
A haemodynamic study of pulmonary hypertension in chronic hypersensitivity pneumonitis.
Oliveira, Rudolf K F; Pereira, Carlos A C; Ramos, Roberta P; Ferreira, Eloara V M; Messina, Carolina M S; Kuranishi, Lilian T; Gimenez, Andrea; Campos, Orlando; Silva, Célia M C; Ota-Arakaki, Jaquelina S
Chronic hypersensitivity pneumonitis is a common fibrotic interstitial lung disease. The prevalence of pulmonary hypertension diagnosed by right heart catheterisation and its cardiopulmonary function findings in patients with chronic hypersensitivity pneumonitis are unknown. Consecutive symptomatic patients with chronic hypersensitivity pneumonitis were prospectively evaluated. All patients were submitted to right heart catheterisation, pulmonary function testing, a 6-min walk test, echocardiography, blood gas determination and N-terminal pro-brain natriuretic peptide analyses. Nonhypoxaemic patients also underwent incremental cardiopulmonary exercise testing. 50 patients underwent right heart catheterisation; 25 (50%) of these had pulmonary hypertension and 22 (44%) had a pre-capillary haemodynamic pattern. The patients with pre-capillary pulmonary hypertension had lower forced vital capacity (mean ± sd 50 ± 17% versus 69 ± 22% predicted, p<0.01), carbon monoxide diffusing capacity (37 ± 12% versus 47 ± 14% predicted, p<0.01), arterial oxygen tension (median (interquartile range) 59.0 (47.8-69.3) versus 73.0 (62.2-78.5) mmHg, p<0.01) and saturation after the 6-min walk test (78 ± 8% versus 86 ± 7%, p<0.01). In pre-capillary pulmonary hypertension, oxygen uptake was also lower at the anaerobic threshold (41 ± 11% versus 50 ± 8% predicted, p=0.04) and at peak exercise (12.8 ± 1.6 versus 15.0 ± 2.5 mL · kg(-1) · min(-1), p=0.02). Pre-capillary pulmonary hypertension is common in symptomatic chronic hypersensitivity pneumonitis and is related to interstitial lung disease severity. Additionally, pulmonary hypertension is more prevalent in hypoxaemic patients with impaired lung function and exercise capacity. ©ERS 2014.
Induction of Hypozincemia and Hepatic Metallothionein Synthesis in Hypersensitivity Reactions.
cells to produce endogenous pyrogen (EP), the mediator of febrile response. Controversial evidence exists, however , concerning the differentiation of LEM...hypersensitivity reactions, Kampschmid t and Pulliam (1) proposed that leukocytic endogenous mediator (LEN) is released from phagocytic cells after... endogenous mediator(s) such as LEN, no conclusive evidence is available to indicate a mRNA requirement for the production of potential mediator(s
Nickel-induced hypersensitivity: etiology, immune reactions, prevention and therapy.
Hostýnek, Jurij J
As a contact allergen causing type I and type IV hypersensitivity, mediated by reagins and allergen-specific T lymphocytes, expressed in a wide range of cutaneous eruptions following dermal or systemic exposure, nickel has acquired the distinction of being among the most frequent causes of hypersensitivity, occupationally as well as among the general population. In synoptic form the many effects that nickel has on the organism are presented, to provide a comprehensive picture of the aspects of that metal with many biologically noxious, but metallurgically indispensable characteristics. This paper reviews the epidemiology, the prognosis for occupational and non-occupational nickel allergic hypersensitivity (NAH), the many types of exposure and the resulting immune responses, immunotoxicity and rate of diffusion through the skin. Alternatives towards prevention and remediation, topical and systemic, for this pervasive and increasing form of morbidity resulting from multiple types of exposure are discussed. Merits and limitations of preventive measures in industry and private life are considered, as well as the effectiveness of topical and systemic therapy in treating NAH.
Cracking the egg: An insight into egg hypersensitivity.
Dhanapala, Pathum; De Silva, Chamika; Doran, Tim; Suphioglu, Cenk
Hypersensitivity to the chicken egg is a widespread disorder mainly affecting 1-2% of children worldwide. It is the second most common food allergy in children, next to cow's milk allergy. Egg allergy is mainly caused by hypersensitivity to four allergens found in the egg white; ovomucoid, ovalbumin, ovotransferrin and lysozyme. However, some research suggests the involvement of allergens exclusively found in the egg yolk such as chicken serum albumin and YGP42, which may play a crucial role in the overall reaction. In egg allergic individuals, these allergens cause conditions such as itching, atopic dermatitis, bronchial asthma, vomiting, rhinitis, conjunctivitis, laryngeal oedema and chronic urticaria, and anaphylaxis. Currently there is no permanent cure for egg allergy. Upon positive diagnosis for egg allergy, strict dietary avoidance of eggs and products containing traces of eggs is the most effective way of avoiding future hypersensitivity reactions. However, it is difficult to fully avoid eggs since they are found in a range of processed food products. An understanding of the mechanisms of allergic reactions, egg allergens and their prevalence, egg allergy diagnosis and current treatment strategies are important for future studies. This review addresses these topics and discusses both egg white and egg yolk allergy as a whole. Copyright © 2015 Elsevier Ltd. All rights reserved.
Suspected zonisamide-related anticonvulsant hypersensitivity syndrome in a cat.
Collinet, Audrey; Sammut, Veronique
CASE DESCRIPTION A 2-year-old neutered male domestic shorthair cat was evaluated for sudden onset of cluster seizures. CLINICAL FINDINGS At an emergency clinic, the cat had hyperimmunoglobulinemia and thrombocytopenia. On referral, treatment with levetiracetam, zonisamide, and phenobarbital initially provided good control of cluster seizure activity (attributable to epilepsy of unknow origin). Two weeks later, assessments revealed that serum phenobarbital concentration was within the ideal range but serum zonisamide concentration exceeded the recommended therapeutic range. The dosage of zonisamide was therefore decreased. Four days after dosage reduction, the cat developed generalized lymphadenopathy. Cytologic analysis of lymph node aspirate samples revealed a heterogeneous population of well-differentiated lymphocytes, interpreted as marked reactivity. Although neoplasia could not be ruled out, hypersensitivity to phenobarbital was suspected, and this treatment was discontinued. TREATMENT AND OUTCOME Despite cessation of phenobarbital administration, generalized peripheral lymphadenopathy progressed and hyperglobulinemia and cytopenias developed. These abnormalities resolved after discontinuation of zonisamide administration. The cat remained seizure free with no recurrence of the aforementioned concerns after reinstitution of phenobarbital treatment. CLINICAL RELEVANCE To the authors' knowledge, this is the first reported case of zonisamide-related lymphadenopathy, hyperglobulinemia, and cytopenias in a cat. Anticonvulsant hypersensitivity syndrome is well documented in human medicine, but little information has been published in the veterinary medical literature. Although the effects of anticonvulsant hypersensitivity syndrome in this cat were serious, these effects were reversible with treatment discontinuation.
Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children
Kidon Mona
Full Text Available Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction after ASA challenge is seen in 0 to 22% of asthmatic children so challenged, ibuprofen at antipyretic doses may cause acute respiratory problems only in a very small number of mild to moderate asthmatics. The recently elucidated mechanism of action of acetaminophen may explain some occurrences of adverse reactions in patients with cross-reactive NSAID hypersensitivity on the basis of its inhibitory activity on the newly described enzyme, cyclooxygenase (COX-3. This nonspecific sensitivity to inhibition of COX is most likely genetically determined and shows a remarkable association with atopic disease even in the very young age group and possibly an increased predilection in specific ethnic groups. This review summarizes state-of-the-art published data on NSAID hypersensitivity in preschool children.
Linezolid desensitization for a patient with multiple medication hypersensitivity reactions.
Bagwell, Autumn D; Stollings, Joanna L; White, Katie D; Fadugba, Olajumoke O; Choi, Jane J
To describe a case in which a linezolid desensitization protocol was successfully used for a polymicrobial surgical wound infection in a patient with multiple drug hypersensitivity reactions. A 24-year-old woman with vocal cord dysfunction requiring tracheostomy was admitted for a surgical wound infection following a tracheostomy fistula closure procedure. The patient reported multiple antibiotic allergies including penicillins (rash), sulfonamides (rash), vancomycin (anaphylaxis), azithromycin (rash), cephalosporins (anaphylaxis), levofloxacin (unspecified), clindamycin (unspecified), and carbapenems (unspecified). Gram stain of the purulent wound drainage demonstrated mixed gram-negative and gram-positive flora, and bacterial cultures were overgrown with Proteus mirabilis, which precluded identification of other pathogens. Following failed test doses of linezolid, tigecycline, and daptomycin, all of which resulted in hypersensitivity reactions, a 16-step linezolid desensitization protocol was developed and successfully implemented without adverse reactions. The patient completed a 2-week course of antibiotic therapy that included linezolid upon finishing the desensitization protocol. Linezolid is useful in treating complicated and uncomplicated skin and soft tissue infections caused by gram-positive bacteria. With precautions, including premedication, a monitored nursing unit, and immediate availability of an emergency anaphylaxis kit, drug desensitization allows patients the ability to safely use medications to which they may have an immediate hypersensitivity reaction. Minimal data exist on linezolid desensitization protocols. Linezolid desensitization can be a viable option in patients requiring antimicrobial therapy for complicated gram-positive skin infections.
The prevalence of dentin hypersensitivity in general dental practices in the northwest United States.
Cunha-Cruz, Joana; Wataha, John C; Heaton, Lisa J; Rothen, Marilynn; Sobieraj, Martin; Scott, JoAnna; Berg, Joel
The prevalence of dentin hypersensitivity is uncertain, yet appropriate diagnosis and treatment of dentin hypersensitivity require accurate knowledge regarding its prevalence. The authors conducted a study to estimate the prevalence of dentin hypersensitivity in general dental practices and to investigate associated risk factors. The authors conducted a cross-sectional survey of 787 adult patients from 37 general dental practices within Northwest Practice-based Research Collaborative in Evidence-based DENTistry (PRECEDENT). Dentin hypersensitivity was diagnosed by means of participants' responses to a question regarding pain in their teeth and gingivae, and practitioner-investigators conducted a clinical examination to rule out alternative causes of pain. Participants recorded their pain level on a visual analog scale and the Seattle Scales in response to a one-second air blast. The authors used generalized estimating equation log-linear models to estimate the prevalence and the prevalence ratios. The prevalence of dentin hypersensitivity was 12.3 percent; patients with hypersensitivity had, on average, 3.5 hypersensitive teeth. The prevalence of dentin hypersensitivity was higher among 18- to 44-year olds than among participants 65 years or older; it also was higher in women than in men, in participants with gingival recession than in those without gingival recession and in participants who underwent at-home tooth whitening than in those who did not. Hypersensitivity was not associated with obvious occlusal trauma, noncarious cervical lesions or aggressive toothbrushing habits. One in eight participants from general practices had dentin hypersensitivity, which was a chronic condition causing intermittent, low-level pain. Patients with hypersensitivity were more likely to be younger, to be female and to have a high prevalence of gingival recession and at-home tooth whitening. Given dentin hypersensitivity's prevalence, clinicians should diagnose it only after
Carboplatin hypersensitivity in children with glial tumors: a report of two cases
Tugce Kazgan
Full Text Available Carboplatin, commonly used chemotherapeutic agent in treatment of pediatric cancers, can cause life-threatening hypersensitivty reactions. Carboplatin hypersensitivity is protocol-specific and associated with repeated doses and prolonged use of the drug. Vincristin and carboplatin combination is used efficiently in treatment of pediatric low-grade gliomas. However, hypersensitivity reactions are frequently observed during usage of this protocol. Desensitization strategies with variable success rates were reported. Failure of these strategies may lead to cessation of carboplatin Here, we report two cases with carboplatin hypersensitivity treated with epinephrine administration, in whom carboplatin was discontinued after hypersensitivity reaction. [Cukurova Med J 2016; 41(4.000: 796-798
Evaluation of basophil activation test in suspected food hypersensitivity.
Pignatti, Patrizia; Yacoub, Mona-Rita; Testoni, Claudia; Pala, Gianni; Corsetti, Maura; Colombo, Giselda; Meriggi, Antonio; Moscato, Gianna
Food hypersensitivity is characterized by a wide range of symptoms. The relationship between symptoms and food is more frequently suspected than objectively proven. Basophil activation test (BAT) is based on the evaluation of activation markers on blood basophils in vitro stimulated with drugs or allergens. The aim of the study was to evaluate the usefulness of BAT when introduced in the routine work-up of suspected food hypersensitivity. BAT was requested in subjects with food adverse reactions when a discrepancy existed among history and skin prick test (SPT) and/or specific IgE. Data from 150 subjects were analysed using CD63 as basophil activation marker. Thirty controls were evaluated for cut-offs. Immunoblots was performed with the sera of representative subjects positive for BAT and negative for SPT and sIgE. 1,024 BAT were carried out, the agreement (positive/positive and negative/negative) was 78.5% for BAT vs. SPT and 78.3% for BAT vs. IgE. Atopic patients, but not atopic controls, more frequently had a positive BAT than non-atopic patients (P tested food) and both negative sIgE and SPT. Immunoblots revealed the presence of sIgE for the tested foods in representative patients with positive BAT, negative SPT and sIgE. Introduction of BAT in routine of food hypersensitivity, limited to subjects with a discrepancy between history and traditional tests, might be useful particularly when total IgE are low. © 2015 International Clinical Cytometry Society. © 2015 International Clinical Cytometry Society.
Considerations on the electromagnetic hypersensitivity and idiopathic environmental intolerances
Perrin, Anne
After having noticed that environmental and health concerns are an important matter of concern in our society, and that always more pathologies are blamed on the environment, the author more particularly addresses electromagnetic hypersensitivity (EHS) which is considered by the WHO as a part of idiopathic environmental intolerances (IEI). He more particularly discusses the various conditions of emergence of these syndromes as they have been noticed, analysed and identified in different countries and in different studies. He discusses the possible definition to be given to these syndromes and their possible meaning
Hypersensitive transition spectrum of f-element and coordination structure
Cao Xuan; Song Chongli; Zhu Youngjun
Some f-f transitions of Ln(An) metallic ions have particular super-sensitivity to the change of coordination environments. This is called super-sensitive transitions. Based on the irreducible tensor operator method, a computation model and corresponding computer program for calculating the hypersensitive transition spectrum of f-element were developed. By comparing the theoretical spectra of all possible coordination structures with experimental one, the possible coordination structures of complex can be determined. The coordination structures of Nd 3+ , Er 3 + hydrate and their extraction complex with H(DEHP) were successfully determined by this method, and the experimental spectra were also assigned
Persistent Skin Reactions and Aluminium Hypersensitivity Induced by Childhood Vaccines
Salik, Elaha; Løvik, Ida; Andersen, Klaus E
There is increasing awareness of reactions to vaccination that include persistent skin reactions. We present here a retrospective investigation of long-lasting skin reactions and aluminium hypersensitivity in children, based on medical records and questionnaires sent to the parents. In the 10-year...... period 2003 to 2013 we identified 47 children with persistent skin reactions caused by childhood vaccinations. Most patients had a typical presentation of persisting pruritic subcutaneous nodules. Five children had a complex diagnostic process involving paediatricians, orthopaedics and plastic surgeons...... treated with potent topical corticosteroids and disappeared slowly. Although we advised families to continue vaccination of their children, one-third of parents omitted or postponed further vaccinations....
Electromagnetic hypersensitivity: The opinion of an observer neurologist
Marc-Vergnes, Jean-Pierre
Electromagnetic hypersensitivity (EHS) is a recent, uncertain and somehow confusing concept. It is now widely agreed that people claiming to be EHS really experience symptoms. However, no evidence for a causal link between the symptoms and electromagnetic fields (EMF) has been reported. Thus, we have to wonder whether EHS constitutes truly a relevant entity. Most of the previous studies suffer from methodological flaws. Owing to the quantification of symptoms, the interdisciplinary assessment of patients, and the use of personal exposimeters, the recent studies are of better quality. A set of convergent associated signs suggests that individual neuropsychic factors take a prominent, but maybe not unique, part in this condition.
Rice hypersensitive induced reaction protein 1 (OsHIR1) associates with plasma membrane and triggers hypersensitive cell death.
Zhou, Liang; Cheung, Ming-Yan; Li, Man-Wah; Fu, Yaping; Sun, Zongxiu; Sun, Sai-Ming; Lam, Hon-Ming
In plants, HIR (Hypersensitive Induced Reaction) proteins, members of the PID (Proliferation, Ion and Death) superfamily, have been shown to play a part in the development of spontaneous hypersensitive response lesions in leaves, in reaction to pathogen attacks. The levels of HIR proteins were shown to correlate with localized host cell deaths and defense responses in maize and barley. However, not much was known about the HIR proteins in rice. Since rice is an important cereal crop consumed by more than 50% of the populations in Asia and Africa, it is crucial to understand the mechanisms of disease responses in this plant. We previously identified the rice HIR1 (OsHIR1) as an interacting partner of the OsLRR1 (rice Leucine-Rich Repeat protein 1). Here we show that OsHIR1 triggers hypersensitive cell death and its localization to the plasma membrane is enhanced by OsLRR1. Through electron microscopy studies using wild type rice plants, OsHIR1 was found to mainly localize to the plasma membrane, with a minor portion localized to the tonoplast. Moreover, the plasma membrane localization of OsHIR1 was enhanced in transgenic rice plants overexpressing its interacting protein partner, OsLRR1. Co-localization of OsHIR1 and OsLRR1 to the plasma membrane was confirmed by double-labeling electron microscopy. Pathogen inoculation studies using transgenic Arabidopsis thaliana expressing either OsHIR1 or OsLRR1 showed that both transgenic lines exhibited increased resistance toward the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. However, OsHIR1 transgenic plants produced more extensive spontaneous hypersensitive response lesions and contained lower titers of the invading pathogen, when compared to OsLRR1 transgenic plants. The OsHIR1 protein is mainly localized to the plasma membrane, and its subcellular localization in that compartment is enhanced by OsLRR1. The expression of OsHIR1 may sensitize the plant so that it is more prone to HR and hence can react more
CT findings associated with survival in chronic hypersensitivity pneumonitis
Chung, Jonathan H.; Montner, Steven M.; Adegunsoye, Ayodeji; Vij, Rekha; Noth, Imre; Strek, Mary E.; Oldham, Justin M.; Husain, Aliya N.
To identify CT findings in chronic hypersensitivity pneumonitis (cHP) associated with survival. Two thoracic radiologists assessed CT scans for specific imaging findings and patterns in 132 subjects with cHP. Survival analyses were performed. The majority of subjects had an inconsistent with usual interstitial pneumonitis pattern on CT (55.3%,73/132). Hypersensitivity pneumonitis (HP) diagnosis on CT was less common in those with fibrosis (66.1%, 74/112) than those without fibrosis (85%,17/20). Smoking was associated with a lower prevalence of HP on CT (p=0.04). CT features of pulmonary fibrosis, especially traction bronchiectasis (HR 8.34, 95% CI 1.98-35.21) and increased pulmonary artery (PA)/aorta ratio (HR 2.49, 95% CI 1.27-4.89) were associated with worse survival, while ground-glass opacity (HR 0.31, 95% CI 0.12-0.79) was associated with improved survival. Survival association with imaging was less pronounced after adjustment for gender, age and physiology score. A substantial proportion of cHP cases have a non-HP-like appearance. Ground-glass opacity, pulmonary fibrosis features and elevated PA/aorta ratio on CT likely reflect varying degrees of disease severity in cHP and may inform future clinical prediction models. (orig.)
Cutaneous and systemic hypersensitivity reactions to metallic implants.
Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous, and vasculitic eruptions may occur. Also, more complex immune reactions may develop around the implants, resulting in pain, inflammation, and loosening. Nickel, cobalt, and chromium are the three most common metals that elicit both cutaneous and extracutaneous allergic reactions from chronic internal exposure. However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions remains to be fully understood. This review provides an update of the current knowledge in this field and should be valuable to health care providers who manage patients with conditions related to this field.
Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation
Najeeba Riyaz
Full Text Available A 45-year-old man, on carbamazepine for the past 3 months, was referred as a case of atypical measles. On examination, he had high-grade fever, generalized itchy rash, cough, vomiting and jaundice. A provisional diagnosis of drug hypersensitivity syndrome to carbamazepine was made with a differential diagnosis of viral exanthema with systemic complications. Laboratory investigations revealed leukocytosis with eosnophilia and elevated liver enzymes. Real-time multiplex polymerase chain reaction (PCR on throat swab and blood was suggestive of human herpesvirus-6 (HHV-6. Measles was ruled out by PCR and serology. The diagnosis of drug-induced hypersensitivity syndrome (DIHS was confirmed, which could explain all the features manifested by the patient. HHV-6 infects almost all humans by age 2 years. It infects and replicates in CD4 T lymphocytes and establishes latency in human peripheral blood monocytes or macrophages and early bone marrow progenitors. In DIHS, allergic reaction to the causative drug stimulates T cells, which leads to reactivation of the herpesvirus genome. DIHS is treated by withdrawal of the culprit drug and administration of systemic steroids. Our patient responded well to steroids and HHV-6 was negative on repeat real-time multiplex PCR at the end of treatment.
Chung, Jonathan H.; Montner, Steven M. [University of Chicago Medical Center, Department of Radiology, Chicago, IL (United States); Adegunsoye, Ayodeji; Vij, Rekha; Noth, Imre; Strek, Mary E. [University of Chicago Medical Center, Section of Pulmonary/Critical Care, Department of Medicine, Chicago, IL (United States); Oldham, Justin M. [University of California at Davis, Section of Pulmonary/Critical Care, Department of Medicine, Sacramento, CA (United States); Husain, Aliya N. [University of Chicago Medical Center, Department of Pathology, Chicago, IL (United States)
Metalworking fluid-associated hypersensitivity pneumonitis: a workshop summary.
Kreiss, K; Cox-Ganser, J
A workshop discussing eight clusters of hypersensitivity pneumonitis in the automotive industry among metalworking fluid-exposed workers concluded that a risk exists for this granulomatous lung disease where water-based fluids are used and unusual microbial contaminants predominate. Strong candidates for microbial etiology are nontuberculous mycobacteria and fungi. Cases of hypersensitivity pneumonitis occur among cases with other work-related respiratory symptoms and chest diseases. Reversibility of disease has occurred in many cases with exposure cessation, allowing return to work to jobs without metalworking fluid exposures or, in some situations, to jobs without the same metalworking fluid exposures. Cases have been recognized with metalworking fluid exposures generally less than 0.5 mg/m3. The workshop participants identified knowledge gaps regarding risk factors, exposure-response relationships, intervention efficacy, and natural history, as well as surveillance needs to define the extent of the problem in this industry. In the absence of answers to these questions, guidance for prevention is necessarily limited.
Patch testers' opinions regarding diagnostic criteria for metal hypersensitivity reactions to metallic implants
Schalock, Peter C; Thyssen, Jacob P
Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated.......Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated....
Genome-wide association study of insect bite hypersensitivity in swedish-born icelandic horses
Shrestha, M.; Eriksson, S.; Schurink, A.; Andersson, L.S.; Sundquist, M.; Frey, R.; Brostrom, H.; Bergstrom, T.; Ducro, B.J.; lindgren, G.
Insect bite hypersensitivity (IBH) is the most common allergic skin disease in horses and is caused by biting midges, mainly of the genus Culicoides. The disease predominantly comprises a type I hypersensitivity reaction, causing severe itching and discomfort that reduce the welfare and commercial
Baroreflex Sensitivity And Autonomic Nervous System Function In Carotid Sinus Hypersensitivity
Brinth, Louise Schouborg; Pors, Kirsten; Theibel, Ann Cathrine
hypersensitivity ranging from reduced to increased sensitivity compared to controls. We wanted to establish whether measures of baroreflex sensitivity and autonomic function differed between patients diagnosed with carotid sinus hypersensitivity and age matched controls. We included 36 patients (12 women; 74 +/-10...... sensitivity may not follow the same neuronal pathways as those responding to the crude external pressures applied during carotid sinus massage...
Successful desensitization protocol for hypersensitivity reaction probably caused by dabrafenib in a patient with metastatic melanoma.
Bar-Sela, Gil; Abu-Amna, Mahmoud; Hadad, Salim; Haim, Nissim; Shahar, Eduardo
Vemurafenib and dabrafenib are both orally bioavailable small molecule agents that block mitogen activated protein kinase signalling in patients with melanoma and BRAF(V600E) mutation. Generalized hypersensitivity reactions to vemurafenib or dabrafenib have not been described. Continuing vemurafenib or dabrafenib therapy despite hypersensitivity reaction is especially important in patients with melanoma and BRAF(V600E) mutation, in whom this mutation plays a critical role in tumour growth. Desensitization protocols to overcome hypersensitivity reactions by gradual reintroduction of small amounts of the offending drug up to full therapeutic doses are available for many anti-cancer agents, including vemurafenib but, to the best of our knowledge, have not been reported for dabrafenib. We describe a patient with metastatic melanoma who developed Type I hypersensitivity reaction to vemurafenib and to subsequent treatment with dabrafenib, and who was successfully treated by drug desensitization which allowed safe prolonged continuation of dabrafenib. The development of hypersensitivity reactions for both dabrafenib and vemurafinib in the current case could be because these drugs have a similar chemical structure and cause a cross-reactivity. However, hypersensitivity reaction to a non-medicinal ingredient shared by the two drugs is also possible. Oral desensitization appears to be an option for patients with hypersensitivity Type I to dabrafenib. This approach may permit clinicians to safely administer dabrafenib to patients who experience hypersensitivity reactions to this life-prolonging medication. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Hypersensitive cell death in plants : its mechanisms and role in plant defense against pathogens
Iakimova, E.T.; Michalczuk, L.; Woltering, E.J.
This review is a recent update in the understanding of the hypersensitive response (HR) of plants with special consideration to the physiological and biochemical determinants in different model systems. Hypersensitive response is reviewed as a form of programmed cell death (PCD) representing one of
Detective quantum efficiency gains compared with speed gains for hypersensitized astronomical plates
Kaye, A.L.
It is reasonable to assume that gains in detective quantum efficiency (DQE) are far better criteria for assessing the performance of hypersensitizing techniques than gains in speed. It is shown here that gains in speed can be misleading, for some methods of hypersensitization give plates of increased speed but reduced detective quantum efficiency. (author)
The glutamate carboxypeptidase AMP1 mediates abscisic acid and abiotic stress responses in Arabidopsis.
Shi, Yiting; Wang, Zheng; Meng, Pei; Tian, Siqi; Zhang, Xiaoyan; Yang, Shuhua
ALTERED MERISTEM PROGRAM1 (AMP1) encodes a glutamate carboxypeptidase that plays an important role in shoot apical meristem development and phytohormone homeostasis. We isolated a new mutant allele of AMP1, amp1-20, from a screen for abscisic acid (ABA) hypersensitive mutants and characterized the function of AMP1 in plant stress responses. amp1 mutants displayed ABA hypersensitivity, while overexpression of AMP1 caused ABA insensitivity. Moreover, endogenous ABA concentration was increased in amp1-20- and decreased in AMP1-overexpressing plants under stress conditions. Application of ABA reduced the AMP1 protein level in plants. Interestingly, amp1 mutants accumulated excess superoxide and displayed hypersensitivity to oxidative stress. The hypersensitivity of amp1 to ABA and oxidative stress was partially rescued by reactive oxygen species (ROS) scavenging agent. Furthermore, amp1 was tolerant to freezing and drought stress. The ABA hypersensitivity and freezing tolerance of amp1 was dependent on ABA signaling. Moreover, amp1 had elevated soluble sugar content and showed hypersensitivity to high concentrations of sugar. By contrast, the contents of amino acids were changed in amp1 mutant compared to the wild-type. This study suggests that AMP1 modulates ABA, oxidative and abotic stress responses, and is involved in carbon and amino acid metabolism in Arabidopsis. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.
National prevalence of asthma and chemical hypersensitivity: an examination of potential overlap.
Caress, Stanley M; Steinemann, Anne C
The objective of this study was to investigate the linkage between asthma and chemical hypersensitivity. The authors conducted a population study with a random sample of 1057 geographically weighted cases to determine the prevalence of both asthma and chemical hypersensitivity in the American population and to explore their co-occurrence. A total of 14.1% of the respondents reported being diagnosed with asthma and 11.2% reported a hypersensitivity to chemicals. Of those with asthma, 27.2% also reported being hypersensitive to chemicals and 7.4% reported also being diagnosed with multiple chemical sensitivities (MCS). Of those diagnosed with MCS, 42% reported also being diagnosed with asthma. Additionally, 29.7% of those with asthma said air fresheners caused breathing difficulties, and 37.2% found scented products irritating. The results indicate that there is significant overlap between some forms of asthma and chemical hypersensitivity.
Linking Anxiety and Insistence on Sameness in Autistic Children: The Role of Sensory Hypersensitivity.
Black, Karen R; Stevenson, Ryan A; Segers, Magali; Ncube, Busiswe L; Sun, Sol Z; Philipp-Muller, Aviva; Bebko, James M; Barense, Morgan D; Ferber, Susanne
Sensory hypersensitivity and insistence on sameness (I/S) are common, co-occurring features of autism, yet the relationship between them is poorly understood. This study assessed the impact of sensory hypersensitivity on the clinical symptoms of specific phobia, separation anxiety, social anxiety and I/S for autistic and typically developing (TD) children. Parents of 79 children completed questionnaires on their child's difficulties related to sensory processing, I/S, and anxiety. Results demonstrated that sensory hypersensitivity mediated 67% of the relationship between symptoms of specific phobia and I/S and 57% of the relationship between separation anxiety and I/S. No relationship was observed between sensory hypersensitivity and social anxiety. These mediation effects of sensory hypersensitivity were found only in autistic children, not in TD children.
Comparative evaluation of Type 1 latex hypersensitivity in patients with chronic urticaria, rubber factory workers and healthy control subjects
Piskin, Gamze; Akyol, Aynur; Uzar, Hatice; Tulek, Necla; Boyvat, Ayse; Gurgey, Erbak
Latex hypersensitivity manifests itself most commonly with contact urticaria. In this study, we investigated the frequency of latex hypersensitivity as a possible aetiological factor in patients with chronic urticaria (CU) and compared latex hypersensitivity of CU patients (n = 50) with that of
B-Lymphocytes from a Population of Children with Autism Spectrum Disorder and Their Unaffected Siblings Exhibit Hypersensitivity to Thimerosal
Martyn A. Sharpe
Full Text Available The role of thimerosal containing vaccines in the development of autism spectrum disorder (ASD has been an area of intense debate, as has the presence of mercury dental amalgams and fish ingestion by pregnant mothers. We studied the effects of thimerosal on cell proliferation and mitochondrial function from B-lymphocytes taken from individuals with autism, their nonautistic twins, and their nontwin siblings. Eleven families were examined and compared to matched controls. B-cells were grown with increasing levels of thimerosal, and various assays (LDH, XTT, DCFH, etc. were performed to examine the effects on cellular proliferation and mitochondrial function. A subpopulation of eight individuals (4 ASD, 2 twins, and 2 siblings from four of the families showed thimerosal hypersensitivity, whereas none of the control individuals displayed this response. The thimerosal concentration required to inhibit cell proliferation in these individuals was only 40% of controls. Cells hypersensitive to thimerosal also had higher levels of oxidative stress markers, protein carbonyls, and oxidant generation. This suggests certain individuals with a mild mitochondrial defect may be highly susceptible to mitochondrial specific toxins like the vaccine preservative thimerosal.
Childhood hypersensitivity pneumonitis associated with fungal contamination of indoor hydroponics.
Engelhart, Steffen; Rietschel, Ernst; Exner, Martin; Lange, Lars
Childhood hypersensitivity pneumonitis (HP) is often associated with exposure to antigens in the home environment. We describe a case of HP associated with indoor hydroponics in a 14-year-old girl. Water samples from hydroponics revealed Aureobasidium pullulans as the dominant fungal micro-organism (10(4)CFU/ml). The diagnosis is supported by the existence of serum precipitating antibodies against A. pullulans, lymphocytic alveolitis on bronchoalveolar lavage (BAL) fluid, a corresponding reaction on a lung biopsy, and the sustained absence of clinical symptoms following the removal of hydroponics from the home. We conclude that hydroponics should be considered as potential sources of fungal contaminants when checking for indoor health complaints.
Adrenergic receptors are a fallible index of adrenergic denervation hypersensitivity
Dejgaard, Anders; Liggett, S B; Christensen, N J
In view of evidence that neither interindividual nor induced intra-individual variations of adrenergic receptor status are related to metabolic or haemodynamic sensitivity to adrenaline in vivo, we took an alternative approach to assessment of the relevance of adrenergic receptor measurement...... by measuring these in a group of subjects with well-documented adrenergic denervation hypersensitivity, patients with diabetic autonomic neuropathy. Mononuclear leukocyte beta 2-adrenergic receptor densities (and binding affinities), measured with 125I-labelled pindolol, and isoproterenol-stimulated cyclic AMP...... accumulation, in samples from patients with insulin-dependent diabetes mellitus (IDDM) with diabetic autonomic neuropathy (n = 8), were no different from those in samples from patients with IDDM without neuropathy (n = 8), or from non-diabetic subjects (n = 8). In addition, platelet alpha 2-adrenergic receptor...
Immediate and delayed contact hypersensitivity to verbena plants
Potter, P C; Mather, S; Lockey, P
Plants from the Verbenaceae family may cause contact dermatitis of unknown nature. This report describes 2 cases of allergic reactions to the Verbena species. A teenage boy developed an anaphylactic allergic response following contact with the leaves of Verbena hybrida. Characterization...... of the patient's specific IgE response to Verbena hybrida, using Western blots and autoradiography, identified the specific 62000 Dalton allergen present in the verbena leaves to which the patient reacted. This is the first report of an IgE-mediated immediate contact hypersensitivity reaction to Verbena hybrida......, a common perennial in South African gardens. The other case was a 23-year-old female gardener who developed immediate and delayed-type contact dermatitis from Verbena elegans 'Cleopatra' produced in a Danish nursery. Prick tests to plant material were considered positive and of an allergic nature....
Allopurinol-induced Severe Hypersensitivity with Acute Renal Failure
I-Hung Chen
Full Text Available A 62-year-old male was sent to the emergency room due to a high fever and generalized skin rash after taking allopurinol for 9 days. Physical examination was normal except for the generalized skin rash presenting with erythematous macules. Complete blood count showed leukocytosis with eosinophilia. Blood biochemistry showed impaired renal and hepatic function. Pathologic examination concluded that the skin rash was erythema multiforme. These findings met the diagnostic criteria for allopurinol-induced hypersensitivity syndrome (AHS. Our patient not only had the most common skin lesion but soon developed acute renal failure that required intermittent hemodialysis, despite rapid discontinuation of allopurinol and adequate hydration and steroid therapy. No other causes of acute renal failure were found. Renal impairment was the worst part of the patient's condition and he never completely recovered. AHS should be considered in the differential diagnosis of acute renal and hepatic failure in patients with evidence of allergy and recent use of allopurinol.
Autophagic components contribute to hypersensitive cell death in Arabidopsis
Hofius, Daniel; Schultz-Larsen, Torsten; Joensen, Jan
Autophagy has been implicated as a prosurvival mechanism to restrict programmed cell death (PCD) associated with the pathogen-triggered hypersensitive response (HR) during plant innate immunity. This model is based on the observation that HR lesions spread in plants with reduced autophagy gene...... expression. Here, we examined receptor-mediated HR PCD responses in autophagy-deficient Arabidopsis knockout mutants (atg), and show that infection-induced lesions are contained in atg mutants. We also provide evidence that HR cell death initiated via Toll/Interleukin-1 (TIR)-type immune receptors through...... the defense regulator EDS1 is suppressed in atg mutants. Furthermore, we demonstrate that PCD triggered by coiled-coil (CC)-type immune receptors via NDR1 is either autophagy-independent or engages autophagic components with cathepsins and other unidentified cell death mediators. Thus, autophagic cell death...
Persistent Skin Reactions and Aluminium Hypersensitivity Induced by Childhood Vaccines.
Salik, Elaha; Løvik, Ida; Andersen, Klaus E; Bygum, Anette
There is increasing awareness of reactions to vaccination that include persistent skin reactions. We present here a retrospective investigation of long-lasting skin reactions and aluminium hypersensitivity in children, based on medical records and questionnaires sent to the parents. In the 10-year period 2003 to 2013 we identified 47 children with persistent skin reactions caused by childhood vaccinations. Most patients had a typical presentation of persisting pruritic subcutaneous nodules. Five children had a complex diagnostic process involving paediatricians, orthopaedics and plastic surgeons. Two patients had skin biopsies performed from their skin lesions, and 2 patients had the nodules surgically removed. Forty-two children had a patch-test performed with 2% aluminium chloride hexahydrate in petrolatum and 39 of them (92%) had a positive reaction. The persistent skin reactions were treated with potent topical corticosteroids and disappeared slowly. Although we advised families to continue vaccination of their children, one-third of parents omitted or postponed further vaccinations.
Desensitization of delayed-type hypersensitivity in mice: suppressive environment
Takashi Katsura
Full Text Available The systemic injection of high doses of antigen into a preimmunized animal results in transient unresponsiveness of cell-mediated immune responses. This phenomenon is known as desensitization. Serum interleukin 2 (IL-2 activity was found transiently in desensitized mice at 3 h after the antigen challenge. These mice could not reveal antigen nonspecific delayed-type hypersensitivity (DTH 1 d after the challenge. Specific suppression of DTH was observed at later stages. Sera from 3 h desensitized mice showed suppressive effects on DTH in preo immunized mice. Administration of recombinant IL-2 into preimmunized mice led to the failure of development of DTH to antigens. These observations suggest that IL-2 plays an important role in the suppressive environment.
On the phenomenon of electromagnetic hypersensitivity; Das Phaenomen der Elektrosensibilitaet
David, E.; Reissenweber, J.; Wojtysiak, A.; Pfotenhauer, M. [Witten-Herdecke Univ., Witten (Germany). Inst. fuer Normale und Pathologische Physiologie; Witten-Herdecke Univ., Witten (Germany). Zentrum fuer Elektropathologie
For more than fifteen years electromagnetic fields (EMFs) are intensively discussed in connection with health hazards in mass media as well as questions of standard setting by the authorities. The present elaboration gives an extended overview over the actual situation of the special electromagnetic hypersensitivity issue in relation to electromagnetic field research in the international scientific community. There are parallels and analogies between the symptoms of electromagnetic hypersensitivity and those of the Multiple-Chemical-Sensitivity-Syndrome and other environmental diseases. The first part deals with the biophysical fundamental knowledge of interactions between electromagnetic fields and biological systems such as man or animal including threshold values and threshold philosophy. Then hypothetical mechanisms of action of EMF are demonstrated, with a special focus on the melatonin hypothesis, which has not been proved in all its parts up to now. Additionally, in the context of our biomedical research into disorders of well-being we conducted an analysis of written and telephone questions about the EMF issue which are sent to our center. The results are of scientific and political interest and are demonstrated in detail. (orig.) [German] Das Phaenomen der Elektrosensibilitaet gewinnt zunehmend an Bedeutung innerhalb der Diskussion um die medizinisch-biologischen Wirkungen elektromagnetischer Felder. Es konnte bisher nicht nachgewiesen werden, dass die Elektrosensibilitaet/Magnetosensibilitaet als eigenstaendige Krankheitseinheit (Krankheitsentitaet) existiert. Es handelt sich dabei um ein Phaenomen, das vor etwa 15 Jahren benannt und zunaechst nicht ernst genommen wurde. Im Rahmen des relativ jungen medizinisch-biologischen Fachgebietes Elektropathologie scheinen weitere Untersuchungen erforderlich, um die teilweise auch widerspruechlichen Befunde aufzuklaeren und zu erfahren, ob Felder Befindlichkeitsstoerungen ausloesen koennen, die in aehnlicher Form
The scientific rationale and development of an optimized dentifrice for the treatment of dentin hypersensitivity.
Tavss, Edward A; Fisher, Steven W; Campbell, Shannon; Bonta, Yolanda; Darcy-Siegel, Joann; Blackwell, Bernie L; Volpe, Anthony R; Miller, Steven E
To describe the development of a new dentin hypersensitivity treatment, Colgate Sensitive Maximum Strength dentifrice, containing 5% potassium nitrate as the anti-hypersensitivity active agent. The objective was to develop a home-use hypersensitivity dentifrice that would be superior to the market leader, improving on what is available, which also contains 5% potassium nitrate as the anti-hypersensitivity active agent. In vivo (clinicals, taste evaluation and rat caries), in vitro (potassium flux) and analytical (rheology, dispensed volume, scanning electron microscopy, electron scanning chemical analysis and radioactive dentin abrasion) methods were performed. The objective was accomplished with the development of a new activated silica technology that resulted in enhanced potassium ion activity. In vitro documentation, supported by clinical studies, demonstrated that the resulting formula is more effective than the market leader for relief of hypersensitivity pain. Fast pain relief in less than 2 weeks and long-lasting protection against pain with regular use have also been clinically documented. Furthermore, FDA-required in vivo and in vitro studies indicate that this formula, which contains 0.45% stannous fluoride (1100 ppm fluoride) as the anti-caries active agent, is effective against caries. Good taste, acceptable rheology, acceptable abrasivity, and cosmetic and chemical stability have all been engineered into this unique dentin hypersensitivity treatment. In summary, a highly efficacious consumer friendly treatment for dentin hypersensitivity has been developed.
Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies.
Tai, Yu-Hsiao; Tai, Yi-Jou; Hsu, Heng-Cheng; Lee, Shu-Ping; Chen, Yun-Yuan; Chiang, Ying-Cheng; Chen, Yu-Li; Chen, Chi-An; Cheng, Wen-Fang
We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease ( P Kruskal-Wallis test), serous and mixed histological types ( P = 0.003, Kruskal-Wallis test), malignant ascites ( P = 0.009, chi-square test), and history of other drug allergy ( P test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P test) and dose (6,816 vs. 3,844 mg, P test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.
Cervical dentin hypersensitivity: a cross-sectional investigation in Athens, Greece.
Rahiotis, C; Polychronopoulou, A; Tsiklakis, K; Kakaboura, A
The purpose of this study was to identify the prevalence of cervical dentin hypersensitivity in a cross-sectional investigation of Greek adults. Seven hundred and sixty-seven subjects were examined. Participants were patients processed for first examination in the Clinic of Oral Diagnosis and Radiology at the Faculty of Dentistry, University of Athens. The evaluation of hypersensitivity was performed using two methods: for each tooth, the response to a) tactile stimulus and b) air-blast stimulus was measured. Additional factors such as smoking habits, oral health behaviour, consumption of acidic foods, type of toothbrush, daily use of fluoride solution and of desensitising toothpaste, gingival recession and non-carious cervical lesions were recorded and evaluated as causative factors. Descriptive statistics on the demographics of the study sample, of oral health behaviour characteristics and of oral examination findings were performed. Comparisons of these characteristics in the presence or absence of hypersensitivity were conducted with the chi-square test. Data were further analysed using multiple logistic regression modelling. Among study participants, 21·3% had at least one cervical dentin hypersensitivity reaction to the tactile stimulus, and 38·6%, to the air-blast stimulus. Multivariate analysis detected association of the hypersensitivity in tactile or air-blast stimulus with the non-carious lesions and with the gingival recessions. Additionally, a relation between hypersensitivity and air-blast stimulus with gender (female) was found. There was no association between the hypersensitivity in both of the stimuli and the level of education, smoking, consumption of acidic foods, type of toothbrush and daily use of fluoride solution or desensitising toothpaste. The overall prevalence of cervical dentin hypersensitivity in the adult population in Athens ranged from 21·3% to 38·6% depending on the type of stimuli. Cervical non-carious lesions and gingival
electro-hypersensitivity: survey among general practitioners, occupational physicians and hygienist from the Netherlands
Bonnet-Belfais, Monique; Salines, Georges
From October 2013 through January 2014, Dutch and Swiss researchers conducted a survey in the Netherlands on electro-hypersensitive (EHS) people among the health care providers likely to be consulted for primary care and prevention. (author)
Hypersensitivity reactions to metallic implants-diagnostic algorithm and suggested patch test series for clinical use
Schalock, Peter C; Menné, Torkil; Johansen, Jeanne D
Cutaneous and systemic hypersensitivity reactions to implanted metals are challenging to evaluate and treat. Although they are uncommon, they do exist, and require appropriate and complete evaluation. This review summarizes the evidence regarding evaluation tools, especially patch and lymphocyte...... transformation tests, for hypersensitivity reactions to implanted metal devices. Patch test evaluation is the gold standard for metal hypersensitivity, although the results may be subjective. Regarding pre-implant testing, those patients with a reported history of metal dermatitis should be evaluated by patch...... testing. Those without a history of dermatitis should not be tested unless considerable concern exists. Regarding post-implant testing, a subset of patients with metal hypersensitivity may develop cutaneous or systemic reactions to implanted metals following implant. For symptomatic patients, a diagnostic...
Nickel in nails, hair and plasma from nickel-hypersensitive women
Gammelgaard, Bente; Veien, Niels
The concentrations of nickel in finger-nails, toe-nails, hair and plasma from 71 nickel-hypersensitive women and 20 non-hypersensitive women were determined. Nickel concentrations in finger-nails were significantly higher than in toe-nails in both the nickel-hypersensitive group and the control...... group. Nickel-sensitive women had significantly higher levels of nickel in toe-nails, hair and plasma than had control subjects, whereas there was no significant difference in nickel concentration in finger-nails between the two groups. No correlation could be demonstrated between nickel levels in any...... combination of nails, hair and plasma in the nickel-hypersensitive or in the control group....
Health-related quality of life in food hypersensitive schoolchildren and their families: parents' perceptions
Marklund Birgitta
Full Text Available Abstract Background About 20% of schoolchildren and adolescents in Sweden suffer from perceived food hypersensitivity (e.g. allergy or intolerance. Our knowledge of how child food hypersensitivity affects parents HRQL and what aspects of the hypersensitivity condition relate to HRQL deterioration in the family is limited. Thus the aim of this study was to investigate the parent-reported HRQL in families with a schoolchild considered to be food hypersensitive. The allergy-associated parameters we operated with were number of offending food items, adverse food reactions, additional hypersensitivity, allergic diseases and additional family members with food hypersensitivity. These parameters, along with age and gender were assessed in relation to child, parent and family HRQL. Methods In May 2004, a postal questionnaire was distributed to parents of 220 schoolchildren with parent-reported food hypersensitivity (response rate 74%. Two questionnaires were used: CHQ-PF28 and a study-specific questionnaire including questions on allergy-associated parameters. In order to find factors that predict impact on HRQL, stepwise multiple linear regression analyses were carried out. Results An important predictor of low HRQL was allergic disease (i.e. asthma, eczema, rhino conjunctivitis in addition to food hypersensitivity. The higher the number of allergic diseases, the lower the physical HRQL for the child, the lower the parental HRQL and the more disruption in family activities. Male gender predicted lower physical HRQL than female gender. If the child had sibling(s with food hypersensitivity this predicted lower psychosocial HRQL for the child and lower parental HRQL. Food-induced gastro-intestinal symptoms predicted lower parental HRQL while food-induced breathing difficulties predicted higher psychosocial HRQL for the child and enhanced HRQL with regards to the family's ability to get along. Conclusion The variance in the child's physical HRQL was to a
Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity
Feng, Bin; La, Jun-ho; Schwartz, Erica S.; Tanaka, Takahiro; McMurray, Timothy P.; Gebhart, G. F.
Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the di...
Expression of antibacterial resistance at the site of a delayed hypersensitivity reaction.
Patel, P J
The site of a delayed hypersensitivity reaction to tuberculin or bovine serum ablumin was shown to contain mechanisms that expressed increased antibacterial activity, as evidenced by restricted growth of a local inoculum of Listeria monocytogenes. As was the case with a delayed hypersensitivity reaction, the local generation of antibacterial activity was antigen specific and T-cell dependent. Antibacterial resistance was always expressed at the site of injection of specific antigen in sensiti...
Food hypersensitivity in patients over 14 years of age suffering from atopic dermatitis
Jarmila Čelakovská
Full Text Available Background: Patients suffering from atopic dermatitis often describe food hypersensitivity. Rising prevalence of food hypersensitivity and severe allergic reactions to foods have been reported, but the data are scarce. Aims and Objectives: Evaluation of food hypersensitivity reactions in patients suffering from atopic dermatitis. Materials and Methods: The dermatological examination was performed in patients of age 14 years and above and the detailed history was taken concerning the food hypersensitivity. Results: A total of 228 patients were examined-72 men, 156 women, average age 26.2 (SD 9.5 years. The food hypersensitivity reactions were recorded in 196 patients from 228 (86%, no reactions were recorded in 32 patients (24%. Foods with the most often recorded reactions are: Nuts (in 35% of patients, tomatoes (in 20%, and kiwi (in 17, 5%, apples and spices (in 16%, tangerines and oranges (in 15%, capsicum (in 13%, fishes (in 12%, celery (in 9%, and chocolate (in 7%. Conclusion: Food hypersensitivity reactions are recorded in 86% of patients suffering from atopic dermatitis. Nuts, tomatoes, and pollen-associated foods play a role in the majority of patients suffering from atopic dermatitis.
Food hypersensitivity in patients over 14 years of age suffering from atopic dermatitis.
Celakovská, Jarmila; Ettler, K; Ettlerová, K; Vaně�ková, J
Patients suffering from atopic dermatitis often describe food hypersensitivity. Rising prevalence of food hypersensitivity and severe allergic reactions to foods have been reported, but the data are scarce. Evaluation of food hypersensitivity reactions in patients suffering from atopic dermatitis. The dermatological examination was performed in patients of age 14 years and above and the detailed history was taken concerning the food hypersensitivity. A total of 228 patients were examined-72 men, 156 women, average age 26.2 (SD 9.5) years. The food hypersensitivity reactions were recorded in 196 patients from 228 (86%), no reactions were recorded in 32 patients (24%). Foods with the most often recorded reactions are: Nuts (in 35% of patients), tomatoes (in 20%), and kiwi (in 17, 5%), apples and spices (in 16%), tangerines and oranges (in 15%), capsicum (in 13%), fishes (in 12%), celery (in 9%), and chocolate (in 7%). Food hypersensitivity reactions are recorded in 86% of patients suffering from atopic dermatitis. Nuts, tomatoes, and pollen-associated foods play a role in the majority of patients suffering from atopic dermatitis.
Desensitization in delayed drug hypersensitivity reactions -- an EAACI position paper of the Drug Allergy Interest Group.
Scherer, K; Brockow, K; Aberer, W; Gooi, J H C; Demoly, P; Romano, A; Schnyder, B; Whitaker, P; Cernadas, J S R; Bircher, A J
Drug hypersensitivity may deprive patients of drug therapy, and occasionally no effective alternative treatment is available. Successful desensitization has been well documented in delayed drug hypersensitivity reactions. In certain situations, such as sulfonamide hypersensitivity in HIV-positive patients or hypersensitivity to antibiotics in patients with cystic fibrosis, published success rates reach 80%, and this procedure appears helpful for the patient management. A state of clinical tolerance may be achieved by the administration of increasing doses of the previously offending drug. However, in most cases, a pre-existent sensitization has not been proven by positive skin tests. Successful re-administration may have occurred in nonsensitized patients. A better understanding of the underlying mechanisms of desensitization is needed. Currently, desensitization in delayed hypersensitivity reactions is restricted to mild, uncomplicated exanthems and fixed drug eruptions. The published success rates vary depending on clinical manifestations, drugs, and applied protocols. Slower protocols tend to be more effective than rush protocols; however, underreporting of unsuccessful procedures is very probable. The decision to desensitize a patient must always be made on an individual basis, balancing risks and benefits. This paper reviews the literature and presents the expert experience of the Drug Hypersensitivity Interest Group of the European Academy of Allergy and Clinical Immunology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
The Relationship between Grandiose and Vulnerable (Hypersensitive Narcissism
Emanuel Jauk
Full Text Available Narcissistic grandiosity is characterized by overt expressions of feelings of superiority and entitlement, while narcissistic vulnerability reflects hypersensitivity and introversive self-absorbedness. Clinical evidence suggests that grandiosity is accompanied by vulnerable aspects, pointing to a common foundation. Subclinical personality research, however, views grandiose and vulnerable narcissism as independent traits. Grandiose narcissism displays substantial correlation with extraversion, while vulnerable narcissism correlates highly with introversion. We investigated if (1 controlling for intro-/extraversion might reveal a "common core� of grandiose and vulnerable narcissism, and if (2 the correlation between both aspects might be higher at higher levels of narcissism. Latent variable structural equation modeling and segmented regression analysis confirmed these hypotheses in a large non-clinical sample (N = 1,006. Interindividual differences in intro-/extraversion mask the common core of grandiose and vulnerable narcissism. The association between both aspects increases at high levels (upper 10% of grandiose narcissism, which suggests a possible transition to clinically relevant (pathological narcissism.
The Relationship between Grandiose and Vulnerable (Hypersensitive) Narcissism
Jauk, Emanuel; Weigle, Elena; Lehmann, Konrad; Benedek, Mathias; Neubauer, Aljoscha C.
Narcissistic grandiosity is characterized by overt expressions of feelings of superiority and entitlement, while narcissistic vulnerability reflects hypersensitivity and introversive self-absorbedness. Clinical evidence suggests that grandiosity is accompanied by vulnerable aspects, pointing to a common foundation. Subclinical personality research, however, views grandiose and vulnerable narcissism as independent traits. Grandiose narcissism displays substantial correlation with extraversion, while vulnerable narcissism correlates highly with introversion. We investigated if (1) controlling for intro-/extraversion might reveal a "common core� of grandiose and vulnerable narcissism, and if (2) the correlation between both aspects might be higher at higher levels of narcissism. Latent variable structural equation modeling and segmented regression analysis confirmed these hypotheses in a large non-clinical sample (N = 1,006). Interindividual differences in intro-/extraversion mask the common core of grandiose and vulnerable narcissism. The association between both aspects increases at high levels (upper 10%) of grandiose narcissism, which suggests a possible transition to clinically relevant (pathological) narcissism. PMID:28955288
Exploring Some Aspects Associated with Dentine Hypersensitivity in Children
Caleb Shitsuka
Full Text Available Background. The etiology of dentine hypersensitivity (DH is still inconclusive and there are few studies concerning it in children. Aim. To evaluate clinical, dietary, and salivary variables in children with DH complaints. Design. Forty-eight children were asked about DH. Data regarding dietary habits were collected from the children's parents and an examination was performed to determine dental erosion. Dental biofilm was estimated by oral hygiene status, according to Greene and Vermillion's Simplified Oral Hygiene Index (OHI-S. Whole saliva was collected under mechanical stimulation and evaluated salivary flow rate, initial pH, buffer capacity, and calcium and phosphate concentrations. The temperature of soft drinks, drinking method, sense of bitter taste, and other variables were also determined. Possible factors associated with DH were analyzed by univariate and multiple Poisson regression analyses. The prevalence ratio (PR values and 95% confidence intervals (95% CI were calculated. Results. DH was associated with the presence of dental erosion (PR; 95% CI = 2.23; 1.05 to 4.71 and salivary flow rate (2.49; 1.05 to 5.91. When the presence of erosion was not included, other variables were retained as follows: bitter taste (2.36; 1.38 to 4.03, OHI-S (0.47; 0.23 to 0.97. Conclusion. DH in children is associated with factors related to dental erosion.
A Case of Immediate Hypersensitivity Reaction to Maltitol
Ana Rodríguez Trabado
Full Text Available Background. Maltitol is a sugar alcohol that is frequently used as a noncaloric sweetener, although it is also used as an excipient, a plasticizer in gelatin capsules, and an emollient. It has not been previously described as an agent involved in immediate hypersensitivity reactions. Methods. We report on an anaphylactoid reaction with pharyngeal occlusion suffered by a 60-year-old man after ingestion of a candy containing maltitol syrup. A prick-to-prick test was performed with the candy and maltitol powder. Other allergens were excluded as causative agents of the adverse reaction, although the patient refused to undergo an oral challenge test with the candy. A basophil activation test (BAT was performed with maltitol powder, and a dose-response curve was generated. The test was also performed in 3 healthy controls. Results. Both prick-to-prick tests were negative. The result of the BAT was positive at all the concentrations tested in the patient's blood and negative in all the controls. Conclusions. The BAT can help to clarify the agents implicated in an adverse reaction and can reduce the risk involved in diagnosis. The BAT can also prove useful in the study of reactions caused by low-molecular-weight antigens, for which routine diagnostic tests are not feasible.
Hypersensitivity pneumonitis with Mycobacterium avium complex among spa workers.
Moraga-McHaley, Stephanie Ann; Landen, Michael; Krapfl, Heidi; Sewell, C Mack
The New Mexico Department of Health (NMDOH) investigated the cause of two cases of hypersensitivity pneumonitis (HP) in spa maintenance workers with laboratory confirmed Mycobacterium avium complex (MAC). The investigation occurred in tandem with worker protection and swimming pool regulatory investigations by the New Mexico Environment Department at the spa where the workers were employed. The investigation was conducted in order to identify unreported cases, exposure source(s), and to prevent further worker exposure. NMDOH surveyed 57 spa employees about symptoms and exposures, categorized jobs according to self-reported exposure to water, and computed odds ratios for symptom reporting by exposure category. Environmental isolates from spa water and filter swabs were cultured and compared to patient isolates by the Environmental and Applied Microbiology Team, Centers for Disease Control and Prevention (CDC). Workers with the highest exposure reported more HP-like symptoms (OR = 9.6), as did intermediate exposure workers (OR = 6.5), compared to workers with no aerosolized water exposure. Two of 13 environmental isolates were closely related to one of the patient isolates. Workers were likely exposed during spray cleaning of cartridge filters in a poorly ventilated work space. Recommendations include inhibiting organism growth in spa systems, assuring the use of respiratory protection, and adequately ventilating work spaces where filters and equipment are cleaned.
Treatment of Dentine Hypersensitivity by Diode Laser: A Clinical Study
Romeo Umberto
Full Text Available Introduction. Dentine hypersensitivity (DH is characterized by pain after stimuli that usually provoke no symptoms. This study compared the effectiveness of GaAlAs diode laser alone and with topical sodium fluoride gel (NaF. Materials and Methods. The study was conducted on 10 patients (8 F/2 M, age 25–60 and 115 teeth with DH assessed by air and tactile stimuli measured by Numeric Rating Scale (NRS. Teeth were randomly divided into G1 (34 teeth treated by 1.25% NaF; G2 (33 teeth lased at 0.5 W PW (T on 100 m and T off 100 ms, fluence 62.2 J/cm2 in defocused mode with a 320 μ fiber. Each tooth received three 1′ applications; G3 (48 teeth received NaF gel plus laser at same G2 parameters. NRS was checked at each control. Results. Significant pain reduction was showed. The NRS reduction percentages were calculated, and there was a concrete decrease of DH above all in G3 than G2 and G1. Conclusion. Diode laser is a useful device for DH treatment if used alone and mainly if used with NaF gel.
Evaluation of the hypersensitivity potential of alternative butter flavorings
Anderson, Stacey E.; Franko, Jennifer; Wells, J.R.; Lukomska, Ewa; Meade, B. Jean
Concern has been raised over the association of diacetyl with lung disease clinically resembling bronchiolitis obliterans in food manufacturing workers. This has resulted in the need for identification of alternative chemicals to be used in the manufacturing process. Structurally similar chemicals, 2,3-pentanedione, 2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione, used as constituents of synthetic flavoring agents have been suggested as potential alternatives for diacetyl, however, immunotoxicity data on these chemicals are limited. The present study evaluated the dermal irritation and sensitization potential of diacetyl alternatives using a murine model. None of the chemicals were identified as dermal irritants when tested at concentrations up to 50%. Similar to diacetyl (EC3 = 17.9%), concentration-dependent increases in lymphocyte proliferation were observed following exposure to all four chemicals, with calculated EC3 values of 15.4% (2,3-pentanedione), 18.2% (2,3-hexanedione), 15.5% (3,4-hexanedione) and 14.1% (2,3-heptanedione). No biologically significant elevations in local or total serum IgE were identified after exposure to 25–50% concentrations of these chemicals. These results demonstrate the potential for development of hypersensitivity responses to these proposed alternative butter flavorings and raise concern about the use of structurally similar replacement chemicals. Additionally, a contaminant with strong sensitization potential was found in varying concentrations in diacetyl obtained from different producers. PMID:24007741
Presumed hydrochlorothiazide-associated immunologic-hypersensitivity-induced pericardial effusion
Michael J Chaskes
Full Text Available A 50-year-old Caucasian female presented for a second opinion regarding a newly diagnosed pericardial effusion. Seven months previously, hydrochlorothiazide was introduced into her pharmacologic regimen to aid in the management of her hypertension. A routine echocardiogram indicated a large pericardial effusion with signs of early cardiac tamponade. The patient subsequently underwent successful pericardiocentesis with complete drainage of the pericardial effusion. The effusion was empirically attributed to a viral etiology. Repeat echocardiograms showed recurrence of the pericardial effusion. Prior to undergoing a second pericardiocentesis with pericardial biopsy, as her physicians recommended, the patient sought a second opinion. While obtaining the patient's history, an allergy to sulfa was elicited. The possibility that the pericardial effusion may be secondary to an immunologic-hypersensitivity reaction was considered. It was recommended the patient discontinue the use of hydrochlorothiazide. Nine days following discontinuation of hydrochlorothiazide and without any other intervention, an echocardiogram was reported to show the size of the pericardial effusion had subsided substantially. Nine weeks following discontinuation, almost complete resolution of the pericardial effusion was reported. It is hypothesized that when treated with hydrochlorothiazide, the patient had an immune response leading to the pericardial effusion.
Hazards of the 'Hard Cash': Hypersensitivity Pneumonitis
Elif Kupeli
Full Text Available Hypersensitivity pneumonitis (HP is a nonimmunoglobulin E-related immune-mediated parenchymal lung disease. A 45-year-old woman who was a lifelong nonsmoker with a six-month history of frequent episodes of cough and dyspnea was admitted to hospital. She had been working as a money counter for 20 years at a central bank. Bibasilar crackles on lung auscultation, ground-glass opacities and a mosaic pattern on high-resolution computed tomography, restrictive abnormality on pulmonary function tests and mild hypoxemia were the prominent findings. Bronchoalveolar lavage fluid analysis revealed a predominance of CD4-positive T cells, and she tested positive on her natural challenge test. She was diagnosed with subacute HP based on established criteria. She was advised to discontinue counting fresh banknotes. Prednisolone was commenced, then tapered to discontinue in the ensuing six months. Clinical and radiological improvement was achieved within two months. To the authors' knowledge, the present report is the first to describe 'hard cash HP', possibly caused by chipping dust or printing dye.
Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis
Ayodeji Adegunsoye
Full Text Available In chronic hypersensitivity pneumonitis (CHP, lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival. Patients with CHP were identified. Demographic features, pulmonary function tests, incidence of treatment-emergent adverse events (TEAEs and transplant-free survival were characterised, compared and analysed between patients stratified by immunosuppressive therapy. A multicentre comparison was performed across four independent tertiary medical centres. Among 131 CHP patients at the University of Chicago medical centre (Chicago, IL, USA, 93 (71% received immunosuppressive therapy, and had worse baseline forced vital capacity (FVC and diffusing capacity, and increased mortality compared with those who did not. Compared to patients treated with prednisone alone, TEAEs were 54% less frequent with azathioprine therapy (p=0.04 and 66% less frequent with mycophenolate mofetil (p=0.002. FVC decline and survival were similar between treatment groups. Analyses of datasets from four external tertiary medical centres confirmed these findings. CHP patients who did not receive immunosuppressive therapy had better survival than those who did. Use of mycophenolate mofetil or azathioprine was associated with a decreased incidence of TEAEs, and no difference in lung function decline or survival when compared with prednisone alone. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP, but more studies are needed.
Change in FVC and survival in chronic fibrotic hypersensitivity pneumonitis.
Gimenez, Andrea; Storrer, Karin; Kuranishi, Lilian; Soares, Maria Raquel; Ferreira, Rimarcs Gomes; Pereira, Carlos A C
The predictive value of the decline in FVC by ≥10% on survival in patients with fibrotic hypersensitivity pneumonitis is unknown. Of 112 patients included, 66 (59%) had surgical lung biopsies. Patients with ≥10% decline in predicted FVC after 6-12 months had a significantly increased risk of all-cause mortality (median survival 53 months, 95% CI 37 to 69 vs 139 months, 95% CI 66 to 212 months, p=0.007). On multivariate analysis remained associated with increasing mortality: decline in FVC by ≥10% (HR 4.13, 95% CI 1.96 to 8.70, p=0.005), lower FVC% (HR 1.03, 95% CI 1.01 to 1.05, p=0.003) and with decreasing mortality improvement with antigen avoidance (HR 0.18, 95% CI 0.04 to 0.77, p=0.021). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Hypersensitive Reaction to Tattoos: A Growing Menace in Rural India.
Shashikumar, B M; Harish, M R; Shwetha, B; Kavya, M; Deepadarshan, K; Phani, H N
Increased enthusiasm toward newer fashion trends among rural India along with the lack of government regulation has led to increased tattoo reactions. The objective of this study is to describe various clinical manifestations of hypersensitive reactions to tattoo ink reported at a tertiary care hospital in Mandya district. An observational study was carried out over a period of 1 year from June 2014 to May 2015 at Mandya Institute of Medical Sciences, Mandya. All the patients reporting with allergic reaction due to tattooing were included in the present study after obtaining informed consent. Transient acute inflammatory reaction, infections, and skin diseases localized on tattooed area were excluded from this study. A detailed history regarding the onset, duration and color used for tattooing were collected. Cutaneous examination and biopsy was to done to know the type of reaction. Fifty cutaneous allergic reactions were diagnosed among 39 patients. Mean age of subjects was 22 years and mean duration before the appearance of lesion was 7 months. Common colors associated with reactions were red (53.9%), black (33.3%), green (5.1%), and multicolor (7.7%). Itching was the predominant symptom. Skin lesions mainly consisted of lichenoid papules and plaques, eczematous lesions, and verrucous lesions. Lichenoid histopathology reaction was the most common tissue allergic reaction. Increasing popularity of tattooing among young people has predisposed to parallel increase in adverse reactions. Red pigment is most common cause of allergic reaction in the present study, and lichenoid reaction is the most common reaction.
Biomaterial Hypersensitivity: Is It Real? Supportive Evidence and Approach Considerations for Metal Allergic Patients following Total Knee Arthroplasty
Andrew J. Mitchelson
Full Text Available The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected.
Diclofenac hypersensitivity: antibody responses to the parent drug and relevant metabolites.
Andrea Harrer
Full Text Available Hypersensitivity reactions against nonsteroidal antiinflammatory drugs (NSAIDs like diclofenac (DF can manifest as Type I-like allergic reactions including systemic anaphylaxis. However, except for isolated case studies experimental evidence for an IgE-mediated pathomechanism of DF hypersensitivity is lacking. In this study we aimed to investigate the possible involvement of drug- and/or metabolite-specific antibodies in selective DF hypersensitivity.DF, an organochemically synthesized linkage variant, and five major Phase I metabolites were covalently coupled to carrier proteins. Drug conjugates were analyzed for coupling degree and capacity to crosslink receptor-bound IgE antibodies from drug-sensitized mice. With these conjugates, the presence of hapten-specific IgE antibodies was investigated in patients' samples by ELISA, mediator release assay, and basophil activation test. Production of sulfidoleukotrienes by drug conjugates was determined in PBMCs from DF-hypersensitive patients. All conjugates were shown to carry more than two haptens per carrier molecule. Immunization of mice with drug conjugates induced drug-specific IgE antibodies capable of triggering mediator release. Therefore, the conjugates are suitable tools for detection of drug-specific antibodies and for determination of their anaphylactic activity. Fifty-nine patients were enrolled and categorized as hypersensitive either selectively to DF or to multiple NSAIDs. In none of the patients' samples evidence for drug/metabolite-specific IgE in serum or bound to allergic effector cells was found. In contrast, a small group of patients (8/59, 14% displayed drug/metabolite-specific IgG.We found no evidence for an IgE-mediated effector mechanism based on haptenation of protein carriers in DF-hypersensitive patients. Furthermore, a potential involvement of the most relevant metabolites in DF hypersensitivity reactions could be excluded.
Association of tinnitus and electromagnetic hypersensitivity: hints for a shared pathophysiology?
Michael Landgrebe
Full Text Available BACKGROUND: Tinnitus is a frequent condition with high morbidity and impairment in quality of life. The pathophysiology is still incompletely understood. Electromagnetic fields are discussed to be involved in the multi-factorial pathogenesis of tinnitus, but data proofing this relationship are very limited. Potential health hazards of electromagnetic fields (EMF have been under discussion for long. Especially, individuals claiming themselves to be electromagnetic hypersensitive suffer from a variety of unspecific symptoms, which they attribute to EMF-exposure. The aim of the study was to elucidate the relationship between EMF-exposure, electromagnetic hypersensitivity and tinnitus using a case-control design. METHODOLOGY: Tinnitus occurrence and tinnitus severity were assessed by questionnaires in 89 electromagnetic hypersensitive patients and 107 controls matched for age-, gender, living surroundings and workplace. Using a logistic regression approach, potential risk factors for the development of tinnitus were evaluated. FINDINGS: Tinnitus was significantly more frequent in the electromagnetic hypersensitive group (50.72% vs. 17.5% whereas tinnitus duration and severity did not differ between groups. Electromagnetic hypersensitivity and tinnitus were independent risk factors for sleep disturbances. However, measures of individual EMF-exposure like e.g. cell phone use did not show any association with tinnitus. CONCLUSIONS: Our data indicate that tinnitus is associated with subjective electromagnetic hypersensitivity. An individual vulnerability probably due to an over activated cortical distress network seems to be responsible for, both, electromagnetic hypersensitivity and tinnitus. Hence, therapeutic efforts should focus on treatment strategies (e.g. cognitive behavioral therapy aiming at normalizing this dysfunctional distress network.
Blast cells transfer experimental hypersensitivity pneumonitis in guinea pigs
Schuyler, M.; Cook, C.; Listrom, M.; Fengolio-Preiser, C.
We previously demonstrated that experimental hypersensitivity pneumonitis (HP) can be transferred by lymph node cells (LNC) cultured in vitro with antigen. The purpose of this study was to identify the cells responsible for transfer and to determine if pulmonary cells can transfer HP. We cultured LNC from sensitized Strain 2 guinea pigs with a soluble extract of Micropolyspora faeni for 72 h, separated lymphoblasts from small lymphocytes, and transferred both subpopulations intravenously to syngeneic recipients. We also transferred irradiated lymphoblasts (1,500 rads), macrophage-depleted, lymphoblast-enriched populations, and pulmonary cells either without culture or after culture with M. faeni. Control animals received an equal volume of medium. All recipient animals were challenged intratracheally (i.t.) with M. faeni 48 h after the cell transfer, and they were killed 4 days after i.t. challenge. Randomly selected microscopic fields of the lung (250/animal) were judged to be normal or abnormal without knowledge of treatment. This measurement was reproducible (r = 0.95 for duplicate measurements, n = 55). All guinea pigs were maintained in HEPA-filtered air. There was a low level of pulmonary response to an i.t. challenge of M. faeni in animals that received medium. Animals that received pulmonary cells, either cultured or noncultured, did not differ from those in the control group. There was a substantial increase (p less than 0.01) in the extent of pulmonary abnormalities in the recipients of the lymphoblast population, with significant correlation (r = 0.87, p less than 0.01) between the number of lymphoblasts transferred and the extent of pulmonary abnormalities
The role for decorin in delayed-type hypersensitivity
Seidler, Daniela G.; Mohamed, Negia A.; Bocian, Carla; Stadtmann, Anika; Hermann, Sven; Schäfers, Klaus; Schäfers, Michael; Iozzo, Renato V.; Zarbock, Alexander; Götte, Martin
Decorin, a small leucine-rich proteoglycan, regulates extracellular matrix organization, growth factor-mediated signaling and cell growth. As decorin may directly modulate immune responses, we investigated its role in a mouse model of contact allergy (oxazolone-mediated delayed-type hypersensitivity, DTH) in decorin-deficient (Dcn−/−) and wild-type mice. Dcn−/− mice showed a reduced ear swelling 24 hours after oxazolone treatment with a concurrent attenuation of leukocyte infiltration. These findings were corroborated by reduced glucose metabolism as determined by 18FDG uptake in positron emission tomography scans. Unexpectedly, polymorphonuclear leukocyte numbers in Dcn−/− blood vessels were significantly increased, accompanied by large numbers of flattened leukocytes adherent to the endothelium. Intravital microscopy, flow chamber and static adhesion assays confirmed increased adhesion and reduced transmigration of Dcn−/− leukocytes. Circulating blood neutrophil numbers were significantly increased in Dcn−/− mice 24 hours after DTH elicitation, but only moderately increased in wild-type mice. Expression of the pro-inflammatory cytokine TNF-α was reduced, while syndecan-1 and ICAM-1 were overexpressed in inflamed ears of Dcn−/− mice, indicating that these adhesion molecules could be responsible for increased leukocyte adhesion. Decorin treatment of endothelial cells increased tyrosine phosphorylation and reduced syndecan-1 expression. Notably, absence of syndecan-1 in a genetic background lacking decorin rescued the attenuated DTH phenotype of Dcn−/− mice. Collectively, these results implicate a role for decorin in mediating DTH responses by influencing polymorphonuclear leukocyte attachment to the endothelium. This occurs via two non-mutually exclusive mechanisms that involve a direct anti-adhesive effect on polymorphonuclear leukocytes and a negative regulation of ICAM-1 and syndecan-1 expression. PMID:22043007
Hypersensitive reaction to tattoos: A growing menace in rural India
B M Shashikumar
Full Text Available Background: Increased enthusiasm toward newer fashion trends among rural India along with the lack of government regulation has led to increased tattoo reactions. Objective: The objective of this study is to describe various clinical manifestations of hypersensitive reactions to tattoo ink reported at a tertiary care hospital in Mandya district. Materials and Methods: An observational study was carried out over a period of 1 year from June 2014 to May 2015 at Mandya Institute of Medical Sciences, Mandya. All the patients reporting with allergic reaction due to tattooing were included in the present study after obtaining informed consent. Transient acute inflammatory reaction, infections, and skin diseases localized on tattooed area were excluded from this study. A detailed history regarding the onset, duration and color used for tattooing were collected. Cutaneous examination and biopsy was to done to know the type of reaction. Results: Fifty cutaneous allergic reactions were diagnosed among 39 patients. Mean age of subjects was 22 years and mean duration before the appearance of lesion was 7 months. Common colors associated with reactions were red (53.9%, black (33.3%, green (5.1%, and multicolor (7.7%. Itching was the predominant symptom. Skin lesions mainly consisted of lichenoid papules and plaques, eczematous lesions, and verrucous lesions. Lichenoid histopathology reaction was the most common tissue allergic reaction. Conclusion: Increasing popularity of tattooing among young people has predisposed to parallel increase in adverse reactions. Red pigment is most common cause of allergic reaction in the present study, and lichenoid reaction is the most common reaction.
Pomalidomide desensitization in a patient hypersensitive to immunomodulating agents
Seki, J.T.; Sakurai, N.; Lam, W.; Reece, D.E.
Despite progressive treatments with tandem stem-cell transplantation, patients with incurable myeloma eventually succumb to relapsed or refractory disease if left untreated. Promising agents such as proteasome inhibitors and immunomodulating imide drugs (imids), including the newer-generation agent pomalidomide, in combination with lower-dose dexamethasone, have been shown to be effective and to significantly improve and prolong survival in pretreated patients. Although the incidence of pomalidomide hypersensitivity reaction (hsr) in this class of drugs is not as well known, we have documented cutaneous toxicity (grade 3 by the Common Terminology Criteria for Adverse Events, version 4) in 2 separate cases (not yet published). Because the imids are chemically, structurally, and pharmacologically similar, it is not unreasonable to consider possible cross-reactivity in pomalidomide recipients who developed hsr when receiving previous lines of imids. As a patient's advocate, it is only prudent to provide a responsible, and yet practical, means to better address cross-sensitivity for patients. Intervention with the use of a rapid desensitization program (rdp) as a preventive measure should be introduced before initiating pomalidomide. Such a proactive measure for the patient's safety will ensure a smooth transition into pomalidomide treatment. A hsr can be either related or non-related to immunoglobulin E. As imids become an essential treatment backbone for myeloma and other plasma-cell diseases, an increasing number of patients could experience skin and other life-threatening toxicities, resulting in unnecessary discontinuation of these life-prolonging agents. An extemporaneously prepared pomalidomide suspension developed at our centre enables patients to undergo rdp safely. Patients enjoy a good quality of life and clinical response after the rdp procedure. PMID:28874903
Association of anticonvulsant hypersensitivity syndrome with Herpesvirus 6, 7.
Oskay, Tuğba; Karademir, Asli; Ertürk, Ozcan I
Anticonvulsant hypersensitivity syndrome (AHS) is one of the most severe forms of drug eruption with potentially lethal, and multiorgan involvement. Recently, it has been suggested that Human Herpesvirus (HHV) infection has been involved in this syndrome, although the pathogenesis of this syndrome remains still unclear. The objective of this study was to determine the clinical characteristics of AHS and the possible role of viral infection as a co-factor. We prospectively analyzed clinical, laboratory and virological findings for 23 cases of AHS. A viral study including viral serology and a polymerase chain reaction (PCR) was performed. The most common anticonvulsant was carbamazepine (12) followed by phenytoin (6), phenobarbital (4) and gabapentin (1). All patients met fulfill the clinical criteria of AHS. Even though internal organ involvement such as liver (52%), kidney (34%), and lung (13%) has been observed, involvement of heart, lung, thyroid, muscle, pancreas, spleen, and brain was less frequent. We also noted two patients who died due to multiorgan failure. No association with viral infection including HSV, VZV, HHV-8, CMV, EBV, measles, rubella and parvovirus B19 was detected in the current series. Increased serum anti-HHV-6 IgG and HHV-7 titers and presence of HHV-6 and -7 DNA in serum, revealed by PCR analysis, suggested reactivation of HHV-6. In contrast to the control groups, DNA for HHV-6 was detected in serum in 5 out of the 23 patients while HHV-7 was seen in two patients. We found an evidence to link reactivation of HHV-6 or HHV-7 in the development of only carbamazepine-induced AHS. We propose that some cases of AHS are accompanied by reactivation of not only HHV-6 but also HHV-7. HHV infection may contribute to the severity, prolongation, or relapse of AHS and may possibly have fatal consequences in some susceptible individuals receiving the anticonvulsants.
Transcriptome Analysis of Cotton (Gossypium hirsutum L. Genotypes That Are Susceptible, Resistant, and Hypersensitive to Reniform Nematode (Rotylenchulus reniformis.
Ruijuan Li
Full Text Available Reniform nematode is a semi-endoparasitic nematode species causing significant yield loss in numerous crops, including cotton (Gossypium hirsutum L.. An RNA-sequencing analysis was conducted to measure transcript abundance in reniform nematode susceptible (DP90 & SG747, resistant (BARBREN-713, and hypersensitive (LONREN-1 genotypes of cotton (Gossypium hirsutum L. with and without reniform nematode infestation. Over 90 million trimmed high quality reads were assembled into 84,711 and 80, 353 transcripts using the G. arboreum and the G. raimondii genomes as references. Many transcripts were significantly differentially expressed between the three different genotypes both prior to and during nematode pathogenesis, including transcripts corresponding to the gene ontology categories of cell wall, hormone metabolism and signaling, redox reactions, secondary metabolism, transcriptional regulation, stress responses, and signaling. Further analysis revealed that a number of these differentially expressed transcripts mapped to the G. raimondii and/or the G. arboreum genomes within 1 megabase of quantitative trait loci that had previously been linked to reniform nematode resistance. Several resistance genes encoding proteins known to be strongly linked to pathogen perception and resistance, including LRR-like and NBS-LRR domain-containing proteins, were among the differentially expressed transcripts mapping near these quantitative trait loci. Further investigation is required to confirm a role for these transcripts in reniform nematode susceptibility, hypersensitivity, and/or resistance. This study presents the first systemic investigation of reniform nematode resistance-associated genes using different genotypes of cotton. The candidate reniform nematode resistance-associated genes identified in this study can serve as the basis for further functional analysis and aid in further development of reniform a nematode resistant cotton germplasm.
Voluntary wheel running delays disease onset and reduces pain hypersensitivity in early experimental autoimmune encephalomyelitis (EAE).
Benson, Curtis; Paylor, John W; Tenorio, Gustavo; Winship, Ian; Baker, Glen; Kerr, Bradley J
Multiple sclerosis (MS) is classically defined by motor deficits, but it is also associated with the secondary symptoms of pain, depression, and anxiety. Up to this point modifying these secondary symptoms has been difficult. There is evidence that both MS and the animal model experimental autoimmune encephalomyelitis (EAE), commonly used to study the pathophysiology of the disease, can be modulated by exercise. To examine whether limited voluntary wheel running could modulate EAE disease progression and the co-morbid symptoms of pain, mice with EAE were allowed access to running wheels for 1h every day. Allowing only 1h every day of voluntary running led to a significant delay in the onset of clinical signs of the disease. The development of mechanical allodynia was assessed using Von Frey hairs and indicated that wheel running had a modest positive effect on the pain hypersensitivity associated with EAE. These behavioral changes were associated with reduced numbers of cFOS and phosphorylated NR1 positive cells in the dorsal horn of the spinal cord compared to no-run EAE controls. In addition, within the dorsal horn, voluntary wheel running reduced the number of infiltrating CD3(+) T-cells and reduced the overall levels of Iba1 immunoreactivity. Using high performance liquid chromatography (HPLC), we observed that wheel-running lead to significant changes in the spinal cord levels of the antioxidant glutathione. Oxidative stress has separately been shown to contribute to EAE disease progression and neuropathic pain. Together these results indicate that in mice with EAE, voluntary motor activity can delay the onset of clinical signs and reduce pain symptoms associated with the disease. Copyright © 2015 Elsevier Inc. All rights reserved.
Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity.
Nóra Kutszegi
Full Text Available L-asparaginase (ASP is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL. However, hypersensitivity reactions (HSRs to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin-Frankfurt-Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01-0.26; p = 4.70E-04, while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176 were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09-0.53; p = 8.48E-04 and OR = 3.02 (1.36-6.73; p = 6.76E-03, respectively. Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect.
Isolation of uvh1, an Arabidopsis mutant hypersensitive to ultraviolet light and ionizing radiation
Harlow, G. R.; Jenkins, M. E.; Pittalwala, T. S.; Mount, D. W.
A genetic screen for mutants of Arabidopsis that are hypersensitive to UV light was developed and used to isolate a new mutant designated uvh1. UV hypersensitivity in uvh1 was due to a single recessive trait that is probably located on chromosome 3. Although isolated as hypersensitive to an acute exposure to UV-C light, uvh1 was also hypersensitive to UV-B wavelengths, which are present in sunlight that reaches the earth's surface. UV-B damage to both wild-type and uvh1 plants could be significantly reduced by subsequent exposure of UV-irradiated plants to photoreactivating light, showing that photoreactivation of UV-B damage is important for plant viability and that uvh1 plants are not defective in photoreactivation. A new assay for DNA damage, the Dral assay, was developed and used to show that exposure of wild-type and uvh1 plants to a given dose of UV light induces the same amount of damage in chloroplast and nuclear DNA. Thus, uvh1 is not defective in a UV protective mechanism. uvh1 plants were also found to be hypersensitive to ionizing radiation. These results suggest that uvh1 is defective in a repair or tolerance mechanism that normally provides plants with resistance to several types of DNA damage.
Harlow, G.R.; Jenkins, M.E.; Pittalwala, T.S.; Mount, D.W.
A genetic screen for mutants of Arabidopsis that are hypersensitive to UV light was developed and used to isolate a new mutant designated uvh1. UV hypersensitivity in uvh1 was due to a single recessive trait that is probably located on chromosome 3. Although isolated as hypersensitive to an acute exposure to UV-C light, uvh1 was also hypersensitive to UV-B wavelengths, which are present in sunlight that reaches the earth's surface. UV-B damage to both wild-type and uvh1 plants could be significantly reduced by subsequent exposure of UV-irradiated plants to photoreactivating light, showing that photoreactivation of UV-B damage is important for plant viability and that uvh1 plants are not defective in photoreactivation. A new assay for DNA damage, the Dral assay, was developed and used to show that exposure of wild-type and uvh1 plants to a given dose of UV light induces the same amount of damage in chloroplast and nuclear DNA. Thus, uvh1 is not defective in a UV protective mechanism. uvh1 plants were also found to be hypersensitive to ionizing radiation. These results suggest that uvh1 is defective in a repair or tolerance mechanism that normally provides plants with resistance to several types of DNA damage
Sensory hypersensitivity predicts enhanced attention capture by faces in the early development of ASD
E.J.H Jones
Full Text Available Sensory sensitivity is prevalent among young children with ASD, but its relation to social communication impairment is unclear. Recently, increased sensory hypersensitivity has been linked to greater activity of the neural salience network (Green et al., 2016. Increased neural sensitivity to stimuli, especially social stimuli, could provide greater opportunity for social learning and improved outcomes. Consistent with this framework, in Experiment 1 we found that parent report of greater sensory hypersensitivity at 2 years in toddlers with ASD (NÂ =Â 27 was predictive of increased neural responsiveness to social stimuli (larger amplitude event-related potential/ERP responses to faces at P1, P400 and Nc at 4 years, and this in turn was related to parent report of increased social approach at 4 years. In Experiment 2, parent report of increased perceptual sensitivity at 6 months in infants at low and high familial risk for ASD (NÂ =Â 35 predicted larger ERP P1 amplitude to faces at 18 months. Increased sensory hypersensitivity in early development thus predicted greater attention capture by faces in later development, and this related to more optimal social behavioral development. Sensory hypersensitivity may index a child's ability to benefit from supportive environments during development. Early sensory symptoms may not always be developmentally problematic for individuals with ASD. Keywords: Autism, Sensory hypersensitivity, Social attention, Salience network, Infant, EEG
Hypersensitivity reaction studies of a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation.
Wang, Hongbo; Cheng, Guang; Du, Yuan; Ye, Liang; Chen, Wenzhong; Zhang, Leiming; Wang, Tian; Tian, Jingwei; Fu, Fenghua
The commercial drug paclitaxel (Taxol) may introduce hypersensitivity reactions associated with the polyethoxylated castor oil-ethanol solvent. To overcome these problems, we developed a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation, known as Lipusu. In this study, we performed in vitro and in vivo experiments to compare the safety profiles of Lipusu and Taxol, with special regard to hypersensitivity reactions. First, Swiss mice were used to determine the lethal dosages, and then to evaluate hypersensitivity reactions, followed by histopathological examination and enzyme-linked immunosorbent assays (ELISAs) of serum SC5b-9 and lung histamine. Additionally, healthy human serum was used to analyze in vitro complement activation. Finally, an MTT assay was used to determine the in vitro anti-proliferation activity. Our data clearly showed that Lipusu displayed a much higher safety margin and did not induce hypersensitivity or hypersensitivity-related lung lesions, which may be associated with the fact that Lipusu did not activate complement or increase histamine release in vivo. Moreover, Lipusu did not promote complement activation in healthy human serum in vitro, and demonstrated anti-proliferative activity against human cancer cells, similar to that of Taxol. Therefore, the improved formulation of paclitaxel, which exhibited a much better safety profile and comparable cytotoxic activity to Taxol, may bring a number of benefits to cancer patients.
Carboplatin Hypersensitivity Reactions in Pediatric Low Grade Glioma Are Protocol Specific and Desensitization Shows Poor Efficacy.
Dodgshun, Andrew J; Hansford, Jordan R; Cole, Theresa; Choo, Sharon; Sullivan, Michael J
The use of carboplatin for the treatment of pediatric low grade gliomas (PLGG) is often limited by the development of carboplatin hypersensitivity. Reported rates of carboplatin hypersensitivity reactions vary between 6% and 32% in these patients. Here we report the frequency of carboplatin hypersensitivity reactions depending on the treatment regimen used, and outcomes of carboplatin desensitization. The records of all patients in a single institution who were treated with carboplatin for PLGG were accessed and all patients receiving more than one dose of carboplatin are reported. Thirty four patients with PLGG were treated with carboplatin according to one of the two different regimens. Carboplatin hypersensitivity was documented in 47% of patients, but the frequency differed by treatment protocol. Those patients treated with 4-weekly single agent carboplatin had carboplatin allergy in 8% of cases whereas 68% of those treated with combined carboplatin and vincristine (every three weeks, according to the SIOP 2004 low grade glioma protocol) had carboplatin reactions (OR 23.6, P Desensitization was only successful in two out of 10 patients in whom it was attempted. Hypersensitivity reactions to carboplatin are more common in this cohort than previously reported and rates are protocol-dependent. Desensitization showed limited effectiveness in this cohort. © 2015 Wiley Periodicals, Inc.
High-resolution computed tomography and histopathological findings in hypersensitivity pneumonitis: a pictorial essay
Torres, Pedro Paulo Teixeira e Silva; Moreira, Marise Amaral Reboucas; Silva, Daniela Graner Schuwartz Tannus; Moreira, Maria Auxiliadora do Carmo [Universidade Federal de Goias (UFG), Goiania, GO (Brazil); Gama, Roberta Rodrigues Monteiro da [Hospital do Cancer de Barretos, Barretos, SP (Brazil); Sugita, Denis Masashi, E-mail: pedroptstorres@yahoo.com.br [Anapolis Unievangelica, Anapolis, GO (Brazil)
Hypersensitivity pneumonitis is a diffuse interstitial and granulomatous lung disease caused by the inhalation of any one of a number of antigens. The objective of this study was to illustrate the spectrum of abnormalities in high-resolution computed tomography and histopathological findings related to hypersensitivity pneumonitis. We retrospectively evaluated patients who had been diagnosed with hypersensitivity pneumonitis (on the basis of clinical-radiological or clinical-radiological-pathological correlations) and had undergone lung biopsy. Hypersensitivity pneumonitis is clinically divided into acute, subacute, and chronic forms; high-resolution computed tomography findings correlate with the time of exposure; and the two occasionally overlap. In the subacute form, centrilobular micronodules, ground glass opacities, and air trapping are characteristic high-resolution computed tomography findings, whereas histopathology shows lymphocytic inflammatory infiltrates, bronchiolitis, variable degrees of organizing pneumonia, and giant cells. In the chronic form, high-resolution computed tomography shows traction bronchiectasis, honeycombing, and lung fibrosis, the last also being seen in the biopsy sample. A definitive diagnosis of hypersensitivity pneumonitis can be made only through a multidisciplinary approach, by correlating clinical findings, exposure history, high-resolution computed tomography findings, and lung biopsy findings. (author)
Yacht-maker's lung: A case of hypersensitivity pneumonitis in yacht manufacturing.
Volkman, Kristen K; Merrick, James G; Zacharisen, Michael C
We present a case of hypersensitivity pneumonitis in a 46-year-old female working at a yacht manufacturing company. She reported a 2-month history of progressive dyspnea, chest tightness, and daytime, nocturnal, and exertional cough in temporal relationship to work where she was exposed to chemicals involved in the manufacture of yachts. Treatment with systemic antibiotic therapy, inhaled bronchodilators, and inhaled corticosteroids provided minimal relief of symptoms. Spirometry revealed a restrictive defect and a chest x-ray demonstrated a diffuse interstitial pattern. She improved on oral corticosteroids and with avoidance of her work environment had resolution of her symptoms and normalization of her spirometry. Among the various chemicals the patient was exposed to, the most likely causative agents for her symptoms were dimethyl phthalate and styrene. Although the specific chemical or antigen could not be determined, the history and objective findings are consistent with occupational hypersensitivity pneumonitis. This represents a case of hypersensitivity pneumonitis related to the manufacture of yachts.
Evidentiation of Paramyosin (Sm-97 as a Modulating Antigen on Granulomatous Hypersensitivity to Schistosoma mansoni Eggs
Hirsch Cristine
Full Text Available A Schistosoma mansoni adult worm anionic fraction (PIII has previously been shown to protect mice against challenge infection and to reduce pulmonary and hepatic granulomatous hypersensitivity. Serum from PIII-immunized rabbit was used to screen a lgt11 cDNA library from S. mansoni adult worm in order to identify antigens capable of modulating granulomatous hypersensitivity. We obtained four clones with 400 (Sm-III.11, 900 (Sm-III.16, 1100 (Sm-III.10 and 1300 (Sm-III.12 bp of length. All clone-specific antibodies were able to recognize most of the PIII components. The sequence analysis showed that these clones presented high homology with S. mansoni paramyosin (Sm-97. These findings ascribe a new function to this antigen with an important role in modulation of granulomatous hypersensitivity to S. mansoni eggs
algorithm to guide the selection of screening allergen series for patch testing is provided. At a minimum, an extended baseline screening series and metal screening is necessary. Static and dynamic orthopaedic implants, intravascular stent devices, implanted defibrillators and dental and gynaecological......Cutaneous and systemic hypersensitivity reactions to implanted metals are challenging to evaluate and treat. Although they are uncommon, they do exist, and require appropriate and complete evaluation. This review summarizes the evidence regarding evaluation tools, especially patch and lymphocyte...... transformation tests, for hypersensitivity reactions to implanted metal devices. Patch test evaluation is the gold standard for metal hypersensitivity, although the results may be subjective. Regarding pre-implant testing, those patients with a reported history of metal dermatitis should be evaluated by patch...
Leukemoid reaction secondary to hypersensitivity syndrome to phenobarbital: a case report.
Zeng, Qinghai; Wu, Yuanqiang; Zhan, Yi; Tang, Ling; Zhou, Yangmei; Yin, Jun; Fan, Fan; Zhang, Guiying; Lu, Qianjin; Xiao, Rong
The most important adverse effects of phenobarbital, an anticonvulsant drug, are behavior and cognitive alterations. Hypersensitivity syndrome caused by phenobarbital presenting with a leukemoid reaction is a rare side effect, which is rarely ever reported and needs to be known. We report on a 27-year-old Chinese woman who experienced hypersensitivity syndrome three weeks after the initiation of phenobarbital. The patient developed fever, skin rash, face swelling, lymphadenopathy, myalgia, hepatitis, eosinophilia, atypical lymphocytes and leukocytosis. Along with the pathological progress of the disease, the patient noticed a gradual exacerbation of her symptoms. And the highest leukocyte count was up to 127.2 x 10(9)/L. After discontinuing of phenobarbital and administration of methylprednisolone combined with the intravenous immunoglobulin shock therapy, all initial symptoms improved and the leukocyte count normalized. This case is reported because of its rarity of the leukemoid reaction secondary to hypersensitivity syndrome to phenobarbital.
Defective DNA cross-link removal in Chinese hamster cell mutants hypersensitive to bifunctional alkylating agents
Hoy, C.A.; Thompson, L.H.; Mooney, C.L.; Salazar, E.P.
DNA repair-deficient mutants from five genetic complementation groups isolated previously from Chinese hamster cells were assayed for survival after exposure to the bifunctional alkylating agents mitomycin C or diepoxybutane. Groups 1, 3, and 5 exhibited 1.6- to 3-fold hypersensitivity compared to the wild-type cells, whereas Groups 2 and 4 exhibited extraordinary hypersensitivity. Mutants from Groups 1 and 2 were exposed to 22 other bifunctional alkylating agents in a rapid assay that compared cytotoxicity of the mutants to the wild-type parental strain, AA8. With all but two of the compounds, the Group 2 mutant (UV4) was 15- to 60-fold more sensitive than AA8 or the Group 1 mutant (UV5). UV4 showed only 6-fold hypersensitivity to quinacrine mustard. Alkaline elution measurements showed that this compound produced few DNA interstrand cross-links but numerous strand breaks. Therefore, the extreme hypersensitivity of mutants from Groups 2 and 4 appeared specific for compounds the main cytotoxic lesions of which were DNA cross-links. Mutant UV5 was only 1- to 4-fold hypersensitive to all the compounds. Although the initial number of cross-links was similar for the three cell lines, the efficiency of removal of cross-links was lowest in UV4 and intermediate in UV5. These results suggest that the different levels of sensitivity are specifically related to different efficiencies of DNA cross-link removal. The phenotype of hypersensitivity to both UV radiation and cross-link damage exhibited by the mutants in Groups 2 and 4 appears to differ from those of the known human DNA repair syndromes
Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats
Alison Diesel
Full Text Available Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly "feline atopic syndrome� when compared to dogs or people. This article aims to review what is currently known in regards to allergic skin disease in the feline patient, with focus on non-flea, non-food hypersensitivity dermatitis.
Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats.
Diesel, Alison
Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly "feline atopic syndrome" when compared to dogs or people. This article aims to review what is currently known in regards to allergic skin disease in the feline patient, with focus on non-flea, non-food hypersensitivity dermatitis.
Cloning and expression of candidate allergens from Culicoides obsoletus for diagnosis of insect bite hypersensitivity in horses
Meide, van der N.M.A.; Roders, N.; Sloet van Oldruitenborgh-Oosterbaan, M.M.; Schaap, P.J.; Oers, van M.M.; Leibold, W.; Savelkoul, H.F.J.; Tijhaar, E.
Insect bite hypersensitivity (IBH) is an IgE-mediated (Type I) hypersensitivity reaction induced by allergens from biting midges of the Culicoides spp. The aim of the present study was to identify, clone and express recombinant allergens from C. obsoletus, the main species found feeding on horses in
Drug hypersensitivity in children: report from the pediatric task force of the EAACI Drug Allergy Interest Group
Gomes, E. R.; Brockow, K.; Kuyucu, S.; Saretta, F.; Mori, F.; Blanca-Lopez, N.; Ott, H.; Atanaskovic-Markovic, M.; Kidon, M.; Caubet, J.-C.; Terreehorst, I.
When questioned, about 10% of the parents report suspected hypersensitivity to at least one drug in their children. However, only a few of these reactions can be confirmed as allergic after a diagnostic workup. There is still a lack of knowledge on drug hypersensitivity (DH) epidemiology, clinical
Natural history of perceived food hypersensitivity and IgE sensitisation to food allergens in a cohort of adults.
Patelis, Antonios; Gunnbjörnsdottir, Maria; Borres, Magnus P; Burney, Peter; Gislason, Thorarinn; Torén, Kjell; Forsberg, Bertil; Alving, Kjell; Malinovschi, Andrei; Janson, Christer
No longitudinal studies exist on the natural history of food hypersensitivity and IgE sensitisation to food allergens in adults. To examine the natural history of food hypersensitivity, the natural history of IgE sensitisation to food allergens and to investigate the risk factors for new onset food hypersensitivity. Food hypersensitivity was questionnaire-assessed in 2307 individuals (aged 20-45 years) from Iceland and Sweden during the European Community Respiratory Health Survey both at baseline and follow-up 9 years later. IgE food and aeroallergen sensitisation were assessed in a subgroup of these individuals (n = 807). Values of 0.35 kU/L and above were regarded as positive sensitisation. Food hypersensitivity was reported by 21% of the subjects and this proportion remained unchanged at follow-up (p = 0.58). Fruits, nuts and vegetables were the three most common causes of food hypersensitivity, with a similar prevalence at baseline and follow-up. The prevalence IgE sensitisation to food allergens decreased in general by 56% (pfood hypersensitivity. The prevalence of food hypersensitivity remained unchanged while the prevalence of IgE sensitisation to food allergens decreased in adults over a 9-year follow-up period. The decrease in prevalence of IgE sensitisation to food allergens was considerably larger than the change in prevalence of IgE sensitisation to aeroallergens.
Hypersensitivity reaction with intravenous GnRH after pulsatile subcutaneous GnRH treatment in male hypogonadotrophic hypogonadism.
Popović, V.; Milosević, Z.; Djukanović, R.; Micić, D.; Nesović, M.; Manojlović, D.; Djordjević, P.; Mićić, J.
Chronic pulsatile subcutaneous administration of low doses of gonadotrophin releasing hormone (GnRH) is an effective therapy for men with hypogonadotrophic hypogonadism. Hypersensitivity reactions to GnRH are rare. We wish to report hypersensitivity reactions with intravenous GnRH after low dose subcutaneous pulsatile GnRH treatment in two men with hypogonadotrophic hypogonadism due to suprasellar disease.
Evidence of isolate-specificity in non-hypersensitive resistance in spring wheat (Triticum aestivum) to wheat leaf rust
Qamar, Maqsood; Niks, R.E.
Isolate-specific aspect of non-hypersensitive resistance in wheat to wheat leaf rust was studied at seedling stage in the green house. Isolate-specific response of non-hypersensitive resistance was assessed from latency period (LP) and infection frequency (IF) of two single-pustule isolates of
Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain
Da-Lu Liu; Na Lu; Wen-Juan Han; Rong-Gui Chen; Rui Cong; Rou-Gang Xie; Yu-Fei Zhang; Wei-Wei Kong; San-Jue Hu; Ceng Luo
Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron?s ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensit...
Microwaves from GSM mobile telephones affect 53BP1 and gamma-H2AX foci in human lymphocytes from hypersensitive and healthy persons.
Markovà , Eva; Hillert, Lena; Malmgren, Lars; Persson, Bertil R R; Belyaev, Igor Y
The data on biologic effects of nonthermal microwaves (MWs) from mobile telephones are diverse, and these effects are presently ignored by safety standards of the International Commission for Non-Ionizing Radiation Protection (ICNIRP). In the present study, we investigated effects of MWs of Global System for Mobile Communication (GSM) at different carrier frequencies on human lymphocytes from healthy persons and from persons reporting hypersensitivity to electromagnetic fields (EMFs). We measured the changes in chromatin conformation, which are indicative of stress response and genotoxic effects, by the method of anomalous viscosity time dependence, and we analyzed tumor suppressor p53-binding protein 1 (53BP1) and phosphorylated histone H2AX (gamma-H2AX), which have been shown to colocalize in distinct foci with DNA double-strand breaks (DSBs), using immunofluorescence confocal laser microscopy. We found that MWs from GSM mobile telephones affect chromatin conformation and 53BP1/gamma-H2AX foci similar to heat shock. For the first time, we report here that effects of MWs from mobile telephones on human lymphocytes are dependent on carrier frequency. On average, the same response was observed in lymphocytes from hypersensitive and healthy subjects.
System-Wide Hypersensitive Response-Associated Transcriptome and Metabolome Reprogramming in Tomato
Etalo, D.W.; Stulemeijer, I.J.E.; Esse, van H.P.; Vos, de R.C.H.; Bouwmeester, H.J.; Joosten, M.H.A.J.
The hypersensitive response (HR) is considered to be the hallmark of the resistance response of plants to pathogens. To study HR-associated transcriptome and metabolome reprogramming in tomato (Solanum lycopersicum), we used plants that express both a resistance gene to Cladosporium fulvum and the
Purple sweet potato (Ipomea Batatas P. as dentin hypersensitivity desensitization gel
Chariza Hanum Mayvita Iskandar
Full Text Available Background: Dentin hypersensitivity is a short sharp sense of pain in the teeth when exposed to excitatory stimulus. A total of 74% of world population experiencing dentin hypersensitivity. Home treatment topical desensitization is rarely found in Indonesia. The use of dentrifice is less practical because it must be done with regular brushing. Indonesia has abundant natural resources, one of which is purple sweet potato. Purple sweet potato (Ipomea Batatas P. has highest potasium ions compared to other foodstuffs. Potassium ions can be a solution of dentin hypersensitivity by temporary blocking the suffix pulp nerve impulses. Purpose: The research objective was to determine the effectiveness of the 10% purple sweet potato extract gel of the dental pain threshold score. Method: An experimental study carried out by dental pain threshold score measurements using vitality tester into the teeth with gum recession. Samples included 32 respondents with a single blind and pre-post test control group design. They were divided into treatment group and negative control group. Paired T-test and Wilcoxon were used as data analysis. Result: The results showed dental pain threshold score increasing either in treatment group and negative control, although not as significant as in the treatment group. Conclusion: 10% purple sweet potato extract gel containing potassium ions is able to reduce the pain of dentin hypersensitivity.
High cytokinin levels induce a hypersensitive-like response in tobacco
Novák, J.; Pavlů, J.; Novák, Ondřej; Nožková-Hlavá�ková, V.; Špundová, M.; Hlavinka, J.; Koukalová, Š.; Skalák, J.; Černý, M.; Brzobohatý, B.
Ro�. 112, �. 1 (2013), s. 41-55 ISSN 0305-7364 R&D Projects: GA MŠk 1M06030; GA MŠk LK21306 Institutional support: RVO:61389030 Keywords : Cytokinin * hypersensitive response * hydrogen peroxide Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.295, year: 2013
Kodak film type SO-394-4-1 mottling and hypersensitization test
Weinstein, M. S.
A number of tests were conducted to show the effects of various environmental conditions in terms of mottling and hypersensitization on Kodak Film type SO-394-4-1. The first two weeks of environmental testing is described, along with the test plan and matrix.
Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation
I.M. van der Sluis (Inge); L.M. Vrooman (Lynda M.); R. Pieters (Rob); A. Baruchel (André); G. Escherich (Gabriele); N. Goulden (Nicholas); V. Mondelaers (Veerle); J.S. de Toledo (Jose Sanchez); C. Rizzari (Carmelo); L.B. Silverman (Lewis); J.A. Whitlock (James A.)
textabstractL-asparaginase is an integral component of therapy for acute lymphoblastic leukemia. However, asparaginase-related complications, including the development of hypersensitivity reactions, can limit its use in individual patients. Of considerable concern in the setting of clinical allergy
Should patients with risk factors be tested for hypersensitivity to contrast media: a prospective study.
Tepetam, Fatma Merve; Çiftaslan, Nezihe; Oruç, Özlem; Duman, Dildar; Ağca, Meltem; Bulut, İsmet; Çolakoğlu, Bahattin
Previous hypersensitivity reactions to contrast media (CM), atopy, atopic disease, drug allergy, and age (20-29 or >55) are risk factors for CM hypersensitivity reactions. Our aim was to evaluate whether these risk factors should prompt skin testing for diagnosing CM allergy. The study was conducted among patients referred for allergy testing with CM. Skin tests were performed with non ionic or gadolinium CM, recommended by a radiologist. After completion of tests patients were telephonically queried on their symptoms of reactions. 151 risk patients (53 men, 98 women; mean age 55.2) were included in the study. Only 13 (9 %) had a history of hypersensitivity reaction to CM. Compared with the other patients, atopy was significantly more common in patients with a history of CM hypersensitivity reactions. Female gender and mean age were also higher, but not significant. All of the tests with CMs were negative. Only one patient reported urticaria within 1-2 min after administration of CM (telephonically). Atopy can increase the risk of CM allergy. However, skin tests with CMs may be inefficient, unnecessary, and time-consuming, except in cases with a history of CM allergy. Premedication protocols appear to be beneficial in patients with a history of CM allergy and cannot be recommended for patients with well-controlled asthma, rhinitis, atopic dermatitis or history of drug allergy.
Identification of factors associated with the development of insect bite hypersensitivity in horses in the Netherlands
Boom, van den R.; Ducro, B.J.; Sloet van Oldruitenborgh-Oosterbaan, M.M.
An Internet-based questionnaire among horse owners was carried out to identify factors affecting the incidence of insect bite hypersensitivity (IBHI) among horses in the Netherlands. Information was obtained for 794 horses of various breeds, but the breed distribution was not representative for the
Effect of Rap1 binding on DNA distortion and potassium permanganate hypersensitivity.
Le Bihan, Yann-Vaï; Matot, Béatrice; Pietrement, Olivier; Giraud-Panis, Marie-Josèphe; Gasparini, Sylvaine; Le Cam, Eric; Gilson, Eric; Sclavi, Bianca; Miron, Simona; Le Du, Marie-Hélène
Repressor activator protein 1 (Rap1) is an essential factor involved in transcription and telomere stability in the budding yeast Saccharomyces cerevisiae. Its interaction with DNA causes hypersensitivity to potassium permanganate, suggesting local DNA melting and/or distortion. In this study, various Rap1-DNA crystal forms were obtained using specifically designed crystal screens. Analysis of the DNA conformation showed that its distortion was not sufficient to explain the permanganate reactivity. However, anomalous data collected at the Mn edge using a Rap1-DNA crystal soaked in potassium permanganate solution indicated that the DNA conformation in the crystal was compatible with interaction with permanganate ions. Sequence-conservation analysis revealed that double-Myb-containing Rap1 proteins all carry a fully conserved Arg580 at a position that may favour interaction with permanganate ions, although it is not involved in the hypersensitive cytosine distortion. Permanganate reactivity assays with wild-type Rap1 and the Rap1[R580A] mutant demonstrated that Arg580 is essential for hypersensitivity. AFM experiments showed that wild-type Rap1 and the Rap1[R580A] mutant interact with DNA over 16 successive binding sites, leading to local DNA stiffening but not to accumulation of the observed local distortion. Therefore, Rap1 may cause permanganate hypersensitivity of DNA by forming a pocket between the reactive cytosine and Arg580, driving the permanganate ion towards the C5-C6 bond of the cytosine.
Culicoides obsoletus extract relevant for diagnostics of insect bite hypersensitivity in horses
Meide, van der N.M.A.; Meulenbroeks, C.; Altena, van S.E.C.; Schurink, A.; Ducro, B.J.; Wagner, B.; Leibold, W.; Rohwer, J.; Jacobs, F.; Sloet van Oldruitenborgh-Oosterbaan, M.M.; Savelkoul, H.F.J.; Tijhaar, E.
Insect bite hypersensitivity (IBH) is an allergic dermatitis in horses caused by the bites of Culicoides species. The aim of the present study was to evaluate the applicability of whole body extracts of C. obsoletus (the main species found feeding on horses in the Netherlands), C. nubeculosus
Seasonal differences in cytokine expression in the skin of Shetland ponies suffering from insect bite hypersensitivity
Meulenbroeks, C.; Meide, van der N.M.A.; Zaiss, D.M.W.; Oldruitenborgh-Oosterbaan, M.M.S.; Lugt, van der J.J.; Smak, J.; Rutten, V.P.M.G.; Willemse, T.
Insect bite hypersensitivity (IBH) in horses is a seasonal, IgE-mediated, pruritic skin disorder primarily caused by Culicoides spp. We hypothesize that a mixed Th2/Th1-type immune status, off season, alters into Th2-dominated immune reactivity in the skin of IBH-affected ponies in the IBM season.
Prevalence of self-reported food hypersensitivity among school children in The Netherlands
Brugman, E.; Meulmeester, J.F.; Spee-Wekke, A. van der; Beuker, R.J.; Radder, J.J.; Verloove-Vanhorick, S.P.
Objectives: To provide national figures on the prevalence of self-reported food hypersensitivity (S-FH), and the association with socio-demographic variables and some health indicators in schoolchildren in The Netherlands. Design: As part of the Child Health Monitoring System, data were collected
Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions.
McCormack, Mark
An association between carbamazepine-induced hypersensitivity and HLA-A*3101 has been reported in populations of both European and Asian descent. We aimed to investigate HLA-A*3101 and other common variants across the genome as markers for cutaneous adverse drug reactions (cADRs) attributed to lamotrigine and phenytoin.
IMMEDIATE AND DELAYED HYPERSENSITIVITY REACTIONS TO LATEX GLOVES IN A DENTAL STUDENT. A case report.
Iliyana Stoeva
Full Text Available The article presents a case of dental student with immediate and delayed hypersensitivity reaction to latex gloves. Symptoms appeared during the second year of regularly using of latex gloves. The student was with no history of allergies and no previous exposure to latex products.
HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.
Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) in the Han Chinese and other Asian populations but not in European populations.
Evaluation of potential regulatory elements identified as DNase I hypersensitive sites in the CFTR gene
Phylactides, M.; Rowntree, R.; Nuthall, H.
hypersensitive sites (DHS) within the locus. We previously identified at least 12 clusters of DHS across the CFTR gene and here further evaluate DHS in introns 2,3,10,16,17a, 18, 20 and 21 to assess their functional importance in regulation of CFTR gene expression. Transient transfections of enhancer/reporter...
Infection or metal hypersensitivity? The diagnostic challenge of failure in metal-on-metal bearings.
Galbraith, John G
The use of second generation metal-on-metal hip articulations has gained favour in the past few years. A hypersensitivity reaction to the metal-on-metal bearing, although rare, is a reported complication and is a novel mode of failure of these implants. Differentiating failure secondary to infection from failure secondary to metal hypersensitivity represents a significant diagnostic challenge. A retrospective review of all cases of hip arthroplasty using metal-on-metal bearings over a 5-year period at a tertiary referral centre identified 3 cases of failure secondary to metal hypersensitivity. Clinical presentation, serological markers, radiological imaging and histological analysis of all cases identified were evaluated. Histological analysis of periprosthetic tissue in all 3 cases identified characteristic features such as perivascular lymphocytic aggregates and chronic inflammation consistent with aseptic lymphocytic vasculitis-associated lesions (ALVAL). This study highlights that failure secondary to metal hypersensitivity must be considered in patients presenting with the reappearance of persistent pain, marked joint effusion, and the development of early osteolysis in the absence of infection.
Decreased delayed hypersensitivity to tuberculin demonstrated in experimental leptospirosis in guinea pigs
Colding, H; Johansen, K S; Bentzon, M W
Skin reactivity to tuberculin has been studied during the course of experimental leptospirosis in guinea pigs. A depression of the delayed hypersensitivity to tuberculin was demonstrated in the infected animals. The depression was most pronounced when icterus had developed. The depression...
Pharmacological evaluation of NSAID-induced gastropathy as a "Translatable" model of referred visceral hypersensitivity.
Hummel, Michele; Knappenberger, Terri; Reilly, Meghan; Whiteside, Garth T
To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice ( n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential (TRP), sodium and acid-sensing ion channels (ASICs) as well as opioid receptors and guanylate cyclase C (GC-C). Results showed that two opioids and a GC-C agonist, morphine, asimadoline and linaclotide, respectively, the TRP antagonists, AMG9810 and HC-030031 and the sodium channel blocker, carbamazepine, elicited a dose- and/or time-dependent attenuation of referred visceral hypersensitivity, while the ASIC blocker, amiloride, was ineffective at all doses tested. Together, these findings implicate opioid receptors, GC-C, and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly, these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties.
Detection of systemic hypersensitivity to drugs using standard guinea pig assays.
Weaver, James L; Staten, David; Swann, Joslyn; Armstrong, George; Bates, Melissa; Hastings, Kenneth L
The most commonly used assays designed to detect either skin or systemic immune-based hypersensitivity reactions are those using guinea pigs (GP). We obtained data from various FDA records to evaluate the correlation between GP assay results and reported post-marketing systemic hypersensitivity reactions. We examined the new drug application (NDA) reviews of approved drugs for the results of GP assays. Post-marketing human data were extracted from the FDA adverse event reporting system (AERS). Drug usage data were obtained from a commercial database maintained by IMS Health Inc. We found 83 (21%) of 396 drugs approved between 1978 and 1998 had reported GP test results. Among these 83 drugs, 14 (17%) were found to have positive results in at least one GP assay. Simple reporting index (RI) values for systemic hypersensitivity reactions were calculated from AERS data and usage to produce the index of adverse event reports per million shipping units of drug. A variety of definitions of positive human response were examined. A statistically significant association was seen for rash between post-marketing and clinical trials adverse event reports. No statistically significant associations between human data and GP test results were observed. These data suggest that standard GP assays have limited ability to predict human systemic hypersensitivity potential for pharmaceuticals.
IL-1β-Dependent Activation of Dendritic Epidermal T Cells in Contact Hypersensitivity
Nielsen, Morten M; Lovato, Paola; Macleod, Amanda S
Substances that penetrate the skin surface can act as allergens and induce a T cell-mediated inflammatory skin disease called contact hypersensitivity (CHS). IL-17 is a key cytokine in CHS and was originally thought to be produced solely by CD4(+) T cells. However, it is now known that several cell...
Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection.
Descamps, V; Mahe, E; Houhou, N; Abramowitz, L; Rozenberg, F; Ranger-Rogez, S; Crickx, B
Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.
Making Sense of Metal Allergy and Hypersensitivity to Metallic Implants in Relation to Hand Surgery.
Christensen, Thomas J; Samant, Shefali A; Shin, Alexander Y
All metals implanted into a biological system undergo some degree of corrosion depending upon its composition. The electrochemical process of corrosion produces free metal ions, which may activate the host's immune system through a variety of mechanisms. Whereas dermal metal hypersensitivity is common, affecting 10% to 15% of the population, the immune reaction from implanted metals is much less common (allergy and hypersensitivity producing a multitude of patient symptoms. Superficial symptoms may be mild to severe forms of dermatitis, urticaria, pruritus, and vasculitis, whereas deep sequelae include metallosis-related pseudotumor, implant loosening, and joint stiffness. Currently, there are clinical tests to evaluate patients for metal hypersensitivity, but there is little agreement regarding the ideal timing and clinical situation prompting the work-up of a patient for a metal allergy or hypersensitivity. An understanding of the epidemiology, etiology, basic science, diagnostic testing, and treatment of patients with suspected metal allergy, as it pertains to the current literature, will aid orthopedic and plastic surgeons of all subspecialties in the management of patients requiring metallic implants. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.
Gender and dose dependent ovalbumin induced hypersensitivity responses in murine model of food allergy
While federal regulations mandate the labeling of major food allergens, allowable food allergen thresholds have yet to be determined. Therefore the aim of this project was to identify the lowest egg allergen ovalbumin (OVA) dose causing hypersensitization using a validated murine model. Mice were or...
Systemic Immediate Hypersensitive Reactions after Treatment with Sweet Bee Venom: A Case Report
NaYoung Jo
Full Text Available Objectives: A previous study showed that bee venom (BV could cause anaphylaxis or other hypersensitivity reactions. Although hypersensitivity reactions due to sweet bee venom (SBV have been reported, SBV has been reported to be associated with significantly reduced sensitization compared to BV. Although no systemic immediate hypersensitive response accompanied by abnormal vital signs has been reported with respect to SBV, we report a systemic immediate hypersensitive response that we experienced while trying to use SBV clinically. Methods: The patient had undergone BV treatment several times at other Oriental medicine clinics and had experienced no adverse reactions. She came to acupuncture & moxibustion department at Semyung university hospital of Oriental medicine (Je-cheon, Korea complaining of facial hypoesthesia and was treated using SBV injections, her first SBV treatment. SBV, 0.05 cc, was injected at each of 8 acupoints, for a total of 0.40 cc: Jichang (ST4, Daeyeong (ST5, Hyeopgeo (ST6, Hagwan (ST7, Yepung (TE17, Imun (TE21, Cheonghoe (GB2, and Gwallyeo (SI18. Results: The patient showed systemic immediate hypersensitive reactions. The main symptoms were abdominal pain, nausea and perspiration, but common symptoms associated with hypersensitivity, such as edema, were mild. Abdominal pain was the most long-lasting symptom and was accompanied by nausea. Her body temperature decreased due to sweating. Her diastolic blood pressure could not be measured on three occasions. She remained alert, though the symptoms persisted. The following treatments were conducted in sequence; intramuscular epinephrine, 1 mg/mL, injection, intramuscular dexamethasone, 5 mg/mL, injection, intramuscular buscopan, 20 mg/mL, injection, oxygen (O2 inhalation therapy, 1 L/minutes, via a nasal prong, and intravascular injection of normal saline, 1 L. After 12 hours of treatment, the symptoms had completely disappeared. Conclusion: This case shows that the use of SBV
Schurink Anouk
Full Text Available Abstract Background Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with insect bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands. Methods Data on 200 Shetland pony mares and 146 Icelandic horses were collected according to a matched case–control design. Cases and controls were matched on various factors (e.g. region, sire to minimize effects of population stratification. Breed-specific genome-wide association studies were performed using 70 k single nucleotide polymorphisms genotypes. Bayesian variable selection method Bayes-C with a threshold model implemented in GenSel software was applied. A 1 Mb non-overlapping window approach that accumulated contributions of adjacent single nucleotide polymorphisms was used to identify associated genomic regions. Results The percentage of variance explained by all single nucleotide polymorphisms was 13% in Shetland pony mares and 28% in Icelandic horses. The 20 non-overlapping windows explaining the largest percentages of genetic variance were found on nine chromosomes in Shetland pony mares and on 14 chromosomes in Icelandic horses. Overlap in identified associated genomic regions between breeds would suggest interesting candidate regions to follow-up on. Such regions common to both breeds (within 15 Mb were found on chromosomes 3, 7, 11, 20 and 23. Positional candidate genes within 2 Mb from the associated windows were identified on chromosome 20 in both breeds. Candidate genes are within the equine lymphocyte antigen class II region, which evokes an immune response by recognizing many foreign molecules. Conclusions The genome-wide association
Common allergies do not influence the prevalence of cutaneous hypersensitivity reactions to antiepileptic drugs.
Bosak, Magdalena; Porębski, Grzegorz; Słowik, Agnieszka; Turaj, Wojciech
The aim of the study was to establish whether the presence of common allergies increases the risk of drug-related hypersensitivity reactions among patients with epilepsy treated with antiepileptic drugs (AEDs). We studied 753 patients with epilepsy seen in tertiary outpatient epilepsy clinic. We obtained data related to epilepsy type, past and ongoing treatment with AEDs, occurrence of maculopapular exanthema or more serious cutaneous adverse reactions (Stevens-Johnson syndrome - SJS) and their characteristics. We noted an occurrence of allergic reactions unrelated to treatment with AED, including rash unrelated to AED, bronchial asthma, persistent or seasonal allergic rhinitis, atopic dermatitis, rash after specific food and other allergic reactions. There were 61 cases of AED-related cutaneous hypersensitivity reaction (including 3 cases of SJS) noted in association with 2319 exposures to AEDs (2.63%) among 55 out of 753 patients (7.3%). Cutaneous hypersensitivity reaction to AED was most commonly noted after lamotrigine (12.1%), carbamazepine (5.4%) and oxcarbazepine (4.1%). Prevalence of allergic reactions unrelated to AED was similar between patients with and without AED-related cutaneous hypersensitivity reaction (rash unrelated to AED: 16.4% vs. 10.2%; bronchial asthma: 1.8% vs. 0.1%; persistent allergic rhinitis: 7.3% vs. 10.2%; seasonal allergic rhinitis: 7.3% vs. 11.7%; atopic dermatitis: 0 vs. 0.7%; rash after specific food: 5.4% vs. 6.4%; other allergic reactions: 5.4% vs. 5.2%, respectively; P>0.1 for each difference). Presence of common allergies is not a significant risk factor for AED-related cutaneous hypersensitivity reaction among patients with epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.
Fatal hypersensitivity reaction to an oral spray of flurbiprofen: a case report.
Calapai, G; Imbesi, S; Cafeo, V; Ventura Spagnolo, E; Minciullo, P L; Caputi, A P; Gangemi, S; Milone, L
Safety of the anti-inflammatory drug flurbiprofen is comparable with that of other non-steroidal anti-inflammatory drugs of the propionic acid class, which are commonly associated with gastrointestinal and renal side effects. Here we report a case of a fatal hypersensitivity reaction to an oral spray of flurbiprofen taken for sore throat. A 29-year-old man came to the emergency care unit reporting sore throat with an intense burning sensation associated with fever. Pharyngotonsillitis was diagnosed, and local treatment with oral flurbiprofen spray was prescribed. Immediately after using the spray, the patient experienced a severe reaction characterized by serious dyspnoea, followed by death. The cause of death was heart failure with acute asphyxia from oedema of the glottis. The cause of death was concluded to be hypersensitivity to flurbiprofen spray. Oral propionic acid derivatives have been associated with a relatively high frequency of allergic reactions. However, allergy to flurbiprofen has rarely been documented. Scientific literature reports two relevant cases of hypersensitivity reaction to flurbiprofen: in one case, a patient presented with a maculopapular rash 48 h after having taken oral flurbiprofen followed by angio-oedema and hypotension. In another case, a single oral dose of flurbiprofen caused itching and swelling around the eyes, redness and increased lacrimation. We describe, for the first time, a fatal case of hypersensitivity reaction to flurbiprofen oral spray. Hypersensitivity reactions to flurbiprofen are infrequent; however, health professionals should be aware of potential adverse reactions, even during topical administration as oral spray. © 2013 John Wiley & Sons Ltd.
Hypersensitivity to DNA-damaging agents in primary degenerations of excitable tissue
Robbins, J.H.
Defects in DNA-repair mechanisms render xeroderma pigmentosum cells hypersensitive to killing by the uv-type of DNA-damaging agent. Some xeroderma pigmentosum patients develop a primary neuronal degeneration, and cell lines from patients with the earliest onset of neurodegeneration are the most sensitive to killing by uv radiation. These findings led to the neuronal DNA integrity theory which holds that when the integrity of neuronal DNA is destroyed by the accumulation of unrepaired DNA damaged spontaneously or by endogenous metabolites, the neurons will undergo a primary degeneration. Cells from patients with Cockayne syndrome, a demyelinating disorder with a primary retinal degeneration, are also hypersensitive to the uv-type of DNA-damaging agent. Cells from patients with the primary neuronal degeneration of ataxia telangiectasia are hypersensitive to the x-ray-type of DNA-damaging agent. Cells from other patients with primary degeneration of excitable tissue also have hypersensitivity to the x-ray-type of DNA-damaging agent. These disorders include (1) primary neuronal degenerations which are either genetic (e.g., Huntington disease, familial dysautonomia, Friedreich ataxia) or sporadic (e.g., Alzheimer disease, Parkinson disease), (2) primary muscle degenerations (e.g., Duchenne muscular dystrophy), and (3) a primary retinal degeneration (Usher syndrome). Death of excitable tissue in vivo in these radiosensitive diseases may result from unrepaired DNA. This hypersensitivity provides the basis for developing suitable presymptomatic and prenatal tests for these diseases, for elucidating their pathogenesis, and for developing future therapies. 119 references, 3 figures, 3 tables
Use of cephalosporins in patients with immediate penicillin hypersensitivity: cross-reactivity revisited.
Lee, Q U
A 10% cross-reactivity rate is commonly cited between penicillins and cephalosporins. However, this figure originated from studies in the 1960s and 1970s which included first-generation cephalosporins with similar side-chains to penicillins. Cephalosporins were frequently contaminated by trace amount of penicillins at that time. The side-chain hypothesis for beta-lactam hypersensitivity is supported by abundant scientific evidence. Newer generations of cephalosporins possess side-chains that are dissimilar to those of penicillins, leading to low cross-reactivity. In the assessment of cross-reactivity between penicillins and cephalosporins, one has to take into account the background beta-lactam hypersensitivity, which occurs in up to 10% of patients. Cross-reactivity based on skin testing or in-vitro test occurs in up to 50% and 69% of cases, respectively. Clinical reactivity and drug challenge test suggest an average cross-reactivity rate of only 4.3%. For third- and fourth-generation cephalosporins, the rate is probably less than 1%. Recent international guidelines are in keeping with a low cross-reactivity rate. Despite that, the medical community in Hong Kong remains unnecessarily skeptical. Use of cephalosporins in patients with penicillin hypersensitivity begins with detailed history and physical examination. Clinicians can choose a cephalosporin with a different side-chain. Skin test for penicillin is not predictive of cephalosporin hypersensitivity, while cephalosporin skin test is not sensitive. Drug provocation test by experienced personnel remains the best way to exclude or confirm the diagnosis of drug hypersensitivity and to find a safe alternative for future use. A personalised approach to cross-reactivity is advocated.
Activated platelets release sphingosine 1-phosphate and induce hypersensitivity to noxious heat stimuli in vivo
Daniela eWeth
Full Text Available At the site of injury activated platelets release various mediators, one of which is sphingosine 1-phosphate (S1P. It was the aim of this study to explore whether activated human platelets had a pronociceptive effect in an in vivo mouse model and whether this effect was based on the release of S1P and subsequent activation of neuronal S1P receptors 1 or 3. Human platelets were prepared in different concentrations (105/µl, 106/µl, 107/µl and assessed in mice with different genetic backgrounds (WT, S1P1fl/fl, SNS-S1P1-/-, S1P3-/-. Intracutaneous injections of activated human platelets induced a significant, dose-dependent hypersensitivity to noxious thermal stimulation. The degree of heat hypersensitivity correlated with the platelet concentration as well as the platelet S1P content and the amount of S1P released upon platelet activation as measured with LC MS/MS. Despite the significant correlations between S1P and platelet count, no difference in paw withdrawal latency (PWL was observed in mice with a global null mutation of the S1P3 receptor or a conditional deletion of the S1P1 receptor in nociceptive primary afferents. Furthermore, neutralisation of S1P with a selective anti-S1P antibody did not abolish platelet induced heat hypersensitivity. Our results suggest that activated platelets release S1P and induce heat hypersensitivity in vivo. However, the platelet induced heat hypersensitivity was caused by mediators other than S1P.
Drug desensitization in the management of hypersensitivity reactions to monoclonal antibodies and chemotherapy.
Mezzano, Veronica; Giavina-Bianchi, Pedro; Picard, Matthieu; Caiado, Joana; Castells, Mariana
Hypersensitivity reactions to monoclonal antibodies and chemotherapy, which may vary in severity from mild to life-threatening, can lead to their discontinuation and replacement by alternative agents that are often less effective, more toxic, and/or more expensive. Drug desensitization has emerged as the best treatment modality capable of allowing re-introduction of the hypersensitivity reaction-inducing medication in highly sensitized patients in need of first line therapies. In recent years, the availability of new anti-neoplastic drugs and therapeutic monoclonal antibodies has increased, as has the potential for hypersensitivity reactions. Development of desensitization protocols for these new medications requires a careful assessment of the potential risks and benefits. The purposes of this review are to provide an overview of the presentation of hypersensitivity reactions amenable to desensitization and to increase awareness of the indications for and outcomes of desensitization protocols. Rapid drug desensitization has proven to be a safe and effective way of administering first line therapy to patients with hypersensitivity reactions, providing an extremely powerful treatment modality for patients for whom alternative drugs are deemed unacceptable. Rapid drug desensitization protocols should be administered only by highly trained allergists and nurses who have experience in determining which reactions are amenable to desensitization, and can identify high risk patients and provide them with appropriate care. Efforts should be made to increase awareness of the remarkable safety and efficacy of rapid drug desensitization among non-allergists, especially in the fields of oncology and rheumatology, so as to favor its universal application. Development of desensitization units to provide state-of-the-art care is possible only through coordinated teamwork.
Dendritic cell populations in patients with self-reported food hypersensitivity
Lied GA
Full Text Available Gülen A Lied1,3,4,*, Petra Vogelsang2,*, Arnold Berstad1,4, Silke Appel2 1Institute of Medicine, 2Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Norway; 3Division of Gastroenterology, Department of Medicine; 4Section of Clinical Allergology, Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway *These authors contributed equally to this workAbstract: Self-reported hypersensitivity to food is a common condition and many of these patients have indications of intestinal immune activation. Dendritic cells (DCs are recognized as the most potent antigen-presenting cells involved in both initiating immune responses and maintaining tolerance. The aims of this study were to evaluate the DC populations with their phenotype and T cell stimulatory capacity in patients with food hypersensitivity and to study its relationship with atopic disease. Blood samples from 10 patients with self-reported food hypersensitivity, divided into atopic and nonatopic subgroups, and 10 gender- and age-matched healthy controls were analyzed by flow cytometry using the Miltenyi Blood Dendritic cells kit. Monocyte-derived DCs (moDCs were evaluated concerning their phenotype and T cell stimulatory capacity. DC populations and cell surface markers were not significantly different between patients and healthy controls, but moDCs from atopic patients expressed significantly more CD38 compared to moDCs from nonatopic patients. Moreover, lipopolysaccharide stimulated moDCs from atopic patients produced significantly more interleukin-10 compared to nonatopic patients. CD38 expression was correlated to total serum immunoglobulin E levels. These findings support the notion of immune activation in some patients with self-reported food hypersensitivity. They need to be confirmed in a larger cohort.Keywords: food hypersensitivity, atopy, dendritic cells, CD38
Fasting mitigates immediate hypersensitivity: a pivotal role of endogenous D-beta-hydroxybutyrate.
Nakamura, Shigeru; Hisamura, Ryuji; Shimoda, Sachiko; Shibuya, Izumi; Tsubota, Kazuo
Fasting is a rigorous type of dietary restriction that is associate with a number of health benefits. During fasting, ketone bodies significantly increase in blood and become major body fuels, thereby sparing glucose. In the present study, we investigated effects of fasting on hypersensitivity. In addition, we also investigated the possible role of D-beta-hydroxybutyrate provoked by fasting in the attenuation of immediate hypersensitivity by fasting. Effects of fasting on systemic anaphylaxis were examined using rat model of toluene 2, 4-diisocyanate induced nasal allergy. In addition to food restriction, a ketogenic high-fat and low-carbohydrate diet that accelerates fatty acid oxidation and systemic instillation of D-beta-hydroxybutyrate were employed to elevate internal D-beta-hydroxybutyrate concentration. We assessed relationship between degranulation of rat peritoneal mast cells and internal D-beta-hydroxybutyrate concentration in each treatment. Changes in [Ca(2+)]i responses to compound 48/80 were analyzed in fura 2-loaded rat peritoneal mast cells derived from the ketogenic diet and fasting. Immediate hypersensitivity reaction was significantly suppressed by fasting. A significant reduction in mast cells degranulation, induced by mast cell activator compound 48/80, was observed in rat peritoneal mast cells delivered from the 24Â hours fasting treatment. In addition, mast cells delivered from a ketogenic diet and D-beta-hydroxybutyrate infusion treatment also had reduced mast cell degranulation and systemic D-beta-hydroxybutyrate concentrations were elevated to similar extent as the fasting state. The peak increase in [Ca(2+)]i was significantly lower in the ketogenic diet and fasting group than that in the control diet group. The results of the present study demonstrates that fasting suppress hypersensitivity reaction, and indicate that increased level of D-beta-hydroxybutyrate by fasting plays an important role, via the stabilization of mast cells, in
Prenatal stress, immunity and neonatal health in farm animal species.
Merlot, E; Quesnel, H; Prunier, A
The high pre-weaning mortality in farm animal species and poor welfare conditions of reproductive females question modern industrial farming acceptability. A growing body of literature has been produced recently, investigating the impact of maternal stress during gestation on maternal and offspring physiology and behavior in farm animals. Until now, the possible impact of prenatal stress on neonatal health, growth and survival could not be consistently demonstrated, probably because experimental studies use small numbers of animals and thus do not allow accurate estimations. However, the data from literature synthesized in the present review show that in ungulates, maternal stress can sometimes alter important maternal parameters of neonatal survival such as colostrum production (ruminants) and maternal care to the newborn (pigs). Furthermore, maternal stress during gestation can affect maternal immune system and impair her health, which can have an impact on the transfer of pathogens from the mother to her fetus or neonate. Finally, prenatal stress can decrease the ability of the neonate to absorb colostral immunoglobulins, and alter its inflammatory response and lymphocyte functions during the first few weeks of life. Cortisol and reproductive hormones in the case of colostrogenesis are pointed out as possible hormonal mediators. Field data and epidemiological studies are needed to quantify the role of maternal welfare problems in neonatal health and survival.
Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD database and the GALEN platform. The Galenda project.
Bousquet, P-J; Demoly, P; Romano, A; Aberer, W; Bircher, A; Blanca, M; Brockow, K; Pichler, W; Torres, M J; Terreehorst, I; Arnoux, B; Atanaskovic-Markovic, M; Barbaud, A; Bijl, A; Bonadonna, P; Burney, P G; Caimmi, S; Canonica, G W; Cernadas, J; Dahlen, B; Daures, J-P; Fernandez, J; Gomes, E; Gueant, J-L; Kowalski, M L; Kvedariene, V; Mertes, P-M; Martins, P; Nizankowska-Mogilnicka, E; Papadopoulos, N; Ponvert, C; Pirmohamed, M; Ring, J; Salapatas, M; Sanz, M L; Szczeklik, A; Van Ganse, E; De Weck, A L; Zuberbier, T; Merk, H F; Sachs, B; Sidoroff, A
Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments.
The definition and diagnosis of cold hypersensitivity in the hands and feet: Finding from the experts survey.
Bae, Kwang-Ho; Jeong, Young-Seok; Go, Ho-Yeon; Sun, Seung-Ho; Kim, Tae-Hoon; Jung, Ki-Yong; Song, Yun-Kyung; Ko, Seong-Gyu; Choi, You-Kyung; Park, Jong-Hyeong; Lee, Siwoo; Lee, Youngseop; Jeon, Chan-Yong
Cold hypersensitivity in the hands and feet (CHHF) is a symptom patients usually feel cold in their hands and feet, but not dealt with a disease in western medicine. However, it is often appealed by patients at a clinic of Korean medicine (KM), considered to be a sort of key diagnostic indicator, and actively treated by physicians. Nevertheless, there is no standardized diagnostic definition for CHHF. Therefore, we surveyed KM experts' opinions to address the clinical definition, diagnostic criteria, and other relevant things on CHHF. We developed a survey to assess the definition, diagnosis, causes, and accompanying symptoms on CHHF. 31 experts who work at specialized university hospitals affiliated with KM hospitals consented to participation. Experts responded to survey questions by selecting multiple-choice answers or stating their opinions. Vast majority of experts (83.8%) agreed with our definition on CHHF ("a feeling of cold as a symptom; that one's hands or feet become colder than those of average people in temperatures that are not normally perceived as cold"). 77.4% of experts considered subjective symptoms on CHHF were more important than medical instrument results. Constitution or genetic factors (87.1%) and stress (64.5%) were the most common causes reported for CHHF. This study offers an expert consensus regarding the themes, opinions, and experiences of practitioners with CHHF. Our results underscore the need for standardized definitions and diagnostic criteria for CHHF.
The diagnostic accuracy of the atopy patch test in diagnosing hypersensitivity to cow's milk and hen's egg in unselected children with and without atopic dermatitis
Osterballe, Morten; Andersen, Klaus E; Bindslev-Jensen, Carsten
BACKGROUND: Previous studies have suggested that the atopy patch test (APT) may make oral challenge superfluous in diagnosing children with food hypersensitivity. OBJECTIVE: To investigate the clinical relevance of APT in predicting hypersensitivity to cow's milk and hen's egg in 486 unselected...... children 3 years of age. METHOD: The children were examined by APT, skin prick (SPT), histamine release (HR), and specific IgE followed by oral challenge when hypersensitivity to cow's milk or hen's egg was suspected. RESULTS: Food hypersensitivity confirmed by oral challenge was 1.6% to hen's egg and 0.......6% to cow's milk. No hypersensitivity to cow's milk or hen's egg was predicted by APT alone. CONCLUSION: APT could not predict food hypersensitivity not predicted by SPT, HR, or specific IgE. Thus, APT cannot be recommended in daily practice for the diagnosis of hypersensitivity to cow's milk and hen's egg...
Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats
Chi, Yan; Liu, Xin-Guang; Wang, Hua-Hong; Li, Jun-Xia; Li, Yi-Xuan
Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT 4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT 4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT 4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg −1 ·day −1 , days 36-42), tegaserod (1 mg·kg −1 ·day −1 , day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT 4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT 4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level
Chi Yan
Full Text Available Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05 and increased 5-HT4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05. Treatment with fluoxetine (10 mg·kg-1·day-1, days 36-42, tegaserod (1 mg·kg-1·day-1, day 43, or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01 but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654. These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.
Involvement of ethylene in lesion development and systemic acquired resistance in tobacco during the hypersensitive reaction to tobacco mosaic virus
Knoester, M.; Linthorst, H.J.M.; Bol, J.F.; Loon, L.C. van
Different approaches were taken to investigate the significance of ethylene in lesion development and systemic acquired resistance (SAR) in tobacco (Nicotiana tabacum) reacting hypersensitively to tobacco mosaic virus (TMV). Gaseous ethylene, the ethylene precursor 1-aminocyclopropane-1-carboxylic
The retreatment of carboplatin via high-dose intraperitoneal chemotherapy in patients with a history of a hypersensitivity reaction
Kerkhof, M.H.; Ruiz Zapata, A.M.; Bril, H.; Bleeker, M.C.G.; Belien, J.A.M.; Stoop, R.; Helder, M.N.
A hypersensitivity reaction attributed to platinum-based chemotherapy is a relatively common occurrence. Hyperthermic intraperitoneal chemotherapy potentially facilitates the safe retreatment of platinum therapy following this complication. We describe 3 ovarian cancer patients who were successfully
DNA alkylation damage as a sensor of nitrosative stress in Mycobacterium tuberculosis
Durbach, S I; Springer, B; Machowski, E E; North, R J; Papavinasasundaram, K G; Colston, M J; Böttger, E C; Mizrahi, V
One of the cellular consequences of nitrosative stress is alkylation damage to DNA. To assess whether nitrosative stress is registered on the genome of Mycobacterium tuberculosis, mutants lacking an alkylation damage repair and reversal operon were constructed. Although hypersensitive to the genotoxic effects of N-methyl-N′-nitro-N-nitrosoguanidine in vitro, the mutants displayed no phenotype in vivo, suggesting that permeation of nitrosative stress to the level of cytotoxic DNA damage is res...
Effect of Schizonepeta tenuifolia extract on mast cell-mediated immediate-type hypersensitivity in rats.
Shin, T Y; Jeong, H J; Jun, S M; Chae, H J; Kim, H R; Baek, S H; Kim, H M
We investigated the effect of an aqueous extract of Schizonepeta tenuifolia (STAE) on mast cell-mediated immediate-type hypersensitivity. STAE inhibited systemic allergic reaction induced by compound 48/80 in rats dose-dependently. STAE also inhibited plasma histamine levels induced by compound 48/80. STAE inhibited local allergic reaction activated by anti-dinitrophenyl (DNP) IgE. In addition, STAE does-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. However, STAE had a significant enhancing effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) production from RPMC. These results indicate that STAE inhibits immediate-type hypersensitivity and suggest that STAE can selectively activate the TNF-alpha production from RPMC.
Immunotherapy using regulatory T cells in cancer suggests more flavors of hypersensitivity type IV.
Pakravan, Nafiseh; Hassan, Zuhair Mohammad
Regulatory T cells (Tregs) profoundly affect tumor microenvironment and exert dominant suppression over antitumor immunity in response to self-antigen expressed by tumor. Immunotherapy targeting Tregs lead to a significant improvement in antitumor immunity. Intradermal injection of tumor antigen results in negative delayed-type hypersensitivity (DTH) type IV. However, anti-Tregs treatment/use of adjuvant along with tumor antigens turns DTH to positive. Considering Tregs as the earliest tumor sensor/responders, tumor can be regarded as Treg-mediated type IV hypersensitivity and negative DTH to tumor antigen is due to anti-inflammatory action of Tregs to tumor antigens at the injection site. Such a view would help us in basic and clinical situations to testify a candidate vaccine via dermal administration and evaluation of Treg proportion at injection site.
[Epidemiology of contact hypersensitivity to rubber components in manufacturers of automobile tires at the Stomil plant].
Rubisz-Brzezińska, J; Bogdanowski, T; Brzezińska-Wcisło, L; Mozdzanowska, K; Bajcar, S
Dermatological examination and patch tests with 34 rubber components were carried out in 114 tire manufacturers, 78 women and 36 men aged 29 years on average, with a mean duration of work in the plant 7 years. For correct interpretation of the obtained results patch tests with the same components were done in two control groups that is in 120 healthy subjects and 120 patients with contact dermatitis. Patch tests with proper concentrations of the studied components were evaluated after 48, 72 and 96 hours. Positive patch tests were found most frequently with antioxidants--16.6% (including IPPD--8.6%), followed by vulcanization accelerators--10.6%, and other rubber components--11.4% in all. During about 3 years of follow-up in 4 manufacturers contact allergic eczema was noted and polyvalent hypersensitivity to antioxidants and vulcanization accelerators without clinical manifestations of this hypersensitivity was diagnosed in 3 other subjects.
Dysmenorrhoea is associated with hypersensitivity in the sigmoid colon and rectum
Brinkert, Willem; Dimcevski, Georg; Arendt-Nielsen, Lars
if dysmenorrhoea is associated with hypersensitivity in the referred somatic skin area or in the large bowel, i.e., viscero-visceral hyperalgesia. We measured skin sensitivity in the referred area of the sigmoid colon as well as stimulus-response relationships in the sigmoid colon and rectum. The latter were...... measured using mechanical (balloon) distension applied via a Barostat in 11 dysmenorrhoea patients without gastro-intestinal complaints and 10 healthy and age matched women, again without gastrointestinal complaints. We found no skin hypersensitivity in the colonic referred area. In contrast, significantly...... lower distension volumes were seen at each threshold in dysmenorrhoea patients, particularly in the sigmoid colon. The mean reduction in colonic distension volume thresholds for dysmenorrhoea patients vs. controls was 57% at the detection threshold and 39% at the pain threshold. There were...
Histographical presentation of frequency distribution of attenuation numbers of hypersensitivity pneumonitis
Uchino, Akira; Nishitani, Hiromu; Onitsuka, Hideo; Baba, Hiromi; Kawahira, Kozaburo
Based on the attenuation numbers in computed tomography of the chest, histograms for 5 patients with hypersensitivity pneumonitis were analysed. For analysis of histograms, we established 3 parameters: A, tan theta, and M. Of histograms in normal subjects, maximum inspiration scan was more stable than maximum expiration scan, and parameter A was most stable. In patients with hypersensitivity pneumonitis, histograms shifted to the range of higher attenuation numbers than normal subjects. Follow up studies showed decrease in the shift, but parameter A and M of maximum inspiration scan never reached to normal ranges. This suggested that organic parenchymal changes never disappeared completely, even in clinical remission stage. Therefore, parameter A or M of maximum inspiration scan was adequate for analysis, and histographic analysis of chest CT scan was considered to be useful also for early detections and follow-up studies of all diffuse pulmonary disorders. (author)
Perceived food hypersensitivity relates to poor asthma control and quality of life in young non-atopic asthmatics.
Full Text Available The relationship between perceived food hypersensitivity in asthmatics, food allergen sensitization, asthma control and asthma-related quality of life has not been studied.Our aim was to study the prevalence of perceived food hypersensitivity in a cohort of young asthmatics, its relation to food allergen sensitization, and any correlation to asthma control and asthma-related quality of life.Perceived food hypersensitivity, as well as IgE sensitization to common food allergens, levels of exhaled nitric oxide (FeNO, and blood eosinophil counts (B-Eos were assessed in 408 subjects (211 women with asthma, aged (mean ± SEM 20.4 ± 0.3 years. Subjects filled out the Asthma Control Test (ACT and the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ. Inflammation was assessed by means of FeNO and B-Eos.Fifty-three per cent of subjects reported food hypersensitivity. A corresponding food allergen sensitization was found in 68% of these subjects. Non-atopic subjects with perceived food hypersensitivity (n = 31 had lower ACT (19 (15 - 22 vs. 21 (20 - 23, p < 0.001 and Mini-AQLQ -scores (5.3 (4.3 - 6.1 vs. 6.1 (5.5 - 6.5, p < 0.001 than subjects with no food hypersensitivity (n = 190, despite lower levels of FeNO and B-Eos (p < 0.05.Food hypersensitivity was commonly reported among young asthmatics. In a majority of cases, a corresponding food allergen sensitization was found. A novel and clinically important finding was that non-atopic subjects with perceived food hypersensitivity were characterized by poorer asthma control and asthma-related quality of life.
Johnson, Jennifer; Borres, Magnus P; Nordvall, Lennart; Lidholm, Jonas; Janson, Christer; Alving, Kjell; Malinovschi, Andrei
The relationship between perceived food hypersensitivity in asthmatics, food allergen sensitization, asthma control and asthma-related quality of life has not been studied. Our aim was to study the prevalence of perceived food hypersensitivity in a cohort of young asthmatics, its relation to food allergen sensitization, and any correlation to asthma control and asthma-related quality of life. Perceived food hypersensitivity, as well as IgE sensitization to common food allergens, levels of exhaled nitric oxide (FeNO), and blood eosinophil counts (B-Eos) were assessed in 408 subjects (211 women) with asthma, aged (mean ± SEM) 20.4 ± 0.3 years. Subjects filled out the Asthma Control Test (ACT) and the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ). Inflammation was assessed by means of FeNO and B-Eos. Fifty-three per cent of subjects reported food hypersensitivity. A corresponding food allergen sensitization was found in 68% of these subjects. Non-atopic subjects with perceived food hypersensitivity (n = 31) had lower ACT (19 (15 - 22) vs. 21 (20 - 23), p < 0.001) and Mini-AQLQ -scores (5.3 (4.3 - 6.1) vs. 6.1 (5.5 - 6.5), p < 0.001) than subjects with no food hypersensitivity (n = 190), despite lower levels of FeNO and B-Eos (p < 0.05). Food hypersensitivity was commonly reported among young asthmatics. In a majority of cases, a corresponding food allergen sensitization was found. A novel and clinically important finding was that non-atopic subjects with perceived food hypersensitivity were characterized by poorer asthma control and asthma-related quality of life.
Minocycline Prevents Muscular Pain Hypersensitivity and Cutaneous Allodynia Produced by Repeated Intramuscular Injections of Hypertonic Saline in Healthy Human Participants.
Samour, Mohamad Samir; Nagi, Saad Saulat; Shortland, Peter John; Mahns, David Anthony
Minocycline, a glial suppressor, prevents behavioral hypersensitivities in animal models of peripheral nerve injury. However, clinical trials of minocycline in human studies have produced mixed results. This study addressed 2 questions: can repeated injections of hypertonic saline (HS) in humans induce persistent hypersensitivity? Can pretreatment with minocycline, a tetracycline antibiotic with microglial inhibitory effects, prevent the onset of hypersensitivity? Twenty-seven healthy participants took part in this double-blind, placebo-controlled study, consisting of 6 test sessions across 2Â weeks. At the beginning of every session, pressure-pain thresholds of the anterior muscle compartment of both legs were measured to determine the region distribution and intensity of muscle soreness. To measure changes in thermal sensitivity in the skin overlying the anterior muscle compartment of both legs, quantitative sensory testing was used to measure the cutaneous thermal thresholds (cold sensation, cold pain, warm sensation, and heat pain) and a mild cooling stimulus was applied to assess the presence of cold allodynia. To induce ongoing hypersensitivity, repeated injections of HS were administered into the right tibialis anterior muscle at 48-hour intervals. In the final 2 sessions (days 9 and 14), only sensory assessments were done to plot the recovery after cessation of HS administrations and drug washout. By day 9, nontreated participants experienced a significant bilateral increase in muscle soreness (PÂ minocycline-treated participants experienced a bilateral 70% alleviation in muscle soreness (PÂ minocycline-treated participants showed cold allodynia. This study showed that repeated injections of HS can induce a hypersensitivity that outlasts the acute response, and the development of this hypersensitivity can be reliably attenuated with minocycline pretreatment. Four repeated injections of HS at 48-hour intervals induce a state of persistent hypersensitivity in
Pain hypersensitivity in congenital blindness is associated with faster central processing of C-fibre input
Slimani, H.; Plaghki, L.; Ptito, M.
Background We have recently shown that visual deprivation from birth exacerbates responses to painful thermal stimuli. However, the mechanisms underlying pain hypersensitivity in congenital blindness are unclear. Methods To study the contribution of Aδ- and C-fibres in pain perception, we measure...... The increased sensitivity to painful thermal stimulation in congenital blindness may be due to more efficient central processing of C-fibre–mediated input, which may help to avoid impending dangerous encounters with stimuli that threaten the bodily integrity....
[Hypersensitivity to platinum salts and taxanes: The value of skin tests and tolerance induction procedures].
Brault, F; Waton, J; Poreaux, C; Schmutz, J-L; Barbaud, A
The rate of hypersensitivity reactions to platinum salts (PS) and taxanes (TX) is on the increase. The aim of our study was to show the value of skin testing and efficacy of rapid drug desensitization. This was a retrospective study conducted between January 2007 and February 2016 in patients consulting for immediate or delayed hypersensitivity to PS and TX. Skin prick tests (pT) and intradermal reaction tests (IDR) were performed according to the ENDA/EAACI recommendations. We used a 12-step desensitization protocol for rapid drug desensitization. Among the 99 patients included (30 men, 69 women, age 60.4) PS were suspected in 86 cases and taxanes in 13 cases. Skin tests were positive in 25 patients (7 pT, 18 IDR), 23 for platinum salts and 2 for taxanes. Rapid drug desensitization was proposed in 50 patients and performed in 33 (30 PS and 3 TX), proved effective in 29 patients, with protocol adaptation being necessary in 7 cases, and was ineffective in 4 patients. The skin tests for the latter 4 patients were positive. Seventy-five percent of patients with positive skin tests to oxaliplatin presented hypersensitivity reactions during desensitization, i.e. twice as many as patients having negative skin tests. Two percent of patient for PS and 7% for TX had cross reactivity. This French study confirms the efficacy of the 12-step protocol that allows patients to receive chemotherapy after hypersensitivity reaction. Skin test permits the detection of cross-reactions but their practice must be considered based on the patient's history. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Hypersensitivity to mechanical and intra-articular electrical stimuli in persons with painful temporomandibular joints
Ayesh, Emad; Jensen, Troels Staehelin; Svensson, P
This study tested whether persons with TMJ arthralgia have a modality-specific and site-specific hypersensitivity to somatosensory stimuli assessed by quantitative sensory tests (QST). Forty-three healthy persons and 20 with TMJ arthralgia participated. The QST consisted of: sensory and pain dete...... of sensitization of the TMJs as well as central nociceptive pathways. QST may facilitate a mechanism-based classification of temporomandibular disorders. Udgivelsesdato: 2007-Dec...
Stratified premedication strategy for the prevention of contrast media hypersensitivity in high-risk patients.
Lee, Suh-Young; Yang, Min Suk; Choi, Young-Hoon; Park, Chang Min; Park, Heung-Woo; Cho, Sang Heon; Kang, Hye-Ryun
Although the severity of hypersensitivity reactions to iodinated contrast media varies, it is well correlated with the severity of recurrent reactions; however, prophylaxis protocols are not severity-stratified. To assess the outcomes of tailored prophylaxis according to the severity of hypersensitivity reactions to iodinated contrast media. Our premedication protocols were stratified based on the severity of previous reactions: (1) 4 mg of chlorpheniramine for mild reactions, (2) adding 40 mg of methylprednisolone for moderate reactions, and (3) adding multiple doses of 40 mg of methylprednisolone for severe index reactions. Cases of reexposure in patients with a history of hypersensitivity reactions were routinely monitored and mandatorily recorded. Among a total of 850 patients who underwent enhanced computed tomography after severity-tailored prophylaxis, breakthrough reactions occurred in 17.1%, but most breakthrough reactions (89.0%) were mild and did not require medical treatment. Additional corticosteroid use did not reduce the breakthrough reaction rate in cases with a mild index reaction (16.8% vs 17.2%, P = .70). However, underpremedication with a single dose of corticosteroid revealed significantly higher rates of breakthrough reaction than did double doses of corticosteroid in cases with a severe index reaction (55.6% vs 17.4%, P = .02). Changing the iodinated contrast media resulted in an additional reduction of the breakthrough reaction rate overall (14.9% vs 32.1%, P = .001). In a total severity-based stratified prophylaxis regimens and changing iodinated contrast media can be considered in patients with a history of previous hypersensitivity reaction to iodinated contrast media to reduce the risk of breakthrough reactions. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Occupational trichloroethylene hypersensitivity syndrome: human herpesvirus 6 reactivation and rash phenotypes.
Kamijima, Michihiro; Wang, Hailan; Yamanoshita, Osamu; Ito, Yuki; Xia, Lihua; Yanagiba, Yukie; Chen, Cishan; Okamura, Ai; Huang, Zhenlie; Qiu, Xinxiang; Song, Xiangrong; Cai, Tingfeng; Liu, Lili; Ge, Yichen; Deng, Yingyu; Naito, Hisao; Yoshikawa, Tetsushi; Tohyama, Mikiko; Li, Laiyu; Huang, Hanlin; Nakajima, Tamie
Trichloroethylene (TCE) is an industrial solvent which can cause severe generalized dermatitis, i.e., occupational TCE hypersensitivity syndrome. Reactivation of latent human herpesvirus 6 (HHV6) can occur in such patients, which has made TCE known as a causative chemical of drug-induced hypersensitivity syndrome (DIHS). This study aimed to clarify HHV6 status, cytokine profiles and their association with rash phenotypes in patients with TCE hypersensitivity syndrome. HHV6 DNA copy numbers, anti-HHV6 antibody titers, and cytokines were measured in blood prospectively sampled 5-7 times from 28 hospitalized patients with the disease. The patients (19 had exfoliative dermatitis (ED) and 9 had non-ED type rash) generally met the diagnostic criteria for DIHS. Viral reactivation defined as increases in either HHV6 DNA (≥100 genomic copies/10(6) peripheral blood mononuclear cells) or antibody titers was identified in 24 (89%) patients. HHV6 DNA, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-5, IL-6 and IL-10 concentrations were remarkably higher in the patients than in the healthy workers (p<0.01). Positive correlations between HHV6 DNA, TNF-α, IFN-γ, IL-6 and IL-10 were significant (p<0.05) except for that between HHV6 DNA and IFN-γ. An increase in HHV6 DNA was positively associated with an increase in TNF-α on admission (p<0.01). HHV6 DNA, the antibody titers, TNF-α and IL-10 concentrations were significantly higher in ED than in the non-ED type (p<0.05). Reactivated HHV6 and the increased cytokines could be biomarkers of TCE hypersensitivity syndrome. The higher-level reactivation and stronger humoral responses were associated with ED-type rash. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Enhancement of cutaneous delayed hypersensitivity reactions by a single exposure to UV-A or PUVA
Moberg, S.; Mobacken, H.
The influence of irradiation with UV-A and PUVA (8-methoxy-psoralen and UV-A) on delayed hypersensitivity reactions to microbial antigens was studied in healthy human individuals. Skin reactions to Candida albicans antigen and PPD were enhanced by UV-A als well as by PUVA compared with nonirradiated tests. A statistically significant difference was reached with UV-A for both antigens. For PUVA, erythemogenic doses to Candida tests produced a significant increase of response. (orig.)
Hypersensitivity to aeroallergens in adult patients with atopic dermatitis develops due to the different immunological mechanisms.
Samochocki, Zbigniew; Owczarek, Witold; Rujna, Paweł; Raczka, Alicja
Atopic dermatitis (AD) is a disease with a complex pathomechanism, it is very difficult to establish the exact factors which can either trigger or exacerbate the disease. Knowledge of the mechanisms involved in AD development can be increased by, among others, applying new diagnostic tests and careful assessment of the results obtained. The aim of this study was to determine the allergic mechanisms of hypersensitivity to selected aeroallergens in patients with AD. The study comprised 109 AD patients. In all the patients the total IgE level was measured and atopy patch tests and skin prick tests were performed. We also assessed the presence of specific IgE against house dust mite, birch-tree, mixed grass pollen and cat dander. The highest incidence of positive results was found for house dust mite allergens, irrespective of the test employed. Analysing hypersensitivity to all the examined allergens we revealed the presence of allergic mechanisms in 85.3% of the patients. In 30.2% of the examined individuals we proved a type I immunological response, in 45.9% -- both types I and IV in 9.2% -- only type IV in one patient. In 14.7% of the patients the results of all the tests performed were negative. Analysing hypersensitivity to particular aeroallergens, negative test results to house dust mite were observed in 25.8% of the patients. The percentage of positive results for birch pollen, grass pollen and cat dander were 45.0, 44.1 and 53.2, respectively. Analysis of the results showed that allergic reactions to the same aeroallergens may develop via different mechanisms. We also revealed that the coexistence of various mechanisms involved in the development of hypersensitivity to a particular aeroallergen may occur in individual patients.
Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly "feline atopic syndrome� when compared to...
Piezo2: A Candidate Biomarker for Visceral Hypersensitivity in Irritable Bowel Syndrome?
Bai, Tao; Li, Ying; Xia, Jing; Jiang, Yudong; Zhang, Lei; Wang, Huan; Qian, Wei; Song, Jun; Hou, Xiaohua
Background/Aims Currently, there exists no biomarker for visceral hypersensitivity in irritable bowel syndrome (IBS). Piezo proteins have been proven to play an important role in the mechanical stimulation to induce visceral pain in other tissues and may also be a biomarker candidate. The aim of this study was to test the expressions of Piezo1 and Piezo2 proteins in the intestinal epithelial cells from different intestinal segments and to explore the correlation between Piezo proteins express...
Exploring the Hypersensitivity of PTEN Deleted Prostate Cancer Stem Cells to WEE1 Tyrosine Kinase Inhibitors
AWARD NUMBER: W81XWH-14-1-0251 TITLE: Exploring the Hypersensitivity of PTEN Deleted Prostate Cancer Stem Cells to WEE1 Tyrosine Kinase... Tyrosine Kinase Inhibitors 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0251 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Kiran Mahajan 5d...ABSTRACT Central to all cycling cells-including prostate cancer stem cells- is the expression of WEE1 tyrosine kinase. WEE1 monitors duplication of
Desensitization to ceftaroline in a patient with multiple medication hypersensitivity reactions.
Jones, Justin M; Richter, Lisa M; Alonto, Augusto; Leedahl, David D
The case of a patient with multiple medication hypersensitivity reactions and a methicillin-resistant Staphylococcus aureus (MRSA) infection who underwent desensitization to ceftaroline is reported. A 32-year-old Caucasian woman with asthma, gastroesophageal reflux disease, heart murmur, and major depression was admitted for MRSA cellulitis with a subcutaneous abscess along the left sternomanubrial joint and clavicular osteomyelitis secondary to port placement after gastric bypass surgery. The patient had an extensive history of hypersensitivity reactions. Pertinent documented allergies were as follows: penicillin (anaphylaxis), daptomycin (anaphylaxis), vancomycin (hives), linezolid (hives), ertapenem (rash), ciprofloxacin (rash), and tigecycline (rash). The patient also reported previous reactions to aztreonam (unknown) and gentamicin (hives). The pharmacy was consulted to develop a desensitization protocol for ceftaroline. The desensitization protocol used three serial dilutions of ceftaroline to make 14 sequential infusions with escalating doses. Intramuscular epinephrine, i.v. diphenhydramine, and i.v. methylprednisolone were ordered as needed for the development of immediate hypersensitivity reactions during or after administration of ceftaroline. The cumulative dose (574.94 mg) was administered intravenously over 225 minutes with no breakthrough symptoms reported during or after the desensitization protocol. Ceftaroline fosamil 600 mg i.v. every 12 hours was continued for six weeks. Desensitization to ceftaroline was conducted for a patient with extensive history of hypersensitivity reactions to other drugs, including penicillin-induced anaphylaxis. Desensitization and subsequent treatment with full doses of ceftaroline were accomplished without apparent adverse effects. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.
Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons
Langeslag Michiel
Full Text Available Abstract Oncostatin M (OSM is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/- and gp130 floxed (gp130fl/fl mice. Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.
Overexpression of the transcription factor NF-YC9 confers abscisic acid hypersensitivity in Arabidopsis.
Bi, Chao; Ma, Yu; Wang, Xiao-Fang; Zhang, Da-Peng
Nuclear factor Y (NF-Y) family proteins are involved in many developmental processes and responses to environmental cues in plants, but whether and how they regulate phytohormone abscisic acid (ABA) signaling need further studies. In the present study, we showed that over-expression of the NF-YC9 gene confers ABA hypersensitivity in both the early seedling growth and stomatal response, while down-regulation of NF-YC9 does not affect ABA response in these processes. We also showed that over-expression of the NF-YC9 gene confers salt and osmotic hypersensitivity in early seedling growth, which is likely to be directly associated with the ABA hypersensitivity. Further, we observed that NF-YC9 physically interacts with the ABA-responsive bZIP transcription factor ABA-INSENSITIVE5 (ABI5), and facilitates the function of ABI5 to bind and activate the promoter of a target gene EM6. Additionally, NF-YC9 up-regulates expression of the ABI5 gene in response to ABA. These findings show that NF-YC9 may be involved in ABA signaling as a positive regulator and likely functions redundantly together with other NF-YC members, and support the model that the NF-YC9 mediates ABA signaling via targeting to and aiding the ABA-responsive transcription factors such as ABI5.
Patch testers' opinions regarding diagnostic criteria for metal hypersensitivity reactions to metallic implants.
Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated. Diagnostic criteria for hypersensitivity reactions after metallic device implantation are evaluated in this study by a multinational group of patch testers using Thyssen's previously published criteria. A total of 119 dermatologists at the 2012 European Contact Dermatitis Society and 2013 American Contact Dermatitis Society meetings answered a survey regarding their opinions on topics relating to metal hypersensitivity. Four major and 5 minor diagnostic criteria emerged. Approximately 80% of respondents found the following criteria useful (major criteria): chronic dermatitis beginning weeks to months after metallic implantation, eruption overlying the metal implant, positive patch test to a metal component of the implant, and complete clearing after removal of the potentially allergenic implant. Minor criteria (metals (eg, lymphocyte transformation test). In the challenging situation such as a symptomatic or failing orthopedic device, applying these 4 major criteria and the 5 supportive minor criteria may be useful for guiding decision making.
Trichloroethylene Hypersensitivity Syndrome Is Potentially Mediated through Its Metabolite Chloral Hydrate.
Huang, Yongshun; Xia, Lihua; Wu, Qifeng; Zeng, Zifang; Huang, Zhenlie; Zhou, Shanyu; Jin, Jiachun; Huang, Hanlin
We documented previously the entity of trichloroethylene (TCE) hypersensitivity syndrome (THS) in occupational workers. To identify the culprit causative compound, determine the type of hypersensitivity of THS, and establish a screening test for subjects at risk of THS. TCE and its main metabolites chloral hydrate (CH), trichloroethanol (TCOH) and trichloroacetic acid (TCA) were used as allergens at different concentrations in skin patch tests. The study included 19 case subjects diagnosed with occupational THS, 22 control healthy workers exposed to TCE (exposure >12 weeks), and 20 validation new workers exposed to TCE for <12 weeks free of THS. All subjects were followed-up for 12 weeks after the patch test. The highest patch test positive rate in subjects with THS was for CH, followed by TCOH, TCA and TCE. The CH patch test positive rate was 100% irrespective of CH concentrations (15%, 10% and 5%). The TCOH patch test positive rate was concentration-dependent (89.5%, 73.7% and 52.6% for 5%, 0.5% and 0.05%, respectively). Lower patch test positive rates were noted for TCA and TCE. All patch tests (including four allergens) were all negative in each of the 22 control subjects. None of the subjects of the validation group had a positive 15% CH patch test. Chloral hydrate seems to be the culprit causative compound of THS and type IV seems to be the major type of hypersensitivity of THS. The CH patch test could be potentially useful for screening workers at risk of THS.
Management of stinging insect hypersensitivity: a 5-year retrospective medical record review.
Johnson, Thomas; Dietrich, Jeffrey; Hagan, Larry
The Joint Task Force on Practice Parameters for Allergy and Immunology recommends that patients with a history of a systemic reaction to an insect sting be educated on ways to avoid insect stings, carry injectable epinephrine for emergency self-treatment, undergo specific IgE testing for stinging insect sensitivity, and be considered for immunotherapy. To review frontline providers' documented care and recommendations for imported fire ant and flying insect hypersensitivity reactions. A retrospective medical record review was performed of emergency department and primary care clinic visits between November 1, 1999, and November 30, 2004. Using International Classification of Diseases, Ninth Revision, codes, medical records were selected for review to identify patients with potential insect hypersensitivity. A total of 769 medical records from patients who experienced an insect sting were reviewed. Of 120 patients with a systemic reaction, 66 (55.0%) received a prescription for injectable epinephrine, and 14 (11.7%) were given information regarding avoidance of the offending insect. Forty-seven patients with systemic reactions (39.2%) were referred to an allergist. Of 28 patients who kept their appointments and underwent skin testing, 3 had negative results and 25 (89%) had positive results and were advised to start immunotherapy. Adherence to the stinging insect hypersensitivity practice parameter recommendations is poor. Many patients who have experienced a systemic reaction after an insect sting and have sought medical care are not afforded an opportunity for potentially lifesaving therapy.
Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde.
Ridpath, John R; Nakamura, Ayumi; Tano, Keizo; Luke, April M; Sonoda, Eiichiro; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Gillespie, David A F; Sale, Julian E; Yamazoe, Mitsuyoshi; Bishop, Douglas K; Takata, Minoru; Takeda, Shunichi; Watanabe, Masami; Swenberg, James A; Nakamura, Jun
Formaldehyde is an aliphatic monoaldehyde and is a highly reactive environmental human carcinogen. Whereas humans are continuously exposed to exogenous formaldehyde, this reactive aldehyde is a naturally occurring biological compound that is present in human plasma at concentrations ranging from 13 to 97 micromol/L. It has been well documented that DNA-protein crosslinks (DPC) likely play an important role with regard to the genotoxicity and carcinogenicity of formaldehyde. However, little is known about which DNA damage response pathways are essential for cells to counteract formaldehyde. In the present study, we first assessed the DNA damage response to plasma levels of formaldehyde using chicken DT40 cells with targeted mutations in various DNA repair genes. Here, we show that the hypersensitivity to formaldehyde is detected in DT40 mutants deficient in the BRCA/FANC pathway, homologous recombination, or translesion DNA synthesis. In addition, FANCD2-deficient DT40 cells are hypersensitive to acetaldehyde, but not to acrolein, crotonaldehyde, glyoxal, and methylglyoxal. Human cells deficient in FANCC and FANCG are also hypersensitive to plasma levels of formaldehyde. These results indicate that the BRCA/FANC pathway is essential to counteract DPCs caused by aliphatic monoaldehydes. Based on the results obtained in the present study, we are currently proposing that endogenous formaldehyde might have an effect on highly proliferating cells, such as bone marrow cells, as well as an etiology of cancer in Fanconi anemia patients.
Influence of PUVA and UVB radiation on delayed hypersensitivity in the guinea pig
Morison, W.L.; Parrish, J.A.; Woehler, M.E.; Krugler, J.I.; Bloch, K.J.
Exposure of guinea pigs to UVA (320--400 nm) radiation following administration of 8-methoxypsoralen by gavage (referred to by the acronym, PUVA) or exposure to UVB (290--320 nm) radiation, produced suppression of the cutaneous delayed hypersensitivity reaction at the site of exposure to radiation and at distant nonexposed sites. In these experiments, the animals were immunized by injection of dinitrophenyl-bovine gamma-globulin (DNP-BGG) in complete Freund's adjuvant and delayed hypersensitivity responses were provoked by intradermal injections of DNP-BGG, DNP and BGG on the flanks. Exposure to erythemogenic doses of either PUVA or UVB radiation for 7 days prior to immunization and for the 7 days between immunization and challenge (total period of radiation: 14 days) produced inhibiton of responses to each of the test substances. In addition, treatment with erythemogenic doses of PUVA either for 7 days prior to immunization or during the interval between immunization and challenge with DNP-BGG, inhibited the delayed hypersensitivity responses at the site of irradiation and at a nonexposed site. These findings suggest that in vivo exposure to nonionizing radiation leads to both local and systemic alteration of certain immune responses
Is Tadpole Pupil in an Adolescent Girl Caused by Denervation Hypersensitivity?
Hansen, Jonas Kjeldbjerg; Møller, Hans Ulrik
Tadpole pupil is a rarely encountered phenomenon caused by episodic, segmental iris dilator muscle spasm of short duration (2-15 minutes), occurring in clusters without a known precipitating factor. It has most commonly been described in women aged 28 to 48 years. A few hypotheses on pathogenesis have been discussed but none has been proved. Here, we present an adolescent girl with bilateral tadpole pupil that appeared during physical exercise. This is the first pediatric case of tadpole pupil, not caused by preceding surgery, to be published. Based on (1) this case in which tadpole pupil developed when the norepinephrine level rose during exercise, (2) the high ratio of patients with tadpole pupil who concurrently have or later develop Horner syndrome, in which denervation hypersensitivity is well described, (3) a previous report of a patient with both tadpole pupil and Horner syndrome who had denervation hypersensitivity on pharmacological testing, (4) a 29-year-old man with unilateral tadpole pupil induced by exercise, and (5) a 19-year-old man with bilateral tadpole pupil and possible autonomic neuropathy, we suggest denervation hypersensitivity as a probable pathogenic mechanism causing tadpole pupil. In addition, a suggestion for investigations to be performed in future pediatric cases is provided. Georg Thieme Verlag KG Stuttgart · New York.
Effects of electroacupuncture on corticotropin-releasing hormone in rats with chronic visceral hypersensitivity.
Liu, Hui-Rong; Fang, Xiao-Yi; Wu, Huan-Gan; Wu, Lu-Yi; Li, Jing; Weng, Zhi-Jun; Guo, Xin-Xin; Li, Yu-Guang
To investigate the effect of electroacupuncture on corticotropin-releasing hormone (CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity. A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7(th) week after the procedure, rats were randomly divided into a model group (MG), electroacupuncture group (EA), and sham electroacupuncture group (S-EA). After treatment, the abdominal withdrawal reflex (AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry (EnVision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and mRNA in the colon, spinal cord, and hypothalamus. The sensitivity of the rats to the colorectal distension stimulus applied at different strengths (20-80 mmHg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased (P 0.05) compared with normal rats (NG). However, the decrease in EA compared with MG rats was statistically significant (P 0.05). Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and mRNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.
Restorative effect of peritoneal macrophages on delayed hypersensitivity following ionizing radiation
Volkman, A.; Collins, F.M.
Sublethal whole-body irradiation in the guinea pig had little demonstrable effect on the development of delayed hypersensitivity but caused a profound, though transient depression of dermal reactivity in previously sensitized animals. Macrophage-rich peritoneal cell suspensions from non-sensitive donors when injected intradermally with eliciting antigen, resulted in the restoration of a significant degree of reactivity following irradiation. Inocula of lymphocytes, on the other hand, failed to yield similar results. These findings, when taken with the persistence of low levels of reactivity following irradiation and the ability to transfer reactivity with peritoneal exudate cells from animals so treated, warrant the conclusion that the presence of macrophages is necessary for the expression of cutaneous delayed hypersensitivity. The spontaneously renewed activity which follows the depressed phase is thus more of a reflection of the recovery of macrophage precursors from radiation injury, rather than the emergence of a new population of sensitized cells. The results, in addition, substantiate the belief that the expression of delayed hypersensitivity requires at least two cell populations, only one of which carries the property of specificity at the outset
Prevalence of hypersensitivity to dental local anesthetic drugs in patients referred to Tehran Allergy clinic (2005-2007
Akhlaghi F.
Full Text Available "nBackground and Aim: According to controversies in the prevalence of hypersensitivity to dental local anesthetic drugs and patients who claim hypersensitivity to these drugs, the aim of this study was to determine the prevalence of hypersensitivity to dental amide local anesthetic drugs in patients referred to Tehran Allergy Clinic in 2005-2007. "nMaterials and Methods: In this Study (Review of existing data, records of 130 patients who were referred to "Tehran allergy Clinic" (2005-2007 were studied. "nResults: The average age of patients was 29.5±18.8 years. 34% of cases showed positive skin reactions to at least one of the tested Lidocain concentrations and 10% of cases showed positive skin reactions to at least one of the tested Prilocain concentrations. There was a statistically significant difference in hypersensitivity to Lidocain 0.01 and 0.001 (p=0.017 and also between Lidocain 0.001 and 0.0001 (p<0.01. There was no statistically significant difference between other tested drug concentrations (p>0.05. "nConclusion: Many patients with history of hypersensitivity, show positive reaction to local dental anesthetic drugs. Prilocain hypersensitivity reactions are less than Lidocain. So application of Prilocain accompanies with less risk but its application should not be considered completely safe.
Salmonella Typhi sense host neuroendocrine stress hormones and release the toxin haemolysin E
Karavolos, Michail H; Bulmer, David M; Spencer, Hannah; Rampioni, Giordano; Schmalen, Ira; Baker, Stephen; Pickard, Derek; Gray, Joe; Fookes, Maria; Winzer, Klaus; Ivens, Alasdair; Dougan, Gordon; Williams, Paul; Khan, C M Anjam
Salmonella enterica serovar Typhi (S. typhi) causes typhoid fever. We show that exposure of S. typhi to neuroendocrine stress hormones results in haemolysis, which is associated with the release of haemolysin E in membrane vesicles. This effect is attributed to increased expression of the small RNA micA and RNA chaperone Hfq, with concomitant downregulation of outer membrane protein A. Deletion of micA or the two-component signal-transduction system, CpxAR, abolishes the phenotype. The hormone response is inhibited by the β-blocker propranolol. We provide mechanistic insights into the basis of neuroendocrine hormone-mediated haemolysis by S. typhi, increasing our understanding of inter-kingdom signalling. PMID:21331094
A case of hypersensitivity pneumonitis with giant cells in a female dental technician.
Kim, Yong-Hyun; Chung, Yun Kyung; Kim, Changhwan; Nam, Eun Suk; Kim, Hyun-Jun; Joo, Youngsu
Dental technicians are exposed to methyl methacrylate(MMA) and hard metal dusts while working, and several cases of hypersensitivity pneumonitis caused by the exposure have been reported. The authors experienced a case of hypersensitivity pneumonitis in a female dental technician who had 10Â years' work experience and report the case with clinical evidence. The patient's work, personal, social, and past and present medical histories were investigated based on patient questioning and medical records. Furthermore, the workplace conditions and tools and materials the patient worked with were also evaluated. Next, the pathophysiology and risk factors of pneumonitis were studied, and studies on the relationship between hypersensitivity pneumonitis and a dental technician's exposure to dust were reviewed. Any changes in the clinical course of her disease were noted for evaluation of the work-relatedness of the disease. The patient complained of cough and sputum for 1Â year. In addition, while walking up the stairs, the patient was not able to ascend without resting due to dyspnea. She visited our emergency department due to epistaxis, and secondary hypertension was incidentally suspected. Laboratory tests including serologic, electrolyte, and endocrinologic tests and a simple chest radiograph showed no specific findings, but chest computed tomography revealed a centrilobular ground-glass pattern in both lung fields. A transbronchial biopsy was performed, and bronchoalveolar washing fluid was obtained. Among the findings of the laboratory tests, microcalcification, noncaseating granuloma containing foreign body-type giant cells, and metal particles within macrophages were identified histologically. Based on these results, hypersensitivity pneumonitis was diagnosed. The patient stopped working due to admission, and she completely quit her job within 2Â months of restarting work due to reappearance of the symptoms. In this study, the patient did not have typical radiologic
Imipramine for Treatment of Esophageal Hypersensitivity and Functional Heartburn: A Randomized Placebo-Controlled Trial.
Limsrivilai, Julajak; Charatcharoenwitthaya, Phunchai; Pausawasdi, Nonthalee; Leelakusolvong, Somchai
Tricyclic antidepressants could be effective in the treatment of symptoms related to hypersensitive esophagus through their pain-modulating effect. We therefore assessed the benefit of imipramine in patients with esophageal hypersensitivity and functional heartburn. Patients with normal endoscopy findings and typical reflux symptoms despite standard-dose proton-pump inhibitor therapy underwent 24-h pH-impedance monitoring. Patients with established esophageal hypersensitivity or functional heartburn were randomly assigned to receive 8 weeks of either once-daily imipramine 25 mg (n=43) or placebo (n=40). The primary end point was satisfactory relief of reflux symptoms, defined as a >50% reduction in the gastroesophageal reflux disease score. The secondary end point was improvement in quality-of-life (QoL) as assessed by the 36-Item Short Form Health Survey score. Patients receiving imipramine did not achieve a higher rate of satisfactory relief of reflux symptoms than did patients receiving placebo (intention-to-treat (ITT) analysis: 37.2 vs. 37.5%, respectively; odds ratio (OR), 0.99; 95% confidence interval (CI), 0.41-2.41; per-protocol (PP) analysis: 45.5 vs. 41.2%, respectively; OR, 1.19; 95% CI, 0.45-3.13). Subgroup analysis to assess the efficacy of imipramine for either esophageal hypersensitivity or functional heartburn yielded similar results. Treatment with imipramine provided significant improvement of QoL by PP analysis (72±17 and 61±19, respectively; P=0.048), but ITT analysis did not reveal any differences between imipramine and placebo (68±19 and 61±19, respectively; P=0.26). Adverse events were similar in both groups; however, constipation was more common with imipramine than placebo (51.2 vs. 22.5%, respectively; P=0.01). Although low-dose imipramine shows potential QoL benefits, it does not relieve symptoms more effectively than does placebo in patients with either esophageal hypersensitivity or functional heartburn.
Plasticity in intact A delta- and C-fibers contributes to cold hypersensitivity in neuropathic rats.
Ji, G; Zhou, S; Kochukov, M Y; Westlund, K N; Carlton, S M
Cold hypersensitivity is a common sensory abnormality accompanying peripheral neuropathies and is difficult to treat. Progress has been made in understanding peripheral mechanisms underlying neuropathic pain but little is known concerning peripheral mechanisms of cold hypersensitivity. The aim of this study was to analyze the contribution of uninjured primary afferents to the cold hypersensitivity that develops in neuropathic rats. Rats with a lumbar 5 (L5) and L6 spinal nerve ligation (SNL, Chung model) but not sham, developed mechanical allodynia, evidenced by decreased paw withdrawal thresholds and increased magnitude of response to von Frey stimulation. Cold hypersensitivity also developed in SNL but not sham rats, evidenced by enhanced nociceptive behaviors induced by placement on a cold plate (6 degrees C) or application of icilin (a transient receptor potential M8 (TRPM8)/transient receptor potential A1 (TRPA1) receptor agonist) to nerve-injured hind paws. Single fiber recordings demonstrated that the mean conduction velocities of intact L4 cutaneous A delta- and C-fibers were not different between naive and SNL rats; however, mechanical thresholds of the A delta- but not the C-fibers were significantly decreased in SNL compared with naive. There was a higher prevalence of C-mechanoheat-cold (CMHC) fibers in SNL compared with naive, but the overall percentage of cold-sensitive C-fibers was not significantly increased compared with naive. This was in contrast to the numerous changes in A delta-fibers: the percentage of L4 cold sensitive A delta-, but not C-fibers, was significantly increased, the percentage of L4 icilin-sensitive A delta-, but not C-fibers, was significantly increased, the icilin-induced activity of L4 A delta-, but not C-fibers, was significantly increased. Icilin-induced activity was blocked by the TRPA1 antagonist Ruthenium Red. The results indicate plasticity in both A delta- and C-uninjured fibers, but A delta fibers appear to provide a
Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice
Ven, Marieke; Andressoo, Jaan-Olle; Holcomb, Valerie; Lindern, Marieke; Jong, Willeke; Zeeuw, Chris; Suh, Yousin; Hasty, Paul; Hoeijmakers, Jan; Horst, Gijsbertus; Mitchell, James
textabstractHow congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cul...
Growth hormone-mediated breakdown of body fat
Johansen, T.; Malmlöf, K.; Richelsen, Bjørn
regimen. Twelve-month-old rats fed first a high-fat diet or a low-fat diet for 14 weeks were injected with saline or growth hormone (4 mg/kg/d) for four days or three weeks in different combinations with either high- or low-fat diets. In adipose tissue, growth hormone generally inhibited lipoprotein...... lipase and also attenuated the inhibiting effect of insulin on hormone-sensitive lipase activity. Growth hormone treatment combined with restricted high-fat feeding reduced the activity of both lipases in adipose tissue and stimulated hormone-sensitive lipase in muscle. Generally, plasma levels of free...... fatty acids, glycerol and cholesterol were reduced by growth hormone, and in combination with restricted high-fat feeding, triglyceride levels improved too. We conclude that growth hormone inhibits lipid storage in adipose tissue by reducing both lipoprotein lipase activity and insulin's inhibitory...
DE71 suppresses thyroid hormone-mediated dendritogenesis and ...
olayemitoyin
Summary: Polybrominated diphenylethers (PBDEs) are synthesized ... Taken together, our study clearly reveals that DE71 can impair TH-mediated .... calbindin-28 K antibody and fluorescein ... spectral type inverted microscope IX81, ..... Steppan, L., Kerkvliet, N.I. (1994). ... Toxicology 86: 49-61. ... Ph.D. Dissertation.
Corticotropin-releasing hormone: Mediator of vertebrate life stage transitions?
Watanabe, Yugo; Grommen, Sylvia V H; De Groef, Bert
Hormones, particularly thyroid hormones and corticosteroids, play critical roles in vertebrate life stage transitions such as amphibian metamorphosis, hatching in precocial birds, and smoltification in salmonids. Since they synergistically regulate several metabolic and developmental processes that accompany vertebrate life stage transitions, the existence of extensive cross-communication between the adrenal/interrenal and thyroidal axes is not surprising. Synergies of corticosteroids and thyroid hormones are based on effects at the level of tissue hormone sensitivity and gene regulation. In addition, in representative nonmammalian vertebrates, corticotropin-releasing hormone (CRH) stimulates hypophyseal thyrotropin secretion, and thus functions as a common regulator of both the adrenal/interrenal and thyroidal axes to release corticosteroids and thyroid hormones. The dual function of CRH has been speculated to control or affect the timing of vertebrate life history transitions across taxa. After a brief overview of recent insights in the molecular mechanisms behind the synergic actions of thyroid hormones and corticosteroids during life stage transitions, this review examines the evidence for a possible role of CRH in controlling vertebrate life stage transitions. Copyright © 2016 Elsevier Inc. All rights reserved.
Turning of COGS moves forward findings for hormonally mediated cancers.
Sakoda, Lori C; Jorgenson, Eric; Witte, John S
The large-scale Collaborative Oncological Gene-environment Study (COGS) presents new findings that further characterize the genetic bases of breast, ovarian and prostate cancers. We summarize and provide insights into this collection of papers from COGS and discuss the implications of the results and future directions for such efforts.
Minimizing the source of nociception and its concurrent effect on sensory hypersensitivity: An exploratory study in chronic whiplash patients
Stratford Paul
Full Text Available Abstract Background The cervical zygapophyseal joints may be a primary source of pain in up to 60% of individuals with chronic whiplash associated disorders (WAD and may be a contributing factor for peripheral and centrally mediated pain (sensory hypersensitivity. Sensory hypersensitivity has been associated with a poor prognosis. The purpose of the study was to determine if there is a change in measures indicative of sensory hypersensitivity in patients with chronic WAD grade II following a medial branch block (MBB procedure in the cervical spine. Methods Measures of sensory hypersensitivity were taken via quantitative sensory testing (QST consisting of pressure pain thresholds (PPT's and cold pain thresholds (CPT's. In patients with chronic WAD (n = 18, the measures were taken at three sites bilaterally, pre- and post- MBB. Reduced pain thresholds at remote sites have been considered an indicator of central hypersensitivity. A healthy age and gender matched comparison group (n = 18 was measured at baseline. An independent t-test was applied to determine if there were any significant differences between the WAD and normative comparison groups at baseline with respect to cold pain and pressure pain thresholds. A dependent t-test was used to determine whether there were any significant differences between the pre and post intervention cold pain and pressure pain thresholds in the patients with chronic WAD. Results At baseline, PPT's were decreased at all three sites in the WAD group (p Conclusions The patients with chronic WAD showed evidence of widespread sensory hypersensitivity to mechanical and thermal stimuli. The WAD group revealed decreased sensory hypersensitivity following a decrease in their primary source of pain stemming from the cervical zygapophyseal joints.
Minimizing the source of nociception and its concurrent effect on sensory hypersensitivity: an exploratory study in chronic whiplash patients.
Schneider, Geoff M; Smith, Ashley D; Hooper, Allen; Stratford, Paul; Schneider, Kathryn J; Westaway, Michael D; Frizzell, Bevan; Olson, Lee
The cervical zygapophyseal joints may be a primary source of pain in up to 60% of individuals with chronic whiplash associated disorders (WAD) and may be a contributing factor for peripheral and centrally mediated pain (sensory hypersensitivity). Sensory hypersensitivity has been associated with a poor prognosis. The purpose of the study was to determine if there is a change in measures indicative of sensory hypersensitivity in patients with chronic WAD grade II following a medial branch block (MBB) procedure in the cervical spine. Measures of sensory hypersensitivity were taken via quantitative sensory testing (QST) consisting of pressure pain thresholds (PPT's) and cold pain thresholds (CPT's). In patients with chronic WAD (n = 18), the measures were taken at three sites bilaterally, pre- and post- MBB. Reduced pain thresholds at remote sites have been considered an indicator of central hypersensitivity. A healthy age and gender matched comparison group (n = 18) was measured at baseline. An independent t-test was applied to determine if there were any significant differences between the WAD and normative comparison groups at baseline with respect to cold pain and pressure pain thresholds. A dependent t-test was used to determine whether there were any significant differences between the pre and post intervention cold pain and pressure pain thresholds in the patients with chronic WAD. At baseline, PPT's were decreased at all three sites in the WAD group (p < 0.001). Cold pain thresholds were increased in the cervical spine in the WAD group (p < 0.001). Post-MBB, the WAD group showed significant increases in PPT's at all sites (p < 0.05), and significant decreases in CPT's at the cervical spine (p < 0.001). The patients with chronic WAD showed evidence of widespread sensory hypersensitivity to mechanical and thermal stimuli. The WAD group revealed decreased sensory hypersensitivity following a decrease in their primary source of pain stemming from the cervical
Neonatal vaginal irritation results in long-term visceral and somatic hypersensitivity and increased hypothalamic–pituitary–adrenal axis output in female mice
Pierce, Angela N.; Zhang, Zhen; Fuentes, Isabella M.; Wang, Ruipeng; Ryals, Janelle M.; Christianson, Julie A.
Abstract Experiencing early life stress or injury increases a woman's likelihood of developing vulvodynia and concomitant dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. To investigate the outcome of neonatal vaginal irritation (NVI), female mouse pups were administered intravaginal zymosan on postnatal days 8 and 10 and were assessed as adults for vaginal hypersensitivity by measuring the visceromotor response to vaginal balloon distension (VBD). Western blotting and calcium imaging were performed to measure transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) in the vagina and innervating primary sensory neurons. Serum corticosterone (CORT), mast cell degranulation, and corticotropin-releasing factor receptor 1 (CRF1) expression were measured as indicators of peripheral HPA axis activation. Colorectal and hind paw sensitivity were measured to determine cross-sensitization resulting from NVI. Adult NVI mice had significantly larger visceromotor response during VBD than naive mice. TRPA1 protein expression was significantly elevated in the vagina, and calcium transients evoked by mustard oil (TRPA1 ligand) or capsaicin (TRPV1 ligand) were significantly decreased in dorsal root ganglion from NVI mice, despite displaying increased depolarization-evoked calcium transients. Serum CORT, vaginal mast cell degranulation, and CRF1 protein expression were all significantly increased in NVI mice, as were colorectal and hind paw mechanical and thermal sensitivity. Neonatal treatment with a CRF1 antagonist, NBI 35965, immediately before zymosan administration largely attenuated many of the effects of NVI. These results suggest that NVI produces chronic hypersensitivity of the vagina, as well as of adjacent visceral and distant somatic structures, driven in part by increased HPA axis activation. PMID:26098441
Multiple hypersensitivity to mutagens in a cell strain (46BR) derived from a patient with immuno-deficiencies
Teo, I.A.; Arlett, C.F.; Harcourt, S.A.; Priestley, A.; Broughton, B.C.
46BR is a fibroblast cell strain established from an individual with hypogammaglobulinaemia. The cells are unique in showing hypersensitivity to the lethal effects of a wide range of DNA-damaging agents. Thus they are hypersensitive to #betta#- and 254-nm UV-irradiation and show a limited capacity to repair potentially lethal #betta#-irradiation damage when compared with fibroblasts from normal individuals. A slight hypersensitivity to mitomycin C was also revealed but we were not able to discriminate 46BR from normals with 4-nitroquinoline oxide. The cells were hypersensitive to the alkylating agents, dimethyl sulphate, methyl methanesulphonate, ethyl methanesulphonate, N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea but not N-ethyl-N-nitrosourea. A consideration of the spectra of DNA lesions produced by these alkylating agents together with the sensitivity to ionising radiation and mitomycin C suggests that 46BR cells are defective in a repair step that is common to all agents. We suggest that the cells are defective in DNA polymerisation or ligation. Support for this suggestion comes from the absence of any hypersensitivity to N-ethyl-N-nitrosourea since its major reaction products are not removed by excision pathways that require polymerisation and ligation. (orig.)
A garlic extract protects from ultraviolet B (280-320 nm) radiation-induced suppression of contact hypersensitivity
Reeve, V.E.; Bosnic, M.; Rozinova, E.; Boehm-Wilcox, C.
Lyophilized aged garlic extract has been incorporated at concentrations of 0.1%, 1% and 4% by weight into semi purified powdered diets and fed to hairless mice. Under moderate UVB exposure conditions resulting in 58% suppression of the systemic contact hypersensitivity response in control-fed mice, a dose-responsive protection was observed in the garlic-fed mice; contact hypersensitivity in the UVB-exposed mice fed 4% garlic extract was suppressed by only 19%. If the UVB exposure was replaced by topical application of one of a series of lotions containing increasing concentrations of cis-urocanic acid, a dose-responsive suppression of contact hypersensitivity was demonstrated in control-fed mice (urocanic acid at 25, 50, 100 and 200 micrograms per mouse resulting in 22-46% suppression). Mice fed a diet containing 1% aged garlic extract were partially protected from cis-urocanic acid-induced suppression of contact hypersensitivity, with greater protection from the lower concentrations of urocanic acid. Mice fed a diet containing 4% aged garlic extract were protected from all concentrations of urocanic acid. The results indicate that aged garlic extract contains ingredient(s) that protect from UVB-induced suppression of contact hypersensitivity and suggest that the mechanism of protection is by antagonism of the cis-urocanic acid mediation of this form of immunosuppression
Practical Management of Patients with a History of Immediate Hypersensitivity to Common non-Beta-Lactam Drugs.
Macy, Eric
Immediate hypersensitivity reactions to medications are among the most feared adverse drug reactions, because of their close association with anaphylaxis. This review discusses a practical management approach for patients with a history of an immediate hypersensitivity to a non-beta-lactam medication, where reexposure to the implicated, or similar, medication is clinically necessary. Mechanisms associated with severe immediate hypersensitivity reactions include IgE-mediated mast cell activation, complement-mediated mast cell activation, and direct mast cell activation. Immediate hypersensitivity reactions may also be mediated by vasodilators, other pharmacologic mechanisms, or be secondary to underlying patient-specific biochemical abnormalities such as endocrine tumors or chronic spontaneous urticaria. The key features in the reaction history and the biochemistry of the implicated medication are discussed. Most individuals with a history of immediate hypersensitivity to a medication, who require reuse of that drug, can be safely retreated with a therapeutic course of the implicated drug after a full-dose challenge, graded challenge, or desensitization, with or without premedication and/or any preliminary diagnostic testing, depending on the specific situation.
Dentinal hypersensitivity following scaling and root planing: comparison of low-level laser and topical fluoride treatment.
Pesevska, Snezana; Nakova, Marija; Ivanovski, Kiro; Angelov, Nikola; Kesic, Ljiljana; Obradovic, Radmila; Mindova, Sonja; Nares, Salvador
The aim of this study is to compare the effectiveness of low-level laser irradiation to traditional topical fluoride treatment for treatment choices of dentinal hypersensitivity following scaling and root planing. The experimental group (15 patients) was treated with low-energy-level diode laser at each site of dentinal hypersensitivity following scaling and root planning. The control group (15 patients) received topical fluoride treatment (protective varnish for desensitization). All the patients were treated at baseline visit, and then at day 2 and 4 after the initial treatment; the pain was subjectively assessed by the patients as strong, medium, medium low, low, or no pain. Total absence of the dental hypersensitivity was reported in 26.66% of the examined group even after the second visit, compared to the control group where complete resolution of the hypersensitivity was not present after the second visit in any of the treated cases. Complete absence of pain was achieved in 86.6% of patients treated with laser and only in 26.6% in the fluoride treated group, after the third visit. Based on our findings, we conclude that low-energy biostimulative laser treatment can be successfully used for treatment of dental hypersensitivity following scaling and root planing.
The preventive effect of resiniferatoxin on the development of cold hypersensitivity induced by spinal nerve ligation: involvement of TRPM8.
Koh, Won Uk; Choi, Seong-Soo; Kim, Ji Hyun; Yoon, Hye Joo; Ahn, Ho-Soo; Lee, Sun Kyung; Leem, Jeong Gil; Song, Jun Gol; Shin, Jin Woo
Resiniferatoxin (RTX) is a potent analog of capsaicin and activates transient receptor potential (TRP) vanilloid type (TRPV) 1. In the current study, we investigated the preventive effect of perineural RTX on the development of cold hypersensitivity induced by spinal nerve ligation (SNL) in rats. Furthermore, we examined the association between the expression level of TRPV1, TRP ankyrin type (TRPA) 1 and TRP melastatin type (TRPM) 8 in the dorsal root ganglion (DRG) and cold hypersensitivity after SNL. RTX pretreatment prevented the development of SNL-induced hypersensitivity to mechanical, thermal, and cold stimuli. Western blot analysis 4Â weeks after RTX pretreatment showed that RTX pretreatment decreased the protein expression level of SNL-induced TRPM8, but not TRPV1 or TRPA1, in the DRG of SNL rats. Immunofluorescent analysis revealed that up-regulated TRPM8-stained neurons after SNL co-localized with neurofilament 200-positive neurons located in the DRG. Pretreatment with perineural RTX significantly inhibits SNL-induced mechanical, thermal, and cold hypersensitivity. The antinociceptive effect of perineural RTX, especially on cold hypersensitivity, may be related to the suppression of TRPM8 expression in DRG.
Effectiveness of a baking soda toothpaste delivering calcium and phosphate in reducing dentinal hypersensitivity.
Ghassemi, A; Hooper, W; Winston, A E; Sowinski, J; Bowman, J; Sharma, N
The purpose of this controlled clinical trial was to determine the effectiveness and safety of a single-phase dentifrice that delivers calcium, phosphate, and fluoride to the tooth surface (Arm & Hammer Enamel Care for Sensitive Teeth toothpaste, United Kingdom) in reducing dentinal hypersensitivity. Two-hundred and eight qualifying subjects were randomly assigned to either the Enamel Care dentifrice group or a control dentifrice group, and brushed twice daily with their assigned dentifrice for eight weeks. Pain/discomfort in response to a thermal stimulus was assessed at baseline, week 4, and week 8 using a Visual Analogue Scale (VAS; primary outcome variable) and the Schiff Thermal Sensitivity Scale (STSS; secondary outcome variable). After eight weeks, volunteers from the Enamel Care group were switched to the control dentifrice and participated in a second eight-week study to determine the degree of persistence of pain reduction. Both groups had statistically significant VAS score reductions from baseline at weeks 4 and 8, with mean VAS scores in the Enamel Care group decreasing by 45.6% at week 4 and 61.1% at week 8 (p < 0.0001). Enamel Care was statistically significantly more effective than the control at weeks 4 and 8, with respective mean VAS reductions of 63% (p < 0.0001) and 33% (p = 0.0004) greater than the control. Consistent with the VAS score results, the Enamel Care group had respective statistically significant STSS score reductions of 77% and 58% greater than the control group (p < 0.0001). The reductions in dentinal hypersensitivity seen in the Enamel Care group at week 8 persisted for an additional eight weeks, during which the subjects discontinued use of Enamel Care and brushed with the control dentifrice. Enamel Care for Sensitive Teeth toothpaste (United Kingdom) is an effective dentifrice for the management of dentinal hypersensitivity, and its efficacy persists for a least eight weeks following discontinued product use.
Constructing a classification of hypersensitivity/allergic diseases for ICD-11 by crowdsourcing the allergist community.
Tanno, L K; Calderon, M A; Goldberg, B J; Gayraud, J; Bircher, A J; Casale, T; Li, J; Sanchez-Borges, M; Rosenwasser, L J; Pawankar, R; Papadopoulos, N G; Demoly, P
The global allergy community strongly believes that the 11th revision of the International Classification of Diseases (ICD-11) offers a unique opportunity to improve the classification and coding of hypersensitivity/allergic diseases via inclusion of a specific chapter dedicated to this disease area to facilitate epidemiological studies, as well as to evaluate the true size of the allergy epidemic. In this context, an international collaboration has decided to revise the classification of hypersensitivity/allergic diseases and to validate it for ICD-11 by crowdsourcing the allergist community. After careful comparison between ICD-10 and 11 beta phase linearization codes, we identified gaps and trade-offs allowing us to construct a classification proposal, which was sent to the European Academy of Allergy and Clinical Immunology (EAACI) sections, interest groups, executive committee as well as the World Allergy Organization (WAO), and American Academy of Allergy Asthma and Immunology (AAAAI) leaderships. The crowdsourcing process produced comments from 50 of 171 members contacted by e-mail. The classification proposal has also been discussed at face-to-face meetings with experts of EAACI sections and interest groups and presented in a number of business meetings during the 2014 EAACI annual congress in Copenhagen. As a result, a high-level complex structure of classification for hypersensitivity/allergic diseases has been constructed. The model proposed has been presented to the WHO groups in charge of the ICD revision. The international collaboration of allergy experts appreciates bilateral discussion and aims to get endorsement of their proposals for the final ICD-11. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Cytokine overproduction and crosslinker hypersensitivity are unlinked in Fanconi anemia macrophages.
Garbati, Michael R; Hays, Laura E; Rathbun, R Keaney; Jillette, Nathaniel; Chin, Kathy; Al-Dhalimy, Muhsen; Agarwal, Anupriya; Newell, Amy E Hanlon; Olson, Susan B; Bagby, Grover C
The Fanconi anemia proteins participate in a canonical pathway that repairs cross-linking agent-induced DNA damage. Cells with inactivated Fanconi anemia genes are universally hypersensitive to such agents. Fanconi anemia-deficient hematopoietic stem cells are also hypersensitive to inflammatory cytokines, and, as importantly, Fanconi anemia macrophages overproduce such cytokines in response to TLR4 and TLR7/8 agonists. We questioned whether TLR-induced DNA damage is the primary cause of aberrantly regulated cytokine production in Fanconi anemia macrophages by quantifying TLR agonist-induced TNF-α production, DNA strand breaks, crosslinker-induced chromosomal breakage, and Fanconi anemia core complex function in Fanconi anemia complementation group C-deficient human and murine macrophages. Although both M1 and M2 polarized Fanconi anemia cells were predictably hypersensitive to mitomycin C, only M1 macrophages overproduced TNF-α in response to TLR-activating signals. DNA damaging agents alone did not induce TNF-α production in the absence of TLR agonists in wild-type or Fanconi anemia macrophages, and mitomycin C did not enhance TLR responses in either normal or Fanconi anemia cells. TLR4 and TLR7/8 activation induced cytokine overproduction in Fanconi anemia macrophages. Also, although TLR4 activation was associated with induced double strand breaks, TLR7/8 activation was not. That DNA strand breaks and chromosome breaks are neither necessary nor sufficient to account for the overproduction of inflammatory cytokines by Fanconi anemia cells suggests that noncanonical anti-inflammatory functions of Fanconi anemia complementation group C contribute to the aberrant macrophage phenotype and suggests that suppression of macrophage/TLR hyperreactivity might prevent cytokine-induced stem cell attrition in Fanconi anemia. © Society for Leukocyte Biology.
Yongshun Huang
Full Text Available We documented previously the entity of trichloroethylene (TCE hypersensitivity syndrome (THS in occupational workers.To identify the culprit causative compound, determine the type of hypersensitivity of THS, and establish a screening test for subjects at risk of THS.TCE and its main metabolites chloral hydrate (CH, trichloroethanol (TCOH and trichloroacetic acid (TCA were used as allergens at different concentrations in skin patch tests. The study included 19 case subjects diagnosed with occupational THS, 22 control healthy workers exposed to TCE (exposure >12 weeks, and 20 validation new workers exposed to TCE for <12 weeks free of THS. All subjects were followed-up for 12 weeks after the patch test.The highest patch test positive rate in subjects with THS was for CH, followed by TCOH, TCA and TCE. The CH patch test positive rate was 100% irrespective of CH concentrations (15%, 10% and 5%. The TCOH patch test positive rate was concentration-dependent (89.5%, 73.7% and 52.6% for 5%, 0.5% and 0.05%, respectively. Lower patch test positive rates were noted for TCA and TCE. All patch tests (including four allergens were all negative in each of the 22 control subjects. None of the subjects of the validation group had a positive 15% CH patch test.Chloral hydrate seems to be the culprit causative compound of THS and type IV seems to be the major type of hypersensitivity of THS. The CH patch test could be potentially useful for screening workers at risk of THS.
Hypersensitivity reactions to penicillins: studies in a group of patients with negative benzylpenicillin G skin test.
Qiao, H-L; Li, Z; Yang, J; Tian, X; Gao, N; Jia, L-J
Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. The rate of positive reactions for the specific IgE antibodies was 59.40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39.10% (52) and 42.86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7.5%), were significantly fewer than the cross-reacting positive cases (36) to PG (P penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. Radioallergosorbent test is a good complementary test in persons who are skin-test negative with PG, and the sensitivity of RAST increases with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross-reactivity.
Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.
Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R; Rago, Carlo; Bhunia, Anil K; Hossain, M Zulfiquer; Paun, Bogdan C; Ren, Yunzhao R; Iacobuzio-Donahue, Christine A; Azad, Nilofer A; Kern, Scott E
Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Use of lymphoblastoid cell lines to evaluate the hypersensitivity to ultraviolet radiation in Cockayne syndrome
Otsuka, F.; Tarone, R.E.; Cayeux, S.; Robbins, J.H.
Cockayne syndrome (CS) is a rare autosomal recessive disease characterized by acute sun sensitivity, cachectic dwarfism, and neurologic and skeletal abnormalities. Cultured skin fibroblasts from patients with this disease are known to be hypersensitive to the lethal effects of 254-nm UV radiation. The authors have studied the sensitivity of 254-nm UV radiation of lymphoblastoid lines derived from 3 typical CS patients, 1 atypical CS patient who had a very late age of onset of clinical manifestations, 2 patients who had both xeroderma pigmentosum (XP) and typical CS, and 3 heterozygous parents of these patients. Post-UV survival was determined by the trypan-blue dye-exclusion method. The lymphoblastoid lines from the 3 typical CS patients, the atypical CS patient, and the 2 patients with both CS and XP had decreased post-UV viability in comparison with lines from normal donors. Lines from the heterozygous parents had normal post-UV viability. The post-UV viability of the typical CS lines was similar to that of a XP complementation group C line. The relative post-UV viability of lymphoblastoid lines from the typical CS patients was similar to the relative post-UV survival of their fibroblast lines. The lymphoblastoid line from the atypical CS patient had a post-UV viability similar to that of the typical CS patients. Thus, the relative hypersensitivity of CS patients cells in vitro does not reflect the severity or age of onset of the patients clinical manifestations. The lymphoblastoid lines from the 2 patients who had both CS and XP were significantly more sensitive to the UV radiation than those from patients with only CS. Our studies demonstrate that lymphoblastoid lines from patients with CS are appropriate and useful cell lines for the study of the inherited hypersensitivity to UV radiation
Human telomeres are hypersensitive to UV-induced DNA Damage and refractory to repair.
Patrick J Rochette
Full Text Available Telomeric repeats preserve genome integrity by stabilizing chromosomes, a function that appears to be important for both cancer and aging. In view of this critical role in genomic integrity, the telomere's own integrity should be of paramount importance to the cell. Ultraviolet light (UV, the preeminent risk factor in skin cancer development, induces mainly cyclobutane pyrimidine dimers (CPD which are both mutagenic and lethal. The human telomeric repeat unit (5'TTAGGG/CCCTAA3' is nearly optimal for acquiring UV-induced CPD, which form at dipyrimidine sites. We developed a ChIP-based technique, immunoprecipitation of DNA damage (IPoD, to simultaneously study DNA damage and repair in the telomere and in the coding regions of p53, 28S rDNA, and mitochondrial DNA. We find that human telomeres in vivo are 7-fold hypersensitive to UV-induced DNA damage. In double-stranded oligonucleotides, this hypersensitivity is a property of both telomeric and non-telomeric repeats; in a series of telomeric repeat oligonucleotides, a phase change conferring UV-sensitivity occurs above 4 repeats. Furthermore, CPD removal in the telomere is almost absent, matching the rate in mitochondria known to lack nucleotide excision repair. Cells containing persistent high levels of telomeric CPDs nevertheless proliferate, and chronic UV irradiation of cells does not accelerate telomere shortening. Telomeres are therefore unique in at least three respects: their biophysical UV sensitivity, their prevention of excision repair, and their tolerance of unrepaired lesions. Utilizing a lesion-tolerance strategy rather than repair would prevent double-strand breaks at closely-opposed excision repair sites on opposite strands of a damage-hypersensitive repeat.
Speech discrimination difficulties in High-Functioning Autism Spectrum Disorder are likely independent of auditory hypersensitivity.
William Andrew Dunlop
Full Text Available Autism Spectrum Disorder (ASD, characterised by impaired communication skills and repetitive behaviours, can also result in differences in sensory perception. Individuals with ASD often perform normally in simple auditory tasks but poorly compared to typically developed (TD individuals on complex auditory tasks like discriminating speech from complex background noise. A common trait of individuals with ASD is hypersensitivity to auditory stimulation. No studies to our knowledge consider whether hypersensitivity to sounds is related to differences in speech-in-noise discrimination. We provide novel evidence that individuals with high-functioning ASD show poor performance compared to TD individuals in a speech-in-noise discrimination task with an attentionally demanding background noise, but not in a purely energetic noise. Further, we demonstrate in our small sample that speech-hypersensitivity does not appear to predict performance in the speech-in-noise task. The findings support the argument that an attentional deficit, rather than a perceptual deficit, affects the ability of individuals with ASD to discriminate speech from background noise. Finally, we piloted a novel questionnaire that measures difficulty hearing in noisy environments, and sensitivity to non-verbal and verbal sounds. Psychometric analysis using 128 TD participants provided novel evidence for a difference in sensitivity to non-verbal and verbal sounds, and these findings were reinforced by participants with ASD who also completed the questionnaire. The study was limited by a small and high-functioning sample of participants with ASD. Future work could test larger sample sizes and include lower-functioning ASD participants.
Updating Allergy and/or Hypersensitivity Diagnostic Procedures in the WHO ICD-11 Revision.
Tanno, Luciana Kase; Calderon, Moises A; Li, James; Casale, Thomas; Demoly, Pascal
The classification of allergy and/or hypersensitivity conditions for the World Health Organization (WHO) International Classification of Diseases (ICD)-11 provides the appropriate corresponding codes for allergic diseases, assuming that the final diagnosis is correct. This classification should be linked to in vitro and in vivo diagnostic procedures. Considering the impact for our specialty, we decided to review the codification of these procedures into the ICD aiming to have a baseline and to suggest changes and/or submit new proposals. For that, we prepared a list of the relevant allergy and/or hypersensitivity diagnostic procedures that health care professionals are dealing with on a daily basis. This was based on the main current guidelines and selected all possible and relevant corresponding terms from the ICD-10 (2015 version) and the ICD-11 β phase foundation (June 2015 version). More than 90% of very specific and important diagnostic procedures currently used by the allergists' community on a daily basis are missing. We observed that some concepts usually used by the allergist community on a daily basis are not fully recognized by other specialties. The whole scheme and the correspondence in the ICD-10 (2015 version) and ICD-11 foundation (June 2015 version) provided us a big picture of the missing or imprecise terms and how they are scattered in the current ICD-11 framework, allowing us to submit new proposals to increase the visibility of the allergy and/or hypersensitivity conditions and diagnostic procedures. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. All rights reserved.
Outcomes of premedication for non-ionic radio-contrast media hypersensitivity reactions in Korea
Kim, Sae-Hoon; Lee, So-Hee; Lee, Sang-Min; Kang, Hye-Ryun; Park, Heung-Woo; Kim, Sun-Sin; Cho, Sang-Heon
Background: Radio-contrast media (CM)-related adverse reactions are important clinical problems that may cause fatal anaphylaxis. Accordingly, it has been common practice to premedicate patients who have had previous reactions to CM with corticosteroids, antihistamines, and H2 blockers to prevent hypersensitive reactions. However, the effectiveness of premedication has not been properly demonstrated, especially in cases related to non-ionic CM. In this study, we evaluated the effectiveness of premedication at preventing of non-ionic CM immediate-type hypersensitivity reactions. Methods: A total of 30 patients who had been pretreated with corticosteroid and H1 antihistamines and/or H2 blockers in a 3-year period were enrolled. The results of premedication were evaluated in terms of clinical characteristics and the features of breakthrough reactions. Results: Hypersensitivity reactions were not prevented in 5 of the 30 patients who had experienced prior CM reactions (overall recurrence rate after premedication 16.7%; 4/17 patients with mild previous reactions, and 1/13 patients with severe previous reactions). The recurrence rate after premedication was significantly higher in patients with mild previous reactions than in those with severe reactions (23.5% vs. 7.7%; p < 0.001). The breakthrough reactions were similar to the prior reactions in terms of severity and clinical manifestations. Conclusion: Premedication with corticosteroid and H1 antihistamines and/or H2 blockers effectively prevent non-ionic CM-related adverse events in most patients who have had severe previous reactions to CM. However, physicians should be aware of the possibility of premedication failing and of breakthrough reactions, even in cases in which the previous reactions were mild.
Li, Wenbo
Salinity is an abiotic stress that substantially limits crop production worldwide. To identify salt stress tolerance determinants, we screened for Arabidopsis mutants that are hypersensitive to salt stress and designated these mutants as short root in salt medium (rsa). One of these mutants, rsa3-1, is hypersensitive to NaCl and LiCl but not to CsCl or to general osmotic stress. Reactive oxygen species (ROS) over-accumulate in rsa3-1 plants under salt stress. Gene expression profiling with Affymetrix microarray analysis revealed that RSA3 controls expression of many genes including genes encoding proteins for ROS detoxification under salt stress. Map-based cloning showed that RSA3 encodes a xyloglucan galactosyltransferase, which is allelic to a gene previously named MUR3/KAM1. The RSA3/ MUR3/KAM1-encoded xylogluscan galactosyltransferase regulates actin microfilament organization (and thereby contributes to endomembrane distribution) and is also involved in cell wall biosynthesis. In rsa3-1, actin cannot assemble and form bundles as it does in the wild-type but instead aggregates in the cytoplasm. Furthermore, addition of phalloidin, which prevents actin depolymerization, can rescue salt hypersensitivity of rsa3-1. Together, these results suggest that RSA3/MUR3/KAM1 along with other cell wall-associated proteins plays a critical role in salt stress tolerance by maintaining the proper organization of actin microfilaments in order to minimize damage caused by excessive ROS. © 2013 The Author.
Equine allergy therapy: update on the treatment of environmental, insect bite hypersensitivity, and food allergies.
Marsella, Rosanna
Allergies are common in horses. It is important to identify and correct as many factors as possible to control pruritus and make the patient comfortable. Culicoides hypersensitivity is a common component in allergic horses. The main treatment continues to be rigorous fly control and avoidance of insect bites. Environmental allergies are best addressed by early identification of the offending allergens and formulation of allergen-specific immunotherapy to decrease the need for rescue medications. Food allergy is best managed with food avoidance. Urticaria is one of the manifestations of allergic disease wherein detection of the triggering cause is essential for management. Copyright © 2013 Elsevier Inc. All rights reserved.
Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire
Ostrov, David A; Grant, Barry J; Pompeu, Yuri A
cells, thus causing the equivalent of an alloreactive T-cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir and that were recognized by T cells of hypersensitive patients. The assays that we have established can be applied to test additional...... unclear. Here we show that abacavir can bind within the F pocket of the peptide-binding groove of HLA-B*57:01, thereby altering its specificity. This provides an explanation for HLA-linked idiosyncratic adverse drug reactions, namely that drugs can alter the repertoire of self-peptides presented to T...
Effect of ranitidine on postoperative suppression of natural killer cell activity and delayed hypersensitivity
Nielsen, Hans Jørgen; Pedersen, B K; Moesgaard, F
hypersensitivity (DTH) antigens, and blood drawn immediately before and 24 hours after skin incision was analyzed for spontaneous and in vitro stimulated (IL-2, IFN-alpha or indomethacin) natural killer (NK) cell activity and PHA and PPD-stimulated lymphocyte proliferation. Lymphocyte subsets (helper......-cell activity (p less than 0.02). Postoperative decrease in helper/inducer-T cell numbers was not significantly lessened (p = 0.07), and ranitidine did not influence the levels of suppressor-T cells. PHA and PPD responses in peripheral blood mononuclear cells were unaltered. The results may suggest potential...
POSSIBILITY OF PHARMACOMODULATION OF THE HYPERSENSITIVE RHINITIS JOINED WITH THE NASAL POLYPOSIS
Dejan Ursulović
Full Text Available The research goai is to examine the effects of the local corticosteroidapplication to the number of eosinophils in the nasal secretion of the patients withhypersensitive rhinitis joined with the nasal polyposis. The study comprises 13patients with hypersensitive rhinitis joined with the nasal polyposis; 9 of them madeup the experimental group. The local corticosteroid (bechomethasone dipropionatein water spray was given at 12 hours in individual doses of 200 micrograms to theexperimental group patients in six weeks. During the treatment it was confirmed thatthere was a highly important reduction of the number of eosinophils of the nasalsecretion in the experimental group patients.
Liver dysfunction induced by systemic hypersensitivity reaction to lamotrigine: case report
Sung Gyu Im
Full Text Available Lamotrigine is an anticonvulsant drug used to treat partial and generalized seizure disorders. Hypersensitivity to lamotrigine usually causes mild symptoms such as fever, rash, and slight invasion of internal organs. However, a 33-year-old male patient who was admitted with Stevens-Johnson syndrome after taking lamotrigine for 15 days experienced hepatic failure and died 5 days after admission. This case demonstrates the importance of realizing that lamotrigine can lead to fatal hepatic failure, and that tests for the normal liver function should be performed when administering lamotrigine.
The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation
Joshua C. Pritchett
Data Sources and Extraction. Drugs identified as causes of (i idiosyncratic reactions, (ii drug-induced hypersensitivity, drug-induced hepatotoxicity, acute liver failure, and Stevens-Johnson syndrome, and (iii human herpes virus reactivation in PubMed since 1997 have been collected and discussed. Results. Data presented in this paper show that HHV-6 reactivation is associated with more severe organ involvement and a prolonged course of disease. Conclusion. This analysis of HHV-6 reactivation associated with drug-induced severe cutaneous reactions and hepatotoxicity will aid in causality assessment and clinical diagnosis of possible life-threatening events and will provide a basis for further patient characterization and therapy.
Epidermal growth factor upregulates serotonin transporter and its association with visceral hypersensitivity in irritable bowel syndrome.
Cui, Xiu-Fang; Zhou, Wei-Mei; Yang, Yan; Zhou, Jun; Li, Xue-Liang; Lin, Lin; Zhang, Hong-Jie
To investigate the role of epidermal growth factor (EGF) in visceral hypersensitivity and its effect on the serotonin transporter (SERT). A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson's correlation analysis. SERT function was examined by tritiated serotonin (5-HT) uptake experiments. Rat intestinal epithelial cells (IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor (EGFR). EGF levels were significantly lower in the rats with visceral hypersensitivity as measured in plasma (2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, P < 0.01) and in colonic tissue (3.244 ± 0.135 ng/100 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P < 0.01) compared with controls. Moreover, the EGF levels were positively correlated with SERT levels (r = 0.820, P < 0.01). EGF displayed dose- and time-dependent increased SERT gene expressions in IEC-6 cells. An EGFR kinase inhibitor inhibited the effect of EGF on SERT gene upregulation. SERT activity was enhanced following treatment with EGF (592.908 ± 31.515 fmol/min per milligram vs 316.789 ± 85.652 fmol/min per milligram protein, P < 0.05) and blocked by the EGFR kinase inhibitor in IEC-6 cells (590.274 ± 25.954 fmol/min per milligram vs 367.834 ± 120.307 fmol/min per milligram protein, P < 0.05). A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT
Type IV Hypersensitivity to Gold Weight Upper-Eyelid Implant: Case Report and Review of the Literature.
Kilduff, Caroline L S; Casswell, Edward J; Imonikhe, Richard; Marjanovic, Branka
Complications associated with gold-weight insertion for lagophthalmos are uncommon, recent reports have provided evidence to suggest that type IV hypersensitivity to gold can cause a persistent inflammatory reaction. We present a case of a 46-year-old man who experienced persistent post-operative inflammation, and summarize previously documented cases. This patient underwent uncomplicated insertion of an upper eyelid gold weight for right-sided facial nerve palsy. He had no allergies or implanted metalwork. Post-operatively erythema was noted at seven-weeks and did not resolve. The weight was removed after six-months. The histopathological findings were in keeping with type IV hypersensitivity and similar to previous cases. Although infrequent, this complication has poor outcomes. The definitive management is removal of the weight. Information regarding implanted gold, and previous reactions should be elicited pre-operatively. Type IV hypersensitivity should be considered in patients with persistent inflammation that do not respond to antibiotic or steroid therapy.
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Peripheral and central P2X3 receptor contributions to colon mechanosensitivity and hypersensitivity in the mouse
Shinoda, Masamichi; Feng, Bin; Gebhart, G. F.
Background & Aims Irritable bowel syndrome is characterized by altered sensory qualities, namely discomfort/pain and colorectal hypersensitivity. In mice, we examined the role of P2X3 receptors in colon mechanosensitivity and intracolonic zymosan-produced hypersensitivity, a model of persistent colon hypersensitivity without colon inflammation. Methods The visceromotor response (VMR) to colon distension (15 – 60 mmHg) was determined before and after intracolonic saline or zymosan (30 mg/mL, 0.1 mL, daily for 3 days) treatment. Colon pathology and intracolonic ATP release was assessed in parallel experiments. To examine P2X3 receptor contributions to colon mechanosensation and hypersensitivity, electrophysiological experiments were performed using an in vitro colon-pelvic nerve preparation. Results VMRs to distension were significantly reduced in P2X3+/−and P2X3−/− mice relative to wildtype mice. Colon hypersensitivity produced by zymosan was virtually absent in P2X3−/− relative to wildtype or P2X3+/− mice. Intralumenal release of the endogenous P2X receptor ligand ATP did not differ between wildtype and P2X3−/− mice or change after intracolonic zymosan treatment. Responses of muscular and muscular-mucosal pelvic nerve afferents to mechanical stretch did not differ between P2X3−/− and wildtype mice. Both muscular and muscular-mucosal afferents in wildtype mice sensitized to application of an inflammatory soup, whereas only muscular-mucosal afferents did so in P2X3−/− mice. Conclusions These results suggest differential roles for peripheral and central P2X3 receptors in colon mechanosensory transduction and hypersensitivity. PMID:19549524
An onion farmer with a case of hypersensitivity pneumonitis caused by Aspergillus niger.
Sakamoto, Tomohiro; Yamasaki, Akira; Funaki, Yoshihiro; Harada, Tomoya; Okazaki, Ryota; Hasegawa, Yasuyuki; Sueda, Yuriko; Fukushima, Takehito; Morita, Masahito; Yamamoto, Akihiro; Kodani, Masahiro; Shimizu, Eiji
A 62-year old man was admitted to our hospital with a 2-week complaint of a dry cough, general fatigue, and dyspnea on effort. He has been an onion farmer for several years and developed these symptoms after cleaning up onion peels with air compressors. A chest roentgenogram and computed tomography showed a ground glass shadow in the bilateral upper lung field. Cellular analysis of the bronchoalveolar lavage fluid showed elevated total cell numbers and lymphocytes. Transbronchial lung biopsies revealed a non-caseating granuloma with both epithelioid cells and Langhans giant cells. After the admission, these symptoms and radiological findings gradually improved without any treatment. Then, a returning-home provocation test was positive only when he worked cleaning up onion peels with air compressors. A. niger was cultured from his workplace and black mold from the onion peels. The precipitation antibody and the antigen were both positive for Aspergillus . Therefore, we diagnosed this case as hypersensitivity pneumonitis caused by inhalation of A. niger . Although hypersensitivity pneumonia caused by A. niger is rare, physicians should aware the possibility of this condition in farmers because A niger is ubiquitously present in several vegetables and fruits.
Transcriptomic analysis of Prunus domestica undergoing hypersensitive response to plum pox virus infection.
Rodamilans, Bernardo; San León, David; Mühlberger, Louisa; Candresse, Thierry; Neumüller, Michael; Oliveros, Juan Carlos; García, Juan Antonio
Plum pox virus (PPV) infects Prunus trees around the globe, posing serious fruit production problems and causing severe economic losses. One variety of Prunus domestica, named 'Jojo', develops a hypersensitive response to viral infection. Here we compared infected and non-infected samples using next-generation RNA sequencing to characterize the genetic complexity of the viral population in infected samples and to identify genes involved in development of the resistance response. Analysis of viral reads from the infected samples allowed reconstruction of a PPV-D consensus sequence. De novo reconstruction showed a second viral isolate of the PPV-Rec strain. RNA-seq analysis of PPV-infected 'Jojo' trees identified 2,234 and 786 unigenes that were significantly up- or downregulated, respectively (false discovery rate; FDR≤0.01). Expression of genes associated with defense was generally enhanced, while expression of those related to photosynthesis was repressed. Of the total of 3,020 differentially expressed unigenes, 154 were characterized as potential resistance genes, 10 of which were included in the NBS-LRR type. Given their possible role in plant defense, we selected 75 additional unigenes as candidates for further study. The combination of next-generation sequencing and a Prunus variety that develops a hypersensitive response to PPV infection provided an opportunity to study the factors involved in this plant defense mechanism. Transcriptomic analysis presented an overview of the changes that occur during PPV infection as a whole, and identified candidates suitable for further functional characterization.
Chronic hypersensitivity pneumonitis: high resolution computed tomography patterns and pulmonary function indices as prognostic determinants
Walsh, Simon L.F.; Devaraj, Anand; Hansell, David M. [Royal Brompton Hospital, Department of Radiology, London (United Kingdom); Sverzellati, Nicola [University of Parma, Department of Clinical Sciences, Section of Radiology, Parma (Italy); Wells, Athol U. [Royal Brompton Hospital, Interstitial Lung Diseases Unit, London (United Kingdom)
To investigate high resolution computed tomography (HRCT) and pulmonary function indices (PFTs) for determining prognosis in patients with chronic fibrotic hypersensitivity pneumonitis (CHP). Case records, PFTs (FEV{sub 1}, FVC and DLco) and HRCTs of ninety-two patients with chronic hypersensitivity pneumonitis were evaluated. HRCT studies were scored by two observers for total disease extent, ground-glass opacification, fine and coarse reticulation, microcystic and macrocystic honeycombing, centrilobular emphysema and consolidation. Traction bronchiectasis within each pattern was graded. Using Cox proportional hazards regression models the prognostic strength of individual HRCT patterns and pulmonary function test variables were determined. There were forty two deaths during the study period. Increasing severity of traction bronchiectasis was the strongest predictor of mortality (HR 1.10, P < 0.001, 95%CI 1.04-1.16). Increasing global interstitial disease extent (HR 1.02, P = 0.02, 95%CI 1.00-1.03), microcystic honeycombing (HR 1.09, P = 0.019, 95%CI 1.01-1.17) and macrocystic honeycombing (HR 1.06, P < 0.01, 95%CI 1.01-1.10) were also independent predictors of mortality. In contrast, no individual PFT variable was predictive of mortality once HRCT patterns were accounted for. HRCT patterns, in particular, severity of traction bronchiectasis and extent of honeycombing are superior to pulmonary function tests for predicting mortality in patients with CHP. (orig.)
Carotid sinus hypersensitivity: Entity warrants a caution in the critical care unit
Sugata Dasgupta
Full Text Available Carotid sinus hypersensitivity (CSH syndrome is an entity caused by an overreaction of the carotid sinus baroreceptors to stimulation. Three subtypes of CSH syndrome are recognized according to the response to carotid sinus massage (CSM: Predominantly cardioinhibitory, predominantly vasodepressor and a mixed subtype. We report here the case of a middle-aged female patient admitted in our critical care unit with respiratory failure requiring mechanical ventilation. There were episodes of severe bradycardia whenever her head was rotated to any side, relieved on neutralizing head position and administering intravenous atropine. CSM revealed she had predominantly cardioinhibitory type of CSH syndrome. A cardioinhibitory form of hypersensitive carotid sinus reflex, which is idiopathic in causation, probably explains the severe bradycardia on head rotation seen in our patient. A heightened awareness of this syndrome is necessary for timely diagnosis and management. CSH syndrome results from an overreaction of the carotid sinus baroreceptors to stimulation, manifesting commonly as bradycardia, hypotension and syncope. It is an entity, which warrants caution during routine critical care practices.
A Pilot Qualitative Investigation of Stakeholders' Experiences and Opinions of Equine Insect Bite Hypersensitivity in England
Hannah R. Lomas
Full Text Available Equine insect bite hypersensitivity (IBH, commonly known as sweet itch or summer eczema, is a frustrating recurrent skin disease in the equine industry involving an immune reaction to the bites of Culicoides spp. midges. To investigate the impact of IBH in the field, an exploratory pilot study was conducted with equine stakeholders in one region of central England. Nine semi-structured, face-to-face interviews were conducted with horse owners and an equine veterinarian. The aim was to gain an understanding of experiences with IBH, and to gauge opinions on the value of the various management strategies horse owners use to control IBH. Awareness of IBH was generally high, particularly in those individuals who had previous experience with the condition. Those with previous experience of IBH commented on the significant effect on daily routines, and the associated cost implications. Most participants supported an integrated approach to hypersensitivity management, and this most commonly involved a combination of physical barriers and chemical repellents, but sometimes included feed supplementation. Overall, attitudes towards IBH suggested that the condition is a notable welfare and economic concern for stakeholders, but veterinary involvement tended to only be in more severe cases. Further research is required in the future to improve understanding, management and potential treatment of this condition.
Bernardo Rodamilans
Full Text Available Plum pox virus (PPV infects Prunus trees around the globe, posing serious fruit production problems and causing severe economic losses. One variety of Prunus domestica, named 'Jojo', develops a hypersensitive response to viral infection. Here we compared infected and non-infected samples using next-generation RNA sequencing to characterize the genetic complexity of the viral population in infected samples and to identify genes involved in development of the resistance response. Analysis of viral reads from the infected samples allowed reconstruction of a PPV-D consensus sequence. De novo reconstruction showed a second viral isolate of the PPV-Rec strain. RNA-seq analysis of PPV-infected 'Jojo' trees identified 2,234 and 786 unigenes that were significantly up- or downregulated, respectively (false discovery rate; FDR≤0.01. Expression of genes associated with defense was generally enhanced, while expression of those related to photosynthesis was repressed. Of the total of 3,020 differentially expressed unigenes, 154 were characterized as potential resistance genes, 10 of which were included in the NBS-LRR type. Given their possible role in plant defense, we selected 75 additional unigenes as candidates for further study. The combination of next-generation sequencing and a Prunus variety that develops a hypersensitive response to PPV infection provided an opportunity to study the factors involved in this plant defense mechanism. Transcriptomic analysis presented an overview of the changes that occur during PPV infection as a whole, and identified candidates suitable for further functional characterization.
Hapten-Induced Contact Hypersensitivity, Autoimmune Reactions, and Tumor Regression: Plausibility of Mediating Antitumor Immunity
Dan A. Erkes
Full Text Available Haptens are small molecule irritants that bind to proteins and elicit an immune response. Haptens have been commonly used to study allergic contact dermatitis (ACD using animal contact hypersensitivity (CHS models. However, extensive research into contact hypersensitivity has offered a confusing and intriguing mechanism of allergic reactions occurring in the skin. The abilities of haptens to induce such reactions have been frequently utilized to study the mechanisms of inflammatory bowel disease (IBD to induce autoimmune-like responses such as autoimmune hemolytic anemia and to elicit viral wart and tumor regression. Hapten-induced tumor regression has been studied since the mid-1900s and relies on four major concepts: (1 ex vivo haptenation, (2 in situ haptenation, (3 epifocal hapten application, and (4 antigen-hapten conjugate injection. Each of these approaches elicits unique responses in mice and humans. The present review attempts to provide a critical appraisal of the hapten-mediated tumor treatments and offers insights for future development of the field.
Gastroesophageal reflux symptoms not responding to proton pump inhibitor: GERD, NERD, NARD, esophageal hypersensitivity or dyspepsia?
Bashashati, Mohammad; Hejazi, Reza A; Andrews, Christopher N; Storr, Martin A
Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy. PMID:24719900
Cannabis use in early adolescence: Evidence of amygdala hypersensitivity to signals of threat
Philip A. Spechler
Full Text Available Cannabis use in adolescence may be characterized by differences in the neural basis of affective processing. In this study, we used an fMRI affective face processing task to compare a large group (n = 70 of 14-year olds with a history of cannabis use to a group (n = 70 of never-using controls matched on numerous characteristics including IQ, SES, alcohol and cigarette use. The task contained short movies displaying angry and neutral faces. Results indicated that cannabis users had greater reactivity in the bilateral amygdalae to angry faces than neutral faces, an effect that was not observed in their abstinent peers. In contrast, activity levels in the cannabis users in cortical areas including the right temporal-parietal junction and bilateral dorsolateral prefrontal cortex did not discriminate between the two face conditions, but did differ in controls. Results did not change after excluding subjects with any psychiatric symptomology. Given the high density of cannabinoid receptors in the amygdala, our findings suggest cannabis use in early adolescence is associated with hypersensitivity to signals of threat. Hypersensitivity to negative affect in adolescence may place the subject at-risk for mood disorders in adulthood.
Effect of DA-9701 on colorectal distension-induced visceral hypersensitivity in a rat model.
Kim, Eun Ran; Min, Byung-Hoon; Lee, Tae Ho; Son, Miwon; Rhee, Poong-Lyul
DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.
Cannabis use in early adolescence: Evidence of amygdala hypersensitivity to signals of threat.
Spechler, Philip A; Orr, Catherine A; Chaarani, Bader; Kan, Kees-Jan; Mackey, Scott; Morton, Aaron; Snowe, Mitchell P; Hudson, Kelsey E; Althoff, Robert R; Higgins, Stephen T; Cattrell, Anna; Flor, Herta; Nees, Frauke; Banaschewski, Tobias; Bokde, Arun L W; Whelan, Robert; Büchel, Christian; Bromberg, Uli; Conrod, Patricia; Frouin, Vincent; Papadopoulos, Dimitri; Gallinat, Jurgen; Heinz, Andreas; Walter, Henrik; Ittermann, Bernd; Gowland, Penny; Paus, Tomáš; Poustka, Luise; Martinot, Jean-Luc; Artiges, Eric; Smolka, Michael N; Schumann, Gunter; Garavan, Hugh
Cannabis use in adolescence may be characterized by differences in the neural basis of affective processing. In this study, we used an fMRI affective face processing task to compare a large group (n=70) of 14-year olds with a history of cannabis use to a group (n=70) of never-using controls matched on numerous characteristics including IQ, SES, alcohol and cigarette use. The task contained short movies displaying angry and neutral faces. Results indicated that cannabis users had greater reactivity in the bilateral amygdalae to angry faces than neutral faces, an effect that was not observed in their abstinent peers. In contrast, activity levels in the cannabis users in cortical areas including the right temporal-parietal junction and bilateral dorsolateral prefrontal cortex did not discriminate between the two face conditions, but did differ in controls. Results did not change after excluding subjects with any psychiatric symptomology. Given the high density of cannabinoid receptors in the amygdala, our findings suggest cannabis use in early adolescence is associated with hypersensitivity to signals of threat. Hypersensitivity to negative affect in adolescence may place the subject at-risk for mood disorders in adulthood. Copyright © 2015. Published by Elsevier Ltd.
Walsh, Simon L.F.; Devaraj, Anand; Hansell, David M.; Sverzellati, Nicola; Wells, Athol U.
To investigate high resolution computed tomography (HRCT) and pulmonary function indices (PFTs) for determining prognosis in patients with chronic fibrotic hypersensitivity pneumonitis (CHP). Case records, PFTs (FEV 1 , FVC and DLco) and HRCTs of ninety-two patients with chronic hypersensitivity pneumonitis were evaluated. HRCT studies were scored by two observers for total disease extent, ground-glass opacification, fine and coarse reticulation, microcystic and macrocystic honeycombing, centrilobular emphysema and consolidation. Traction bronchiectasis within each pattern was graded. Using Cox proportional hazards regression models the prognostic strength of individual HRCT patterns and pulmonary function test variables were determined. There were forty two deaths during the study period. Increasing severity of traction bronchiectasis was the strongest predictor of mortality (HR 1.10, P < 0.001, 95%CI 1.04-1.16). Increasing global interstitial disease extent (HR 1.02, P = 0.02, 95%CI 1.00-1.03), microcystic honeycombing (HR 1.09, P = 0.019, 95%CI 1.01-1.17) and macrocystic honeycombing (HR 1.06, P < 0.01, 95%CI 1.01-1.10) were also independent predictors of mortality. In contrast, no individual PFT variable was predictive of mortality once HRCT patterns were accounted for. HRCT patterns, in particular, severity of traction bronchiectasis and extent of honeycombing are superior to pulmonary function tests for predicting mortality in patients with CHP. (orig.)
The Edible Brown Seaweed Ecklonia cava Reduces Hypersensitivity in Postoperative and Neuropathic Pain Models in Rats
Jae Goo Kim
Full Text Available The current study was designed to investigate whether edible brown seaweed Ecklonia cava extracts exhibits analgesic effects in plantar incision and spared nerve injury (SNI rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT and thermal hypersensitivity tests measured by von Frey filaments and a hot/cold plate analgesia meter. Pain-related behavior was also determined through analysis of ultrasonic vocalization. The results of experiments showed MWT values of the group that was treated with E. cava extracts by 300 mg/kg significantly increased; on the contrary, number of ultrasonic distress vocalization of the treated group was reduced at 6 h and 24 h after plantar incision operation (62.8%, p < 0.05. Moreover, E. cava 300 mg/kg treated group increased the paw withdrawal latency in hot-and cold-plate tests in the plantar incision rats. After 15 days of continuous treatment with E. cava extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity response by MWT compared with the control group. In conclusion, these results suggest that E. cava extracts have potential analgesic effects in the case of postoperative pain and neuropathic pain in rats.
Dentin hypersensitivity clinical study comparing LILT and LEDT keeping the same irradiation parameters
Lizarelli, R F Z; Miguel, F A C; Bagnato, V S; Freitas-Pontes, K M; Villa, G E P; Nunez, S C
Dentin hypersensitivity is a common condition associated with high dental pain. A new LED-based (light emitting diode) light source has been used as an experimental tool in some studies. Purpose: The main objective was to compare these two light sources emitting in the same spectral band (red – from 625 to 660 nm) to promote pain relief. Material and methods: A total of 6 sessions were accomplished, being three irradiation sessions and three follow-up sessions. This single-blind study compared a control group (Placebo) and two other groups with different equipments: low laser intensity treatment (LILT) and a light emitting diode system treatment (LEDT). Results: The results showed that there is no statistical difference between LILT and LEDT groups, however, both were better than control group (p ≤ 0.01) in terms of treatment efficiency; there is no difference between the second and the third sessions for both treatment, it means that the third session was not necessary; finally, the improvement at the end of the entire research (follow up care of 30 days) was very expressive in comparison to pre-treatment situation for all teeth (p ≤ 0.01). Conclusion: LILT and LEDT were equally effective to treat dentine hypersensitivity, a 3rd treatment session was not necessary/two sessions are enough
Evaluating the statistical methodology of randomized trials on dentin hypersensitivity management.
Matranga, Domenica; Matera, Federico; Pizzo, Giuseppe
The present study aimed to evaluate the characteristics and quality of statistical methodology used in clinical studies on dentin hypersensitivity management. An electronic search was performed for data published from 2009 to 2014 by using PubMed, Ovid/MEDLINE, and Cochrane Library databases. The primary search terms were used in combination. Eligibility criteria included randomized clinical trials that evaluated the efficacy of desensitizing agents in terms of reducing dentin hypersensitivity. A total of 40 studies were considered eligible for assessment of quality statistical methodology. The four main concerns identified were i) use of nonparametric tests in the presence of large samples, coupled with lack of information about normality and equality of variances of the response; ii) lack of P-value adjustment for multiple comparisons; iii) failure to account for interactions between treatment and follow-up time; and iv) no information about the number of teeth examined per patient and the consequent lack of cluster-specific approach in data analysis. Owing to these concerns, statistical methodology was judged as inappropriate in 77.1% of the 35 studies that used parametric methods. Additional studies with appropriate statistical analysis are required to obtain appropriate assessment of the efficacy of desensitizing agents.
Immediate Hypersensitivity Reactions Induced by Triamcinolone in a Patient with Atopic Dermatitis.
Son, Jee Hee; Park, Sook Young; Cho, Yong Se; Chung, Bo Young; Kim, Hye One; Park, Chun Wook
Corticosteroids are potent anti-inflammatory and anti-allergic agents used in the treatment of various inflammatory diseases, including allergic disease. They are frequently considered the therapy-of-choice for many skin diseases. However, allergic reactions caused by corticosteroids have been reported. Among these, delayed reactions to topical steroids are more common, whereas immediate reactions to systemic steroids are rare. Herein, we report the case of a 32-year-old woman with triamcinolone-induced immediate hypersensitivity reaction, in which the patient had a positive prick test result with triamcinolone. She has had atopic dermatitis (AD) for three years. She had used systemic steroid, cyclosporine, and antihistamine with topical steroids for AD. In clinic, approximately 10 minutes after intralesional injection of triamcinolone, she complained of erythematous patches with slight elevation and itching on the face, trunk, and both hands. After intravenous injection of dexamethasone, her symptoms got worse. After treatment with epinephrine, all symptoms resolved within two hours. We performed an open test and skin prick test. She had a positive result only from the prick test with triamcinolone; all other steroids showed negative results from the open tests. Dermatologists should be aware of the possibility of anaphylaxis or other allergic hypersensitivity in response to corticosteroids. © 2018 The Korean Academy of Medical Sciences.
Hyperacusis Questionnaire as a Tool for Measuring Hypersensitivity to Sound in a Tinnitus Research Population
Kathryn Fackrell
Full Text Available Hypersensitivity to external sounds is often comorbid with tinnitus and may be significant for adherence to certain types of tinnitus management. Therefore, a clear measure of sensitivity to sound is important. The aim of this study was to evaluate the validity and reliability of the Hyperacusis Questionnaire (HQ for use as a measurement tool using data from a sample of 264 adults who took part in tinnitus research. We evaluated the HQ factor structure, internal consistency, convergent and discriminant validity, and floor and ceiling effects. Internal consistency was high (Cronbach's alpha = 0.88 and moderate correlations were observed between the HQ, uncomfortable loudness levels, and other health questionnaires. Confirmatory factor analysis revealed that the original HQ three-factor solution and a one-factor solution were both a poor fit to the data. Four problematic items were removed and exploratory factor analysis identified a two-factor (attentional and social solution. The original three-factor structure of the HQ was not confirmed. All fourteen items do not accurately assess hypersensitivity to sound in a tinnitus population. We propose a 10-item (2-factor version of the HQ, which will need to be confirmed using a new tinnitus and perhaps nontinnitus population.
A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans.
Reitz, Marie-Céline; Hrncic, Dragan; Treede, Rolf-Detlef; Caspani, Ombretta
The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P pain models (P pain sensitivity, but probe size and shape should be standardized. Hypersensitivity to blunt pressure-the leading positive sensory sign after peripheral nerve injury in humans-is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species.
Hypersensitivity Reaction Associated with Abacavir Therapy in an Indian HIV Patient - A Case Report.
Janardhanan, Manju; Amberkar V, Mohan Babu; Vidyasagar, Sudha; Kumari K, Meena; Holla, Sadhana N
The most important and unique adverse effect of abacavir (ABC) is fatal hypersensitivity reaction (HSR). The objective of this report is to describe a case of ABC induced HSR that occurred in an Indian HIV patient during treatment. Although this adverse effect is not uncommon, it is perhaps underreported or has never been reported so far in an Indian case scenario. A 44-year-old known case of HIV-1 was admitted in view of his worsening condition and very low CD4 cell counts 3 cells/μL. He was on anti-retroviral therapy since three years but not regular. On the basis of treatment failure, non-compliance and progressive low CD4 counts, the anti HIV regime was switched over to abacavir 600 mg+ atazanavir/ ritonavir 300mg/100mg Two weeks after ABC therapy he presented with maculopapular rash, headache and signs of hepatic damage (serum AST, ALP and ALT increased to 3-4 fold) suggestive of hypersensitivity reaction. As we know discontinuation of the drug is the ultimate litmus test to confirm diagnosis of drug induced adverse reaction. We did confirm ABC induced HSR by de-challenge wherein, rash disappeared within 2-3 days and LFT came back to normal within 5 days. However, no rechallenge was done. HSR was more in favour of ABC because atazanavir failed to produce any similar reaction after re-challenge.
Are some people more sensitive than others to EME? how to approach the question of hypersensitivity?
McKenzie, R.J.
Full text: 'Hypersensitivity' is a term applied to those individuals who report subjective symptoms such as headache, dizziness and nausea when exposed to electromagnetic fields that are below those stipulated in the science based exposure standards that are in effect in Australia and internationally. These standards, based on scientifically established effects, are formulated quite conservatively, so that all members of the population, including the young, the elderly, and the infirm, are amply protected with large safety factors. Consequently, the reporting of any symptoms arising from such exposures is of concern to regulators and researchers, as it questions the adequacy of current safety standards. However, before raising unnecessary concern, it is important to determine if there is any body of established fact on which to warrant any further assessment of the science in this regard. This paper advocates that the only sensible approach to the hypersensitive debate is to subject it to controlled, objective, scientific examination. Accordingly, this paper will attempt to review the published literature on the topic of hypersensitive symptoms, examining some of the putative mechanisms, and weight the evidence in favour of that obtained and reported from controlled scientific studies rather than self reported case studies. In terms of controlled studies, the most recent work of Hietanen et al, Lyskov et al and Koivisto et al are good examples of controlled provocation studies. The Hietanen and Lyskov studies used self reported EMF hypersensitives, while the Koivisto study used healthy subjects. The Lyskov study looked at ELF magnetic field exposures rather than mobile phone exposures, but this does not make it irrelevant as the claimed hypersensitivity is rarely limited to radiofrequencies alone. All the studies produced very similar results in that no correlation was found between any exposure condition and the physiological endpoints measured, nor were subjects
Talent in autism: hyper-systemizing, hyper-attention to detail and sensory hypersensitivity.
Baron-Cohen, Simon; Ashwin, Emma; Ashwin, Chris; Tavassoli, Teresa; Chakrabarti, Bhismadev
We argue that hyper-systemizing predisposes individuals to show talent, and review evidence that hyper-systemizing is part of the cognitive style of people with autism spectrum conditions (ASC). We then clarify the hyper-systemizing theory, contrasting it to the weak central coherence (WCC) and executive dysfunction (ED) theories. The ED theory has difficulty explaining the existence of talent in ASC. While both hyper-systemizing and WCC theories postulate excellent attention to detail, by itself excellent attention to detail will not produce talent. By contrast, the hyper-systemizing theory argues that the excellent attention to detail is directed towards detecting 'if p, then q' rules (or [input-operation-output] reasoning). Such law-based pattern recognition systems can produce talent in systemizable domains. Finally, we argue that the excellent attention to detail in ASC is itself a consequence of sensory hypersensitivity. We review an experiment from our laboratory demonstrating sensory hypersensitivity detection thresholds in vision. We conclude that the origins of the association between autism and talent begin at the sensory level, include excellent attention to detail and end with hyper-systemizing.
Hyperacusis Questionnaire as a Tool for Measuring Hypersensitivity to Sound in a Tinnitus Research Population.
Fackrell, Kathryn; Fearnley, Constance; Hoare, Derek J; Sereda, Magdalena
Hypersensitivity to external sounds is often comorbid with tinnitus and may be significant for adherence to certain types of tinnitus management. Therefore, a clear measure of sensitivity to sound is important. The aim of this study was to evaluate the validity and reliability of the Hyperacusis Questionnaire (HQ) for use as a measurement tool using data from a sample of 264 adults who took part in tinnitus research. We evaluated the HQ factor structure, internal consistency, convergent and discriminant validity, and floor and ceiling effects. Internal consistency was high (Cronbach's alpha = 0.88) and moderate correlations were observed between the HQ, uncomfortable loudness levels, and other health questionnaires. Confirmatory factor analysis revealed that the original HQ three-factor solution and a one-factor solution were both a poor fit to the data. Four problematic items were removed and exploratory factor analysis identified a two-factor (attentional and social) solution. The original three-factor structure of the HQ was not confirmed. All fourteen items do not accurately assess hypersensitivity to sound in a tinnitus population. We propose a 10-item (2-factor) version of the HQ, which will need to be confirmed using a new tinnitus and perhaps nontinnitus population.
Hypersensitivity reactions to food colours with special reference to the natural colour annatto extract (butter colour).
Mikkelsen, H; Larsen, J C; Tarding, F
It is well known that synthetic food colours especially some azo dyes can provoke hypersensitivity reactions such as urticaria, angioneurotic oedema, and astma (Michaëlsson and Juhlin, 1973, Granholt and Thune, 1975). Natural food colours are scarcely investigated with respect to potential allergic properties. Annatto extract, a commonly used food colour in edible fats e.g. butter, has been tested in patients. Among 61 consecutive patients suffereing from chornic urticaria and/or angioneurotic oedema 56 patients were orally provoked by annatto extract during elimination diet. Challenge was performed with a dose equivalent to the amount used in 25 grammes of butter. Twentysix per cent of the patients reacted to this colour 4 hours (SD: 2,6) after intake. Similar challenges with synthetic dyes showed the following results: Tartrazine 11%, Sunset Yellow FCF 17%, Food Red 17 16%, Amaranth 9%, Ponceau 4 R 15%, Erythrosine 12% and Brillant Blue FCF 14%. The present study indicates that natural food colours may induce hypersensitivity reactions as frequent as synthetic dyes.
Brown coal derived humate inhibits contact hypersensitivity; An efficacy, toxicity and teratogenicity study in rats
Van Rensburg, C.E.J.; Snyman, J.R.; Mokoele, T.; Cromarty, A.D. [University of Pretoria, Pretoria (South Africa). Faculty of Health Science
The effects of two humate products were compared to that of prednisolone on a contact hypersensitivity rat model. Rats, sensitized with dinitrofluorobenzene (DNFB), were placed on a daily oral treatment of 61 mg/kg BW of humate derived from either leonardite or bituminous coal or on prednisolone at one mg/kg BW and challenged 6 days later with a topical application of DNFB to the right ear. The inflamed ears were measured daily. In a toxicity study rats were exposed to daily oral treatment of leonardite humate at 1,000 mg/kg BW for 1 month. A teratogenicity study was done where pregnant rats were treated with 500 mg/kg BW on days 5 to 17 of pregnancy. Only the leonardite humate compared favourably with prednisolone in suppressing contact hypersensitivity. No signs of toxicity were observed and weight gain was normal during the 6-day and 1 month treatments and during the teratogenicity study with the leonardite humate. However, the rats on the other two products experienced slower weight gain. The identification of a naturally occurring nontoxic compound with anti-inflammatory activity is exciting and merits further evaluation in the treatment of patients suffering from inflammatory conditions.
Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011.
Sicherer, Scott H; Leung, Donald Y M
This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century.
Castells Guitart, M C
The frequency of hypersensitivity reactions (HSR) to drugs has risen in the last 10 years owing to increased exposure to better and more allergenic medications including monoclonal antibodies. HSRs prevent patients from using their first-line therapy, leading to decreased quality of life and life expectancy. Although premedication with antihistamines, leukotriene blockers, and corticosteroids can protect against mild-to-moderate HSR, none of these medications has provided protection against anaphylaxis. Rapid drug desensitization is a treatment option for patients with HSR to their first-line medication that protects against anaphylaxis.Although the mechanisms of drug desensitization are not completely understood, in vitro mast cell models of IgE antigen desensitization have led to the design of safe and effective in vivo protocols aimed at protecting highly sensitized patients from hypersensitivity reactions and anaphylaxis. This review provides an insight into the mechanisms of IgE/mast cell desensitization, the principles and practice of drug desensitization, and an overview of the different desensitization protocols and their safety and efficacy profiles. Drug desensitization should only be performed by allergists, trained nurses, and experienced pharmacists, since this high-risk procedure involves reintroducing allergenic medication to highly sensitized patients, with the consequent potential for severe or fatal HSRs.
A practical and successful desensitization protocol for immediate hypersensitivity reactions to iron salts.
Demir, Semra; Olgac, Muge; Unal, Derya; Gelincik, Asli; Colakoglu, Bahauddin; Buyukozturk, Suna
Orally administered iron salts (OAS) are widely used in the management of iron deficiency anemia and hypersensitivity reactions to OAS are not common. If an offending drug is the sole option or is significantly more effective than its alternatives, it can be readministered by desensitization. The oral desensitization protocols for iron published so far concern either desensitization that was completed only over a long period or did not attain the recommended therapeutic dose. We aimed to develop a more effective protocol. We report here on 2 patients who experienced hypersensitivity reactions to OAS. After confirming the diagnosis, both patients were desensitized to oral ferrous (II) glycine sulfate complex according to a 2-day desensitization protocol. A commercial suspension of oral ferrous glycine sulfate, which contains 4 mg of elemental iron in 1 ml, was preferred. We started with a dose as low as 0.1 ml from a 1/100 dilution (0.004 mg elemental iron) of the original suspension and reached the maximum effective dose in 2 days. Both patients were successfully desensitized and they went on to complete the 6-month iron treatment without any adverse effects. Although hypersensitvity reactions to iron are not common, there is no alternative for iron administration. Therefore, desensitization has to be the choice. This easy desensitization protocol seems to be a promising option. © 2014 S. Karger AG, Basel.
A SAFE PROTOCOL FOR RAPID DESENSITIZATION IN PATIENTS WITH CYSTIC FIBROSIS AND ANTIBIOTIC HYPERSENSITIVITY
Legere, Henry J.; Palis, Ross I.; Bouza, Tito Rodriguez; Uluer, Ahmet Z.; Castells, Mariana C.
Background CF patients often demonstrate hypersensitivity to one or multiple antibiotics due to frequent and repeated exposures. Attempts at antibiotic desensitization in this population are historically complicated by higher reaction rates, failure to complete the procedure and consequent withholding of first-line therapy. This study evaluates the outcomes of a rapid desensitization protocol developed at our institution. Methods We retrospectively reviewed the medical records of 15 patients undergoing 52 rapid antibiotic desensitizations at Brigham and Women's Hospital and Children's Hospital Boston utilizing our protocol. Results Mean FEV1 % predicted was 44.1 (SD 16.5), with two patients at desensitized during bilateral lung transplantation. Adverse reactions during desensitization occurred in 13.4%, and most were mild. 100% of patients completed the protocol and ultimately tolerated subsequent full-strength antibiotic courses. Conclusions CF patients with antibiotic hypersensitivity can safely receive first-line antibiotics via our rapid desensitization protocol, including those with severe obstructive lung disease. PMID:19740711
Evaluation of dentin hypersensitivity treatment with glass ionomer cements: A randomized clinical trial
Marina de Matos MADRUGA
Full Text Available Abstract A randomized, double-blind, split-mouth clinical trial was performed compared the desensitizing efficacy of the resin-modified glass ionomer cement (GIC ClinproTM XT (3M ESPE, Minnesota, USA and the conventional GIC Vidrion R (SS White, Gloucester, UK in a 6-month follow-up. Subjects were required to have at least two teeth with dentin hypersensitivity. Teeth were divided at random into 2 groups, one group received Clinpro XT and the other conventional GIC Vidrion R. Treatments were assessed by tactile and air blast tests using Visual Analogue Scale (VAS at baseline, after 20 minutes, and at 7, 15, 21, 30, 90 and 180 days post-treatment. Twenty subjects (152 teeth were included. Both tests (tactile and air blast showed a significant reduction of dentin hypersensitivity immediately after the application of Vidrion R and Clinpro XT (20 min. VAS scores obtained along the 6-month follow-up were statistically lower when compared to initial rates (p 0.05. Both cements provided satisfactory results in long-term dental sensitivity reduction.
Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice
Patterson, Rachel; Vega, Libia; Trouba, Kevin; Bortner, Carl; Germolec, Dori
Previous studies in our laboratory indicate that arsenic alters secretion of growth promoting and inflammatory cytokines in the skin that can regulate the migration and maturation of Langerhans cells (LC) during allergic contact dermatitis. Therefore, we hypothesized that arsenic may modulate hypersensitivity responses to cutaneous sensitizing agents by altering cytokine production, LC migration, and T-cell proliferation. To investigate this hypothesis, we examined the induction and elicitation phases of dermal sensitization. Mice exposed to 50 mg/l arsenic in the drinking water for 4 weeks demonstrated a reduction in lymph node cell (LNC) proliferation and ear swelling following sensitization with 2,4-dinitrofluorobenzene (DNFB), compared to control mice. LC and T-cell populations in the draining lymph nodes of DNFB-sensitized mice were evaluated by fluorescence-activated cell sorting; activated LC were reduced in cervical lymph nodes, suggesting that LC migration may be altered following arsenic exposure. Lymphocytes from arsenic-treated animals sensitized with fluorescein isothiocyanate (FITC) exhibited reduced proliferative responses following T-cell mitogen stimulation in vitro; however, lymphocyte proliferation from nonsensitized, arsenic-treated mice was comparable to controls. Arsenic exposure also reduced the number of thioglycollate-induced peritoneal macrophages and circulating neutrophils. These studies demonstrate that repeated, prolonged exposure to nontoxic concentrations of sodium arsenite alters immune cell populations and results in functional changes in immune responses, specifically attenuation of contact hypersensitivity
The combined predictive capacity of rat models of algogen-induced and neuropathic hypersensitivity to clinically used analgesics varies with nociceptive endpoint and consideration of locomotor function
Munro, Gordon; Storm, Ann; Hansen, Merete K.
deficits developed quickly and persisted for at least 3 weeks post-injury. In contrast, evoked cold hypersensitivity, or movement-associated behavioural deficits (rotarod, beam-walking) were less manifested or dissipated rapidly post-injury. Mechanical hypersensitivity was dose-dependently reversed...
The effect of chemically induced colitis, psychological stress and their combination on visceral pain in female Wistar rats.
Deiteren, Annemie; Vermeulen, Wim; Moreels, Tom G; Pelckmans, Paul A; De Man, Joris G; De Winter, Benedicte Y
Visceral sensitivity is of pathophysiological importance in abdominal pain disorders and can be modulated by inflammation and stress. However, it is unclear whether inflammation and stress alter visceral perception independently of each other or in conjunction through neuroendocrine interactions. Therefore, we compared the short- and long-term effects of experimental colitis and water avoidance stress (WAS), alone or in combination, on visceral sensitivity in female Wistar rats. Colitis was induced by trinitrobenzene sulfonic acid (TNBS) and colonoscopically confirmed. During WAS, rats were placed on a platform surrounded by water for 1 h. Visceral sensitivity was assessed by quantifying the visceromotor responses (VMRs) to colorectal distension. Activation of the hypothalamic-pituitary-adrenal axis was determined by measuring serum corticosterone in a separate protocol. TNBS instillation resulted in overt colitis, associated with significant visceral hypersensitivity during the acute inflammatory phase (3 days post-TNBS; n = 8/group); after colitis had subsided (28 days post-TNBS), hypersensitivity was resolved (n = 4-8/group). Single WAS was associated with increased VMRs of a magnitude comparable to acute TNBS-induced hypersensitivity (n = 8/group). However, after repetitive WAS no significant hypersensitivity was present (n = 8/group). No additive effect of colitis and stress was seen on visceral pain perception (n = 6-8/group). Corticosterone levels were only increased in acute TNBS-colitis, acute WAS and their combination. To conclude, both colitis and stress successfully induced short-term visceral hypersensitivity and activated the hypothalamic-pituitary-adrenal axis, but long-term effects were absent. In addition, our current findings do not support an additive effect of colitis and stress on visceral sensitivity in female Wistar rats.
Early activation of lipoxygenase in lentil (Lens culinaris) root protoplasts by oxidative stress induces programmed cell death
Vliegenthart, J.F.G.; Maccarrone, M.; Zadelhoff, G. van; Veldink, G.A.; Finazzi Agrò, A.
Oxidative stress caused by hydrogen peroxide (H2O2) triggers the hypersensitive response of plants to pathogens. Here, short pulses of H2O2 are shown to cause death of lentil (Lens culinaris) root protoplasts. Dead cells showed DNA fragmentation and ladder formation, typical hallmarks of apoptosis
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Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans
Tamura, Akitoshi; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi
It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased
Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi
Hypersensitivity pneumonitis due to metal working fluids: Sporadic or under reported?
Gupta, Amit; Rosenman, Kenneth D
Occupational exposure to metal working fluids (MWF) is common with over 1.2 million workers in the United States involved in machine finishing, machine tooling, and other metalworking operations. MWF is a known cause of hypersensitivity pneumonitis (HP). Recent reports of outbreaks of hypersensitivity HP secondary to exposure to MWF are reported. Cases were identified through the Occupational Disease surveillance system in the State of Michigan and from referrals for evaluation to the Division of Occupational and Environmental Medicine at Michigan State University (MSU). Each patient underwent a clinical examination including an occupational history, lung function studies, radiographic imaging, and in some cases lung biopsies. Following the diagnosis of definite HP, an industrial hygiene investigation was carried out, which included a plant walk-through, and review of the "Injury and Illness" log. Air monitoring and microbial sampling results were reviewed. As part of Michigan's mandatory surveillance system for occupational illnesses, seven cases of suspected HP were identified in 2003-2004 from three facilities manufacturing automobile parts in Michigan. Each plant used semi-synthetic MWFs, and conducted a MWF management program including biocide additions. Two facilities had recently changed the MWF before the cases arose. Growth of mycobacteria was found in these two MWFs. Breathing zone samples for particulates of two employees in plant A (two cases) ranged from 0.48 to 0.56 mg/m3. In plant B (four cases), two employees' sampling results ranged from 0.10 to 0.14 mg/m3. No air sampling data were available from plant C. Hypersensitivity pneumonitis due to exposure to MWFs is under-recognized by health care providers, and current surveillance systems are inadequate to provide a true estimate of its occurrence. HP arose from environments with exposures well below the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for MWF, and
Use of an ex vivo local lymph node assay to assess contact hypersensitivity potential.
Piccotti, Joseph R; Kawabata, Thomas T
The local lymph node assay (LLNA) is used to assess the contact hypersensitivity potential of compounds. In the standard assay, mice are treated topically with test compound to the dorsum of both ears on Days 1-3. The induction of a hypersensitivity response is assessed on Day 6 by injecting [(3)H]-thymidine into a tail vein and measuring thymidine incorporation into DNA of lymph node cells draining the ears. The ex vivo LLNA is conducted similarly except lymphocyte proliferation is assessed after in vitro incubation of lymph node cells with [(3)H]-thymidine, which significantly reduces the amount of radioactive waste. The current study tested the use of this approach for hazard assessment of contact hypersensitivity and to estimate allergenic potency. Female BALB/c mice were treated on Days 1-3 with two nonsensitizers (4' -methoxyacetophenone, diethyl phthalate), three weak sensitizers (hydroxycitronellal, eugenol, citral), one weak-to-moderate sensitizer (hexylcinnamic aldehyde), two moderate sensitizers (isoeugenol, phenyl benzoate), and one strong sensitizer (dinitrochlorobenzene). On Day 6, isolated lymph node cells were incubated overnight with [(3)H]-thymidine and thymidine incorporation was measured by liquid scintillation spectrophotometry. The ex vivo LLNA accurately distinguished the contact sensitizers from the nonsensitizing chemicals, and correctly ranked the relative potency of the compounds tested. The EC3 values, i.e., the effective concentration of test substance needed to induce a stimulation index of 3, were as follows: 4' -methoxyacetophenone (> 50%), diethyl phthalate (> 50%), hydroxycitronellal (20.4%), eugenol (13.6%), citral (8.9%), isoeugenol (3.8%), hexylcinnamic aldehyde (2.7%), phenyl benzoate (2%), and dinitrochlorobenzene (0.02%). In addition, low inter-animal and inter-experiment variability was seen with 25% hexyl-cinnamic aldehyde (assay positive control). The results of the ex vivo LLNA in the current study were consistent with
Occupational Hypersensitivity Pneumonitis Reported to the Czech National Registry of Occupational Diseases in the Period 1992-2005
Fenclová, Z.; Pelclová, D.; Urban, P.; Navrátil, Tomáš; Klusá�ková, P.; Lebedová, J.
Ro�. 47, �. 4 (2009), s. 443-448 ISSN 0019-8366 Institutional research plan: CEZ:AV0Z40400503 Keywords : Hypersensitivity pneumonitis * Incidence * Branch of economic activity * Occupation Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.215, year: 2009
Tumor Necrosis Factor Alpha Signaling in Trigeminal Ganglion Contributes to Mechanical Hypersensitivity in Masseter Muscle During Temporomandibular Joint Inflammation.
Ito, Reio; Shinoda, Masamichi; Honda, Kuniya; Urata, Kentaro; Lee, Jun; Maruno, Mitsuru; Soma, Kumi; Okada, Shinji; Gionhaku, Nobuhito; Iwata, Koichi
To determine the involvement of tumor necrosis factor alpha (TNFα) signaling in the trigeminal ganglion (TG) in the mechanical hypersensitivity of the masseter muscle during temporomandibular joint (TMJ) inflammation. A total of 55 male Sprague-Dawley rats were used. Following injection of Complete Freund's Adjuvant into the TMJ, the mechanical sensitivities of the masseter muscle and the overlying facial skin were measured. Satellite glial cell (SGC) activation and TNFα expression in the TG were investigated immunohistochemically, and the effects of their inhibition on the mechanical hypersensitivity of the masseter muscle were also examined. Student t test or two-way repeated-measures analysis of variance followed by Bonferroni multiple comparisons test were used for statistical analyses. P < .05 was considered to reflect statistical significance. Mechanical allodynia in the masseter muscle was induced without any inflammatory cell infiltration in the muscle after TMJ inflammation. SGC activation and an increased number of TNFα-immunoreactive cells were induced in the TG following TMJ inflammation. Intra-TG administration of an inhibitor of SGC activity or of TNFα-neutralizing antibody depressed both the increased number of TG cells encircled by activated SGCs and the mechanical hypersensitivity of the masseter following TMJ inflammation. These findings suggest that persistent masseter hypersensitivity associated with TMJ inflammation was mediated by SGC-TG neuron interactions via TNFα signaling in the TG.
Hypersensitivity reactions to anticancer agents: Data mining of the public version of the FDA adverse event reporting system, AERS
Sakaeda Toshiyuki
Full Text Available Abstract Background Previously, adverse event reports (AERs submitted to the US Food and Drug Administration (FDA database were reviewed to confirm platinum agent-associated hypersensitivity reactions. The present study was performed to confirm whether the database could suggest the hypersensitivity reactions caused by anticancer agents, paclitaxel, docetaxel, procarbazine, asparaginase, teniposide, and etoposide. Methods After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving candidate agents were analyzed. The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 was applied to evaluate the susceptibility to hypersensitivity reactions, and standardized official pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Results Based on 1,644,220 AERs from 2004 to 2009, the signals were detected for paclitaxel-associated mild, severe, and lethal hypersensitivity reactions, and docetaxel-associated lethal reactions. However, the total number of adverse events occurring with procarbazine, asparaginase, teniposide, or etoposide was not large enough to detect signals. Conclusions The FDA's adverse event reporting system, AERS, and the data mining methods used herein are useful for confirming drug-associated adverse events, but the number of co-occurrences is an important factor in signal detection.
IN VITRO MODELS TO EVALUATE DRUG-INDUCED HYPERSENSITIVITY: POTENTIAL TEST BASED ON ACTIVATION OF DENDRITIC CELLS
Valentina Galbiati
Full Text Available Hypersensitivity drug reactions (HDRs are the adverse effect of pharmaceuticals that clinically resemble allergy. HDRs account for approximately 1/6 of drug-induced adverse effects, and include immune-mediated ('allergic' and non immune-mediated ('pseudo allergic' reactions. In recent years, the severe and unpredicted drug adverse events clearly indicate that the immune system can be a critical target of drugs. Enhanced prediction in preclinical safety evaluation is, therefore, crucial. Nowadays, there are no validated in vitro or in vivo methods to screen the sensitizing potential of drugs in the pre-clinical phase. The problem of non-predictability of immunologically-based hypersensitivity reactions is related to the lack of appropriate experimental models rather than to the lack of -understanding of the adverse phenomenon.We recently established experimental conditions and markers to correctly identify drug associated with in vivo hypersensitivity reactions using THP-1 cells and IL-8 production, CD86 and CD54 expression. The proposed in vitro method benefits from a rationalistic approach with the idea that allergenic drugs share with chemical allergens common mechanisms of cell activation. This assay can be easily incorporated into drug development for hazard identification of drugs, which may have the potential to cause in vivo hypersensitivity reactions. The purpose of this review is to assess the state of the art of in vitro models to assess the allergenic potential of drugs based on the activation of dendritic cells.
Hypersensitivity to acid is associated with impaired esophageal mucosal integrity in patients with gastroesophageal reflux disease with and without esophagitis
Weijenborg, Pim W.; Smout, André J. P. M.; Verseijden, Caroline; van Veen, Henk A.; Verheij, Joanne; de Jonge, Wouter J.; Bredenoord, Albert J.
Increased esophageal sensitivity and impaired mucosal integrity have both been described in patients with gastroesophageal reflux disease, but the relationship between hypersensitivity and mucosal integrity is unclear. The aim of the present study was to investigate acid sensitivity in patients with
Role of Histamine Release Test for the Evaluation of Patients with Immediate Hypersensitivity Reactions to Clavulanic Acid
Pineda, F.; Ariza, A.; Mayorga, C.
Immediate hypersensitivity reactions to clavulanic acid (CLV) seem to be on the increase. Diagnosis is mainly based on skin testing and the drug provocation test (DPT), procedures that are not risk free. The aim of this study was to evaluate whether the histamine release test (HRT) could help eva...
Shared peptide binding of HLA Class I and II alleles associate with cutaneous nevirapine hypersensitivity and identify novel risk alleles
Pavlos, Rebecca; McKinnon, Elizabeth J.; Ostrov, David A.
Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP), is...
Recombinant culicoides obsoletus complex allergens stimulate antigen-specific T cells on insect bite hypersensitive Shetland ponies in vitro
Meulenbroeks, C.; Meide, van der N.M.A.; Willemse, T.; Rutten, V.; Tijhaar, E.J.
Background Ponies may suffer from Insect bite hypersensitivity (IBH), an allergic IgE-mediated pruritic skin disorder, induced by allergens from biting midges of the Culicoides spp. Hypothesis/Objectives To determine whether recombinant Culicoides obsoletus allergens are able to activate T cells of
Cytoplasmic and nuclear localizations are important for the hypersensitive response conferred by maize autoactive Rp1-D21 protein
Disease resistance (R-) genes have been isolated from many plant species. Most encode nucleotide binding leucine-rich-repeat (NLR) proteins that trigger a rapid localized programmed cell death termed the hypersensitive response (HR) upon pathogen recognition. Despite their structural similarities, d...
Tunicate-Inspired Gallic Acid/Metal Ion Complex for Instant and Efficient Treatment of Dentin Hypersensitivity.
Prajatelistia, Ekavianty; Ju, Sung-Won; Sanandiya, Naresh D; Jun, Sang Ho; Ahn, Jin-Soo; Hwang, Dong Soo
Dentin hypersensitivity is sharp and unpleasant pains caused by exposed dentinal tubules when enamel outside of the tooth wears away. The occlusion of dentinal tubules via in situ remineralization of hydroxyapatite is the best method to alleviate the symptoms caused by dentin hypersensitivity. Commercially available dental desensitizers are generally effective only on a specific area and are relatively toxic, and their performance usually depends on the skill of the clinician. Here, a facile and efficient dentin hypersensitivity treatment with remarkable aesthetic improvement inspired by the tunicate-self-healing process is reported. As pyrogallol groups in tunicate proteins conjugate with metal ions to heal the torn body armor of a tunicate, the ingenious mechanism by introducing gallic acid (GA) as a cheap, abundant, and edible alternative to the pyrogallol groups of the tunicate combined with a varied daily intake of metal ion sources is mimicked. In particular, the GA/Fe(3+) complex exhibits the most promising results, to the instant ≈52% blockage in tubules within 4 min and ≈87% after 7 d of immersion in artificial saliva. Overall, the GA/metal ion complex-mediated coating is facile, instant, and effective, and is suggested as an aesthetic solution for treating dentin hypersensitivity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Variation in plant defense against invasive herbivores: evidence for a hypersensitive response in eastern hemlocks (Tsuga canadensis).
Radville, Laura; Chaves, Arielle; Preisser, Evan L
Herbivores can trigger a wide array of morphological and chemical changes in their host plants. Feeding by some insects induces a defensive hypersensitive response, a defense mechanism consisting of elevated H(2)O(2) levels and tissue death at the site of herbivore feeding. The invasive hemlock woolly adelgid Adelges tsugae ('HWA') and elongate hemlock scale Fiorinia externa ('EHS') feed on eastern hemlocks; although both are sessile sap feeders, HWA causes more damage than EHS. The rapid rate of tree death following HWA infestation has led to the suggestion that feeding induces a hypersensitive response in hemlock trees. We assessed the potential for an herbivore-induced hypersensitive response in eastern hemlocks by measuring H(2)O(2) levels in foliage from HWA-infested, EHS-infested, and uninfested trees. Needles with settled HWA or EHS had higher H(2)O(2) levels than control needles, suggesting a localized hypersensitive plant response. Needles with no direct contact to settled HWA also had high H(2)O(2) levels, suggesting that HWA infestation may induce a systemic defense response in eastern hemlocks. There was no similar systemic defensive response in the EHS treatment. Our results showed that two herbivores in the same feeding guild had dramatically different outcomes on the health of their shared host.
Characterization of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database.
Suwankesawong, Wimon; Saokaew, Surasak; Permsuwan, Unchalee; Chaiyakunapruk, Nathorn
Andrographis paniculata (andrographis) is one of the herbal products that are widely used for various indications. Hypersensitivity reactions have been reported among subjects receiving Andrographis paniculata in Thailand. Understanding of characteristics of patients, adverse events, and clinical outcomes is essential for ensuring population safety.This study aimed to describe the characteristics of hypersensitivity reactions reported in patients receiving andrographis containing products in Thailand using national pharmacovigilance database. Thai Vigibase data from February 2001 to December 2012 involving andrographis products were used. This database includes the reports submitted through the spontaneous reporting system and intensive monitoring programmes. The database contained patient characteristic, adverse events associated with andrographis products, and details on seriousness, causality, and clinical outcomes. Case reports were included for final analysis if they met the inclusion criteria; 1) reports with andrographis being the only suspected cause, 2) reports with terms consistent with the constellation of hypersensitivity reactions, and 3) reports with terms considered critical terms according to WHO criteria. Descriptive statistics were used. A total of 248 case reports of andrographis-associated adverse events were identified. Only 106 case reports specified andrographis herbal product as the only suspected drug and reported at least one term consistent with constellation of hypersensitivity reactions. Most case reports (89%) came from spontaneous reporting system with no previously documented history of drug allergy (88%). Of these, 18 case reports were classified as serious with 16 cases requiring hospitalization. For final assessment, the case reports with terms consistent with constellation of hypersensitivity reactions and critical terms were included. Thirteen case reports met such criteria including anaphylactic shock (n = 5), anaphylactic
A single-arm Phase II validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: the AVOID trial
Yoshida Y
Full Text Available Yoichiro Yoshida,1 Keiji Hirata,2 Hiroshi Matsuoka,3 Shigeyoshi Iwamoto,4 Masahito Kotaka,5 Hideto Fujita,6 Naoya Aisu,1 Seiichiro Hoshino,1 Takeo Kosaka,6 Kotaro Maeda,3 Fumiaki Kiyomi,7 Yuichi Yamashita1 1Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan; 2Department of Surgery, Fukuoka Sanno Hospital, Fukuoka, Japan; 3Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan; 4Department of Surgery, Kansai Medical University Hirakata Hospital, Osaka, Japan; 5Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan; 6Department of Surgical Oncology, Kanazawa Medical University, Uchinada, Japan; 7Academia, Industry and Government Collaborative Research Institute of Translational Medicine for Life Innovation, Fukuoka University, Fukuoka, Japan Background: Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%–20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found that the pH of a solution of dexamethasone and oxaliplatin was less than 7.4, and that hypersensitivity to oxaliplatin could have been prevented by coinfusion of dexamethasone. We aimed to evaluate the effectiveness of coinfusion of dexamethasone and oxaliplatin to prevent oxaliplatin-induced hypersensitivity reactions.Patients and methods: The AVOID trial was a prospective, multicenter, open-label, single-arm Phase II trial conducted from January to September 2013. The study included 73 patients who received capecitabine plus oxaliplatin (XELOX or XELOX plus bevacizumab therapy for colorectal cancer. In all patients, oxaliplatin was administered in combination with dexamethasone. The primary outcome measure was the presence of
Visceral hypersensitivity is provoked by 2,4,6-trinitrobenzene sulfonic acid-induced ileitis in rats
Manoj Kumar Shah
Full Text Available Background and Aims: Crohn's Disease (CD, a chronic Inflammatory Bowel Disease, can occur in any part of the gastrointestinal tract, but most frequently in the ileum. Visceral hypersensitivity contributes for development of chronic abdominal pain in this disease. Currently, the understanding of the mechanism underlying hypersensitivity of Crohn's ileitis has been hindered by a lack of specific animal model. The present study is undertaken to investigate the visceral hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS-induced ileitis rats.Methods: Male Sprague-Dawley rats were anaesthetized and laparotomized for intraileal injection of TNBS (0.6 ml, 80 mg/kg body weight in 30% ethanol, n = 48, an equal volume of 30% Ethanol (n = 24 and Saline (n = 24, respectively. Visceral hypersensitivity was assessed by visceromotor responses (VMR to 20, 40, 60, 80 and 100 mmHg colorectal distension pressure (CRD at day 1, 3, 7, 14, 21 and 28. Immediately after CRD test, the rats were euthanized for collecting the terminal ileal segment for histopathological examinations and ELISA of myleoperoxidase and cytokines (TNF-α, IL-1β, IL-6, and dorsal root ganglia (T11 for determination of calcitonin gene-related peptide by immunohistochemistry, respectively. Results: Among all groups, TNBS-treatment showed transmural inflammation initially at 3 days, reached maximum at 7 days and persisted up to 21 days. The rats with ileitis exhibited (P < 0.05 VMR to CRD at day 7 to day 21. The calcitonin gene-related peptide-immunoreactive positive cells increased (P < 0.05 in dorsal root ganglia at day 7 to 21, which was persistently consistent with visceral hypersensitivity in TNBS-treated rats.Conclusions: TNBS injection into the ileum induced transmural ileitis including granuloma and visceral hypersensitivity. As this model mimics clinical manifestations of CD, it may provide a road map to probe the pathogenesis of gut inflammation and visceral
Cellular dynamics in the draining lymph nodes during sensitization and elicitation phases of contact hypersensitivity
Larsen, Jeppe Madura; Geisler, Carsten; Nielsen, Martin Weiss
BACKGROUND: The different role of various immunological effector cells in contact hypersensitivity (CHS) is receiving increased attention. During the past decade, the involvement of different cell types in CHS has been investigated by the use of antibody-induced depletion of specific subtypes...... of immunological cells and by studying knockout mice lacking one or more of these immunological cell populations. OBJECTIVES: To develop a method for studying the collective cellular dynamics of immune cells in the draining lymph nodes during CHS in intact animals. PATIENTS/METHODS: Mice were sensitized and....../or challenged with 2,4-dinitrofluorobenzene or oxazolone. Using multi-parameter flow cytometry we determined the proliferation, activation state, and absolute number of helper T cells, cytotoxic T cells, B cells, and natural killer cells in the draining lymph nodes. RESULTS: The presented method can be applied...
Loss of inducible photorepair in a frog cell line hypersensitive to solar UV light
Chao, C.C.-K.
The induction of enzymatic photorepair (EPR) in ICR 2A frog cells and a derived mutant cell line DRP36 hypersensitive to solar UV was studied. Using clonogenic assays, when induced wild-type cells demonstrated an 8-fold increase of EPR the mutant cells displayed a near-background level of inducible EPR. The constitutive EPR in mutant cells, however, was the same as in wild-type cells. A mixed culture of ICR 2A and DRP36 cells showed an intermediate inducible EPR depending upon the cell ratio. Inducible EPR was also detected at the DNA level in wild-type cells, but not in mutant cells. 29 refs.; 2 figs.; 2 tabs
Drug allergy passport and other documentation for patients with drug hypersensitivity
Brockow, Knut; Aberer, Werner; Atanaskovic-Markovic, M
The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical...... history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed...... a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed...
Relationship between systemic inflammation and delayed-type hypersensitivity response to Candida antigen in older adults.
Brandt D Pence
Full Text Available Research has shown that aging is associated with increased systemic inflammation as well as a reduction in the strength of immune responses. However, little evidence exists linking the decrease in cell-mediated immunity in older adults with other health parameters. We sought to examine the relationship between cell-mediated immunity as measured in vivo by the delayed-type hypersensitivity (DTH response to candida antigen and demographic and physiological variables in older (65-80 y.o. adults. Candida antigen response was not related to gender or obesity, or to a number of other physiological variables including fitness and body composition. However, positive responders had significantly lower serum C-reactive protein levels (CRP, p4.75 mg•L(-1. Therefore, positive responses to candida antigen in older adults appears to be related to lower levels of systemic inflammation.
Parkinson's disease and Alzheimer's disease: hypersensitivity to X-rays in cultured cell lines
Robbins, J H; Otsuka, Fujio; Tarone, R E; Polinsky, R J; Nee, L E; Brumback, R A
Fibroblast and/or lymphoblastoid lines from patients with several inherited primary neuronal degenerations are hypersensitive to DNA-damaging agents. Therefore, lymphoblastoid lines were irradiated from patients with sporadic Parkinson's disease (PD), Alzheimer's disease, and amyotrophic lateral sclerosis. The mean survival values of the eight Parkinson's disease and of the six Alzheimer's disease lines, but not of the five amyotrophic lateral sclerosis lines, were less than that of the 28 normal lines. Our results with Parkinson's disease and Alzheimer's disease cells can be explained by a genetic defect arising as a somatic mutation during embryogenesis, causing defective repair of the X-ray type of DNA damage. Such a DNA repair defect could cause an abnormal accumulation of spontaneously occurring DNA damage in Parkinson's disease and Alzheimer's disease neurons in vivo, resulting in their premature death.
Odor and Noise Intolerance in Persons with Self-Reported Electromagnetic Hypersensitivity
Steven Nordin
Full Text Available Lack of confirmation of symptoms attributed to electromagnetic fields (EMF and triggered by EMF exposure has highlighted the role of individual factors. Prior observations indicate intolerance to other types of environmental exposures among persons with electromagnetic hypersensitivity (EHS. This study assessed differences in odor and noise intolerance between persons with EHS and healthy controls by use of subscales and global measures of the Chemical Sensitivity Scale (CSS and the Noise Sensitivity Scale (NSS. The EHS group scored significantly higher than the controls on all CSS and NSS scales. Correlation coefficients between CSS and NSS scores ranged from 0.60 to 0.65 across measures. The findings suggest an association between EHS and odor and noise intolerance, encouraging further investigation of individual factors for understanding EMF-related symptoms.
Bronchiolitis obliterans organising pneumonia associated with anticonvulsant hypersensitivity syndrome induced by lamotrigine.
Ghandourah, Hasan; Bhandal, Samarjeet; Brundler, Marie-Anne; Noseworthy, Mary
A 14-year-old girl who was known to have a seizure disorder and on lamotrigine treatment was admitted to the hospital, with a history of rash, fever and cough. Her condition deteriorated with clinical features suggestive of anticonvulsant hypersensitivity syndrome (ACHS) complicated with bronchiolitis obliterans organising pneumonia (BOOP). Her chest CT showed multifocal parenchymal opacities and lung biopsy was typical for BOOP. Initially, the lamotrigine was discontinued since the onset of the rash, then she was treated for pneumonia with antibiotics, which may have delayed the diagnosis. Eventually, BOOP was considered and she was treated with a high dose of corticosteroid. She improved clinically and her repeated chest CT showed a marked resolution of the lesions. This case illustrates the possible occurrence of BOOP as a complication of ACHS secondary to lamotrigine treatment. 2016 BMJ Publishing Group Ltd.
Fexofenadine Suppresses Delayed-Type Hypersensitivity in the Murine Model of Palladium Allergy
Ryota Matsubara
Full Text Available Palladium is frequently used in dental materials, and sometimes causes metal allergy. It has been suggested that the immune response by palladium-specific T cells may be responsible for the pathogenesis of delayed-type hypersensitivity in study of palladium allergic model mice. In the clinical setting, glucocorticoids and antihistamine drugs are commonly used for treatment of contact dermatitis. However, the precise mechanism of immune suppression in palladium allergy remains unknown. We investigated inhibition of the immune response in palladium allergic mice by administration of prednisolone as a glucocorticoid and fexofenadine hydrochloride as an antihistamine. Compared with glucocorticoids, fexofenadine hydrochloride significantly suppressed the number of T cells by interfering with the development of antigen-presenting cells from the sensitization phase. Our results suggest that antihistamine has a beneficial effect on the treatment of palladium allergy compared to glucocorticoids.
Hypersensitivity pneumonitis. A series of nine cases with surgical lung biopsy
Ricardo A Gómez Tejada
Full Text Available In a series of nine patients with histopathological diagnosis of hypersensitivity pneumonitis, we retrospectively evaluated clinical data, exposure related factors, pulmonary function tests and chest computed tomography scans. A restrictive abnormality with reduction of diffusion capacity for carbon monoxide was mainly found. Chest scans showed fibrotic patterns in most cases; ground glass attenuation areas with mosaic pattern and consolidation in the rest. Exposure to avian antigens, cereal grains and air conditioners contaminated with fungi yeasts and bacteria, were suspected from clinical data in two-thirds of the cases. Since there are no unique features that allow differentiation from other interstitial lung diseases, a high clinical suspicion is required and a careful search of environmental exposure to possible antigens is needed that, together with clinical, radiological and pathological data, may lead to diagnosis.
Robbins, J.H.; Otsuka, Fujio; Tarone, R.E.; Polinsky, R.J.; Nee, L.E.; Brumback, R.A.
Fibroblast and/or lymphoblastoid lines from patients with several inherited primary neuronal degenerations are hypersensitive to DNA-damaging agents. Therefore, lymphoblastoid lines were irradiated from patients with sporadic Parkinson's disease (PD), Alzheimer's disease, and amyotrophic lateral sclerosis. The mean survival values of the eight Parkinson's disease and of the six Alzheimer's disease lines, but not of the five amyotrophic lateral sclerosis lines, were less than that of the 28 normal lines. Our results with Parkinson's disease and Alzheimer's disease cells can be explained by a genetic defect arising as a somatic mutation during embryogenesis, causing defective repair of the X-ray type of DNA damage. Such a DNA repair defect could cause an abnormal accumulation of spontaneously occurring DNA damage in Parkinson's disease and Alzheimer's disease neurons in vivo, resulting in their premature death. (author)
Hypersensitivity to Contingent Behavior in Paranoia: A New Virtual Reality Paradigm.
Fornells-Ambrojo, Miriam; Elenbaas, Maaike; Barker, Chris; Swapp, David; Navarro, Xavier; Rovira, Aitor; Sanahuja, Josep Maria Tomà s; Slater, Mel
Contingency in interpersonal relationships is associated with the development of secure attachment and trust, whereas paranoia arises from the overattribution of negative intentions. We used a new virtual reality paradigm to experimentally investigate the impact of contingent behavior on trust along the paranoia continuum. Sixty-one healthy participants were randomly allocated to have a social interaction with a pleasant virtual human (avatar) programmed to be highly responsive or not (high/low contingency). Perceived trustworthiness and trusting behavior were assessed alongside control variables attachment and anxiety. Higher paranoia and dismissive attachment were associated with larger interpersonal distances. Unexpectedly, extremely paranoid individuals experienced the highly contingent avatar as more trustworthy than their low contingency counterpart. Higher dismissive attachment was also associated with more subjective trust in both conditions. Extreme paranoia is associated with hypersensitivity to noncontingent behavior, which might explain experiences of mistrust when others are not highly responsive in everyday social situations.
Ultraviolet-irradiated urocanic acid suppresses delayed-type hypersensitivity to herpes simplex virus in mice
Ross, J.A.; Howie, S.E.; Norval, M.; Maingay, J.; Simpson, T.J.
Ultraviolet radiation is known to induce a transient defect in epidermal antigen presentation which leads to the generation of antigen-specific suppression of the delayed-type hypersensitivity (DTH) response. The putative receptor in skin for the primary event in UV-suppression is urocanic acid (UCA) which may then interact locally, or systemically, with antigen presenting cells or initiate a cascade of events resulting in suppression. We present the first direct evidence that UCA, when irradiated with a dose (96 mJ/cm2) of UVB radiation known to suppress the DTH response to herpes simplex virus, type 1 (HSV-1) in mice, can induce suppression following epidermal application or s.c. injection of the irradiated substance. This suppression is transferable with nylon wool-passed spleen cells
Hypothesis: SLC12A3 Polymorphism modifies thiazide hypersensitivity of antenatal Bartter syndrome to thiazide resistance.
Mammen, Cherry; Rupps, Rosemarie; Trnka, Peter; Boerkoel, Cornelius F
We report a 5-year-old boy with thiazide-resistant Bartter syndrome. This is highly unusual since thiazide hypersensitivity is a common diagnostic finding in Bartter syndrome patients. Subsequent molecular testing identified compound heterozygosity for two novel mutations in KCNJ1, (c.556A > G and c.683G > A) which is associated with Bartter syndrome, and a paternally inherited polymorphism in SLC12A3 (c.791G > C). Mutations in SLC12A3 cause the thiazide-resistant tubulopathy Gitelman syndrome. Based on published studies of this polymorphism in SLC12A3 and the features of the proband's father, we postulate that this polymorphism modifies the phenotype of Bartter syndrome in the proband to thiazide resistance. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Diagnosis of hypersensitivity pneumonitis by measurement of antibodies against environmental antigens
Dewair, M.
Hypersensitivity pneumonitis (HP), an immunologically mediated chronic pulmonary disease, is the result of an inflammatory response of the lung initiated by the inhalation of environmental organic dusts. These organic dusts usually contain substances (antigens) capable of eliciting immune responses in humans. The symptoms of HP generally present as recurrent flu-like episodes which makes it difficult to establish the proper diagnosis. However, detection in patients' sera of high-titer antibodies against the environmental antigens could be of great help in identifying those materials causing the disease and which must be avoided. A highly specific and sensitive serodiagnostic test, a radioimmuno assay (RIA), was developed for measurement of antibodies against antigens relevant to Farmer's Lung Disease (FLD), a type of HP affecting farmers
Carbamazepine-hypersensitivity: assessment of clinical and in vitro chemical cross-reactivity with phenytoin and oxcarbazepine.
Pirmohamed, M; Graham, A; Roberts, P; Smith, D; Chadwick, D; Breckenridge, A M; Park, B K
1. Seven patients clinically diagnosed as being hypersensitive to carbamazepine and one patient hypersensitive to both carbamazepine and oxcarbazepine have been identified. They have been compared with a control group (hereafter referred to as 'control subjects') comprising five patients on chronic carbamazepine therapy without adverse effects and 12 healthy volunteers who have never been exposed to anticonvulsants. 2. An in vitro cytotoxicity assay employing mononuclear leucocytes as target cells has been used first, to determine the ability of 10 different human livers to bioactivate carbamazepine to a cytotoxic metabolite, and secondly, to compare the cell defences of carbamazepine-hypersensitive patients and control subjects to oxidative drug metabolites generated by a murine microsomal system, using a blinded protocol. 3. With human liver microsomes, the metabolism-dependent cytotoxicity of carbamazepine increased with increasing microsomal protein concentration. At a protein concentration of 2 mg per incubation, the cytotoxicity of carbamazepine with human liver microsomes (n = 10 livers) increased from 7.2 +/- 0.8% (baseline) to 16.4 +/- 2.1% (with NADPH; P = 0.002). 4. In the presence of phenobarbitone-induced mouse microsomes and NADPH, the mean increase in cytotoxicity above the baseline with carbamazepine was significantly greater (P less than 0.001) for the cells from the carbamazepine-hypersensitive patients (7.9 +/- 0.8%) than from control subjects (2.6 +/- 0.3%). 5. In the presence of phenobarbitone-induced mouse microsomes and NADPH, there was no significant difference in cytotoxicity between the cells from carbamazepine hypersensitive patients and from control subjects in the presence of either phenytoin or oxcarbazepine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1768568
The diamine oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs.
José A G Agúndez
Full Text Available UNLABELLED: Non-steroidal anti-inflammatory drugs (NSAIDs are the drugs most frequently involved in hypersensitivity drug reactions. Histamine is released in the allergic response to NSAIDs and is responsible for some of the clinical symptoms. The aim of this study is to analyze clinical association of functional polymorphisms in the genes coding for enzymes involved in histamine homeostasis with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced three or more episodes with two or more different NSAIDs were included. If this requirement was not met diagnosis was established by challenge. A total of 414 healthy unrelated controls ethnically matched with patients and from the same geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met allele (rs10156191, which causes decreased metabolic capacity, is overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR  = 1.7 (95% CI  = 1.3-2.1; Pc  = 0.0003 with a gene-dose effect (P = 0.0001. The association was replicated in two populations from different geographic areas (Pc  = 0.008 and Pc  = 0.004, respectively. CONCLUSIONS AND IMPLICATIONS: The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response.
Antibiotic-induced immediate type hypersensitivity is a risk factor for positive allergy skin tests for neuromuscular blocking agents.
Hagau, Natalia; Gherman, Nadia; Cocis, Mihaela; Petrisor, Cristina
Skin tests for neuromuscular blocking agents (NMBAs) are not currently recommended for the general population undergoing general anaesthesia. In a previous study we have reported a high incidence of positive allergy tests for NMBAs in patients with a positive history of non-anaesthetic drug allergy, a larger prospective study being needed to confirm those preliminary results. The objective of this study was to compare the skin tests results for patients with a positive history of antibiotic-induced immediate type hypersensitivity reactions to those of controls without drug allergies. Ninety eight patients with previous antibiotic hypersensitivity and 72 controls were prospectively included. Skin tests were performed for atracurium, pancuronium, rocuronium, and suxamethonium. We found 65 positive skin tests from the 392 tests performed in patients with a positive history of antibiotic hypersensitivity (1 6.58%) and 23 positive skin tests from the 288 performed in controls (7.98%), the two incidences showing significant statistical difference (p = 0.0011). The relative risk for having a positive skin test for NMBAs for patients versus controls was 1.77 (1.15-2.76). For atracurium, skin tests were more often positive in patients with a positive history of antibiotic hypersensitivity versus controls (p = 0.02). For pancuronium, rocuronium and suxamethonium the statistical difference was not attained (p-values 0.08 for pancuronium, 0.23 for rocuronium, and 0.26 for suxamethonium). Patients with a positive history of antibiotic hypersensitivity seem to have a higher incidence of positive skin tests for NMBAs. They might represent a group at higher risk for developing intraoperative anaphylaxis compared to the general population. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
Dental Erosion and Dentin Hypersensitivity among Adult Asthmatics and Non-asthmatics Hospital-based: A Preliminary Study.
Farag, Zahra Hassan Abdelaziz; Awooda, Elhadi Mohieldin
Asthma is a chronic inflammatory condition affecting the airways leading to spasm and swelling of the airways. The medications taken for the treatment of asthma can result in dental erosion and dentin hypersensitivity. The aims of this study were to investigate the severity of dental erosion amongst adult asthmatics according to: gender, type and duration of medication taken and to compare dental erosion and dentin hypersensitivity between asthmatics and non-asthmatics. Comparative, cross-sectional hospital based study among 40 asthmatics (M=15 & F=25) and 40 non-asthmatics (M=18 & F=22) in the age range of 18-60 year selected purposefully from Al-Shaab Teaching Hospital in Khartoum city. The Basic Erosive Wear Index was used for dental erosion assessment. Dentine hypersensitivity was determined by giving ice cold water and rated using the Visual Analogue Scale. Chi-square and Student's t-test were used for statistical analysis with P value ≤.05. There was an association between severity of dental erosion and presence of asthma (P=0.03), where asthmatics had a higher degree of erosion (moderate and severe) and non-asthmatics a lower degree. No significant association was found between dental erosion and gender, type and duration of medication among asthmatics group. A statistically significant difference was revealed in the degree of dentin hypersensitivity (P=0.00) among asthmatics (35.13%) and non-asthmatics (14.13%). Asthmatic patients had a higher degree of dental erosion and dentin hypersensitivity compared to non-asthmatics. Among asthmatic patients there was no association between severity of dental erosion and gender, type and duration medication was taken for.
Specific alteration of rhythm in temperature-stressed rats possess features of abdominal pain in IBS patients
Yasuo Itomi
Full Text Available It is known that specific alteration of rhythm in temperature (SART stress produces somatic pain. However, it remains to be investigated whether SART stress induces visceral pain. In this study, we investigated the visceral hypersensitivity in the SART stress model by pharmacological tools and heterotopical nociception. Four-week-old Sprague–Dawley rats were exposed to repeated cold stress. Visceral pain was measured by visceromotor response to colorectal distension, and the effects of alosetron and duloxetine on visceral pain were investigated in SART rats. Heterotopical nociception was given by capsaicin injection into the left forepaw to induce diffuse noxious inhibitory controls (DNIC. SART stress induced visceral hypersensitivity that was sustained at minimum for one week. In pharmacological analysis, alosetron and duloxetine improved SART stress-induced visceral hypersensitivity. Heterotopical nociception induced DNIC in normal conditions, but was disrupted in SART rats. On the other hand, RMCP-II mRNA in distal colon was not affected by SART stress. In conclusion, SART rats exhibit several features of visceral pain in IBS, and may be a useful model for investigating the central modification of pain control in IBS.
The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury
Vega-Avelaira David
Full Text Available Abstract Background Peripheral nerve injuries can trigger neuropathic pain in adults but cause little or no pain when they are sustained in infancy or early childhood. This is confirmed in rodent models where neonatal nerve injury causes no pain behaviour. However, delayed pain can arise in man some considerable time after nerve damage and to examine this following early life nerve injury we have carried out a longer term follow up of rat pain behaviour into adolescence and adulthood. Results Spared nerve injury (SNI or sham surgery was performed on 10 day old (P10 rat pups and mechanical nociceptive reflex thresholds were analysed 3, 7, 14, 21, 28, 38 and 44 days post surgery. While mechanical thresholds on the ipsilateral side are not significantly different from controls for the first 2–3 weeks post P10 surgery, after that time period, beginning at 21 days post surgery (P31, the SNI group developed following early life nerve injury significant hypersensitivity compared to the other groups. Ipsilateral mechanical nociceptive threshold was 2-fold below that of the contralateral and sham thresholds at 21 days post surgery (SNI-ipsilateral 28 (±5 g control groups 69 (±9 g, p Conclusions We report a novel consequence of early life nerve injury whereby mechanical hypersensitivity only emerges later in life. This delayed adolescent onset in mechanical pain thresholds is accompanied by neuroimmune activation and NMDA dependent central sensitization of spinal nociceptive circuits. This delayed onset in mechanical pain sensitivity may provide clues to understand the long term effects of early injury such as late onset phantom pain and the emergence of complex adolescent chronic pain syndromes.
Hypersensitivity reactions to the Sabin vaccine in children with cow's milk allergy.
Parisi, C A S; Smaldini, P L; Gervasoni, M E; Maspero, J F; Docena, G H
The Sabin vaccine is used world-wide, and most children with food allergies receive it without incident. However, in the 2009 vaccination campaign conducted in Argentina, four children experienced immediate-type hypersensitivity reactions following vaccination. We aimed to review the medical history of the affected children, study their allergic condition after the episodes and analyse the presence of allergenic vaccine components. Patients were selected based on their immediate allergic reactions following vaccination. They were assessed for allergies to cow's milk and hen's egg. The presence of cow's milk proteins in the vaccine was tested by various immunoassays involving cow's milk- or α-lactalbumin-specific polyclonal rabbit antiserum and patient sera. All of the patients had a history of milk allergy, and no history or current evidence of egg hypersensitivity was found. Levels of cow's milk- and Sabin vaccine-specific IgE were increased, and the result of a skin prick test with cow's milk proteins or the Sabin vaccine was positive in each patient. In addition, an ELISA using specific rabbit antiserum detected α-lactalbumin in the Sabin vaccine. When α-lactalbumin was employed as a soluble inhibitor in a competitive ELISA, binding to vaccine-coated plates by cow's milk- or α-lactalbumin-specific rabbit antiserum or by patient serum containing IgE was inhibited. We have demonstrated that these patients were allergic to cow's milk, and had circulating and mast cell-bound IgE antibodies specific to cow's milk proteins. We found that the Sabin vaccine contained α-lactalbumin, which may have been responsible for the reactions elicited following vaccination with the Sabin and dual viral vaccines in combination. © 2012 Blackwell Publishing Ltd.
Energy and environmental intolerance: electromagnetic hypersensitivity, wind turbine syndrome. What is the reality?
Bonnet-Belfais, Monique; Lambrozo, Jacques; Souques, Martine; Piotrowski, Aleksandra; Tossa, Paul
The current debate about means of power generation, in the framework of the energy transition, must necessarily consider questions about different forms of idiopathic environmental intolerance, notably hypersensitivity attributed to electromagnetic fields and the wind turbine syndrome, which incriminates the low frequency- and infra-sound waves emitted by industrial wind turbines. This article attempts to take stock of current knowledge about each of these conditions, highlighting their differences and similarities. Although the offending sources are different, the symptoms, variable and not specific to any particular disease, are very similar. Nor has any consensual clinical definition of these conditions or their diagnostic criteria been established. Despite the lack of objective diagnostic criteria, many studies have investigated the existence of a potential causal link between the symptoms and the environmental factors implicated, attempting to highlight a possible plausible underlying mechanism, either biological or psychological. Although there is no doubt about the reality or the potential severity of the symptoms of electromagnetic hypersensitivity, no causal link with electromagnetic fields has been demonstrated to date, and no biological mechanism appears plausible. For the wind turbine syndrome, no direct health effect on the ear or other organs due to the noise emission of wind turbines, including low frequency and infra-sound waves, has been demonstrated. The frequently mentioned discomfort has most often been linked to a negative perception of wind turbines. Psychological mechanisms have been explored for both syndromes, including a potential nocebo effect. Studies are also beginning to investigate the weight of the collective and sociological aspects that might favor the emergence of these forms of intolerance. Finally, in terms of medical care, the article considers the relation of these emerging environmental sensitivities to functional disorders
Expression of Mycobacterium smegmatis pyrazinamidase in Mycobacterium tuberculosis confers hypersensitivity to pyrazinamide and related amides.
Boshoff, H I; Mizrahi, V
A pyrazinamidase (PZase)-deficient pncA mutant of Mycobacterium tuberculosis, constructed by allelic exchange, was used to investigate the effects of heterologous amidase gene expression on the susceptibility of this organism to pyrazinamide (PZA) and related amides. The mutant was highly resistant to PZA (MIC, >2,000 microg/ml), in accordance with the well-established role of pncA in the PZA susceptibility of M. tuberculosis (A. Scorpio and Y. Zhang, Nat. Med. 2:662-667, 1996). Integration of the pzaA gene encoding the major PZase/nicotinamidase from Mycobacterium smegmatis (H. I. M. Boshoff and V. Mizrahi, J. Bacteriol. 180:5809-5814, 1998) or the M. tuberculosis pncA gene into the pncA mutant complemented its PZase/nicotinamidase defect. In both pzaA- and pncA-complemented mutant strains, the PZase activity was detected exclusively in the cytoplasm, suggesting an intracellular localization for PzaA and PncA. The pzaA-complemented strain was hypersensitive to PZA (MIC, /=20 microg/ml) and was also sensitive to benzamide (MIC, 20 microg/ml), unlike the wild-type and pncA-complemented mutant strains, which were highly resistant to this amide (MIC, >500 microg/ml). This finding was consistent with the observation that benzamide is hydrolyzed by PzaA but not by PncA. Overexpression of PzaA also conferred sensitivity to PZA, nicotinamide, and benzamide on M. smegmatis (MIC, 150 microg/ml in all cases) and rendered Escherichia coli hypersensitive for growth at low pH.
The Effect of Calcium Sodium Phosphosilicate on Dentin Hypersensitivity: A Systematic Review and Meta-Analysis.
Mengjiao Zhu
Full Text Available To investigate the effect of calcium sodium phosphosilicate (CSPS in treating dentin hypersensitivity (DH and to compare this effect to that of a negative (placebo control.Several databases, including Medline, EMBASE, Web of Science, The Cochrane Library, and the Chinese Biomedical Literature Database, were searched to identify relevant articles published through January 2015; grey literature (i.e., academic literature that is not formally published was also searched. Two authors performed data extraction independently and jointly using data collection forms. The primary outcome was the DH pain response to routine activities or to thermal, tactile, evaporative, or electrical stimuli, and the secondary outcome was the side effects of CSPS use. Each study was evaluated using the Cochrane Collaboration tool for assessing risk bias. Meta-analysis of studies with the same participant demographics, interventions, controls, assessment methods and follow-up periods was performed. The Grading of Recommendations Assessment Development and Evaluation System was used to assess the quality of the evidence and the risk of bias across studies.Meta-analysis demonstrated that toothpaste containing 5% CSPS was more effective than the negative control at relieving dentin sensitivity, with the level of evidence classified as "moderate". In addition, prophylaxis paste containing 15% calcium sodium phosphosilicate was favored over the negative control at reducing post-periodontal therapy hypersensitivity, with the level of evidence categorized as "low". Only two studies reported side effects of CSPS use.The majority of studies found that calcium sodium phosphosilicate was more effective than the negative control at alleviating DH. Because strong evidence is scarce, high-quality, well-designed clinical trials are required in the future before definitive recommendations can be made.
Cloning of genes required for hypersensitivity and pathogenicity in Pseudomonas syringae pv. aptata.
Minardi, P
A genomic library of Pseudomonas syringae pv. aptata strain NCPPB 2664, which causes bacterial blight of sugar beet, lettuce and other plants, was constructed in the cosmid vector pCPP31. The 13.4 kb EcoRI fragment of the cosmid pHIR11, containing the hrp (hypersensitive response and pathogenicity) gene cluster of the closely related bacterium Pseudomonas syringae pv. syringae strain 61, was used as a probe to identify a homologous hrp gene cluster in P. syringae pv. aptata. Thirty of 2500 cosmid clones, screened by colony hybridization, gave a strong hybridization signal with the probe, but none of these conferred to the non-pathogenic bacterium, Pseudomonas fluorescens, the ability to elicit the hypersensitive response (HR) in tobacco. Southern blot analysis of EcoRI-digested genomic DNA of P. syringae pv. aptata showed hybridizing bands of 12 kb and 4.4 kb. Only a 12 kb fragment hybridized in digests of the cosmids. Cosmid clone pCPP1069 was mutagenized with Tn10-minitet and marker-exchanged into the genome of P. syringae pv. aptata. Three resulting prototrophic mutant strains failed to elicit the HR in tobacco and to cause disease in lettuce. The DNA flanking the Tn10-minitet insertions from mutated derivatives of pCPP1069 hybridized with the 10.6 kb Bg/II fragment of pHIR11. These results indicate that P. syringae pv. aptata harbours hrp genes that are similar to, but arranged differently from, homologous hrp genes of P. syringae pv. syringae.
Cold hypersensitivity increases with age in mice with sickle cell disease
Zappia, Katherine J.; Garrison, Sheldon R.; Hillery, Cheryl A.; Stucky, Cheryl L.
Sickle cell disease (SCD) is associated with acute vaso-occlusive crises that trigger painful episodes and frequently involves ongoing, chronic pain. Additionally, both humans and mice with SCD experience heighted cold sensitivity. However, studies have not addressed the mechanism(s) underlying the cold sensitization, nor its progression with age. Here we measured thermotaxis behavior in young and aged mice with severe SCD. Sickle mice had a marked increase in cold sensitivity measured by a cold preference test. Further, cold hypersensitivity worsened with advanced age. We assessed whether enhanced peripheral input contributes to the chronic cold pain behavior by recording from C fibers, many of which are cold-sensitive, in skin-nerve preparations. We observed that C fibers from sickle mice displayed a shift to warmer (more sensitive) cold-detection thresholds. To address mechanisms underlying the cold sensitization in primary afferent neurons, we quantified mRNA expression levels for ion channels thought to be involved in cold detection. These included the Transient Receptor Potential Melastatin 8 (Trpm8) and TRP Ankyrin 1 (Trpa1) channels, as well as the two-pore domain potassium channels, TREK-1 (Kcnk2), TREK-2 (Kcnk4), and TRAAK (Kcnk10). Surprisingly, transcript expression levels of all of these channels were comparable between sickle and control mice. We further examined transcript expression of 83 additional pain-related genes and found increased mRNA levels for endothelin 1 and tachykinin receptor 1. These factors may contribute to hypersensitivity in sickle mice at both the afferent and behavioral levels. Sensory neurons from sickle cell disease mice are sensitized to cold, mirroring behavioral observations, and have increased expression of endothelin 1 and tachykinin receptor 1. PMID:24953902
Evaluation of the irritancy and hypersensitivity potential following topical application of didecyldimethylammonium chloride
Anderson, Stacey E.; Shane, Hillary; Long, Carrie; Lukomska, Ewa; Meade, B. Jean; Marshall, Nikki B.
Didecyldimethylammonium chloride (DDAC) is a dialkyl-quaternary ammonium compound that is used in numerous products for its bactericidal, virucidal and fungicidal properties. There have been clinical reports of immediate and delayed hypersensitivity reactions in exposed individuals; however, the sensitization potential of DDAC has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAC following dermal exposure in a murine model. DDAC induced significant irritancy (0.5 and 1%), evaluated by ear swelling in female Balb/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625–1%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.17%. Dermal exposure to DDAC did not induce increased production of IgE as evaluated by phenotypic analysis of draining lymph node B-cells (IgE+B220+) and measurement of total serum IgE levels. Additional phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4+ T-cells, CD8+ T-cells and dendritic cells in the draining lymph nodes, along with significant increases in the percentage of B-cells (0.25% and 1% DDAC) at Day 10 following 4 days of dermal exposure. There was also a significant and dose-responsive increase in the number of activated CD44 + CD4 + and CD8+ T-cells and CD86+ B-cells and dendritic cells following exposure to all concentrations of DDAC. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAC following dermal exposure and raise concerns about the use of this chemical and other quaternary ammonium compounds that may elicit similar effects. PMID:27216637
IgE-mediated hypersensitivity reactions to cannabis in laboratory personnel.
Herzinger, T; Schöpf, P; Przybilla, B; Ruëff, F
There have been sporadic reports of hypersensitivity reactions to plants of the Cannabinaceae family (hemp and hops), but it has remained unclear whether these reactions are immunologic or nonimmunologic in nature. We examined the IgE-binding and histamine-releasing properties of hashish and marijuana extracts by CAP-FEIA and a basophil histamine release test. Two workers at a forensic laboratory suffered from nasal congestion, rhinitis, sneezing and asthmatic symptoms upon occupational contact with hashish or marijuana, which they had handled frequently for 25 and 16 years, respectively. Neither patient had a history of atopic disease. Serum was analyzed for specific IgE antibodies to hashish or marijuana extract by research prototype ImmunoCAP, and histamine release from basophils upon exposure to hashish or marijuana extracts was assessed. Results were matched to those of 4 nonatopic and 10 atopic control subjects with no known history of recreational or occupational exposure to marijuana or hashish. Patient 1 had specific IgE to both hashish and marijuana (CAP class 2), and patient 2 to marijuana only (CAP class 2). Controls proved negative for specific IgE except for 2 atopic individuals with CAP class 1 to marijuana and 1 other atopic individual with CAP class 1 to hashish. Stimulation of basophils with hashish or marijuana extracts elicited histamine release from basophils of both patients and 4 atopic control subjects. Our results suggest an IgE-related pathomechanism for hypersensitivity reactions to marijuana or hashish. Copyright © 2011 S. Karger AG, Basel.
Pathogen-induced ERF68 regulates hypersensitive cell death in tomato.
Liu, An-Chi; Cheng, Chiu-Ping
Ethylene response factors (ERFs) are a large plant-specific transcription factor family and play diverse important roles in various plant functions. However, most tomato ERFs have not been characterized. In this study, we showed that the expression of an uncharacterized member of the tomato ERF-IX subgroup, ERF68, was significantly induced by treatments with different bacterial pathogens, ethylene (ET) and salicylic acid (SA), but only slightly induced by bacterial mutants defective in the type III secretion system (T3SS) or non-host pathogens. The ERF68-green fluorescent protein (ERF68-GFP) fusion protein was localized in the nucleus. Transactivation and electrophoretic mobility shift assays (EMSAs) further showed that ERF68 was a functional transcriptional activator and was bound to the GCC-box. Moreover, transient overexpression of ERF68 led to spontaneous lesions in tomato and tobacco leaves and enhanced the expression of genes involved in ET, SA, jasmonic acid (JA) and hypersensitive response (HR) pathways, whereas silencing of ERF68 increased tomato susceptibility to two incompatible Xanthomonas spp. These results reveal the involvement of ERF68 in the effector-triggered immunity (ETI) pathway. To identify ERF68 target genes, chromatin immunoprecipitation combined with high-throughput sequencing (ChIP-seq) was performed. Amongst the confirmed target genes, a few genes involved in cell death or disease defence were differentially regulated by ERF68. Our study demonstrates the function of ERF68 in the positive regulation of hypersensitive cell death and disease defence by modulation of multiple signalling pathways, and provides important new information on the complex regulatory function of ERFs. © 2016 BSPP AND JOHN WILEY & SONS LTD.
Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.
Schappacher, Katie A; Styczynski, Lauren; Baccei, Mark L
Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.
Utility of opium seed extract tests in preventing hypersensitivity reactions during surgery.
Armentia, A; Pineda, F; Palacios, R; Martín-Gil, F-J; Miguel, A S; Arenal, J J; Tejedor, J; Tef, B M
Anaphylaxis during anaesthesia is fatal in 3-9% of patients and analgesics, including opioids, and is the second most common medicament-related cause, although the prevalence is underestimated. We recently found that patients may generate IgE antibodies to opium seeds. To determine the diagnostic accuracy of specific antibodies to morphine, codeine, rocuronium and oil body and aqueous fractions of Papaver somniferum seeds in the diagnosis and prevention of allergy to opioids. Patients with hypersensitivity reactions during surgery, and severe clinical allergy (pollen, tobacco), and illicit heroin users were selected. The sensitivity, specificity and predictive values of in vivo and in vitro diagnostic techniques including oil body and aqueous fractions of P. somniferum seeds were measured. We studied 203 patients, with mean age 35.1±17.1 and 200 healthy controls. Patients sensitised to heroin or with hypersensitivity reactions during surgery responded to P. somniferum seed tests. Of patients not known to be sensitised to opioids, the highest positivity was in patients sensitised to tobacco (pOpium seed skin tests and IgE, especially the oil body fraction, were more sensitive (64.2%) and specific (98.4%) than morphine, codeine and rocuronium tests for opioid sensitivity. Pollen allergy was not a risk factor for sensitisation to morphine. Sensitivity to opioids and intraoperative anaphylaxis can be diagnosed by routine tests. IgE and skin tests for the oil body fraction of P. somniferum had the highest sensitivity for sensitisation to opioids. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.
Decision-making and addiction (part II): myopia for the future or hypersensitivity to reward?
Bechara, Antoine; Dolan, Sara; Hindes, Andrea
On a decision-making instrument known as the "gambling task" (GT), a subgroup of substance dependent individuals (SDI) opted for choices that yield high immediate gains in spite of higher future losses. This resembles the behavior of patients with ventromedial (VM) prefrontal cortex lesions. In this study, we addressed the possibility that hypersensitivity to reward may account for the "myopia" for the future in this subgroup of SDI. We used a variant version of the GT, in which the good decks yielded high immediate punishment but higher delayed reward. The bad decks yielded low immediate punishment and lower delayed reward. We measured the skin conductance response (SCR) of subjects after receiving reward (reward SCR) and during their pondering from which deck to choose (anticipatory SCR). A subgroup of SDI who was not impaired on the original GT performed normally on the variant GT. The subgroup of SDI who was impaired on the original GT showed two levels of performance on the variant GT. One subgroup (36% of the sample) performed poorly on the variant GT, and showed similar behavioral and physiological impairments to VM patients. The other subgroup of SDI (64% of the sample) performed normally on the variant task, but had abnormally large physiological responses to reward, i.e. large SCR after receiving reward (reward SCR) and large SCR in anticipation of outcomes that yield large reward. Thus, the combined cognitive and physiological approach of assessing decision-making characterizes three sub-populations of SDI. One sub-population is without impairments that can be detected by any measure of the GT paradigm. Another sub-population is similar to VM patients in that they are insensitive to the future, both positive and negative. A third sub-population is hypersensitive to reward, so that the presence or the prospect of receiving, reward dominates their behavior.
A preconditioning nerve lesion inhibits mechanical pain hypersensitivity following subsequent neuropathic injury
Wu Ann
Full Text Available Abstract Background A preconditioning stimulus can trigger a neuroprotective phenotype in the nervous system - a preconditioning nerve lesion causes a significant increase in axonal regeneration, and cerebral preconditioning protects against subsequent ischemia. We hypothesized that a preconditioning nerve lesion induces gene/protein modifications, neuronal changes, and immune activation that may affect pain sensation following subsequent nerve injury. We examined whether a preconditioning lesion affects neuropathic pain and neuroinflammation after peripheral nerve injury. Results We found that a preconditioning crush injury to a terminal branch of the sciatic nerve seven days before partial ligation of the sciatic nerve (PSNL; a model of neuropathic pain induced a significant attenuation of pain hypersensitivity, particularly mechanical allodynia. A preconditioning lesion of the tibial nerve induced a long-term significant increase in paw-withdrawal threshold to mechanical stimuli and paw-withdrawal latency to thermal stimuli, after PSNL. A preconditioning lesion of the common peroneal induced a smaller but significant short-term increase in paw-withdrawal threshold to mechanical stimuli, after PSNL. There was no difference between preconditioned and unconditioned animals in neuronal damage and macrophage and T-cell infiltration into the dorsal root ganglia (DRGs or in astrocyte and microglia activation in the spinal dorsal and ventral horns. Conclusions These results suggest that prior exposure to a mild nerve lesion protects against adverse effects of subsequent neuropathic injury, and that this conditioning-induced inhibition of pain hypersensitivity is not dependent on neuroinflammation in DRGs and spinal cord. Identifying the underlying mechanisms may have important implications for the understanding of neuropathic pain due to nerve injury.
The Dapsone Hypersensitivity Syndrome revisited: a potentially fatal multisystem disorder with prominent hepatopulmonary manifestations
Chi David S
Full Text Available Abstract 4,4'-Diaminodiphenylsulphone (Dapsone is widely used for a variety of infectious, immune and hypersensitivity disorders, with indications ranging from Hansen's disease, inflammatory disease and insect bites, all of which may be seen as manifestations in certain occupational diseases. However, the use of dapsone may be associated with a plethora of adverse effects, some of which may involve the pulmonary parenchyma. Methemoglobinemia with resultant cyanosis, bone marrow aplasia and/or hemolytic anemia, peripheral neuropathy and the potentially fatal dapsone hypersensitivity syndrome (DHS, the focus of this review, may all occur individually or in combination. DHS typically presents with a triad of fever, skin eruption, and internal organ (lung, liver, neurological and other systems involvement, occurring several weeks to as late as 6 months after the initial administration of the drug. In this sense, it may resemble a DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms. DHS must be promptly identified, as untreated, the disorder could be fatal. Moreover, the pulmonary/systemic manifestations may be mistaken for other disorders. Eosinophilic infiltrates, pneumonitis, pleural effusions and interstitial lung disease may be seen. This syndrome is best approached with the immediate discontinuation of the offending drug and prompt administration of oral or intravenous glucocorticoids. An immunological-inflammatory basis of the syndrome can be envisaged, based on the pathological picture and excellent response to antiinflammatory therapy. Since dapsone is used for various indications, physicians from all specialties may encounter DHS and need to familiarize themselves with the salient features about the syndrome and its management.
Interleukin-17A and Neutrophils in a Murine Model of Bird-Related Hypersensitivity Pneumonitis.
Masahiro Ishizuka
Full Text Available Hypersensitivity pneumonitis (HP is an immune mediated lung disease induced by the repeated inhalation of a wide variety of antigens. Bird-related hypersensitivity pneumonitis (BRHP is one of the most common forms of HP in human and results from the inhalation of avian antigens. The findings of a recent clinical analysis suggest that in addition to Th1 factors, the levels of interleukin(IL-17 and IL-17-associated transcripts are increased in the setting of HP, and that both IL-17A and neutrophils are crucial for the development of pulmonary inflammation in murine models of HP. Our objectives were to investigate the roles of IL-17A and neutrophils in granuloma-forming inflammation in an acute HP model. We developed a mouse model of acute BRHP using pigeon dropping extract. We evaluated the process of granuloma formation and the roles of both IL-17A and neutrophils in a model. We found that the neutralization of IL-17A by the antibody attenuated granuloma formation and the recruitment of neutrophils, and also decreased the expression level of chemokine(C-X-C motif ligand 5 (CXCL5 in the acute HP model. We confirmed that most of the neutrophils in the acute HP model exhibited immunoreactivity to the anti-IL-17 antibody. We have identified the central roles of both IL-17A and neutrophils in the pathogenesis of granuloma formation in acute HP. We have also assumed that neutrophils are an important source of IL-17A in an acute HP model, and that the IL-17A-CXCL5 pathway may be responsible for the recruitment of neutrophils.
This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insects, as well as advances in allergic skin disease that were reported in the Journal in 2009. Among key epidemiologic observations, several westernized countries report that more than 1% of children have peanut allergy, and there is some evidence that environmental exposure to peanut is a risk factor. The role of regulatory T cells, complement, platelet-activating factor, and effector cells in the development and expression of food allergy were explored in several murine models and human studies. Delayed anaphylaxis to mammalian meats appears to be related to IgE binding to the carbohydrate moiety galactose-alpha-1,3-galactose, which also has implications for hypersensitivity to murine mAb therapeutics containing this oligosaccharide. Oral immunotherapy studies continue to show promise for the treatment of food allergy, but determining whether the treatment causes tolerance (cure) or temporary desensitization remains to be explored. Increased baseline serum tryptase levels might inform the risk of venom anaphylaxis and might indicate a risk for mast cell disorders in persons who have experienced such episodes. Reduced structural and immune barrier function contribute to local and systemic allergen sensitization in patients with atopic dermatitis, as well as increased propensity of skin infections in these patients. The use of increased doses of nonsedating antihistamines and potential usefulness of omalizumab for chronic urticaria was highlighted. These exciting advances reported in the Journal can improve patient care today and provide insights on how we can improve the diagnosis and treatment of these allergic diseases in the future. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Platinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study.
Altwerger, Gary; Gressel, Gregory M; English, Diana P; Nelson, Wendelin K; Carusillo, Nina; Silasi, Dan-Arin; Azodi, Masoud; Santin, Alessandro; Schwartz, Peter E; Ratner, Elena S
The carboplatin desensitization (CD) protocol presented here allows patients with either a positive skin test or a prior hypersensitivity reaction (HSR) to safely, rapidly and effectively continue with carboplatin infusions. Newly described factors can identify patients at risk for developing adverse events during CD. A retrospective review was performed on patients with gynecologic cancer who underwent CD between 2005 and 2014. The CD protocol uses a four-step dilution process over 3.5h. 129 patients underwent CD and completed a total of 788cycles. The desensitization protocol prevented HSRs in 96% (753 out of 788) of these cycles. Patients achieved an average of 6.1cycles (SD±4.55, range 0-23) with CD. The CD protocol allowed 73% (94 of 129) of the patients to undergo carboplatin infusion without reaction. Patients with moderate to life-threatening HSRs (grade 2 through 4) were 10.5years younger at initial CD than patients with grades 0 or 1 HSRs (52.3 vs. 63, P = 0.0307). One patient death occurred during her thirteenth desensitization cycle. The HSR in this case was complicated by pre-exisiting pulmonary hypertension. This is the largest study of its kind showing a safe, effective and rapid (3.5h) CD protocol. The majority of patients with a history of either carboplatin hypersensitivity reaction or a positive skin test completed the CD protocol without HSRs. Age was identified as a risk factor for HSR severity during CD. Age can be employed along with pre-load dependent cardiac conditions as a way to help risk stratify patients undergoing CD. Copyright © 2016 Elsevier Inc. All rights reserved.
PENINGKATAN CD8 DAN IFN-γ PADA HYPERSENSITIVITY PNEUMONITIS (HP AKIBAT PAJANAN DEBU PENGGILINGAN PADI
Isa Ma'rufi
Full Text Available Abstrak   Masalah klinis kesehatan kerja pada pekerja penggilingan padi saat ini adalah penyakit saluran pernafasan. Penelitian ini bertujuan untuk menganalisis peningkatan CD8 dan IFN-γ pada Pneumonitis Hipersensitif (HP akibat pajanan debu penggilingan padi pada mencit (Musmusculus BALB/C. Penelitian yang dilakukan adalah penelitian eksperimental laboratoris dengan hewan coba mencit (Musmusculus BALB/C, rancangan penelitian yang digunakan adalah Randomized the post test only control group design. Mencit (Musmusculus BALB/C dipajan dengan debu penggilingan padi selama empat jam/hari selama tiga puluh hari dengan konsentrasi 0.50 mg/m3, 0.75 mg/m3, 1.00 mg/m3. Variabel bebas adalah debu penggilingan padi, sedangkan variabel tergantung adalah  CD8 dan IFN-γ, serta gambaran histopatologis paru mencit, sedangkan variabel kendali adalah strain, berat badan, dan umur. Hasil penelitian menunjukkan bahwa terjadi peningkatan kadar CD8 antara kontrol dengan perlakuan, dan secara statistik ada perbedaan yang bermakna. Kemudian terjadi peningkatan IFN-γ dan secara statistik ada perbedaan yang bermakna antara kontrol dan perlakuan pada mencit (Musmusculus BALB/C. Hasil penelitian dapat digunakan sebagai dasar upaya pencegahan dan pemberian terapi penyakit HP lebih dini sehingga dapat meningkatkan kualitas paru.  Kata Kunci: CD8, IFN-γ,  debu penggilingan padi   Abtract  The purpose of this research was to analyze increase of CD8 and IFN-γ of Hypersensitivity Pneumonitis (HP as a result from the exposure of dust from paddy milling on mice (MusmusculusBALB/C. The research done was a laboratory experimental research with mice (MusMusculus as experimental animal. The research design used was the post only control group design using mice (MusMusculus Balb/c as experimental animal. Mice (Musmusculus Balb/c were exposed to dust from paddy milling for four (4 hours/day and it was done for thirty (30 days with the exposed
Fever as the only manifestation of hypersensitivity reactions associated with oxaliplatin in a patient with colorectal cancer Oxaliplatin-induced hypersensitivity reaction
Hypersensitivity reactions (HSR) to oxaliplatin in patients with colorectal cancer include facial flushing, erythema,pruritis, fever, tachycardia, dyspnea, tongue swelling,rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. We report a patient with fever as the sole manifestation of initial HSR, review the literature and discuss the management of HSR. A 57-year-old female with T3N2M0 rectal adenocarcinoma received modified FOLFOX-6. She tolerated the first 8 cycles without any toxicities except grade 1 peripheral neuropathy and nausea. During 9th and 10th infusions,she developed fever to a maximum of 38.3℃ with stable hemodynamic status despite medications. During 11th infusion, she developed grade 3 HSR consisting of symptomatic bronchospasm, hypotension, nausea,vomiting, cough, and fever. On examination, she was pale, cyanotic, with a temperature of 38.8℃, BP dropped to 95/43 mm Hg, pulse of 116/min and O2 saturation of 88%-91%. She was hospitalized for management and recovered in 24 h. Fever alone is not a usual symptom of oxaliplatin HSR. It may be indicative that the patient may develop serious reactions subsequently, as did our patient who developed hypotension with the third challenge. Treatment and prevention consists of slowing the infusion rate, use of steroids and antagonists of Type 1 and 2 histamine receptor antagonists, whereas desensitization could help to provide the small number of patients who experience severe HSR with the ability to further receive an effective therapy for their colorectal cancer.
Outcome of pediatric patients with acute lymphoblastic leukemia/lymphoblastic lymphoma with hypersensitivity to pegaspargase treated with PEGylated Erwinia asparaginase, pegcrisantaspase: A report from the Children's Oncology Group
Rau, Rachel E.; Dreyer, ZoAnn; Choi, Mi Rim; Liang, Wei; Skowronski, Roman; Allamneni, Krishna P.; Devidas, Meenakshi; Raetz, Elizabeth A.; Adamson, Peter C.; Blaney, Susan M.; Loh, Mignon L; Hunger, Stephen P.
Background Erwinia asparaginase is a Food and Drug Administration approved agent for the treatment of acute lymphoblastic leukemia (ALL) for patients who develop hypersensitivity to Escherichia coli derived asparaginases. Erwinia asparaginase is efficacious, but has a short half-life, requiring six doses to replace one dose of the most commonly used first-line asparaginase, pegaspargase, a polyethylene glycol (PEG) conjugated E. coli asparaginase. Pegcristantaspase, a recombinant PEGylated Erwinia asparaginase with improved pharmacokinetics, was developed for patients with hypersensitivity to pegaspargase. Here, we report a series of patients treated on a pediatric phase 2 trial of pegcrisantaspase. Procedure Pediatric patients with ALL or lymphoblastic lymphoma and hypersensitivity to pegaspargase enrolled on Children's Oncology Group trial AALL1421 (Jazz 13-011) and received intravenous pegcrisantaspase. Serum asparaginase activity (SAA) was monitored before and after dosing; immunogenicity assays were performed for antiasparaginase and anti-PEG antibodies and complement activation was evaluated. Results Three of the four treated patients experienced hypersensitivity to pegcrisantaspase manifested as clinical hypersensitivity reactions or rapid clearance of SAA. Immunogenicity assays demonstrated the presence of anti-PEG immunoglobulin G antibodies in all three hypersensitive patients, indicating a PEG-mediated immune response. Conclusions This small series of patients, nonetheless, provides data, suggesting preexisting immunogenicity against the PEG moiety of pegaspargase and poses the question as to whether PEGylation may be an effective strategy to optimize Erwinia asparaginase administration. Further study of larger cohorts is needed to determine the incidence of preexisting antibodies against PEG-mediated hypersensitivity to pegaspargase. PMID:29090524
Liu, Da-Lu; Lu, Na; Han, Wen-Juan; Chen, Rong-Gui; Cong, Rui; Xie, Rou-Gang; Zhang, Yu-Fei; Kong, Wei-Wei; Hu, San-Jue; Luo, Ceng
Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron's ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensitivity. Amongst nociceptive DRG neurons, a mechanically sensitive neuron, isolectin B4 negative Aδ-type (IB4− Aδ) DRG neuron displays spontaneous activity with hyperexcitability after chronic compression of cervical DRGs. Focal mechanical stimulation on somata of IB4- Aδ neuron induces abnormal hypersensitivity. Upregulated HCN1 and HCN3 channels and increased Ih current on this subset of primary nociceptors underlies the spontaneous activity together with neuronal mechanical hypersensitivity, which further contributes to the behavioral mechanical hypersensitivity associated with CRP. This study sheds new light on the functional plasticity of a specific subset of nociceptive DRG neurons to mechanical stimulation and reveals a novel mechanism that could underlie the mechanical hypersensitivity associated with cervical radiculopathy. PMID:26577374
Healthy Lifestyle Stress management By Mayo Clinic Staff Stress basics Stress is a normal psychological and physical reaction to the demands of life. ... some people's alarm systems rarely shut off. Stress management gives you a range of tools to reset ...
... Manage Stress Print This Topic En español Manage Stress Browse Sections The Basics Overview Signs and Health ... and Health Effects What are the signs of stress? When people are under stress, they may feel: ...
Stress incontinence Overview Urinary incontinence is the unintentional loss of urine. Stress incontinence happens when physical movement or activity — such ... coughing, sneezing, running or heavy lifting — puts pressure (stress) on your bladder. Stress incontinence is not related ...
Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization.
Sutton, Blair C; Opp, Mark R
Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased
Effect of the 5-HT{sub 4} receptor and serotonin transporter on visceral hypersensitivity in rats
Chi, Yan; Liu, Xin-Guang; Wang, Hua-Hong; Li, Jun-Xia; Li, Yi-Xuan [Department of Gastroenterology, Peking University First Hospital, Beijing (China)
Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT{sub 4} receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT{sub 4} receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT{sub 4} receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg{sup −1}·day{sup −1}, days 36-42), tegaserod (1 mg·kg{sup −1}·day{sup −1}, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT{sub 4} receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT{sub 4} receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT
Reversal of visceral hypersensitivity in rat by Menthacarin , a proprietary combination of essential oils from peppermint and caraway, coincides with mycobiome modulation
Botschuijver, S.; Welting, O.; Levin, E.; Maria-Ferreira, D.; Koch, E.; Montijn, R. C.; Seppen, J.; Hakvoort, T. B. M.; Schuren, F. H. J.; de Jonge, W. J.; van den Wijngaard, R. M.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder associated with altered gastrointestinal microflora and increased nociception to colonic distension. This visceral hypersensitivity can be reversed in our rat maternal separation model by fungicides. Menthacarin is a proprietary
[Assessment of hypersensitivity to honey-bee venom in beekeepers by skin tests].
Becerril-�ngeles, Martín; Núñez-Velázquez, Marco; Marín-Martínez, Javier
Beekeepers are exposed to frequent honey-bee stings, and have the risk to develop hypersensitivity to bee venom, but long-term exposure can induce immune tolerance in them. Up to 30% of beekeepers show positive skin tests with honey-bee venom. The prevalence of systemic reactions to bee stings in beekeepers is from 14% to 42%. To know the prevalence of hypersensitivity to honeybee venom in Mexican beekeepers and non-beekeepers by the use of skin tests. A group of 139 beekeepers and a group of 60 non-beekeeper volunteers had a history and physical related to age, sex, family and personal atopic history and time of exposure to bee stings. Both groups received intradermal skin tests with honey-bee venom, 0.1 mcg/mL and 1 mcg/mL, and histamine sulphate 0.1 mg/mL and Evans solution as controls. The skin tests results of both groups were compared by chi-squared test. Of the group of beekeepers, 116 were men (83%) and 23 women, average age was 39.3 years, had atopic family history 28% and personal atopy 13%, average time of exposure to bee stings was 10.9 years, skin tests with honey-bee venom were positive in 16.5% and 11% at 1 mcg/mL and 0.1 mcg/mL, respectively. In the non-beekeepers group venom skin tests were positive in 13.3% and 6.7% at 1 mcg/mL and 0.1 mcg/mL. We did not find significant differences between the two venom concentrations tested in both groups, neither in the number of positive skin tests between the two groups. We found hypersensivity to honey-bee venom slightly higher in the beekeepers than in the group apparently not exposed. Both honey-bee venom concentrations used did not show difference in the results of the skin tests. The similarity of skin tests positivity between both groups could be explained by immune tolerance due to continued exposure of beekeepers.
Effects of long-term vasodilator therapy in patients with carotid sinus hypersensitivity.
Brignole, M; Menozzi, C; Gaggioli, G; Musso, G; Foglia-Manzillo, G; Mascioli, G; Fradella, G; Bottoni, N; Mureddu, R
In patients affected by carotid sinus hypersensitivity, long-term vasodilator therapy might increase the risk of syncopal episodes by reducing systolic blood pressure and venous return to the heart. Thirty-two patients (mean age 73 +/- 9 years; 20 men) who met all the following criteria were included: (1) one or more episodes of syncope occurring during long-term (>6 months) treatment with angiotensin-converting enzyme inhibitors, long-acting nitrates, calcium antagonists, or a combination of these; (2) a positive response to carotid sinus massage, defined as the reproduction of spontaneous syncope in the presence of ventricular asystole > or =3 seconds or a fall in systolic blood pressure > or =50 mm Hg; (3) negative workup for other causes of syncope. The patients were randomly assigned to continue or to discontinue use of vasodilators; carotid sinus massage was repeated 2 weeks after randomization. By the end of the study period, the baseline values of systolic blood pressure were significantly different between the 2 groups of patients both in supine (P=.01) and upright (P=.03) positions. Syncope had been induced by carotid sinus massage in 81% of patients in the "on-vasodilator" group and in 62% of patients in the "off-vasodilator" group (P=.21). The cardioinhibitory reflex was of similar magnitude in the 2 groups, being found in 50% of the patients in each group, with a maximum ventricular pause of 7.1 +/- 2.7 and 6.7 +/- 1.8 seconds, respectively. The percentage decrease of blood pressure did not differ between the 2 groups, even if, in absolute values, the baseline difference of blood pressure roughly persisted for the duration of the test. In consequence of that, the rise of blood pressure to similar values was delayed approximately 30 seconds in the "on-vasodilator" group and took more than 2 minutes to return to baseline values. In patients affected by carotid sinus hypersensitivity, chronic vasodilator therapy does not have a direct effect on carotid
Application of the oscillator strength of 'hypersensitive' transitions to the investigation of complex equilibria of lanthanide ions
Bukietynska, K.; Mondry, A.; Osmeda, E.
Stability constants and thermodynamic parameters of Nd 3+ , Ho 3+ and Er 3+ complexes with acetates, propionates, glycolates, lactates and α-hydroxyisobutyrates were determined by a spectroscopic method based upon the measurements of the variation of oscillator strengths of 'hypersensitive' 4f-4f-transitions. The sets of βsub (n) values at 21 0 C are in a good agreement with those found potentiometrically. The stability constants of the complexes evaluated at 5 different temperatures were used for the calculation of ΔG, ΔH, ΔS values. The evaluated thermodynamic parameters are in a satisfactory agreement with those found calorimetrically. The thermodynamic parameters calculated from two independent 'hypersensitive' transitions of the Er 3+ ion are also consistent. (author)
Hypersensitivity pneumonitis associated with mushroom worker's lung: an update on the clinical significance of the importation of exotic mushroom varieties.
Moore, John E; Convery, Rory P; Millar, B Cherie; Rao, Juluri R; Elborn, J Stuart
Hypersensitivity pneumonitis remains an important industrial disease in mushroom workers. It has a significant morbidity, and early diagnosis and removal from exposure to the antigen are critically important in its management. Recently, several new allergens have been described, particularly those from mushroom species originating in the Far East, which are of clinical significance to workers occupationally exposed to such allergens in cultivation, picking, and packing of commercial mushroom crops. Importing of exotic mushrooms including Shiitake is common in EU countries, and some of the exotic species of mushrooms are cultivated for local markets. This practice may contribute to an increase in clinical cases of mushroom hypersensitivity pneumonitis. This update reviews the recent literature and examines changing trends of mushroom worker's lung, with increased movement of commercial product and labour markets worldwide.
Comparative clinical study using laser and LED-therapy for orofacial pain relief: dentin hypersensitivity and cervicogenic headache
Lizarelli, Rosane F. Z.; Pizzo, Renata C. A.; Florez, Fernando L. E.; Grecco, Clovis; Speciali, Jose G.; Bagnato, Vanderlei S.
Considering several clinical situations, low intensity laser therapy has been widely applied in pain relief or analgesia mechanism. With the advent of new LED-based (light emitting diode) light sources, the need of further clinical experiments aiming to compare the effectiveness among them is paramount. The LED system therapeutic use can be denominated as LEDT - Light Emitting Diode Therapy. This study proposed two clinical evaluations of pain relief effect: to dentin hypersensitivity and to cervicogenic headache using different sources of lasers (low and high intensity) and light emitting diodes (LEDs), one emitting at the spectral band of red (630+/- 5nm) and the other one at infrared band (880+/- 5nm). Two different clinical studies were performed and presented interesting results. Considering dentin hypersensitivity, red and infrared led were so effective than the control group (high intensity laser system); by the other side, considering cervicogenic headache, control group (infrared laser) was the best treatment in comparison to red and infrared led system.
Aberrant neural signatures of decision-making: Pathological gamblers display cortico-striatal hypersensitivity to extreme gambles
Gelskov, Sofie V.; Madsen, Kristoffer Hougaard; Ramsøy, Thomas Z.
subjects underwent functional magnetic resonance imaging while they accepted or rejected mixed gain/loss gambles with fifty-fifty chances of winning or losing. Contrary to healthy individuals, gamblers showed a U-shaped response profile reflecting hypersensitivity to the most appetitive and most aversive...... such as the ventral striatum. However, previous studies have produced contradictory results regarding the implication of this network, revealing either hypo- or hypersensitivity to monetary gains and losses. One possible explanation is that the gambling brain might be misrepresenting the benefits and costs when...... weighting the potential outcomes, and not the gains and losses per se. To address this issue, we investigated whether pathological gambling is associated with abnormal brain activity during decisions that weight the utility of possible gains against possible losses. Pathological gamblers and healthy human...
Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization
Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.; Gebhart, G. F.
The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined chann...
Lack of evidence that the XqYq pairing tips at meiosis in the mouse show hypersensitivity to DNAse I.
Separovic, E R; Chandley, A C
In situ nick translation procedures have been applied to meiotic metaphase I divisions of the normal and XY, Sxr mouse. Unlike in man, where the pairing tips of the XY bivalent show a special sensitivity to DNAse I nicking, no such sensitivity can be detected for either of these types of mouse. Hypersensitivity in the D-band equivalent region of the X chromosome does, however, exist, this site being early replicating in somatic cells and housing the X inactivation centre (Xce).
Safety and skin delayed-type hypersensitivity response in vervet monkeys immunized with Leishmania donovani sonicate antigen delivered with adjuvants
Mutiso,Joshua M.; Macharia,John C.; Taracha,Evans; Wafula,Kellern; Rikoi,Hitler; Gicheru,Michael M.
In this study, we report on the safety and skin delayed-type hypersensitivity (DTH), responses of the Leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-BCG (AlBCG), Montanide ISA 720 (MISA) or Monophosphoryl lipid A (MPLA) in groups of vervet monkeys. Following three intradermal injections of the inoculums on days 0, 28 and 42, safety and DTH responses were assessed. Preliminary tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels ...
Validation of the cephalosporin intradermal skin test for predicting immediate hypersensitivity: a prospective study with drug challenge.
Yoon, S-Y; Park, S Y; Kim, S; Lee, T; Lee, Y S; Kwon, H-S; Cho, Y S; Moon, H-B; Kim, T-B
Cephalosporin is a major offending agent in terms of drug hypersensitivity along with penicillin. Cephalosporin intradermal skin tests (IDTs) have been widely used; however, their validity for predicting immediate hypersensitivity has not been studied. This study aimed to determine the predictive value of cephalosporin intradermal skin testing before administration of the drug. We prospectively conducted IDTs with four cephalosporins, one each of selected first-, second-, third-, or fourth-generation cephalosporins: ceftezol; cefotetan or cefamandole; ceftriaxone or cefotaxime; and flomoxef, respectively, as well as with penicillin G. After the skin test, whatever the result, one of the tested cephalosporins was administered intravenously and the patient was carefully observed. We recruited 1421 patients who required preoperative cephalosporins. Seventy-four patients (74/1421, 5.2%) were positive to at least one cephalosporin. However, none of responders had immediate hypersensitivity reactions after a challenge dose of the same or different cephalosporin, which were positive in the skin test. Four patients who suffered generalized urticaria and itching after challenge gave negative skin tests for the corresponding drug. The IDT for cephalosporin had a sensitivity of 0%, a specificity of 97.5%, a negative predictive value of 99.7%, and a positive predictive value (PPV) of 0%, when challenged with the same drugs that were positive in the skin test. Routine skin testing with a cephalosporin before its administration is not useful for predicting immediate hypersensitivity because of the extremely low sensitivity and PPV of the skin test (CRIS registration no. KCT0000455). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
The reduction efficacy of dentinal hypersensitivity by two commercially available desensitizing toothpastes: Vantej and Colgate Pro- Argin
Aditya Rao
Full Text Available Background : Dentin hypersensitivity is a commonly experienced problem that is triggered by an external stimulus, such as hot and cold temperature changes, pressure from tooth brushing and osmotic changes caused due to sweet or sour food and beverages. Various treatment modalities are tried and tested, amongst them desensitizing pastes have been used extensively in the past decades. Objective: The objective of these 15 days, single center, randomized clinical pilot study was to evaluate the dentin hypersensitivity reducing efficacy of two commercially available desensitizing toothpastes: One with Pro-Argin technology and the other with Novamin. Materials and Methods: Eighty subjects of dentin hypersensitivity were sampled in the present pilot study. Subjects were randomly selected and the pastes were prescribed for both the groups. Subjects were advised to brush twice daily for 2 min with the desensitizing paste and also were advised for topical application of the desensitizing paste on sensitive teeth and were asked not to rinse until morning. The evaluation was done by Air blast technique using sensitivity visual analog scale consisting of mild, moderate, and severe parameters rated on a scale of 0-10. Efficacy was compared on baseline, after 1 min of application and after 15 days. Statistical Analysis: t-test was performed and P value ≤ 0.05 was considered as statistically significant. Results: There was no statistically significant difference between the two groups after 1 min of examination, but there was a statistically significant difference in reduction of dentin hypersensitivity after 15 days interval favoring Vantej group (P ≤ 0.02. Conclusion: Desensitizing paste containing 5% NovaMin crystals provided a statistically significant reduction at 15 days interval when compared with the one containing Pro-Arginine.
Acupuncture Alleviates Colorectal Hypersensitivity and Correlates with the Regulatory Mechanism of TrpV1 and p-ERK
Shao-Jun Wang
Full Text Available Here we used a mouse model of zymosan-induced colorectal hypersensitivity, a similar model of IBS in our previous work, to evaluate the effectiveness of the different number of times of acupuncture and elucidate its potential mechanism of EA treatment. Colorectal distension (CRD tests show that intracolonic zymosan injection does, while saline injection does not, induce a typical colorectal hypersensitivity. EA treatment at classical acupoints Zusanli (ST36 and Shangjuxu (ST37 in both hind limbs for 15 min slightly attenuated and significantly blunted the hypersensitive responses after first and fifth acupunctures, respectively, to colorectal distention in zymosan treatment mice, but not in saline treatment mice. Western blot results indicated that ion channel and TrpV1 expression in colorectum as well as ERK1/2 MAPK pathway activation in peripheral and central nerve system might be involved in this process. Hence, we conclude that EA is a potential therapeutic tool in the treatment and alleviation of chronic abdominal pain, and the effectiveness of acupuncture analgesia is accumulative with increased number of times of acupuncture when compared to that of a single time of acupuncture.
Transfection of normal human and Chinese hamster DNA corrects diepoxybutane-induced chromosomal hypersensitivity of Fanconi anemia fibroblasts
Shaham, M.; Adler, B.; Ganguly, S.; Chaganti, R.S.K.
Cultured cells from individuals affected with Fanconi anemia (FA) exhibit spontaneous chromosome breakage and hypersensitivity to the cell killing and clastogenic effects of the difunctional alkylating agent diepoxybutane (DEB). The authors report here the correction of both of these DEB-hypersensitivity phenotypes of FA cells achieved by cotransfection of normal placental of Chinese hamster lung cell DNA and the plasmid pSV2-neo-SVgpt. Transfectants were selected for clonogenic survival after treatment with DEB at a dose of 5 μgml. At this dose of DEB, the clonogenicity of normal fibroblasts was reduced to 50% and that of FA fibroblasts was reduced to zero. DEB-resistant (DEB/sup r/) colonies selected in this system exhibited a normal response to DEB-induced chromosome breakage and resistance to repeated DEB treatment. The neo and gpt sequences were detected by Southern blot analysis of DNA from one of four DEB/sup r/ colonies independently derived from transfection of human DNA and one of three DEB/sup r/ colonies independently derived from transfection of Chinese hamster DNA. The results demonstrate that DNA sequences that complement the two hallmark cellular phenotypes (cellular and chromosomal hypersensitivity to alkylating agents) of FA are present in human as well as Chinese hamster DNA. The cloning of these genes using transfection strategies can be expected to enable molecular characterization of FA
p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC- and FANCA-deficient mononuclear phagocytes
Anur, Praveen; Yates, Jane; Garbati, Michael R.; Vanderwerf, Scott; Keeble, Winifred; Rathbun, Keaney; Hays, Laura E.; Tyner, Jeffrey W.; Svahn, Johanna; Cappelli, Enrico; Dufour, Carlo
Fanconi anemia, complementation group C (FANCC)–deficient hematopoietic stem and progenitor cells are hypersensitive to a variety of inhibitory cytokines, one of which, TNFα, can induce BM failure and clonal evolution in Fancc-deficient mice. FANCC-deficient macrophages are also hypersensitive to TLR activation and produce TNFα in an unrestrained fashion. Reasoning that suppression of inhibitory cytokine production might enhance hematopoiesis, we screened small molecules using TLR agonist–stimulated FANCC- and Fanconi anemia, complementation group A (FANCA)–deficient macrophages containing an NF-κB/AP-1–responsive reporter gene (SEAP). Of the 75 small molecules screened, the p38 MAPK inhibitor BIRB 796 and dasatinib potently suppressed TLR8-dependent expression of the reporter gene. Fanconi anemia (FA) macrophages were hypersensitive to the TLR7/8 activator R848, overproducing SEAP and TNFα in response to all doses of the agonist. Low doses (50nM) of both agents inhibited p38 MAPK–dependent activation of MAPKAPK2 (MK2) and suppressed MK2-dependent TNFα production without substantially influencing TNFα gene transcription. Overproduction of TNFα by primary FA cells was likewise suppressed by these agents and involved inhibition of MK2 activation. Because MK2 is also known to influence production and/or sensitivity to 2 other suppressive factors (MIP-1α and IFNγ) to which FA hematopoietic progenitor cells are uniquely vulnerable, targeting of p38 MAPK in FA hematopoietic cells is a rational objective for preclinical evaluation. PMID:22234699
Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose.
Sesé, L; Gaouar, H; Autegarden, J-E; Alari, A; Amsler, E; Vial-Dupuy, A; Pecquet, C; Francès, C; Soria, A
The diagnosis of HSR to iodinated contrast media (ICM) is challenging based on clinical history and skin tests. This study evaluates the negative predictive value (NPV) of skin tests and intravenous provocation test (IPT) with low-dose ICM in patients with suspected immediate hypersensitivity reaction (HSR) to ICM. Thirty-seven patients with suspected immediate hypersensitivity reaction to ICM were included retrospectively. Skin tests and a single-blind placebo-controlled intravenous provocation test (IPT) with low-dose iodinated contrast media (ICM) were performed. Skin tests with ICM were positive in five cases (one skin prick test and five intradermal test). Thirty-six patients were challenged successfully by IPT, and only one patient had a positive challenge result, with a grade I reaction by the Ring and Messmer classification. Ten of 23 patients followed up by telephone were re-exposed to a negative tested ICM during radiologic examination; two experienced a grade I immediate reaction. For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44-97%). © 2016 John Wiley & Sons Ltd.
Isolation and partial characterisation of a mammalian cell mutant hypersensitive to topoisomerase II inhibitors and X-rays
Davies, S.M.; Davies, S.L.; Hickson, I.D.; Hall, A.G.
The authors have isolated, following one-step mutagenesis, a Chinese hamster ovary cell mutant hypersensitive to the intercalating agent, adriamycin. This agent exerts at least part of its cytotoxic action via inhibition of the nuclear enzyme, topoisomerase II. The mutant, designated ADR-3, showed hypersensitivity to all classes of topoisomerase II inhibitors, inlcuding actinomycin D, amsacrine (m-AMSA), etoposide (VP16) and mitoxantrone. ADR-3 cells also showed cross-sensitivity to ionizing radiation, but not no UV light. Topoisomerase II activity was elevated to a small but significant degree in ADR-3 cells, and this was reflected in a 1.5-fold higher level of topoisomerase II protein in ADR-3 than in CHO-K1 cells, as judged by Western blotting. ADR-3 cells were hypersensitive to cumene hydroperoxide but cross-resistant to hydrogen peroxide, suggesting possible abnormality in the detoxification of peroxides by glutathione peroxidase or catalase. Glutathione peroxidase activity against hydroperoxide was elevated to a small but significant extent in mutant cells. Catalase levels were not significantly different in ADR-3 and CHO-K1 cells. ADR-3 cells were recessive in hybrids with parental CHO-K1 cells with respect to sensitivity to topoisomerase II inhibitors and X-rays, and represent a different genetic complementation group from the previously reported adriamycin-sensitive mutant, ADR-1. (author). 34 refs.; 5 figs.; 3 tabs
Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.
Boyd R Rorabaugh
Full Text Available We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury.Adult male and female rats received daily injections of methamphetamine (5 mg/kg or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining.Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine.Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.
Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart
Seeley, Sarah L.; Stoops, Thorne S.; D'Souza, Manoranjan S.
Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091
p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC- and FANCA-deficient mononuclear phagocytes.
Anur, Praveen; Yates, Jane; Garbati, Michael R; Vanderwerf, Scott; Keeble, Winifred; Rathbun, Keaney; Hays, Laura E; Tyner, Jeffrey W; Svahn, Johanna; Cappelli, Enrico; Dufour, Carlo; Bagby, Grover C
Fanconi anemia, complementation group C (FANCC)-deficient hematopoietic stem and progenitor cells are hypersensitive to a variety of inhibitory cytokines, one of which, TNFα, can induce BM failure and clonal evolution in Fancc-deficient mice. FANCC-deficient macrophages are also hypersensitive to TLR activation and produce TNFα in an unrestrained fashion. Reasoning that suppression of inhibitory cytokine production might enhance hematopoiesis, we screened small molecules using TLR agonist-stimulated FANCC- and Fanconi anemia, complementation group A (FANCA)-deficient macrophages containing an NF-κB/AP-1-responsive reporter gene (SEAP). Of the 75 small molecules screened, the p38 MAPK inhibitor BIRB 796 and dasatinib potently suppressed TLR8-dependent expression of the reporter gene. Fanconi anemia (FA) macrophages were hypersensitive to the TLR7/8 activator R848, overproducing SEAP and TNFα in response to all doses of the agonist. Low doses (50nM) of both agents inhibited p38 MAPK-dependent activation of MAPKAPK2 (MK2) and suppressed MK2-dependent TNFα production without substantially influencing TNFα gene transcription. Overproduction of TNFα by primary FA cells was likewise suppressed by these agents and involved inhibition of MK2 activation. Because MK2 is also known to influence production and/or sensitivity to 2 other suppressive factors (MIP-1α and IFNγ) to which FA hematopoietic progenitor cells are uniquely vulnerable, targeting of p38 MAPK in FA hematopoietic cells is a rational objective for preclinical evaluation.
Involvement of plasma membrane calcium influx in bacterial induction of the K+/H+ and hypersensitive responses in tobacco
Atkinson, M.M.; Keppler, L.D.; Orlandi, E.W.; Baker, C.J.; Mischke, C.F.
An early event in the hypersensitive response of tobacco to Pseudomonas syringae pv syringae is the initiation of a K + /H + response characterized by specific plasma membrane K + efflux, extracellular alkalinization, and intracellular acidification. We investigated the role of calcium in induction of these host responses. Suspension-cultured tobacco cells exhibited a baseline Ca 2+ influx of 0.02 to 0.06 micromole per gram per hour as determined from 45 Ca 2+ uptake. Following bacterial inoculation, uptake rates began to increase coincidently with onset of the K + /H + response. Rates increased steadily for 2 to 3 hours, reaching 0.5 to 1 micromole per gram per hour. This increased Ca 2+ influx was prevented by EGTA and calcium channel blockers such as La 3+ , Co 2+ , and Cd 2+ but not by verapamil and nifedipine. Lanthanum, cobalt, cadmium, and EGTA inhibited the K + /H + response in both suspension-cultured cells and leaf discs and prevented hypersensitive cell death in leaf discs. We conclude that increase plasmalemma Ca 2+ influx is required for the K + /H + and hypersensitive responses in tobacco
Hypersensitivity to certain food and food ingredients in the function of age and employment of customers on a cruise ship
Vuksanović Nikola D.
Full Text Available Over the last few decades there has been a tendency to use the word 'allergy' to describe all kinds of unexpected reactions to certain foods and food ingredients. The recent literature is plentiful and discusses food allergens and people who are hypersensitive to certain foods. The literature suggests the prevalence of food allergy to specific allergens to be changing with age. The aim of this empirical research was to examine the hypersensitivity to certain foods in relation to age and employment of the population consisting of customers on cruise ships. The study included 404 tourists on a cruise ship who voluntarily filled food sensitivity questionnaires and submitted them to the ship staff. These questionnaires were used to analyze the allergy trends and their connection to age and employment. The procedures of descriptive statistics and Chi-square test were used to process the obtained data. The results of the research suggested that there was a statistically significant relationship between the persons who were hypersensitive to certain foods relative to employment and age.
Critical disease windows shaped by stress exposure alter allocation trade-offs between development and immunity.
Kirschman, Lucas J; Crespi, Erica J; Warne, Robin W
Ubiquitous environmental stressors are often thought to alter animal susceptibility to pathogens and contribute to disease emergence. However, duration of exposure to a stressor is likely critical, because while chronic stress is often immunosuppressive, acute stress can temporarily enhance immune function. Furthermore, host susceptibility to stress and disease often varies with ontogeny; increasing during critical developmental windows. How the duration and timing of exposure to stressors interact to shape critical windows and influence disease processes is not well tested. We used ranavirus and larval amphibians as a model system to investigate how physiological stress and pathogenic infection shape development and disease dynamics in vertebrates. Based on a resource allocation model, we designed experiments to test how exposure to stressors may induce resource trade-offs that shape critical windows and disease processes because the neuroendocrine stress axis coordinates developmental remodelling, immune function and energy allocation in larval amphibians. We used wood frog larvae (Lithobates sylvaticus) to investigate how chronic and acute exposure to corticosterone, the dominant amphibian glucocorticoid hormone, mediates development and immune function via splenocyte immunohistochemistry analysis in association with ranavirus infection. Corticosterone treatments affected immune function, as both chronic and acute exposure suppressed splenocyte proliferation, although viral replication rate increased only in the chronic corticosterone treatment. Time to metamorphosis and survival depended on both corticosterone treatment and infection status. In the control and chronic corticosterone treatments, ranavirus infection decreased survival and delayed metamorphosis, although chronic corticosterone exposure accelerated rate of metamorphosis in uninfected larvae. Acute corticosterone exposure accelerated metamorphosis increased survival in infected larvae. Interactions
Role of histone deacetylases HDA6 and HDA19 in ABA and abiotic stress response
Chen, Li-Ting; Wu, Keqiang
Our recent study revealed the involvement of the Arabidopsis histone deacetylase HDA6 in modulating ABA and salt stress responses. In this report, we further investigated the role of HDA19 in ABA and salt stress responses. The Arabidopsis HDA19 T-DNA insertion mutant, hda19-1, displayed a phenotype that was hypersensitive to ABA and salt stress. Compared with wild-type plants, the expression of ABA responsive genes, ABI1, ABI2, KAT1, KAT2 and RD29B, was decreased in hda19-1 plants when treate...
Hypersensitivity of mouse NEIL1-knockdown cells to hydrogen peroxide during S phase
Yamamoto, Ryohei; Ohshiro, Yukari; Shimotani, Tatsuhiko; Yamamoto, Mizuki; Matsuyama, Satoshi; Ide, Hiroshi; Kubo, Kihei
Oxidative base damage occurs spontaneously due to reactive oxygen species generated as byproducts of respiration and other pathological processes in mammalian cells. Many oxidized bases are mutagenic and/or toxic, and most are repaired through the base excision repair pathway. Human endonuclease VIII-like protein 1 (hNEIL1) is thought to play an important role during the S phase of the cell cycle by removing oxidized bases in DNA replication fork-like (bubble) structures, and the protein level of hNEIL1 is increased in S phase. Compared with hNEIL1, there is relatively little information on the properties of the mouse ortholog mNEIL1. Since mouse cell nuclei lack endonuclease III-like protein (NTH) activity, in contrast to human cell nuclei, mNEIL1 is a major DNA glycosylase for repair of oxidized pyrimidines in mouse nuclei. In this study, we made mNEIL1-knockdown cells using an shRNA expression vector and examined the cell cycle-related variation in hydrogen peroxide (H 2 O 2 ) sensitivity. Hypersensitivity to H 2 O 2 caused by mNEIL1 knockdown was more significant in S phase than in G1 phase, suggesting that mNEIL1 has an important role during S phase, similarly to hNEIL1
Can interpersonal hypersensitivity under subconscious condition explain paranoid symptom in schizophrenia?
Zhu, Yikang; Yang, Zhi; Zhao, Jinping; Li, Ting; Wang, Meijuan; Qian, Jie; Jiang, Yi; Wang, Jijun; Weng, Xuchu; Yu, Dehua; Li, Chunbo
Interpersonal hypersensitivity is often observed in schizophrenia and has been associated with psychopathological deficits in schizophrenia. Here, we investigated dysfunctions of interpersonal information processing in schizophrenia at both conscious and subconscious levels. The experiment included 143 schizophrenia patients and 59 healthy controls. A continuous flashing suppression approach based on binocular rivalry was employed, which included two modes: invisible (subconscious) and visible (conscious). The accuracy and reaction time of a Gabor patch direction-detection task were assessed under three types of stimuli in both modes: images with no person (type 1), images with two to three noncommunicating persons (type 2), and images with more than three communicating individuals (type 3). In the visible mode, the accuracy of the Gabor patch direction-detection task in the case group was significantly lower than in the control group for the third type of stimuli (P = 0.015). In the invisible mode, however, the accuracy was higher in the case group than in the control group (P = 0.037). The response time difference of the Gabor patch direction-detection task for the third type of images in the invisible mode was negatively correlated with the duration of the illness (P = 0.008). These findings suggest that schizophrenia patients exhibit attentional bias to interpersonal interaction behaviors at both conscious and subliminal levels but toward opposite directions. Our findings shed light on the subconscious deficits under the paranoid symptom in schizophrenia. © 2015 Wiley Publishing Asia Pty Ltd.
Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice
Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin
Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28 d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice.
A quick and robust method for quantification of the hypersensitive response in plants
Oskar N. Johansson
Full Text Available One of the most studied defense reactions of plants against microbial pathogens is the hypersensitive response (HR. The HR is a complex multicellular process that involves programmed cell death at the site of infection. A standard method to quantify plant defense and the HR is to measure the release of cellular electrolytes into water after infiltration with pathogenic bacteria. In this type of experiment, the bacteria are typically delivered into the plant tissue through syringe infiltration. Here we report the development of a vacuum infiltration protocol that allows multiple plant lines to be infiltrated simultaneously and assayed for defense responses. Vacuum infiltration did not induce more wounding response in Arabidopsis leaf tissue than syringe inoculation, whereas throughput and reproducibility were improved. The method was used to study HR-induced electrolyte loss after treatment with the bacterium Pseudomonas syringae pv. tomato DC3000 harboring the effector AvrRpm1, AvrRpt2 or AvrRps4. Specifically, the influence of bacterial titer on AvrRpm1-induced HR was investigated. Not only the amplitude, but also the timing of the maximum rate of the HR reaction was found to be dose-dependent. Finally, using vacuum infiltration, we were able quantify induction of phospholipase D activity after AvrRpm1 recognition in leaves labeled with 33PO4.
Automated computer-based CT stratification as a predictor of outcome in hypersensitivity pneumonitis
Jacob, Joseph; Mak, S.M.; Mok, W.; Hansell, D.M.; Bartholmai, B.J.; Rajagopalan, S.; Karwoski, R.; Della Casa, G.; Sugino, K.; Walsh, S.L.F.; Wells, A.U.
Hypersensitivity pneumonitis (HP) has a variable clinical course. Modelling of quantitative CALIPER-derived CT data can identify distinct disease phenotypes. Mortality prediction using CALIPER analysis was compared to the interstitial lung disease gender, age, physiology (ILD-GAP) outcome model. CALIPER CT analysis of parenchymal patterns in 98 consecutive HP patients was compared to visual CT scoring by two radiologists. Functional indices including forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLco) in univariate and multivariate Cox mortality models. Automated stratification of CALIPER scores was evaluated against outcome models. Univariate predictors of mortality included visual and CALIPER CT fibrotic patterns, and all functional indices. Multivariate analyses identified only two independent predictors of mortality: CALIPER reticular pattern (p = 0.001) and DLco (p < 0.0001). Automated stratification distinguished three distinct HP groups (log-rank test p < 0.0001). Substitution of automated stratified groups for FVC and DLco in the ILD-GAP model demonstrated no loss of model strength (C-Index = 0.73 for both models). Model strength improved when automated stratified groups were combined with the ILD-GAP model (C-Index = 0.77). CALIPER-derived variables are the strongest CT predictors of mortality in HP. Automated CT stratification is equivalent to functional indices in the ILD-GAP model for predicting outcome in HP. (orig.)
Jacob, Joseph; Mak, S.M.; Mok, W.; Hansell, D.M. [Royal Brompton and Harefield NHS Foundation Trust, Department of Radiology, Royal Brompton Hospital, London (United Kingdom); Bartholmai, B.J. [Mayo Clinic Rochester, Division of Radiology, Rochester, MN (United States); Rajagopalan, S.; Karwoski, R. [Mayo Clinic Rochester, Biomedical Imaging Resource, Rochester, MN (United States); Della Casa, G. [Universita degli Studi di Modena e Reggio Emilia, Modena, Emilia-Romagna (Italy); Sugino, K. [Toho University Omori Medical Centre, Tokyo (Japan); Walsh, S.L.F. [Kings College Hospital, London (United Kingdom); Wells, A.U. [Royal Brompton and Harefield NHS Foundation Trust, Interstitial Lung Disease Unit, Royal Brompton Hospital, London (United Kingdom)
Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors
Maithili P. Dalvi
Full Text Available Although non-small cell lung cancer (NSCLC patients benefit from standard taxane-platin chemotherapy, many relapse, developing drug resistance. We established preclinical taxane-platin-chemoresistance models and identified a 35-gene resistance signature, which was associated with poor recurrence-free survival in neoadjuvant-treated NSCLC patients and included upregulation of the JumonjiC lysine demethylase KDM3B. In fact, multi-drug-resistant cells progressively increased the expression of many JumonjiC demethylases, had altered histone methylation, and, importantly, showed hypersensitivity to JumonjiC inhibitors in vitro and in vivo. Increasing taxane-platin resistance in progressive cell line series was accompanied by progressive sensitization to JIB-04 and GSK-J4. These JumonjiC inhibitors partly reversed deregulated transcriptional programs, prevented the emergence of drug-tolerant colonies from chemo-naive cells, and synergized with standard chemotherapy in vitro and in vivo. Our findings reveal JumonjiC inhibitors as promising therapies for targeting taxane-platin-chemoresistant NSCLCs.
Our experiences with the use of atopy patch test in the diagnosis of cow's milk hypersensitivity.
Pustisek, Nives; Jaklin-Kekez, Alemka; Frkanec, Ruza; Sikanić-Dugić, Nives; Misak, Zrinjka; Jadresin, Oleg; Kolacek, Sanja
Atopy patch test has been recognized as a diagnostic tool for the verification of food allergies in infants and small children suffering from atopic dermatitis. The test also has a role in the diagnosis of food allergies characterized by clinical signs associated with the digestive system. Yet, in spite of numerous studies, the test itself has hitherto not been standardized. Our study enlisted 151 children less than two years of age, who exhibited suspect skin and/or gastrointestinal manifestations of food allergy to cow's milk, and in whom tests failed to prove early type of allergic reaction. Atopy patch test was positive in 28% of the children with atopic dermatitis, 43% of the children with suspect gastrointestinal manifestation and 32% of the children with skin and gastrointestinal manifestations of food allergy. In our experience, atopy patch test is an excellent addition to the hitherto used tests for the diagnosis of food allergies. It targets specifically delayed type hypersensitivity reactions, which are difficult to confirm with other diagnostic tools. It is furthermore simple to perform, noninvasive and produces a minimum of undesired side effects. For these reasons, it should become part of the routine diagnostic toolset for food allergies to cow's milk in infants and children, and applied before a food challenge test.
Porcine malignant hyperthermia susceptibility: hypersensitive calcium-release mechanism of skeletal muscle sarcoplasmic reticulum.
O'Brien, P J
This study tested the hypothesis that calcium-release from sarcoplasmic reticulum isolated from malignant hyperthermia swine had abnormal concentration-dependency on release modulators. Halothane stimulated half-maximal calcium-release at similar concentrations for malignant hyperthermia and control sarcoplasmic reticulum (0.10 +/- 0.04 mM). However, concentrations causing half-maximal calcium-release were lower for malignant hyperthermia sarcoplasmic reticulum (P less than 0.001) by an order of magnitude for Ca2+ (28.1 +/- 8.3 versus 1.23 +/- 0.45 nM), adenosine triphosphate (0.33 +/- 0.09 versus 0.023 +/- 0.014 mM) and caffeine (7.79 +/- 1.56 versus 0.80 +/- 0.44 mM). Half-maximal inhibition by Mg2+ occurred at threefold higher concentrations for malignant hyperthermia sarcoplasmic reticulum (0.23 +/- 0.02 versus 0.78 +/- 0.17 mM). The Ca2+-sensitivity curves for calcium-release by sarcoplasmic reticulum isolated from heterozygotes for the malignant hyperthermia-defect were indistinguishable from the averages of the curves for controls and malignant hyperthermia-homozygotes. Results of this study suggest that malignant hyperthermia is initiated due to a hypersensitive calcium-release mechanism which is inherited in an autosomal, codominant pattern and may be diagnosed using calcium-release sensitivity-tests on isolated sarcoplasmic reticulum. Images Fig. 1. PMID:3742367
Lack of the purinergic receptor P2X7 results in resistance to contact hypersensitivity
Weber, Felix C.; Esser, Philipp R.; Müller, Tobias; Ganesan, Jayanthi; Pellegatti, Patrizia; Simon, Markus M.; Zeiser, Robert; Idzko, Marco; Jakob, Thilo
Sensitization to contact allergens requires activation of the innate immune system by endogenous danger signals. However, the mechanisms through which contact allergens activate innate signaling pathways are incompletely understood. In this study, we demonstrate that mice lacking the adenosine triphosphate (ATP) receptor P2X7 are resistant to contact hypersensitivity (CHS). P2X7-deficient dendritic cells fail to induce sensitization to contact allergens and do not release IL-1β in response to lipopolysaccharide (LPS) and ATP. These defects are restored by pretreatment with LPS and alum in an NLRP3- and ASC-dependent manner. Whereas pretreatment of wild-type mice with P2X7 antagonists, the ATP-degrading enzyme apyrase or IL-1 receptor antagonist, prevents CHS, IL-1β injection restores CHS in P2X7-deficient mice. Thus, P2X7 is a crucial receptor for extracellular ATP released in skin in response to contact allergens. The lack of P2X7 triggering prevents IL-1β release, which is an essential step in the sensitization process. Interference with P2X7 signaling may be a promising strategy for the prevention of allergic contact dermatitis. PMID:21059855
Modulation of oxazolone-induced hypersensitivity in mice by selective PDE inhibitors
I. Moodley
Full Text Available The effects of PDE inhibitors on oxazolone-induced contact hypersensitivity (CS were studied in mice. Rolipram, Ro 20-1724 and theophylline dose dependently inhibited CS but none caused >53% inhibition. ED30 values at 24 h before challenge for rolipram, Ro 20-1724 and theophylline were 2.1, 5.4 and 30.4 mg/kg, p.o., respectively. Milrinone and SKF 94836 at 30 mg/kg caused a small, but significant inhibition of 13% and 18%, respectively, although the inhibition (8% caused by zaprinast was not significant. Betamethasone (10 mg/kg, p.o. caused a marked inhibition (80% as did indomethacin (65% at 5 mg/kg, p.o.. Rolipram and Ro 20-1724 inhibited proliferation of mouse lymphoblasts with IC50 values of 0.08 μM and 0.83 μM, respectively. In contrast, zaprinast caused only a weak inhibition (IC50 = 119 μM of lymphocyte proliferation, whereas SKF 94836 and theophylline failed to cause any significant inhibition at 100 μM (26% and 2%, respectively. These findings suggest that PDE IV isozymes play a principal role in mediating CS by inhibiting lymphocyte activation.
Immunosuppressive Effect of Litsea cubeba L. Essential Oil on Dendritic Cell and Contact Hypersensitivity Responses
Hsin-Chun Chen
Full Text Available Litsea cubeba L., also named as Makauy, is a traditional herb and has been used as cooking condiment or tea brewing to treat diseases for aborigines. The present study was undertaken to explore the chemical compositions of the fruit essential oil of L. cubeba (LCEO and the immunomodulatory effect of LCEO on dendritic cells and mice. The LCEO was analyzed using gas chromatography (GC and gas chromatography/mass spectrometry (GC/MS with direct injection (DI/GC or headspace-solid phase microextraction (HS-SPME/GC. In total, 56 components were identified, of which 48 were detected by DI/GC and 49 were detected by HS-SPME/GC. The principal compounds were citral (neral and geranial. An immunosuppressive activity of LCEO was investigated with bone marrow-derived dendritic cells (DCs which have a critical role to trigger the adaptive immunity. Additionally, the inhibitory effect of LCEO on immune response was elucidated by performing the contact hypersensitivity (CHS responses in mice. Our results clearly showed that LCEO decreases the production of TNF-α and cytokine IL-12 in a dose-dependent manner in lipopolysaccharide (LPS-stimulated DCs. CHS response and the infiltrative T cells were inhibited in the tested ears of the mice co-treated with LCEO. We demonstrate, for the first time, that the LCEO mainly containing citral exhibits an immunosuppressive effect on DCs and mice, indicating that LCEO can potentially be applied in the treatment of CHS, inflammatory diseases, and autoimmune diseases.
The value of family history in the diagnosis of hypersensitivity pneumonitis in children
Joana Cardoso
Full Text Available Hypersensitivity pneumonitis (HP, or extrinsic allergic alveolitis, is an immunologically mediated disease resulting from the inhalation of organic substances that trigger an inflammatory response in the alveolar wall, bronchioles, and interstitium in susceptible individuals. Although HP is predominantly an occupational disease, seen in adulthood, cases in children have been described. The diagnosis of HP requires a high degree of suspicion. The treatment consists in avoiding contact with the antigen, and, in some cases, systemic corticosteroids might be necessary in order to prevent its progression to pulmonary fibrosis. We report the clinical cases of three children with a history of contact with birds and a family history of HP. All three patients presented with cough and dyspnea on exertion. The disease was diagnosed on the basis of the clinical history and ancillary diagnostic test results consistent with the diagnosis, including a predominance of lymphocytes (> 60%, CD8+ T lymphocytes in particular in bronchoalveolar lavage fluid and a ground-glass pattern seen on HRCT of the chest. Early diagnosis is crucial in order to prevent HP from progressing to pulmonary fibrosis. Hereditary factors seem to influence the onset of the disease.
para-Phenylenediamine Hypersensitivity: A Report From Budapest, Hungary, 2007-2014.
Pónyai, Györgyi; Diczig, Brigitte Mária; Németh, Ilona; Temesvári, Erzsébet
para-Phenylenediamine (PPD) is a potent allergen with frequent exposure through use of hair dyes or henna tattoos. We wished to determine if prevalence of PPD sensitivity is changing through time as trends in its use change. A total of 3631 patients were patch tested consecutively with the environmental standard series between 2007 and 2014 to map the prevalence of PPD sensitivity and its distribution according to age, sex, and diagnosis. Two hundred nine patients (5.75%) were proven to be PPD sensitive. Most PPD-sensitive patients were approximately in their 60s in 2007, whereas in 2014, they were in their 20s and 30s. In 2014, 61.1% of the patients were younger than 35 years and 50% were younger than 25 years. Of 209 PPD-sensitive patients, 32.5% had present relevance related to hair dyeing and eyebrow or eyelash coloring procedures. All affected male patients were hairdressers. Adverse reaction to henna was detected in only 1 case after henna hair dye use. The 5.75% prevalence of PPD sensitization in our study was higher compared with that in the European data. It is alarming that PPD hypersensitivity occurred even among teenagers. This may be mainly explained by hair dyeing at an early age.
Calcitonin gene-related peptide regulates type IV hypersensitivity through dendritic cell functions.
Norihisa Mikami
Full Text Available Dendritic cells (DCs play essential roles in both innate and adaptive immune responses. In addition, mutual regulation of the nervous system and immune system is well studied. One of neuropeptides, calcitonin gene-related peptide (CGRP, is a potent regulator in immune responses; in particular, it has anti-inflammatory effects in innate immunity. For instance, a deficiency of the CGRP receptor component RAMP 1 (receptor activity-modifying protein 1 results in higher cytokine production in response to LPS (lipopolysaccharide. On the other hand, how CGRP affects DCs in adaptive immunity is largely unknown. In this study, we show that CGRP suppressed Th1 cell differentiation via inhibition of IL-12 production in DCs using an in vitro co-culture system and an in vivo ovalbumin-induced delayed-type hypersensitivity (DTH model. CGRP also down-regulated the expressions of chemokine receptor CCR2 and its ligands CCL2 and CCL12 in DCs. Intriguingly, the frequency of migrating CCR2(+ DCs in draining lymph nodes of RAMP1-deficient mice was higher after DTH immunization. Moreover, these CCR2(+ DCs highly expressed IL-12 and CD80, resulting in more effective induction of Th1 differentiation compared with CCR2(- DCs. These results indicate that CGRP regulates Th1 type reactions by regulating expression of cytokines, chemokines, and chemokine receptors in DCs.
Analysis of deep tissue hypersensitivity to pressure pain in professional pianists with insidious mechanical neck pain
Linari-Melfi Marcela
Full Text Available Abstract Background The aim of this study was to investigate whether pressure pain hyperalgesia is a feature of professional pianists suffering from neck pain as their main playing-related musculoskeletal disorder. Methods Twenty-three active expert pianists, 6 males and 17 females (age: 36 ± 12 years with insidious neck pain and 23 pianists, 9 males and 14 females (age: 38 ± 10 years without neck pain the previous year were recruited. A numerical pain rate scale, Neck Disability Index, hand size and pressure pain thresholds (PPT were assessed bilaterally over the C5-C6 zygapophyseal joint, deltoid muscle, the second metacarpal and the tibialis anterior muscle in a blinded design. Results The results showed that PPT levels were significantly decreased bilaterally over the second metacarpal and tibialis anterior muscles (P 0.10, in pianists with neck pain as compared to healthy pianists. Pianists with neck pain had a smaller (P Conclusions Our findings revealed pressure pain hypersensitivity over distant non-symptomatic distant points but not over the symptomatic areas in pianists suffering from neck pain. In addition, pianists with neck pain also had smaller hand size than those without neck pain. Future studies are needed to further determine the relevance of these findings in the clinical course of neck pain as playing-related musculoskeletal disorder in professional pianists.
Background The aim of this study was to investigate whether pressure pain hyperalgesia is a feature of professional pianists suffering from neck pain as their main playing-related musculoskeletal disorder. Methods Twenty-three active expert pianists, 6 males and 17 females (age: 36 ± 12 years) with insidious neck pain and 23 pianists, 9 males and 14 females (age: 38 ± 10 years) without neck pain the previous year were recruited. A numerical pain rate scale, Neck Disability Index, hand size and pressure pain thresholds (PPT) were assessed bilaterally over the C5-C6 zygapophyseal joint, deltoid muscle, the second metacarpal and the tibialis anterior muscle in a blinded design. Results The results showed that PPT levels were significantly decreased bilaterally over the second metacarpal and tibialis anterior muscles (P 0.10), in pianists with neck pain as compared to healthy pianists. Pianists with neck pain had a smaller (P neck pain (mean: 188. 6 ± 13.1). PPT over the tibialis anterior muscles was negatively correlated with the intensity of neck pain. Conclusions Our findings revealed pressure pain hypersensitivity over distant non-symptomatic distant points but not over the symptomatic areas in pianists suffering from neck pain. In addition, pianists with neck pain also had smaller hand size than those without neck pain. Future studies are needed to further determine the relevance of these findings in the clinical course of neck pain as playing-related musculoskeletal disorder in professional pianists. PMID:22111912
Performance of genetic risk factors in prediction of trichloroethylene induced hypersensitivity syndrome.
Dai, Yufei; Chen, Ying; Huang, Hanlin; Zhou, Wei; Niu, Yong; Zhang, Mingrong; Bin, Ping; Dong, Haiyan; Jia, Qiang; Huang, Jianxun; Yi, Juan; Liao, Qijun; Li, Haishan; Teng, Yanxia; Zang, Dan; Zhai, Qingfeng; Duan, Huawei; Shen, Juan; He, Jiaxi; Meng, Tao; Sha, Yan; Shen, Meili; Ye, Meng; Jia, Xiaowei; Xiang, Yingping; Huang, Huiping; Wu, Qifeng; Shi, Mingming; Huang, Xianqing; Yang, Huanming; Luo, Longhai; Li, Sai; Li, Lin; Zhao, Jinyang; Li, Laiyu; Wang, Jun; Zheng, Yuxin
Trichloroethylene induced hypersensitivity syndrome is dose-independent and potentially life threatening disease, which has become one of the serious occupational health issues and requires intensive treatment. To discover the genetic risk factors and evaluate the performance of risk prediction model for the disease, we conducted genomewide association study and replication study with total of 174 cases and 1761 trichloroethylene-tolerant controls. Fifty seven SNPs that exceeded the threshold for genome-wide significance (P < 5 × 10(-8)) were screened to relate with the disease, among which two independent SNPs were identified, that is rs2857281 at MICA (odds ratio, 11.92; P meta = 1.33 × 10(-37)) and rs2523557 between HLA-B and MICA (odds ratio, 7.33; P meta = 8.79 × 10(-35)). The genetic risk score with these two SNPs explains at least 20.9% of the disease variance and up to 32.5-fold variation in inter-individual risk. Combining of two SNPs as predictors for the disease would have accuracy of 80.73%, the area under receiver operator characteristic curves (AUC) scores was 0.82 with sensitivity of 74% and specificity of 85%, which was considered to have excellent discrimination for the disease, and could be considered for translational application for screening employees before exposure.
Bilateral widespread mechanical pain hypersensitivity as sign of central sensitization in patients with cluster headache.
Fernández-de-Las-Peñas, César; Ortega-Santiago, Ricardo; Cuadrado, María L; López-de-Silanes, Carlos; Pareja, Juan A
To investigate bilateral widespread pressure pain hyperalgesia in deep tissues over symptomatic (trigemino-cervical) and nonsymptomatic (distant pain-free) regions in patients with cluster headache (CH). Central sensitization is claimed to play a relevant role in CH. No study has previously searched for widespread pressure hyperalgesia in deep tissues over both symptomatic (trigemino-cervical) and nonsymptomatic (distant pain-free) regions in patients with CH. Sixteen men (mean age: 43 ± 11 years) with CH in a remission phase and 16 matched controls were recruited. Pressure pain thresholds (PPTs) were bilaterally measured over the supra-orbital (V1), infra-orbital (V2), mental (V3), median (C5), radial (C6), and ulnar (C7) nerves, C5-C6 zygapophyseal joint, mastoid process, and tibialis anterior muscle by an assessor blinded to the subjects' condition. The results showed that PPT levels were significantly decreased bilaterally in patients with CH as compared with healthy controls (all sites, P hypersensitivity in patients with CH confirming the presence of central sensitization mechanisms in this headache condition. © 2010 American Headache Society.
Comparison of Esophageal Function Tests in Chinese Patients with Functional Heartburn and Reflux Hypersensitivity
Feng Gao
Full Text Available Objective. To investigate the differences in the results of esophageal function tests for functional heartburn (FH and reflux hypersensitivity (RH. Methods. Patients with FH and RH and healthy volunteers (HVs from the Department of Gastroenterology, Beijing Anzhen Hospital and Beijing Chao-Yang hospital, who underwent high-resolution manometry and impedance (HRIM, and 24-hour multichannel intraluminal impedance and pH recording (MII/pH between 2014 and 2016, were enrolled in this study. Results. 36 HV, 147 FH patients, and 91 RH patients were enrolled. The postreflux swallow-induced peristaltic wave index (PSPW index and mean nocturnal baseline impedance (MNBI values were significantly lower in RH than in FH and HV. The ineffective esophageal motility (IEM, fragmented peristalsis rates, total bolus exposure, proximal total reflux events, and distal total reflux events were significantly greater in RH than in FH and HV. Conclusions. Compared to HV and FH patients, RH patients exhibited greater IEM and fragmented peristalsis rates, a greater total bolus exposure, more proximal total and distal total reflux events, and reduced chemical clearance and mucosal integrity. By using the above described parameters, HRIM and MII/pH assays could be used to correctly classify RH and FH and hence allow physicians to provide adequate relief from associated symptoms.
Transformation of UV-hypersensitive Chinese hamster ovary cell mutants with UV-irradiated plasmids
Nairn, R.S.; Humphrey, R.M.; Adair, G.M.
Transfection of UV-hypersensitive, DNA repair-deficient Chinese hamster ovary (CHO) cell lines and parental, repair-proficient CHO cells with UV-irradiated pHaprt-1 or pSV2gpt plasmids resulted in different responses by recipient cell lines to UV damage in transfected DNA. Unlike results reported for human cells, UV irradiation of transfecting DNA did not stimulate genetic transformation of CHO recipient cells. In repair-deficient CHO cells, proportionally fewer transformants were produced with increasing UV damage than in repair-proficient cells in transfections with UV-irradiated hamster adenine phosphoribosyltransferase (APRT) gene contained in plasmid pHaprt-1. Transfection of CHO cells with UV-irradiated pSV2gpt resulted in neither decline in transformation frequencies in repair-deficient cell lines relative to repair-proficient cells nor stimulation of genetic transformation by UV damage in the plasmid. Blot hybridization analysis of DNA samples isolated from transformed cells showed no dramatic changes in copy number or arrangement of transfected plasmid DNA with increasing UV dose. The authors conclude responses of recipient cells to UV-damaged transfecting plasmids depend on type of recipient cell and characteristics of the genetic sequence used for transfection. (author)
Recurrent Syncope Due to Carotid Sinus Hypersensitivity and Sick Sinus Syndrome
Feng-Yu Kuo
Full Text Available Syncope is a sudden and brief loss of consciousness with postural tone. Its recovery is usually spontaneous. There are various causes of syncope including cardiac, vascular, neurologic, metabolic and miscellaneous origins. The tracing is usually time-consuming and costly. The diagnosis of carotid sinus syncope may sometimes be difficult since the symptoms are nonspecific, especially in older persons. Here, we report the case of a 72-year-old woman who sought medical attention at our hospital due to repeated syncope episodes over the previous 5 years. Neurologic examinations showed negative results (including brain computed tomography. Twenty-four-hour ambulatory electrocardiogram monitoring showed atrial and ventricular premature contractions only. Electrophysiologic study disclosed prolonged corrected sinus node recovery time (1,737 ms with poor atrioventricular conduction. Drop of blood pressure together with sinus bradycardia developed after left side carotid sinus massage. Both carotid sinus hypersensitivity with sick sinus syndrome contributed to this patient's syncope, and after pacemaker placement together with selective serotonin reuptake inhibitor treatment, she was free from syncope thereafter.
Spinal Microgliosis Due to Resident Microglial Proliferation Is Required for Pain Hypersensitivity after Peripheral Nerve Injury
Full Text Available Peripheral nerve injury causes neuropathic pain accompanied by remarkable microgliosis in the spinal cord dorsal horn. However, it is still debated whether infiltrated monocytes contribute to injury-induced expansion of the microglial population. Here, we found that spinal microgliosis predominantly results from local proliferation of resident microglia but not from infiltrating monocytes after spinal nerve transection (SNT by using two genetic mouse models (CCR2RFP/+:CX3CR1GFP/+ and CX3CR1creER/+:R26tdTomato/+ mice as well as specific staining of microglia and macrophages. Pharmacological inhibition of SNT-induced microglial proliferation correlated with attenuated neuropathic pain hypersensitivities. Microglial proliferation is partially controlled by purinergic and fractalkine signaling, as CX3CR1−/− and P2Y12−/− mice show reduced spinal microglial proliferation and neuropathic pain. These results suggest that local microglial proliferation is the sole source of spinal microgliosis, which represents a potential therapeutic target for neuropathic pain management.
The re-establishment of hypersensitive cells in the crypts of irradiated mouse intestine
Ijiri, K.; Potten, C.S.
Two doses of γ-radiation separated by various time intervals have been used to investigate when after irradiation the cell population susceptible to acute cell death is re-established. Dead cells were scored 3 or 6 h after the second dose. Within 1-2 days of small doses (0.5 Gy) the sensitive cells, recognized histologically as apoptotic cells, are re-established at the base of the crypt (around cell position 6). After higher doses (9.0 Gy) they are not re-established until about the fourth day after irradiation. Even in the enlarged regenerating crypts the sensitive cells are found at the same position at the crypt base. It has been estimated that the crypt contains five or six cells that are susceptible to low doses (0.5 Gy) (hypersensitive cells) and up to a total of only seven or eight susceptible cells that can be induced by any dose to enter the sequence of changes implicit in apoptosis. Between 4 and 10 days after an intitial irradiation of 9.0 Gy the total number of susceptible cells increased from seven to eight to about 10 to 13 per crypt. (author)
Hypersensitivity Reaction and Acute Respiratory Distress Syndrome in Pyrethroid Poisoning and Role of Steroid Therapy
Jisa George
Full Text Available Background: Pyrethroids are generally of low toxicity to humans, but in suicidal poisonings which are usually associated with ingestion of high doses, they lead to severe systemic effects. Case Report: A 30-year old woman presented to emergency department with a history of intentional ingestion of about 15 mL of prallethrin around 3 days earlier. She complained of shortness of breath along with chest pain for the last 2 days. She reported no vomiting or stomach pain prior to presentation to hospital. On chest auscultation, breath sounds were mildly decreased in bilateral infrascapular areas with generalized crepitation. Arterial blood gas analysis revealed respiratory alkalosis. Chest X ray and computed tomography of thorax revealed widespread confluent areas of consolidation with interlobular septal thickening involving bilateral parahilar regions suggestive of acute respiratory distress syndrome (ARDS. The patient did not respond to broad spectrum antibiotic coverage, diuretics and oxygen inhalation. Intravenous methylprednisolone (2 mg/kg/day divided 6 hourly was started and slowly tapered off during the next days. The patient discharged after 3 weeks in good health. Discussion: As pyrethroids can affect sodium channels, the osmotic gradient of alveolar epithelium probably disrupts and therefore, alveolar infiltrations gradually spread over lungs. In addition, there is a possibility of hypersensitivity reactions to pyrethroids, which can cause progressive inflammation and involve respiratory tract in severe cases. Conclusion: Pyrethroid poisoning can lead to ARDS. Steroid therapy may help such patients tide over the pulmonary crisis.
Identification of 4 ataxia telangiectasia cell lines hypersensitive to. gamma. -irradiation but not to hydrogen peroxide
Cantoni, O.; Sestili, P.; Santoro, M.P.; Tannoia, M.C.; Cattabeni, F. (Universita degli Studi di Urbino (Italy). Istituto di Farmacologia e Farmacognosia and Centro di Farmacologia Oncologia Sperimentale); Novelli, G.; Dallapiccola, B. (Universit degli Studi di Urbino (Italy). Cattedra di Genetica); Fiorilli, M. (Universita di Roma ' La Sapienze' (Italy). Cattedra di Allergologia e Immunologia Clinica)
The effct of hydrogen peroxide on the rate of semi-conservative DNA synthesis in ataxia telangiectasia (AT) and normal human lymphoblastoid cells was investigated. The rate of DNA synthesis in AT cells was not depressed to a lesser extent than in normal cells, as might have been expected since H{sub 2O2} is a radiomimetic agent. On the contrary, 4 AT cell lines displayed a higher sensitivity to the inhibitory effect of H{sub 2O2} on DNA synthesis than 2 normal cell lines. Comparable levels of cytotoxicity were detected in cell vaibility studies. Furthermore, neither the level of DNA breakage produced by H{sub 2O2}, nor the rate of repair of these lesions was signigicantly different in normal and AT cells. Together, these results indicate that the AT cell lines utilized in this study are not hypersensitive to the oxidant. It is suggested that H-2-O-2 may not induce lethality via the direct ation of the hydroxyl radical (OH). (Author). 20 refs.; 3 figs.; 1 tab.
Cell division in Escherichia coli BS-12 is hypersensitive to deoxyribonucleic acid damage by ultraviolet light
Bridges, B.A.; Mottershead, R.P.; Green, M.H.
Escherichia coli BS-12 uvrA lon is hypersensitive to ultraviolet light. On minimal agar plates at densities in excess of about 10(7) bacteria per plate, as few as one or two photoreversible pyrimidine dimers in the entire genome are sufficient to cause inhibition of cell division. Most of the resulting filaments are unable to divide or form a viable colony. Inhibition of cell division appears to be a rapid consequence of replication of deoxyribonucleic acid containing a pyrimidine dimer. Photoreversibility of the inhibition of cell division persists indefinitely, indicating that the continued presence of the pyrimidine dimers (or the continued generation of daughter strand gaps) is necessary to maintain the division-inhibited state. In view of the kinetics for the production of filamentation by ultraviolet light and the extremely low average inducing fluence (0.03 J/m2), it is concluded that the initiating signal is not the same as that causing other inducible phenomena such as prophage induction or Weigle reactivation
Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects.
This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported primarily in the Journal in 2005. Although studies documented deficiencies in community management of anaphylaxis, guidelines and National Institutes of Health summary reports provide direction toward improved research and education. At least 9% of young children "outgrow" a tree nut allergy. Advances in food allergy diagnosis include reports of probability of reactions to peanut at various peanut-specific IgE concentrations and skin test response size and the utility of evaluating IgE binding to specific epitopes. Future food allergy treatments might include selection of "less allergenic" fruit cultivars, genetic silencing of major allergens, and treatment of allergic patients with Chinese herbal remedies. Osteopontin might be a useful biomarker for success of venom immunotherapy. Progress in our understanding of the immunology of atopic dermatitis and autoimmune urticaria has also been made. These observations will likely contribute toward optimizing management of these common allergic disorders.
A case study of arithmetic facts dyscalculia caused by a hypersensitivity-to-interference in memory.
De Visscher, Alice; Noël, Marie-Pascale
While the heterogeneity of developmental dyscalculia is increasingly recognized, the different profiles have not yet been clearly established. Among the features underpinning types of developmental dyscalculia suggested in the literature, an impairment in arithmetic fact retrieval is particularly prominent. In this paper, we present a case study of an adult woman (DB) with very good cognitive capacities suffering from a specific and developmental arithmetic fact retrieval deficit. We test the main hypotheses about developmental dyscalculia derived from literature. We first explore the influential hypothesis of an approximate number system deficit, through estimation tasks, comparison tasks and a priming comparison task. Secondly, we evaluate whether DB's mathematical deficiencies are caused by a rote verbal memory deficit, using tasks involving completion of expressions, and reciting automatic series such as the alphabet and the months of the year. Alternatively, taking into account the extreme similarity of the arithmetic facts, we propose that a heightened sensitivity to interference could have prevented DB from memorizing the arithmetic facts. The pattern of DB's results on different tasks supports this hypothesis. Our findings identify a new etiology of a specific impairment of arithmetic facts storage, namely a hypersensitivity-to-interference. Copyright © 2012 Elsevier Ltd. All rights reserved.
Serial-order learning impairment and hypersensitivity-to-interference in dyscalculia.
De Visscher, Alice; Szmalec, Arnaud; Van Der Linden, Lize; Noël, Marie-Pascale
In the context of heterogeneity, the different profiles of dyscalculia are still hypothetical. This study aims to link features of mathematical difficulties to certain potential etiologies. First, we wanted to test the hypothesis of a serial-order learning deficit in adults with dyscalculia. For this purpose we used a Hebb repetition learning task. Second, we wanted to explore a recent hypothesis according to which hypersensitivity-to-interference hampers the storage of arithmetic facts and leads to a particular profile of dyscalculia. We therefore used interfering and non-interfering repeated sequences in the Hebb paradigm. A final test was used to assess the memory trace of the non-interfering sequence and the capacity to manipulate it. In line with our predictions, we observed that people with dyscalculia who show good conceptual knowledge in mathematics but impaired arithmetic fluency suffer from increased sensitivity-to-interference compared to controls. Secondly, people with dyscalculia who show a deficit in a global mathematical test suffer from a serial-order learning deficit characterized by a slow learning and a quick degradation of the memory trace of the repeated sequence. A serial-order learning impairment could be one of the explanations for a basic numerical deficit, since it is necessary for the number-word sequence acquisition. Among the different profiles of dyscalculia, this study provides new evidence and refinement for two particular profiles. Copyright © 2015 Elsevier B.V. All rights reserved.
Immunotoxicity of epicutaneously applied anticoagulant rodenticide warfarin: evaluation by contact hypersensitivity to DNCB in rats
Kataranovski, Milena; Vlaski, Marija; Kataranovski, Dragan; Tosic, Natasa; Mandic-Radic, Slavka; Todorovic, Vera
The immunotoxicity of epicutaneously administered anticoagulant rodenticide warfarin (WF) was examined in this work by using experimental contact hypersensitivity (CHS) reaction to hapten dinitrochlorobenzene (DNCB). WF (0.05 and 0.5 mg/kg) administration 24 h before the induction of CHS does not change expression of CHS evaluated by ear swelling assay. Regional draining lymph node response during sensitization phase was characterized by decreased cellularity but increased spontaneous and IL-2 stimulated proliferation of draining lymph node cells (DLC). No changes in IL-2 production and in numbers of CD25 + cells were noted and even decreased proliferative index (ratio of IL-2 stimulated to unstimulated DLC proliferation) was detected. Increase in granulocyte activity (MTT reduction and adhesion to plastic) was noted following application of WF solely with further increase following subsequent application of DNCB, when granulocyte activation (NBT reduction) was noted also. Access of WF into general circulation might be responsible for observed changes, what was supported by ex vivo changes in DLC and granulocyte functions assessed before initiation of sensitization and by in vitro effect of exogenous WF as well. Differential effects of WF on lymphocytes and granulocytes noted in this study highlight the need for simultaneous testing of both cell type activity what might constitute a more integrated approach in immunotoxicity studies
The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations.
Andersson, Lisa S; Swinburne, June E; Meadows, Jennifer R S; Broström, Hans; Eriksson, Susanne; Fikse, W Freddy; Frey, Rebecka; Sundquist, Marie; Tseng, Chia T; Mikko, Sofia; Lindgren, Gabriella
Insect bite hypersensitivity (IBH) is a chronic allergic dermatitis common in horses. Affected horses mainly react against antigens present in the saliva from the biting midges, Culicoides ssp, and occasionally black flies, Simulium ssp. Because of this insect dependency, the disease is clearly seasonal and prevalence varies between geographical locations. For two distinct horse breeds, we genotyped four microsatellite markers positioned within the MHC class II region and sequenced the highly polymorphic exons two from DRA and DRB3, respectively. Initially, 94 IBH-affected and 93 unaffected Swedish born Icelandic horses were tested for genetic association. These horses had previously been genotyped on the Illumina Equine SNP50 BeadChip, which made it possible to ensure that our study did not suffer from the effects of stratification. The second population consisted of 106 unaffected and 80 IBH-affected Exmoor ponies. We show that variants in the MHC class II region are associated with disease susceptibility (p (raw) = 2.34 × 10(-5)), with the same allele (COR112:274) associated in two separate populations. In addition, we combined microsatellite and sequencing data in order to investigate the pattern of homozygosity and show that homozygosity across the entire MHC class II region is associated with a higher risk of developing IBH (p = 0.0013). To our knowledge this is the first time in any atopic dermatitis suffering species, including man, where the same risk allele has been identified in two distinct populations.
Participation of the phosphoinositide metabolism in the hypersensitive response of Citrus limon against Alternaria alternata
XIMENA ORTEGA
Full Text Available Lemon seedlings inoculated with Alternaria alternata develop a hypersensitive response (HR that includes the induction of Phenylalanine ammonia-lyase (PAL, E. C. 4.3.1.5 and the synthesis of scoparone. The signal transduction pathway involved in the development of this response is unknown. We used several inhibitors of the Phosphoinositide (PI animal system to study a possible role of Inositol-1,4,5-triphosphate (IP3 in the transduction of the fungal conidia signal in Citrus limon. The HR was only partially inhibited by EGTA, suggesting that not only external but internal calcium as well are necessary for a complete development of the HR. In this plant system, Alternaria alternata induced an early accumulation of the second messenger IP3. When lemon seedlings were watered long term with LiCl, an inhibitor of the phosphoinositide cycle, the IP3 production was reduced, and the LiCl-watered plants could neither induce PAL nor synthesize scoparone in response to fungal conidia. Furthermore, neomycin, a Phospholipase C (PLC, E. C. 3.1.4.3 inhibitor, also inhibited PAL induction and scoparone synthesis in response to A. alternata. These results suggest that IP3 could be involved in the signal transduction pathway for the development of the HR of Citrus limon against A. alternata
Prevalence of parent-reported immediate hypersensitivity food allergy in Chilean school-aged children.
Hoyos-Bachiloglu, R; Ivanovic-Zuvic, D; �lvarez, J; Linn, K; Thöne, N; de los �ngeles Paul, M; Borzutzky, A
Food allergies (FAs) affect 2-4% of school-aged children in developed countries and strongly impact their quality of life. The prevalence of FA in Chile remains unknown. Cross-sectional survey study of 488 parents of school-aged children from Santiago who were asked to complete a FA screening questionnaire. Parents who reported symptoms suggestive of FA were contacted to answer a second in-depth questionnaire to determine immediate hypersensitivity FA prevalence and clinical characteristics of school-aged Chilean children. A total of 455 parents answered the screening questionnaire: 13% reported recurrent symptoms to a particular food and 6% reported FA. Forty-three screening questionnaires (9%) were found to be suggestive of FA. Parents of 40 children answered the second questionnaire; 25 were considered by authors to have FA. FA rate was 5.5% (95% CI: 3.6-7.9). Foods reported to frequently cause FA included walnut, peanut, egg, chocolate, avocado, and banana. Children with FA had more asthma (20% vs. 7%, Phistory compatible with anaphylaxis. Of 13 children who sought medical attention, 70% were diagnosed with FA; none were advised to acquire an epinephrine autoinjector. Up to 5.5% of school-aged Chilean children may suffer from FA, most frequently to walnut and peanut. It is critical to raise awareness in Chile regarding FA and recognition of anaphylaxis, and promote epinephrine autoinjectors in affected children. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.
Intraoperative Ephedrine Allergy in a Patient Who Received Chemotherapy and Perioperative Hypersensitivity Reactions.
Hakimoğlu, Sedat; Tuzcu, Kasım; Davarcı, Işıl; Karcıoğlu, Murat; Kurt, Raziye; Dikey, İsmail
Anaesthesia represents a specific set-up in respect to pharmacology, and during this time, early hypersensitivity reactions or anaphylaxis may occur in patients who are exposed to a great number of foreign substances. Intravenous ephedrine (5 mg) was applied to a 37-year-old patient due to the development of intraoperative hypotension in a total abdominal hysterectomy operation. After application, hyperaemia was seen in the track of the intravenous catheter of that extremity. Approximately 15 minutes later, urticarial plaques were observed extensively in the abdomen and in both extremities. Methylprednisolone (100 mg+100 mg) and pheniramine (45.5 mg) were given with an increasing infusion rate of intravenous crystalloid. The patient was extubated without any problem and removed to the recovery unit for observation. After the total disappearance of lesions at postoperative 60 minutes and because of the stability of vital signs, the patient was removed to the service. In the follow-up of surgery, no complication developed, and the patient was discharged on postoperative day 2.
Parents' and caregivers' experiences and behaviours when eating out with children with a food hypersensitivity.
Begen, Fiona M; Barnett, Julie; Barber, Miriam; Payne, Ros; Gowland, M Hazel; Lucas, Jane S
For parents and caregivers of food hypersensitive (FH) children, accommodating their child's dietary needs when eating out can be a challenging experience. This study explored caregivers' experiences and behaviours when eating out with their FH child in order to gain insights into how they support and prepare their child in negotiating safe eating out experiences. A cross-sectional, qualitative design was used. In depth, semi-structured interviews were carried out with 15 caregivers of children with FH. Interviews were analysed using framework analysis. Caregivers reported a number of issues relating to eating out with their FH child, or allowing their child to eat out without their supervision. Through themes of 'family context', 'child-focused concerns', and 'venue issues', caregivers described how they managed these and explained the limitations and sacrifices that FH imposed on their child, themselves, and family members. Through deeper understanding of the anxieties, negotiations and compromises experienced by caregivers of children with FH when they are eating out, clinicians and support charities can tailor their support to meet the needs of caregivers and children. Support and education provision should focus on providing caregivers of children with FH the tools and strategies to help enable safe eating out experiences.
Potential immediate hypersensitivity reactions following immunization in preschool aged children in Victoria, Australia.
Baxter, C-M; Clothier, H J; Perrett, K P
Immediate hypersensitivity reactions (IHR) are rare but potentially serious adverse events following immunization (AEFI). Surveillance of Adverse Events following Vaccination in the Community (SAEFVIC) is an enhanced passive surveillance system that collects, analyses and reports information about AEFI in Victoria, Australia. We describe the incidence, timing and type of potential IHR following vaccination in preschool children reported over an 8-year period. A total of 2110 AEFI were reported in 1620 children, of which 23.5% (496) were classified as potential IHR. Of these, 37.1% (184) were suspected to be IgE-mediated, (including anaphylaxis, angioedema and/or urticaria) and 83.5% (414) occurred within 15Â minutes of vaccination. The incidence of potential IHR was 5.4 per 100,000 doses, with that of suspected IgE-mediated IHR being 2.0 per 100,000 doses. The incidence of anaphylaxis was extremely low (0.13 per 100,000 doses) and is consistent with other published studies. Potential IHR following immunization should be reported to appropriate local pharmacovigilance systems and patients reviewed by specialists able to evaluate, investigate and manage future vaccinations.
... Persantine stress test; Thallium stress test; Stress test - nuclear; Adenosine stress test; Regadenoson stress test; CAD - nuclear stress; Coronary artery disease - nuclear stress; Angina - nuclear ...
Cellulose synthesis genes CESA6 and CSI1 are important for salt stress tolerance in Arabidopsis.
Zhang, Shuang-Shuang; Sun, Le; Dong, Xinran; Lu, Sun-Jie; Tian, Weidong; Liu, Jian-Xiang
Two salt hypersensitive mutants she1 and she2 were identified through genetic screening. SHE1 encodes a cellulose synthase CESA6 while SHE2 encodes a cellulose synthase-interactive protein CSI1. Both of them are involved in cellulose deposition. Our results demonstrated that the sustained cellulose synthesis is important for salt stress tolerance in Arabidopsis. © 2015 Institute of Botany, Chinese Academy of Sciences.
The cell wall and endoplasmic reticulum stress responses are coordinately regulated in Saccharomyces cerevisiae
Krysan, Damian J
The unfolded protein response (UPR) is an intracellular signaling pathway that regulates the cellular response to the accumulation of misfolded proteins in eukaryotes. Our group has demonstrated that cell wall stress activates UPR in yeast through signals transmitted by the cell wall integrity (CWI) mitogen-activated protein (MAP) kinase cascade. The UPR is required to maintain cell wall integrity; mutants lacking a functional UPR have defects in cell wall biosynthesis and are hypersensitive ...
Modest Amounts of Voluntary Exercise Reduce Pain- and Stress-Related Outcomes in a Rat Model of Persistent Hind Limb Inflammation.
Pitcher, Mark H; Tarum, Farid; Rauf, Imran Z; Low, Lucie A; Bushnell, Catherine
Aerobic exercise improves outcomes in a variety of chronic health conditions, yet the support for exercise-induced effects on chronic pain in humans is mixed. Although many rodent studies have examined the effects of exercise on persistent hypersensitivity, the most used forced exercise paradigms that are known to be highly stressful. Because stress can also produce analgesic effects, we studied how voluntary exercise, known to reduce stress in healthy subjects, alters hypersensitivity, stress, and swelling in a rat model of persistent hind paw inflammation. Our data indicate that voluntary exercise rapidly and effectively reduces hypersensitivity as well as stress-related outcomes without altering swelling. Moreover, the level of exercise is unrelated to the analgesic and stress-reducing effects, suggesting that even modest amounts of exercise may impart significant benefit in persistent inflammatory pain states. Modest levels of voluntary exercise reduce pain- and stress-related outcomes in a rat model of persistent inflammatory pain, independently of the amount of exercise. As such, consistent, self-regulated activity levels may be more relevant to health improvement in persistent pain states than standardized exercise goals. Published by Elsevier Inc.
Cannabinoid 1 receptor knockout mice display cold allodynia, but enhanced recovery from spared-nerve injury-induced mechanical hypersensitivity.
Sideris, Alexandra; Piskoun, Boris; Russo, Lori; Norcini, Monica; Blanck, Thomas; Recio-Pinto, Esperanza
The function of the Cannabinoid 1 receptor (CB1R) in the development of neuropathic pain is not clear. Mounting evidence suggest that CB1R expression and activation may contribute to pain. Cannabinoid 1 receptor knockout mice (CB1R-/-) generated on a C57Bl/6 background exhibit hypoalgesia in the hotplate assay and formalin test. These findings suggest that Cannabinoid 1 receptor expression mediates the responses to at least some types of painful stimuli. By using this mouse line, we sought to determine if the lack of Cannabinoid 1 receptor unveils a general hypoalgesic phenotype, including protection against the development of neuropathic pain. The acetone test was used to measure cold sensitivity, the electronic von Frey was used to measure mechanical thresholds before and after spared-nerve injury, and analysis of footprint patterns was conducted to determine if motor function is differentially affected after nerve-injury in mice with varying levels of Cannabinoid 1 receptor. At baseline, CB1R-/- mice were hypersensitive in the acetone test, and this phenotype was maintained after spared-nerve injury. Using calcium imaging of lumbar dorsal root ganglion (DRG) cultures, a higher percentage of neurons isolated from CB1R-/- mice were menthol sensitive relative to DRG isolated from wild-type (CB1R+/+) mice. Baseline mechanical thresholds did not differ among genotypes, and mechanical hypersensitivity developed similarly in the first two weeks following spared-nerve injury (SNI). At two weeks post-SNI, CB1R-/- mice recovered significantly from mechanical hypersensitivity, while the CB1R+/+ mice did not. Heterozygous knockouts (CB1R+/-) transiently developed cold allodynia only after injury, but recovered mechanical thresholds to a similar extent as the CB1R-/- mice. Sciatic functional indices, which reflect overall nerve health, and alternation coefficients, which indicate uniformity of strides, were not significantly different among genotypes. Cold allodynia and