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Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways
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Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: email@example.com [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)
Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.
Behavioural actions of vasoactive intestinal peptide (VIP)
Kloet, E.R.; Cottrell, G.A.; Veldhuis, H.D.; Rostene, W.H.
The effect of vasoactive intestinal peptide (VIP) was studied on fear-motivated behaviours, exploration of a novel environment and on novelty and ACTH-induced grooming. VIP was administered via a plastic cannula into the lateral ventricle. Retention of a step-through passive avoidance task was
Radioiodination of vasoactive intestinal peptide (VIP)
International Nuclear Information System (INIS)
Wang, Y.; Wang, L.; Yin, D.
In recent years, increasing biochemical and radiochemical research has been performed to develop radiolabelled peptides as specific ligands for tumour associated receptors. VIP, a 28-amino acid peptide containing two tyrosines and three lysines, has demonstrated that various tumour cells express significantly higher amounts of VIP-receptors and could be applied to the clinic diagnosis. For these purposes, radiohalogenation of VIP by direct and indirect method was studied. Direct labelling works well for radioiodine but is limited to dehalogenation of labelling products in vivo. Conjugate labelling methods including Boltonhunter and wood reagents were developed but introduction of such a molecule to peptides may lead to the decrease of biological activity in vivo. In order to resolve these problems, N-Succinimidyl-3-(tri-nbutylstannyl) benzoate (ATE) was elected for the radioiodination of VIP and already employed to radioiodination of IgG successfully. The in vitro stability and biological activity would be compared in these two methods. Vasoactive intestinal peptide (VIP) and human immunoglobulin (IgG) were radioiodinated by direct and indirect methods. Iodogen was employed in direct method and N-Succinimidyl-3-(tri-n-butylstannyl) benzoate (ATE) was applied as a prosthetic group in the conjugation labelling. The subject of our study was optimizing the radiohalogenation of IgG and VIP followed by separation and analysis of reaction products. The advantages and disadvantages were illustrated by comparing the in vitro stability and biological activity in these two methods. Na 123 I was prepared by nuclear reaction of 124 Te(p, 2n) 123 I using cyclone-30. More than 95% of radiochemical purity, more than 95% of radionuclide purity and about 100 mCi/mL of radioactivity concentration were obtained. ATE was supplied by Dr. Pozzi and radioiodinated with iodogen and 96% of labelling efficiency was obtained. The stability of radioactive S 125 IB kept well in dark at 4
The indirect radioiodination of vasoactive intestinal peptide
International Nuclear Information System (INIS)
Wang Lihua; Li Junling; Yin Duanzhi; Zhang Lei; Zhang Xiuli; Wang Yongxian
Objective: To seek for an effective way to acquire radiolabeled vasoactive intestinal peptide (VIP) with excellent in vivo stability. N-succinimidyl-3-iodo-125-benzoate (S 125 IB) came from radioiodination of N-succinimidyl-3-(tri-n-butylstannyl) benzoate (ATE) precursor and then conjugated with VIP to form 125 IBA-VIP. The labelling procedure was optimized; the in vitro stability and biological activity were evaluated. Methods: 1) Radiolabeling of ATE precursor was achieved with iodogen oxidant and the influential factors were considered in this procedure. The labeling efficiency was determined by thin layer chromatography (TLC) and the purification was carried out by Sep-pak silica gel cartridge. The stability was detected by TLC after 2 h storage in dark at 4 degree C. 2) Conjugation of S 125 IB and VIP. The labelling efficiency was determined with RP TLC and the purification was carried out with high performance liquid chromatography (HPLC, RP C18 column). Trichloroacetic acid (TCA) precipitation method was applied to evaluate the in vitro stability while the biological activity was determined by cell binding experiments with SGC7901 cell lines. Results: 1) S 125 IB experiments. The radioiodination of ATE was performed well for 5 min at 25 degree C with 10 micrograms of iodogen at suitable mole ratio (3-8:1) of ATE/Na 125 I, the labelling efficiency was about 96%. The stability was kept well at 4 degree C in dark, no significant decrease of S 125 IB was observed. 2) The conjugation efficiency of S 125 IB and VIP was above 75% with TLC. HPLC showed the different retention time (t R ) as follows, 125 IBA-VIP: 13.3 min, S 125 IB: 19.6 min, VIP: 8.32 min. The stability of 125 IBA-VIP was better than 125 I-VIP from direct radioiodination of VIP with iodogen oxidant, only 2.85% decrease was found after 7 d at 4 degree C. The biological activity of 125 IBA-VIP was kept as well as 125 I-VIP under the condition of 37 degree C 60 min. Conclusions: The indirect
Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis.
Bevins, Charles L; Salzman, Nita H
Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.
Food Derived Bioactive Peptides and Intestinal Barrier Function
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Olga Martínez-Augustin
Full Text Available A wide range of food-derived bioactive peptides have been shown to exert health-promoting actions and are therefore considered functional foods or nutraceuticals. Some of these actions are related to the maintenance, reinforcement or repairment of the intestinal barrier function (IBF whose role is to selectively allow the absorption of water, nutrients and ions while preventing the influx of microorganisms from the intestinal lumen. Alterations in the IBF have been related to many disorders, such as inflammatory bowel disease or metabolic syndrome. Components of IBF are the intestinal epithelium, the mucus layer, secretory immunoglobulin A and cells of the innate and adaptive immune systems. Here we review the effects of food derived bioactive peptides on these IBF components. In vitro and in vivo effects, both in healthy and disease states, have been reviewed. Although limited, the available information indicates a potential for food-derived peptides to modify IBF and to contribute to disease treatment, but further research is needed to better isolate responsible peptides, and to help define their mode of action.
A role for antimicrobial peptides in intestinal microsporidiosis
Leitch, Gordon J.; Ceballos, Carolina
SUMMARY Clinical isolates from three microsporidia species, Encephalitozoon intestinalis and Encephalitozoon hellem, and the insect parasite Anncaliia (Brachiola, Nosema) algerae, were used in spore germination and enterocyte-like (C2Bbe1) cell infection assays to determine the effect of a panel of antimicrobial peptides. Spores were incubated with lactoferrin (Lf), lysozyme (Lz), and human beta defensin 2 (HBD2), human alpha defensin 5 (HD5), and human alpha defensin 1 (HNP1), alone and in combination with Lz, prior to germination. Of the Encephalitozoon species only E. hellem spore germination was inhibited by HNP1, while A. algerae spore germination was inhibited by Lf, HBD2, HD5 and HNP1, although HBD2 and HD5 inhibition required the presence of Lz. The effects of HBD2 and HD5 on microsporidia enterocyte infection paralleled their effects on spore germination. Lysozyme alone only inhibited infection with A. algerae, while Lf inhibited infection by E. intestinalis and A. algerae. HNP1 significantly reduced enterocyte infection by all three parasite species and a combination of Lf, Lz and HNP1 caused a further reduced infection with A. algerae. These data suggest that intestinal antimicrobial peptides contribute to the defense of the intestine against infection by luminal microsporidia spores and may partially determine which parasite species infects the intestine. PMID:19079820
Designing of peptides with desired half-life in intestine-like environment
Sharma, Arun; Singla, Deepak; Rashid, Mamoon; Raghava, Gajendra Pal Singh
hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical
Effect of vasoactive intestinal peptide, carbachol and other agonists on the membrane voltage of pancreatic duct cells
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Pahl, C; Novak, I
pancreatic ducts and, as a physiological response, we measured the basolateral membrane voltage of the duct cells (Vbl) with microelectrodes. Pancreatic ducts were dissected from pancreas of normal rats and bathed in a HCO(3-)(-containing solution. Under control conditions, the average Vbl was between -50...
Vasoactive intestinal peptide and electrical activity influence neuronal survival
International Nuclear Information System (INIS)
Brenneman, D.E.; Eiden, L.E.
Blockage of electrical activity in dissociated spinal cord cultures results in a significant loss of neurons during a critical period in development. Decreases in neuronal cell numbers and 125 I-labeled tetanus toxin fixation produced by electrical blockage with tetrodotoxin (TTX) were prevented by addition of vasoactive intestinal peptide (VIP) to the nutrient medium. The most effective concentration of VIP was 0.1 nM. At higher concentrations, the survival-enhancing effect of VIP on TTX-treated cultures was attenuated. Addition of the peptide alone had no significant effect on neuronal cell counts or tetanus toxin fixation. With the same experimental conditions, two closely related peptides, PHI-27 (peptide, histidyl-isoleucine amide) and secretin, were found not to increase the number of neurons in TTX-treated cultures. Interference with VIP action by VIP antiserum resulted in neuronal losses that were not significantly different from those observed after TTX treatment. These data indicate that under conditions of electrical blockade a neurotrophic action of VIP on neuronal survival can be demonstrated
Glucagon-like peptide-2 induces rapid digestive adaptation following intestinal resection in preterm neonates
Short bowel syndrome (SBS) is a frequent complication after intestinal resection in infants suffering from intestinal disease. We tested whether treatment with the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) increases intestinal volume and function in the period immediately following in...
Select cognitive deficits in Vasoactive Intestinal Peptide deficient mice
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Hagopian Arkady
Full Text Available Abstract Background The neuropeptide vasoactive intestinal peptide (VIP is widely distributed in the adult central nervous system where this peptide functions to regulate synaptic transmission and neural excitability. The expression of VIP and its receptors in brain regions implicated in learning and memory functions, including the hippocampus, cortex, and amygdala, raise the possibility that this peptide may function to modulate learned behaviors. Among other actions, the loss of VIP has a profound effect on circadian timing and may specifically influence the temporal regulation of learning and memory functions. Results In the present study, we utilized transgenic VIP-deficient mice and the contextual fear conditioning paradigm to explore the impact of the loss of this peptide on a learned behavior. We found that VIP-deficient mice exhibited normal shock-evoked freezing behavior and increases in corticosterone. Similarly, these mutant mice exhibited no deficits in the acquisition or recall of the fear-conditioned behavior when tested 24-hours after training. The VIP-deficient mice exhibited a significant reduction in recall when tested 48-hours or longer after training. Surprisingly, we found that the VIP-deficient mice continued to express circadian rhythms in the recall of the training even in those individual mice whose wheel running wheel activity was arrhythmic. One mechanistic explanation is suggested by the finding that daily rhythms in the expression of the clock gene Period2 continue in the hippocampus of VIP-deficient mice. Conclusion Together these data suggest that the neuropeptide VIP regulates the recall of at least one learned behavior but does not impact the circadian regulation of this behavior.
Primary structure and conformational analysis of peptide methionine-tyrosine, a peptide related to neuropeptide Y and peptide YY isolated from lamprey intestine
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Conlon, J M; Bjørnholm, B; Jørgensen, Flemming Steen
A peptide belonging to the pancreatic-polypeptide-fold family of regulatory peptides has been isolated from the intestine of an Agnathan, the sea lamprey (Petromyzon marinus). The primary structure of the peptide (termed peptide methionine-tyrosine) was established as Met-Pro-Pro-Lys-Pro-Asp-Asn-...... in a preferred structure in which the conformation of the beta-turn between the two helical domains (residues 9-14) is appreciably different....
Actions of vasoactive intestinal peptide and secretin on chief cells prepared from guinea pig stomach
International Nuclear Information System (INIS)
Sutliff, V.E.; Raufman, J.P.; Jensen, R.T.; Gardner, J.D.
Vasoactive intestinal peptide and secretin increased cellular cAMP and pepsinogen secretion in dispersed chief cells from guinea pig gastric mucosa. With each peptide there was a close correlation between the dose-response curve for changes in cellular cAMP and that for changes in pepsinogen secretion. Vasoactive intestinal peptide- (10-28) and secretin- (5-27) had no agonist activity and antagonized the actions of vasoactive intestinal peptide and secretin on cellular cAMP and pepsinogen secretion. Studies of binding of 125 I-vasoactive intestinal peptide and of 125 -secretin indicated that gastric chief cells possess four classes of binding sites for vasoactive intestinal peptide and secretin and that occupation of two of these classes of binding sites correlates with the abilities of vasoactive intestinal peptide and secretin to increase cellular cAMP and pepsinogen secretion. What function, in any, is mediated by occupation by the other two classes of binding sites remains to be determined
Complete sequences of glucagon-like peptide-1 from human and pig small intestine
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Orskov, C; Bersani, M; Johnsen, A H
intestine of the proglucagon precursor were determined by pairs of basic amino acid residues flanking the two peptides. Earlier studies have shown that synthetic glucagon-like peptide-1 (GLP-1) synthesized according to the proposed structure (proglucagon 71-108 or because residue 108 is Gly, 72-107 amide......) had no physiological effects, whereas a truncated from of GLP-1, corresponding to proglucagon 78-107 amide, strongly stimulated insulin secretion and depressed glucagon secretion. To determine the amino acid sequence of the naturally occurring peptide we isolated GLP-1 from human small intestine...
Designing of peptides with desired half-life in intestine-like environment
Sharma, Arun
Background: In past, a number of peptides have been reported to possess highly diverse properties ranging from cell penetrating, tumor homing, anticancer, anti-hypertensive, antiviral to antimicrobials. Owing to their excellent specificity, low-toxicity, rich chemical diversity and availability from natural sources, FDA has successfully approved a number of peptide-based drugs and several are in various stages of drug development. Though peptides are proven good drug candidates, their usage is still hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical properties and half-life.Results: In this study, we have used 10mer (HL10) and 16mer (HL16) peptides dataset to develop prediction models for peptide half-life in intestine-like environment. First, SVM based models were developed on HL10 dataset which achieved maximum correlation R/R2 of 0.57/0.32, 0.68/0.46, and 0.69/0.47 using amino acid, dipeptide and tripeptide composition, respectively. Secondly, models developed on HL16 dataset showed maximum R/R2 of 0.91/0.82, 0.90/0.39, and 0.90/0.31 using amino acid, dipeptide and tripeptide composition, respectively. Furthermore, models that were developed on selected features, achieved a correlation (R) of 0.70 and 0.98 on HL10 and HL16 dataset, respectively. Preliminary analysis suggests the role of charged residue and amino acid size in peptide half-life/stability. Based on above models, we have developed a web server named HLP (Half Life Prediction), for predicting and designing peptides with desired half-life. The web server provides three facilities; i) half-life prediction, ii) physicochemical properties calculation and iii) designing mutant peptides.Conclusion: In summary, this study describes a web server \\'HLP\\' that has been developed for assisting scientific
Vasoactive intestinal peptide is a local mediator in a gut-brain neural axis activating intestinal gluconeogenesis.
De Vadder, F; Plessier, F; Gautier-Stein, A; Mithieux, G
Intestinal gluconeogenesis (IGN) promotes metabolic benefits through activation of a gut-brain neural axis. However, the local mediator activating gluconeogenic genes in the enterocytes remains unknown. We show that (i) vasoactive intestinal peptide (VIP) signaling through VPAC1 receptor activates the intestinal glucose-6-phosphatase gene in vivo, (ii) the activation of IGN by propionate is counteracted by VPAC1 antagonism, and (iii) VIP-positive intrinsic neurons in the submucosal plexus are increased under the action of propionate. These data support the role of VIP as a local neuromodulator released by intrinsic enteric neurons and responsible for the induction of IGN through a VPAC1 receptor-dependent mechanism in enterocytes. © 2015 John Wiley & Sons Ltd.
Gp96 Peptide Antagonist gp96-II Confers Therapeutic Effects in Murine Intestinal Inflammation
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Claudia A. Nold-Petry
Full Text Available BackgroundThe expression of heat shock protein gp96 is strongly correlated with the degree of tissue inflammation in ulcerative colitis and Crohn's disease, thereby leading us to the hypothesis that inhibition of expression via gp96-II peptide prevents intestinal inflammation.MethodsWe employed daily injections of gp96-II peptide in two murine models of intestinal inflammation, the first resulting from five daily injections of IL-12/IL-18, the second via a single intrarectal application of TNBS (2,4,6-trinitrobenzenesulfonic acid. We also assessed the effectiveness of gp96-II peptide in murine and human primary cell culture.ResultsIn the IL-12/IL-18 model, all gp96-II peptide-treated animals survived until day 5, whereas 80% of placebo-injected animals died. gp96-II peptide reduced IL-12/IL-18-induced plasma IFNγ by 89%, IL-1β by 63%, IL-6 by 43% and tumor necrosis factor (TNF by 70% compared to controls. The clinical assessment Disease Activity Index of intestinal inflammation severity was found to be significantly lower in the gp96-II-treated animals when compared to vehicle-injected mice. gp96-II peptide treatment in the TNBS model limited weight loss to 5% on day 7 compared with prednisolone treatment, whereas placebo-treated animals suffered a 20% weight loss. Histological disease severity was reduced equally by prednisolone (by 40% and gp96-II peptide (35%. Mice treated with either gp96-II peptide or prednisolone exhibited improved endoscopic scores compared with vehicle-treated control mice: vascularity, fibrin, granularity, and translucency scores were reduced by up to 49% by prednisolone and by up to 30% by gp96-II peptide. In vitro, gp96-II peptide reduced TLR2-, TLR4- and IL-12/IL-18-induced cytokine expression in murine splenocytes, with declines in constitutive IL-6 (54%, lipopolysaccharide-induced TNF (48%, IL-6 (81% and in Staphylococcus epidermidis-induced TNF (67% and IL-6 (81%, as well as IL-12/IL-18-induced IFNγ (75%. gp
Glucagon-like peptide 2 treatment may improve intestinal adaptation during weaning
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Thymann, Thomas; Le Huërou-Luron, I; Petersen, Y M
Transition from sow's milk to solid feed is associated with intestinal atrophy and diarrhea. We hypothesized that the intestinotrophic hormone glucagon-like peptide 2 (GLP-2) would induce a dose- and health status-dependent effect on gut adaptation. In Exp. 1, weaned pigs (average BW at weaning 4...
Transport of peptidomimetic drugs by the intestinal Di/tri-peptide transporter, PepT1
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Brodin, Birger; Nielsen, Carsten Uhd; Steffansen, Bente
The apical membrane of small intestinal enterocytes possess an uptake system for di- and tripeptides. The physiological function of the system is to transport small peptides resulting from digestion of dietary protein. Moreover, due to the broad substrate specificity of the system, it is also cap...
Immunoneutralization of endogenous glucagon-like peptide-2 reduces adaptive intestinal growth in diabetic rats
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Hartmann, Bolette; Thulesen, Jesper; Hare, Kristine Juul
in the proximal part of the small intestine (10.84+/-0.44 mm(2)). Antibody treatment had no effect on body weight, blood glucose concentrations and food intake. Thus, blocking of endogenous GLP-2 in a model of adaptive intestinal growth reduces the growth response, providing strong evidence for a physiological......Supraphysiological doses of glucagon-like peptide-2 (GLP-2) have been shown to induce intestinal growth by increasing villus height and crypt depth and by decreasing apoptosis, but a physiological effect of GLP-2 has not yet been demonstrated. Earlier, we found elevated levels of endogenous GLP-2...... in untreated streptozotocin diabetic rats associated with marked intestinal growth. In the present study, we investigated the role of endogenous GLP-2 for this adaptive response. We included four groups of six rats: (1) diabetic rats treated with saline, (2) diabetic rats treated with non-specific antibodies...
Autoradiographic quantification of vasoactive intestinal peptide binding sites in sections from human blood mononuclear cell pellets
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Gutkind, J.S.; Kurihara, M.; Castren, E.; Saavedra, J.M.
Quantitative autoradiographic methods were utilized to characterize specific, high-affinity vasoactive intestinal peptide binding sites (Kd = 310 +/- 60 pmol/L; Bmax = 93 +/- 11 fmol/mg protein) in frozen sections obtained from a mononuclear cell pellet derived from 20 ml of human blood. The method is at least one order of magnitude more sensitive than conventional membrane binding techniques, and it has the potential for wide applications in studies of neuropeptide, biogenic amine, and drug binding in clinical samples.
Autoradiographic quantification of vasoactive intestinal peptide binding sites in sections from human blood mononuclear cell pellets
International Nuclear Information System (INIS)
Gutkind, J.S.; Kurihara, M.; Castren, E.; Saavedra, J.M.
Quantitative autoradiographic methods were utilized to characterize specific, high-affinity vasoactive intestinal peptide binding sites (Kd = 310 +/- 60 pmol/L; Bmax = 93 +/- 11 fmol/mg protein) in frozen sections obtained from a mononuclear cell pellet derived from 20 ml of human blood. The method is at least one order of magnitude more sensitive than conventional membrane binding techniques, and it has the potential for wide applications in studies of neuropeptide, biogenic amine, and drug binding in clinical samples
Acylation of salmon calcitonin modulates in vitro intestinal peptide flux through membrane permeability enhancement
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Trier, Sofie; Linderoth, Lars; Bjerregaard, Simon
hypothesize that tailoring the acylation may be used to optimize intestinal translocation. This work aims to characterize acylated analogues of the therapeutic peptide salmon calcitonin (sCT), which lowers blood calcium, by systematically increasing acyl chain length at two positions, in order to elucidate...... to be optimal, as elongating the chain causes greater binding to the cell membrane but similar permeability, and we speculate that increasing the chain length further may decrease the permeability. In conclusion, acylated sCT acts as its own in vitro intestinal permeation enhancer, with reversible effects...... on Caco-2 cells, indicating that acylation of sCT may represent a promising tool to increase intestinal permeability without adding oral permeation enhancers....
Vasoactive intestinal polypeptide and other preprovasoactive intestinal polypeptide-derived peptides in the female and male genital tract: localization, biosynthesis, and functional and clinical significance
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Ottesen, B; Fahrenkrug, J
Vasoactive intestinal polypeptide, a neuropeptide with wide distribution in the central and peripheral nervous system, has a broad spectrum of biologic actions. The demonstration of vasoactive intestinal polypeptide containing nerve fibers within the female and male genital tract 17 years ago...... indicated a putative role for this peptide in the local nervous control of reproductive functions. The genes encoding the preprovasoactive intestinal polypeptide precursor molecule and the vasoactive intestinal polypeptide receptor have been identified. The gene expression has been studied by the use...... in the genital tracts (i.e., blood flow and nonvascular smooth muscle relaxation). In the ovary vasoactive intestinal polypeptide seems to play an important role as regulator and/or modulator of folliculogenesis and steroidogenesis. In the male genital tract vasoactive intestinal polypeptide seems to participate...
Iodinated derivatives of vasoactive intestinal peptide (VIP), PHI and PHM: purification, chemical characterization and biological activity
International Nuclear Information System (INIS)
McMaster, D.; Suzuki, Y.; Rorstad, O.; Lederis, K.
The iodination of vasoactive intestinal peptide (VIP) was studied, using a variety of enzymatic and chemical iodination methods. Reversed phase high performance liquid chromatography (HPLC) was used to purify the reaction products. The lactoperoxidase-glucose oxidase method gave excellent results in terms of reproducibility, iodine incorporation, and yield of the non-oxidized products [Tyr(I)10]VIP and [Tyr(I)22]VIP, and was used to prepare both 125 I and 127 I labelled derivatives. In both cases, direct application to HPLC and a single column system were used. Although the oxidized peptides [Tyr(I)10,Met(O)17]VIP and [Tyr(I)22,Met(O)17]VIP could be generated to varying degrees directly by iodination of VIP, these were most conveniently prepared by iodination of [Met(O)17]VIP. Iodinated derivatives of the homologous peptides PHI and PHM were likewise prepared by rapid, one-step HPLC procedures. The site and degree of iodination were determined by HPLC peptide mapping of tryptic digests and amino acid analyses, and in the case of [Tyr(I)10]VIP also by sequencing. The vasorelaxant activities of the iodinated peptides in bovine cerebral artery preparations did not differ significantly from those of the corresponding noniodinated peptides, with the exception of [Tyr(I)10,Met(O)17]VIP and [Tyr(I)22,Met(O)17]VIP which, unlike [Met(O)17]VIP itself, had slightly lower potency than VIP
Glucagon-like peptide-2 protects impaired intestinal mucosal barriers in obstructive jaundice rats.
Chen, Jun; Dong, Jia-Tian; Li, Xiao-Jing; Gu, Ye; Cheng, Zhi-Jian; Cai, Yuan-Kun
To observe the protective effect of glucagon-like peptide-2 (GLP-2) on the intestinal barrier of rats with obstructive jaundice and determine the possible mechanisms of action involved in the protective effect. Thirty-six Sprague-Dawley rats were randomly divided into a sham operation group, an obstructive jaundice group, and a GLP-2 group; each group consisted of 12 rats. The GLP-2 group was treated with GLP-2 after the day of surgery, whereas the other two groups were treated with the same concentration of normal saline. Alanine aminotransferase (ALT), total bilirubin, and endotoxin levels were recorded at 1, 3, 7, 10 and 14 d. Furthermore, on the 14(th) day, body weight, the wet weight of the small intestine, pathological changes of the small intestine and the immunoglobulin A (IgA) expressed by plasma cells located in the small intestinal lamina propria were recorded for each group. In the rat model, jaundice was obvious, and the rats' activity decreased 4-6 d post bile duct ligation. Compared with the sham operation group, the obstructive jaundice group displayed increased yellow staining of abdominal visceral serosa, decreased small intestine wet weight, thinning of the intestinal muscle layer and villi, villous atrophy, uneven height, fusion, partial villous epithelial cell shedding, substantial inflammatory cell infiltration and significantly reduced IgA expression. However, no significant gross changes were noted between the GLP-2 and sham groups. With time, the levels of ALT, endotoxin and bilirubin in the GLP-2 group were significantly increased compared with the sham group (P jaundice group than in the GLP-2 group (P jaundice rats, which might be attributed to increased intestinal IgA and reduced bilirubin and endotoxin.
How the intestinal peptide transporter PEPT-1 contributes to an obesity phenotype in Caenorhabditits elegans.
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Britta Spanier
Full Text Available BACKGROUND: Amino acid absorption in the form of di- and tripeptides is mediated by the intestinal proton-coupled peptide transporter PEPT-1 (formally OPT-2 in Caenorhabditits elegans. Transporter-deficient animals (pept-1(lg601 show impaired growth, slowed postembryonal development and major changes in amino acid status. PRINCIPAL FINDINGS: Here we demonstrate that abolished intestinal peptide transport also leads to major metabolic alterations that culminate in a two fold increase in total body fat content. Feeding of C. elegans with [U-(13C]-labelled E. coli revealed a decreased de novo synthesis of long-chain fatty acids in pept-1(lg601 and reduced levels of polyunsaturated fatty acids. mRNA profiling revealed increased transcript levels of enzymes/transporters needed for peroxisomal beta-oxidation and decreased levels for those required for fatty acid synthesis, elongation and desaturation. As a prime and most fundamental process that may account for the increased fat content in pept-1(lg601 we identified a highly accelerated absorption of free fatty acids from the bacterial food in the intestine. CONCLUSIONS: The influx of free fatty acids into intestinal epithelial cells is strongly dependent on alterations in intracellular pH which is regulated by the interplay of PEPT-1 and the sodium-proton exchanger NHX-2. We here provide evidence for a central mechanism by which the PEPT-1/NHX-2 system strongly influences the in vivo fat content of C. elegans. Loss of PEPT-1 decreases intestinal proton influx leading to a higher uptake of free fatty acids with fat accumulation whereas loss of NHX-2 causes intracellular acidification by the PEPT-1 mediated proton/dipeptide symport with an almost abolished uptake of fatty acids and a lean phenotype.
Effect of Cordyceps sinensis mycelium on serum vasoactive intestinal peptide and substance P in mice with intestinal dysbacteriosis
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Kai-zhong DONG
Full Text Available Objective To observe the effect of Cordyceps sinensis mycelium on serum vasoactive intestinal peptide (VIP and substance P (SP in mice with dysbacteriosis induced by antibiotics. Methods Forty-eight healthy SPF BALB/c mice were randomly divided into the normal control group (normal drink, the dysbacteriosis model group (induced by oral administration of 0.5 g/L ceftriaxone sodium, the natural recovery group (oral sterile water to replace antibiotic after reproduction of dysbacteriosis, and Cordyceps sinensis mycelium treatment group (treated by intragastric administration of Cordyceps sinensis mycelium. The feces were collected without contamination, and the change in intestinal bacterial number was observed with the plate dilution method. The volatile fatty acid was detected by chromatography. The serum VIP and SP contents were assayed with enzyme linked immunosorbent assay (ELISA. Results Compared with the normal control group, the numbers of probiotics, volatile fatty acids and serum VIP significantly decreased in the model group, while the serum SP markedly increased (P<0.01. Compared with the natural recovery group, the bacteria number, the quantities of volatile fatty acids and serum VIP significantly increased after the Cordyceps sinensis mycelium treatment, while the serum SP significantly decreased (P<0.01, P<0.05. Conclusion Cordyceps sinensis mycelium may effectively adjust the proportion of the probiotics in the mice with dysbacteriosis, and the mechanism is apparently related to alteration in the VIP and SP. DOI: 10.11855/j.issn.0577-7402.2014.11.06
β-Casein(94-123)-derived peptides differently modulate production of mucins in intestinal goblet cells.
Plaisancié, Pascale; Boutrou, Rachel; Estienne, Monique; Henry, Gwénaële; Jardin, Julien; Paquet, Armelle; Léonil, Joëlle
We recently reported the identification of a peptide from yoghurts with promising potential for intestinal health: the sequence (94-123) of bovine β-casein. This peptide, composed of 30 amino acid residues, maintains intestinal homoeostasis through production of the secreted mucin MUC2 and of the transmembrane-associated mucin MUC4. Our study aimed to search for the minimal sequence responsible for the biological activity of β-CN(94-123) by using several strategies based on (i) known bioactive peptides encrypted in β-CN(94-123), (ii) in silico prediction of peptides reactivity and (iii) digestion of β-CN(94-123) by enzymes of intestinal brush border membranes. The revealed sequences were tested in vitro on human intestinal mucus-producing HT29-MTX cells. We demonstrated that β-CN(108-113) (an ACE-inhibitory peptide) and β-CN(114-119) (an opioid peptide named neocasomorphin-6) up-regulated MUC4 expression whereas levels of the secreted mucins MUC2 and MUC5AC remained unchanged. The digestion of β-CN(94-123) by intestinal enzymes showed that the peptides β-CN(94-108) and β-CN(117-123) were present throughout 1·5 to 3 h of digestion, respectively. These two peptides raised MUC5AC expression while β-CN(117-123) also induced a decrease in the level of MUC2 mRNA and protein. In addition, this inhibitory effect was reproduced in airway epithelial cells. In conclusion, β-CN(94-123) is a multifunctional molecule but only the sequence of 30 amino acids has a stimulating effect on the production of MUC2, a crucial factor of intestinal protection.
A Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure
DEFF Research Database (Denmark)
Sigalet, David L; Brindle, Mary; Boctor, Dana
BACKGROUND AND AIMS: A glucagon-like peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure. METHODS: Native...... human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2...... nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement...
Intestinal permeability and glucagon-like peptide-2 in children with autism
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Robertson, Marli A; Sigalet, David L; Holst, Jens Juul
We measured small intestinal permeability using a lactulose:mannitol sugar permeability test in a group of children with autism, with current or previous gastrointestinal complaints. Secondly, we examined whether children with autism had an abnormal glucagon-like peptide-2 (GLP-2) response...... to feeding. Results were compared with sibling controls and children without developmental disabilities. We enrolled 14 children with autism, 7 developmentally normal siblings of these children and 8 healthy, developmentally normal, unrelated children. Our study did not detect differences in these measures...... of gastrointestinal function in a group of children with autism....
Fundamental and clinical evaluation of vasoactive intestinal peptide (VIP) in pancreatitis by radioimmunoassay kit
International Nuclear Information System (INIS)
Uehara, Soichiro; Nakamura, Takayuki; Ihara, Kenichi; Isogawa, Shin; Hirayama, Akio
Plasma vasoactive intestinal peptide (VIP) concentrations of normal individuals and patients with pancreatitis were studied using a VIP RIA kit. The inter-assay and intra-assay variation of this kit were between 2.1 and 9.4 %. The VIP levels increased in the acute phase of acute pancreatitis and patients with chronic pancreatitis. The VIP concentration increased during the first 30 min of glucose tolerance test, but this increase was much smaller than that in insulin. These results suggest that this kit is useful for physiologic and pathologic changes in the VIP level. (author)
Oral absorption of peptides and nanoparticles across the human intestine: Opportunities, limitations and studies in human tissues.
Lundquist, P; Artursson, P
In this contribution, we review the molecular and physiological barriers to oral delivery of peptides and nanoparticles. We discuss the opportunities and predictivity of various in vitro systems with special emphasis on human intestine in Ussing chambers. First, the molecular constraints to peptide absorption are discussed. Then the physiological barriers to peptide delivery are examined. These include the gastric and intestinal environment, the mucus barrier, tight junctions between epithelial cells, the enterocytes of the intestinal epithelium, and the subepithelial tissue. Recent data from human proteome studies are used to provide information about the protein expression profiles of the different physiological barriers to peptide and nanoparticle absorption. Strategies that have been employed to increase peptide absorption across each of the barriers are discussed. Special consideration is given to attempts at utilizing endogenous transcytotic pathways. To reliably translate in vitro data on peptide or nanoparticle permeability to the in vivo situation in a human subject, the in vitro experimental system needs to realistically capture the central aspects of the mentioned barriers. Therefore, characteristics of common in vitro cell culture systems are discussed and compared to those of human intestinal tissues. Attempts to use the cell and tissue models for in vitro-in vivo extrapolation are reviewed. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
In vitro and in vivo evaluation of a water-in-oil microemulsion system for enhanced peptide intestinal delivery.
Liu, Dongyun; Kobayashi, Taku; Russo, Steven; Li, Fengling; Plevy, Scott E; Gambling, Todd M; Carson, Johnny L; Mumper, Russell J
Peptide and protein drugs have become the new generation of therapeutics, yet most of them are only available as injections, and reports on oral local intestinal delivery of peptides and proteins are quite limited. The aim of this work was to develop and evaluate a water-in-oil (w/o) microemulsion system in vitro and in vivo for local intestinal delivery of water-soluble peptides after oral administration. A fluorescent labeled peptide, 5-(and-6)-carboxytetramethylrhodamine labeled HIV transactivator protein TAT (TAMRA-TAT), was used as a model peptide. Water-in-oil microemulsions consisting of Miglyol 812, Capmul MCM, Tween 80, and water were developed and characterized in terms of appearance, viscosity, conductivity, morphology, and particle size analysis. TAMRA-TAT was loaded and its enzymatic stability was assessed in modified simulated intestinal fluid (MSIF) in vitro. In in vivo studies, TAMRA-TAT intestinal distribution was evaluated using fluorescence microscopy after TAMRA-TAT microemulsion, TAMRA-TAT solution, and placebo microemulsion were orally gavaged to mice. The half-life of TAMRA-TAT in microemulsion was enhanced nearly three-fold compared to that in the water solution when challenged by MSIF. The treatment with TAMRA-TAT microemulsion after oral administration resulted in greater fluorescence intensity in all intestine sections (duodenum, jejunum, ileum, and colon) compared to TAMRA-TAT solution or placebo microemulsion. The in vitro and in vivo studies together suggested TAMRA-TAT was better protected in the w/o microemulsion in an enzyme-containing environment, suggesting that the w/o microemulsions developed in this study may serve as a potential delivery vehicle for local intestinal delivery of peptides or proteins after oral administration.
Bile acids induce glucagon-like peptide 2 secretion with limited effects on intestinal adaptation in early weaned pigs
DEFF Research Database (Denmark)
Ipharraguerre, Ignacio R; Tedó, Gemma; Menoyo, David
Early weaning is a stressful event characterized by a transient period of intestinal atrophy that may be mediated by reduced secretion of glucagon-like peptide (GLP) 2. We tested whether enterally fed bile acids or plant sterols could increase nutrient-dependent GLP-2 secretion and improve.......05) but did not affect plasma GLP-1 and feed intake. The intestinal expression of glucagon-like peptide 2 receptor, sodium-dependent bile acid transporter, farnesoid X receptor, and guanosine protein-coupled bile acid receptor genes were not affected by CDC treatment. The intragastric administration of CDC...
Effects of pig antibacterial peptides on growth performance and intestine mucosal immune of broiler chickens.
Bao, H; She, R; Liu, T; Zhang, Y; Peng, K S; Luo, D; Yue, Z; Ding, Y; Hu, Y; Liu, W; Zhai, L
Currently, substitutions for antibiotic growth promoters in animals are attracting interest. This study investigated the effects of pig antibacterial peptides (PABP) on growth performance and small intestine mucosal immune responses in broilers. Three hundred 1-d-old Arbor Acre male broiler chickens were randomly allocated to 5 groups with 60 birds per group. The groups were control group; PABP administered in drinking water at 20 and 30 mg/L of water; or PABP supplemented in feed at 150 and 200 mg/kg of diet. The birds were fed a corn-soybean based diet for 6 wk. Chickens were weighed weekly and killed after 42 d of feeding, and growth performance was measured. Samples of the duodenum and jejunum were collected. The villus height, mucosa thickness, alkaline phosphatase activity, and numbers of secreting IgA and goblet cells were evaluated. The PABP-treated groups had greater BW and average daily gain, greater height of villus and thickness of gut mucosa, greater activity of alkaline phosphatase, higher ratio of secreting IgA, and a greater number of goblet cells compared with the control group (P<0.05). In conclusion, PABP can improve the growth performance, increase the intestinal ability to absorb nutrients, and improve the mucosal immunity of the intestine.
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in the circulation after sumatriptan
DEFF Research Database (Denmark)
Hansen, Jakob Møller; Fahrenkrug, Jan; Petersen, Jesper Troensegaard
The origin of migraine pain is still elusive, but increasingly researchers focus on the neuropeptides in the perivascular space of cranial vessels as important mediators of nociceptive input during migraine attacks. The parasympathetic neurotransmitters, pituitary adenylate cyclase activating...... peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) may be released from parasympathetic fibres and activate sensory nerve fibres during migraine attacks. Triptans are effective and well tolerated in acute migraine management but the exact mechanism of action is still debated. Triptans might...
Receptors for vasoactive intestinal peptide in rat anterior pituitary glands: Localization of binding to lactotropes
International Nuclear Information System (INIS)
Wanke, I.E.; Rorstad, O.P.
Vasoactive intestinal peptide (VIP) has been implicated as a physiological PRL-releasing factor; however, characterization of VIP receptors on normal pituitaries using radioligand-binding methods has been problematic. In this study we demonstrated specific receptors for VIP in anterior pituitary glands of female rats using HPLC-purified monoiodinated [Tyr(125I)10]VIP. Binding of VIP was reversible, saturable to receptor and radioligand, regulated by guanine nucleotides, and dependent on time and temperature. Scatchard analysis of competitive binding studies indicated high and low affinity binding sites, with equilibrium dissociation constants (Kd) of 0.19 +/- 0.03 and 28 +/- 16 nM, respectively. The corresponding maximum numbers of binding sites were 158 +/- 34 fmol/mg and 11.7 +/- 6.9 pmol/mg. Binding was specific, as peptides with structural homology to VIP were less than 100th as potent as VIP. The rank order of potency of the peptides tested was VIP greater than rat (r) peptide histidine isoleucine = human (h) PHI greater than rGRF greater than bovine GRF = porcine PHI = VIP-(10-28) greater than hGRF greater than secretin greater than apamin greater than glucagon. Radioligand binding was associated primarily with lactotrope-enriched fractions prepared by unit gravity sedimentation of dispersed anterior pituitary cells. VIP stimulated PRL release from cultured rat anterior pituitary cells, with an ED50 of 1 nM. These results, comprising the first identification of specific VIP receptors in normal rat anterior pituitary tissue using radioligand-binding methods, provide additional support for a biological role of VIP in lactotrope function
Exenatide, a Glucagon-like Peptide-1 Receptor Agonist, Acutely Inhibits Intestinal Lipoprotein Production in Healthy Humans
Xiao, Changting; Bandsma, Robert H. J.; Dash, Satya; Szeto, Linda; Lewis, Gary F.
Objective-Incretin-based therapies for the treatment of type 2 diabetes mellitus improve plasma lipid profiles and postprandial lipemia, but their exact mechanism of action remains unclear. Here, we examined the acute effect of the glucagon-like peptide-1 receptor agonist, exenatide, on intestinal
Expression of an antimicrobial peptide, digestive enzymes and nutrient transporters in the intestine of E. praecox-infected chickens
Coccidiosis is a major intestinal disease of poultry, caused by several species of the protozoan Eimeria. The objective of this study was to examine changes in expression of digestive enzymes, nutrient transporters and an antimicrobial peptide following an Eimeria praecox challenge of chickens at d...
Model prodrugs for the intestinal peptide transporter. a synthetic approach for coupling of hydroxy-containing compounds to dieptides
DEFF Research Database (Denmark)
Friedrichsen, G; Nielsen, Carsten Uhd; Steffansen, Bente
The human peptide transporter, hPepT1, situated in the small intestine, may be exploited to increase absorption of drugs or model drugs by attaching them to a dipeptide, which is recognised by hPepT1. A synthetic protocol for this kind of model prodrugs was developed, in which model drugs...
A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure
DEFF Research Database (Denmark)
Sigalet, David L; Brindle, Mary E; Boctor, Dana
BACKGROUND & AIMS: Glucagon-like peptide 2 (GLP-2) analogues are approved for adults with intestinal failure (IF), but no studies have included infants. This study examined the pharmacokinetics (PK), safety, and nutritional effects of GLP-2 in infants with IF. METHODS: With parental consent (Health...
Clostridium difficile suppresses colonic vasoactive intestinal peptide associated with altered motility
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A. Nassif
Full Text Available We investigated whether Clostridium difficile toxin alters colonic tissue levels of vasoactive intestinal peptide (VIP at the expense of changes in colonic motility in the isolated perfused rabbit left colon. Colonic inflammation was induced by the intracolonic administration of 10−8 M C. difflcile toxin. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. C. difflcile administration produced histologic changes consistent with epithelial damage. This was associated with an increased production of prostaglandin E2 and thromboxane B2. Tissue levels of VIP but not substance P were significantly reduced. This was associated with an increased number of contractions per minute and an average force of each colonic contraction. These results suggest that tissue levels of VIP are suppressed by C. difflcile and may participate in colonic dysmotility during active inflammation.
Design, Recombinant Fusion Expression and Biological Evaluation of Vasoactive Intestinal Peptide Analogue as Novel Antimicrobial Agent
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Chunlan Xu
Full Text Available Antimicrobial peptides represent an emerging category of therapeutic agents with remarkable structural and functional diversity. Modified vasoactive intestinal peptide (VIP (VIP analogue 8 with amino acid sequence "FTANYTRLRRQLAVRRYLAAILGRR" without haemolytic activity and cytotoxicity displayed enhanced antimicrobial activities against Staphylococcus aureus (S. aureus ATCC 25923 and Escherichia coli (E. coli ATCC 25922 than parent VIP even in the presence of 180 mM NaCl or 50 mM MgCl2, or in the range of pH 4–10. VIP analogue 8 was expressed as fusion protein thioredoxin (Trx-VIP8 in E. coli BL21(DE at a yield of 45.67 mg/L. The minimum inhibitory concentration (MIC of the recombinant VIP analogue 8 against S. aureus ATCC 25923 and E. coli ATCC 25922 were 2 μM. These findings suggest that VIP analogue 8 is a promising candidate for application as a new and safe antimicrobial agent.
Expression of host defense peptides in the intestine of Eimeria-challenged chickens.
Su, S; Dwyer, D M; Miska, K B; Fetterer, R H; Jenkins, M C; Wong, E A
Avian coccidiosis is caused by the intracellular protozoan Eimeria, which produces intestinal lesions leading to weight gain depression. Current control methods include vaccination and anticoccidial drugs. An alternative approach involves modulating the immune system. The objective of this study was to profile the expression of host defense peptides such as avian beta-defensins (AvBDs) and liver expressed antimicrobial peptide 2 (LEAP2), which are part of the innate immune system. The mRNA expression of AvBD family members 1, 6, 8, 10, 11, 12, and 13 and LEAP2 was examined in chickens challenged with either E. acervulina, E. maxima, or E. tenella. The duodenum, jejunum, ileum, and ceca were collected 7 d post challenge. In study 1, E. acervulina challenge resulted in down-regulation of AvBD1, AvBD6, AvBD10, AvBD11, AvBD12, and AvBD13 in the duodenum. E. maxima challenge caused down-regulation of AvBD6, AvBD10, and AvBD11 in the duodenum, down-regulation of AvBD10 in the jejunum, but up-regulation of AvBD8 and AvBD13 in the ceca. E. tenella challenge showed no change in AvBD expression in any tissue. In study 2, which involved challenge with only E. maxima, there was down-regulation of AvBD1 in the ileum, AvBD11 in the jejunum and ileum, and LEAP2 in all 3 segments of the small intestine. The expression of LEAP2 was further examined by in situ hybridization in the jejunum of chickens from study 2. LEAP2 mRNA was expressed similarly in the enterocytes lining the villi, but not in the crypts of control and Eimeria challenged chickens. The lengths of the villi in the Eimeria challenged chickens were less than those in the control chickens, which may in part account for the observed down-regulation of LEAP2 mRNA quantified by PCR. Overall, the AvBD response to Eimeria challenge was not consistent; whereas LEAP2 was consistently down-regulated, which suggests that LEAP2 plays an important role in modulating an Eimeria infection. Published by Oxford University Press on
Enteroendocrine-derived glucagon-like peptide-2 controls intestinal amino acid transport.
Lee, Jennifer; Koehler, Jacqueline; Yusta, Bernardo; Bahrami, Jasmine; Matthews, Dianne; Rafii, Mahroukh; Pencharz, Paul B; Drucker, Daniel J
Glucagon-like peptide-2 (GLP-2) is co-secreted with GLP-1 from gut endocrine cells, and both peptides act as growth factors to expand the surface area of the mucosal epithelium. Notably, GLP-2 also enhances glucose and lipid transport in enterocytes; however, its actions on control of amino acid (AA) transport remain unclear. Here we examined the mechanisms linking gain and loss of GLP-2 receptor (GLP-2R) signaling to control of intestinal amino acid absorption in mice. Absorption, transport, and clearance of essential AAs, specifically lysine, were measured in vivo by Liquid Chromatography triple quadrupole Mass Spectrometry (LC-MS/MS) and ex vivo with Ussing chambers using intestinal preparations from Glp2 r +/+ and Glp2r - / - mice. Immunoblotting determined jejunal levels of protein components of signaling pathways (PI3K-AKT, and mTORC1-pS6-p4E-BP1) following administration of GLP-2, protein gavage, and rapamycin to fasted Glp2 r +/+ and Glp2r - / - mice. Expression of AA transporters from full thickness jejunum and 4F2hc from brush border membrane vesicles (BBMVs) was measured by real-time PCR and immunoblotting, respectively. Acute administration of GLP-2 increased basal AA absorption in vivo and augmented basal lysine transport ex vivo . GLP-2-stimulated lysine transport was attenuated by co-incubation with wortmannin, rapamycin, or tetrodotoxin ex vivo . Phosphorylation of mTORC1 effector proteins S6 and 4E-BP1 was significantly increased in wild-type mice in response to GLP-2 alone, or when co-administered with protein gavage, and abolished following oral gavage of rapamycin. In contrast, activation of GLP-1R signaling did not enhance S6 phosphorylation. Disruption of GLP-2 action in Glp2r -/- mice reduced lysine transport ex vivo and attenuated the phosphorylation of S6 and 4E-BP1 in response to oral protein. Moreover, the expression of cationic AA transporter slc7a9 in response to refeeding, and the abundance of 4F2hc in BBMVs following protein
Unusual chemical properties of N-terminal histidine residues of glucagon and vasoactive intestinal peptide
International Nuclear Information System (INIS)
Hefford, M.A.; Evans, R.M.; Oda, G.; Kaplan, H.
An N-terminal histidine residue of a protein or peptide has two functional groups, viz., an alpha-amino group and an imidazole group. A new procedure, based on the competitive labeling approach described by Duggleby and Kaplan has been developed by which the chemical reactivity of each functional group in such a residue can be determined as a function of pH. Only very small amounts of material are required, which makes it possible to determine the chemical properties in dilute solution or in proteins and polypeptides that can be obtained in only minute quantities. With this approach, the reactivity of the alpha-amino group of histidylglycine toward 1-fluoro-2,4-dinitrobenzene gave an apparent pK /sub a/ value of 7.64 +/- 0.07 at 37 degrees C, in good agreement with a value of 7.69 +/- 0.02 obtained by acid-base titration. However, the reactivity of the imidazole function gave an apparent pK /sub a/ value of 7.16 +/- 0.07 as compared to the pK /sub a/ value of 5.85 +/- 0.01 obtained by acid-base titration. Similarly, in glucagon and vasoactive intestinal peptide (VIP), apparent pKa values of 7.60 +/- 0.04 and 7.88 +/- 0.18, respectively, were obtained for the alpha-amino of their N-terminal histidine, and pKa values of 7.43 +/- 0.09 and 7.59 +/- 0.18 were obtained for the imidazole function
LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose.
Powell, David R; Smith, Melinda; Greer, Jennifer; Harris, Angela; Zhao, Sharon; DaCosta, Christopher; Mseeh, Faika; Shadoan, Melanie K; Sands, Arthur; Zambrowicz, Brian; Ding, Zhi-Ming
LX4211 [(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol], a dual sodium/glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor, is thought to decrease both renal glucose reabsorption by inhibiting SGLT2 and intestinal glucose absorption by inhibiting SGLT1. In clinical trials in patients with type 2 diabetes mellitus (T2DM), LX4211 treatment improved glycemic control while increasing circulating levels of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). To better understand how LX4211 increases GLP-1 and PYY levels, we challenged SGLT1 knockout (-/-) mice, SGLT2-/- mice, and LX4211-treated mice with oral glucose. LX4211-treated mice and SGLT1-/- mice had increased levels of plasma GLP-1, plasma PYY, and intestinal glucose during the 6 hours after a glucose-containing meal, as reflected by area under the curve (AUC) values, whereas SGLT2-/- mice showed no response. LX4211-treated mice and SGLT1-/- mice also had increased GLP-1 AUC values, decreased glucose-dependent insulinotropic polypeptide (GIP) AUC values, and decreased blood glucose excursions during the 6 hours after a challenge with oral glucose alone. However, GLP-1 and GIP levels were not increased in LX4211-treated mice and were decreased in SGLT1-/- mice, 5 minutes after oral glucose, consistent with studies linking decreased intestinal SGLT1 activity with reduced GLP-1 and GIP levels 5 minutes after oral glucose. These data suggest that LX4211 reduces intestinal glucose absorption by inhibiting SGLT1, resulting in net increases in GLP-1 and PYY release and decreases in GIP release and blood glucose excursions. The ability to inhibit both intestinal SGLT1 and renal SGLT2 provides LX4211 with a novel dual mechanism of action for improving glycemic control in patients with T2DM.
Neuropeptide Y-like immunoreactivity in rat cranial parasympathetic neurons: coexistence with vasoactive intestinal peptide and choline acetyltransferase
International Nuclear Information System (INIS)
Leblanc, G.C.; Trimmer, B.A.; Landis, S.C.
Neuropeptide Y (NPY) is widely distributed in the sympathetic nervous system, where it is colocalized with norepinephrine. The authors report here that NPY-immunoreactive neurons are also abundant in three cranial parasympathetic ganglia, the otic, sphenopalatine, and ciliary, in the rat measured by radioimmunoassay. High-performance liquid chromatographic analysis of the immunoreactive material present in the otic ganglion indicates that this material is very similar to porcine NPY and indistinguishable from the NPY-like immunoreactivity present in rat sympathetic neurons. These findings raise the possibility that NPY acts as a neuromodulator in the parasympathetic as well as the sympathetic nervous system. In contrast to what had been observed for sympathetic neurons, NPY-immunoreactive neurons in cranial parasympathetic ganglia do not contain detectable catecholamines or tyrosine hydroxylase immunoreactivity, and many do contain immunoreactivity for vasoactive intestinal peptide and/or choline acetyltransferase. These findings suggest that there is no simple rule governing coexpression of NPY with norepinephrine, acetylcholine, or vasoactive intestinal peptide in autonomic neurons. Further, while functional studies have indicated that NPY exerts actions on the peripheral vasculature which are antagonistic to those of acetylcholine and vasoactive intestinal peptide, the present results raise the possibility that these three substances may have complementary effects on other target tissues
Enteral peptide formulas inhibit radiation induced enteritis and apoptosis in intestinal epithelial cells and suppress the expression and function of Alzheimer's and cell division control gene products
International Nuclear Information System (INIS)
Cope, F.O.; Issinger, O.G.; McArdle, A.H.; Shapiro, J.; Tomei, L.D.
Studies have shown that patients receiving enteral peptide formulas prior to irradiation have a significantly reduced incidence of enteritis and express a profound increase in intestinal cellularity. Two conceptual approaches were taken to describe this response. First was the evaluation in changes in programmed intestinal cell death and secondly the evaluation of a gene product controlling cell division cycling. This study provided a relationship between the ratio of cell death to cell formulations. The results indicate that in the canine and murine models, irradiation induces expression of the Alzheimer's gene in intestinal crypt cells, while the incidence of apoptosis in apical cells is significantly increased. The use of peptide enteral formulations suppresses the expression of the Alzheimer's gene in crypt cells, while apoptosis is eliminated in the apical cells of the intestine. Concomitantly, enteral peptide formulations suppress the function of the CK-II gene product in the basal and baso-lateral cells of the intestine. These data indicate that although the mitotic index is significantly reduced in enterocytes, this phenomenon alone is not sufficient to account for the peptide-induced radio-resistance of the intestine. The data also indicate a significant reduction of normal apoptosis in the upper lateral and apical cells of the intestinal villi. Thus, the ratio of cell death to cell replacement is significantly decreased resulting in an increase in villus height and hypertrophy of the apical villus cells. Thus, peptide solutions should be considered as an adjunct treatment both in radio- and chemotherapy
Effects of vasoactive intestinal peptide on vascular conductance are unaffected by anesthesia
International Nuclear Information System (INIS)
Bouder, T.G.; Huffman, L.J.; Hedge, G.A.
In rats anesthetized with ketamine and pentobarbital (KET/PB), vasoactive intestinal peptide (VIP) increases vascular conductance (VC) in the salivary gland, pancreas, and thyroid gland, whereas no changes in VC are observed in a number of other organs. Because anesthesia may alter the responsiveness of physiological systems, we compared the effects of VIP on organ VC in conscious or anesthetized rats. Chronically catheterized rats were studied in the conscious state or 30 min after induction of anesthesia with KET/PB, isoflurane, or Inactin. Blood flows were measured by the reference sample version of the radioactive microsphere (MS) technique using two MS injections ( 141 Ce-MS/ 85 Sr-MS). Mean arterial blood pressure was monitored and used in the calculation of VC. Organ VCs were similar under basal conditions in conscious and anesthetized rats. VIP infusion caused systemic hypotension and increased VCs in the salivary gland, pancreas, and thyroid gland, and these responses were largely unaffected by anesthesia. These results indicate that the anesthetics used do not alter basal VC or the responsiveness of the vasculature to exogenous VIP
Electroacupuncture Inhibits Inflammation Reaction by Upregulating Vasoactive Intestinal Peptide in Rats with Adjuvant-Induced Arthritis
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Tian-Feng He
Full Text Available Acupuncture is emerging as an alternative therapy for rheumatoid arthritis (RA. However, the molecular mechanism underlying this beneficial effect of acupuncture has not been fully understood. Here, we demonstrated that electroacupuncture at acupoints Zusanli (ST36, Xuanzhong (GB39; and Shenshu (BL23 markedly decreased the paw swelling and the histologic scores of inflammation in the synovial tissue, and reduced the body weight loss in an adjuvant-induced arthritis rat model. However, the electrical stimulation at nonacupoint did not produce any beneficial effects against the experimental arthritis. Most interestingly, the electroacupuncture treatment resulted in an enhanced immunostaining for vasoactive intestinal peptide (VIP, a potent anti-inflammatory neuropeptide, in the synovial tissue. Moreover, the VIP-immunostaining intensity was significantly negatively correlated with the scores of inflammation in the synovial tissue (r=−0.483, P=.0026. In conclusion, these findings suggest that electroacupuncture may offer therapeutic benefits for the treatment of RA, at least partially through the induction of VIP expression.
Vasoactive intestinal peptide and somatostatin in the plasma and sigmoid mucosa in irritable bowel syndrome
International Nuclear Information System (INIS)
Zhang Ru; Wang Fuxian
To investigate the possible role and clinical significance of vasoactive intestinal peptide (VIP) and somatostatin(SS) in the irritable bowel syndrome (IBS), the VIP and SS in the plasma and sigmoid mucosa were measured by radioimmunoassay in the control group and the IBS group. The VIP concentration in the plasma and sigmoid mucosa of the IBS patients with constipation was significantly higher than that of the control group (P<0.01), while that of the IBS patients with diarrhea was significantly lower than that of the control group (P<0.05). The SS concentration in two sites was significantly elevated in IBS patients of both types and was significantly higher in IBS with constipation than in IBS with diarrhea (P<0.05). Conclusion: The VIP and SS in IBS are abnormal, which might play a role in the pathogenesis of IBS. The plasma and mucosa concenration of VIP and SS in two kinds of IBS patients are significantly different, which indicates that there might be different pathophysiological basis involved in the pathogenesis of the two kinds of IBS patients. (authors)
Structure-activity studies of vasoactive intestinal peptide (VIP): cyclic disulfide analogs.
Bolin, D R; Cottrell, J; Garippa, R; O'Neill, N; Simko, B; O'Donnell, M
Analogs of vasoactive intestinal peptide with cysteine residues incorporated at selected sites within the sequence were prepared by solid phase methods, oxidized to the corresponding cyclic disulfides and purified to homogeneity by preparative HPLC. The cyclic compounds were assayed as smooth muscle relaxants on isolated guinea pig trachea, as bronchodilators in vivo in guinea pigs, and for binding to VIP receptors in guinea pig lung membranes. Of the analogs prepared at the N-terminus, one compound, Ac-[D-Cys6,D-Cys11,Lys12,Nle17,Val26,Th r28]-VIP, was found to be a full agonist with slightly more than one tenth the potency of native VIP. Most other cyclic analogs in the N-terminal region were found to be inactive. A second analog, Ac-[Lys12,Cys17,Val26,Cys28]-VIP, was also found to be a full agonist with potency about one third that of native VIP. Furthermore, this compound was active as a bronchodilator in vivo in guinea pig, but with somewhat diminished potency as compared to native VIP. Strikingly, this cyclic compound was found to have significantly longer duration of action (> 40 min) when compared to an analogous acyclic compound (5 min). The conformational restrictions imposed by formation of the cyclic ring structures may have stabilized the molecule to degradation, thus enhancing the effective duration of action. Analysis of this series of cyclic analogs has also yielded information about the requirements for the receptor-active conformation of VIP.
Vasoactive intestinal peptide (VIP) labelling with iodine-131 by direct method
International Nuclear Information System (INIS)
Colturato, M.T.; Silva, C.P.G. da; Araujo, E.B.
The Vasoactive Intestinal Peptide (VIP) is a 28-amino acid polypeptide with a great numbers of receptors in tumoral cells, including adenocarcinomas and pancreatic and colon carcinomas. The VIP molecule contains two tyrosine residues, in positions 10 and 22, that are theoretically equally susceptible to iodination, The VIP was labeled with 131-iodine by direct method using Iodogen as oxidant agent: 15.03 mmol VIP + 0.10 nmol KI + [ 131 I]NaI + 13.9 mmol Iodogen; the final volume was adjust to 100 μL using 0.2 M phosphate buffer, pH 7.5 and the reaction proceed with stirring for 30 minutes at room temperature. The radiochemical purity was determined by electrophoresis (Whatman 1MM paper; 0.05 M barbital buffer; pH 8.6; 150 V; 40 minutes) that indicates low percent of free 131-iodine. The high performance liquid chromatography (HPLC) system using RPC 18 , 10 μm, 4 x 250mm column, was able to separate the different radiochemical species, only when an isocratic mixture of acetonitrile: 0.1% trifluoroacetic acid (27:73) was used, with 0.5 mL/min. flux. (author)
Direct demonstration of guanine nucleotide sensitive receptors for vasoactive intestinal peptide in the anterior lobe of the rat pituitary gland
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Agui, T.; Matsumoto, K.
The vasoactive intestinal peptide (VIP) receptors were identified on the membranes from the rat anterior pituitary gland with [ 125 I]VIP. The dissociation constant (Kd) and the maximal binding capacity (Bmax) values were estimated from the competitive inhibition data. The Kd and Bmax values were 1.05 +/- 0.75 nM and 103 +/- 11 fmol/mg protein, respectively. The order of molar potency of related peptides to inhibit [ 125 I]VIP binding was VIP greater than peptide histidine isoleucine (PHI) greater than secretin greater than glucagon. Glucagon was not effective to inhibit the binding. [ 125 I]VIP binding was effectively inhibited by the addition of guanine nucleotides. The order of molar potency to inhibit the binding was Gpp(NH)p greater than GTP greater than GDP greater than GMP greater than ATP. These results directly suggest the coupling of VIP receptors with guanine nucleotide binding proteins in the anterior pituitary gland
Mechanistic studies of a cell-permeant peptide designed to enhance myosin light chain phosphorylation in polarized intestinal epithelia.
Almansour, Khaled; Taverner, Alistair; Eggleston, Ian M; Mrsny, Randall J
Tight junction (TJ) structures restrict the movement of solutes between adjacent epithelial cells to maintain homeostatic conditions. A peptide, termed PIP 640, with the capacity to regulate the transient opening of intestinal TJ structures through an endogenous mechanism involving the induction of myosin light chain (MLC) phosphorylation at serine 19 (MLC-pS 19 ) has provided a promising new method to enhance the in vivo oral bioavailability of peptide therapeutics. PIP 640 is a decapeptide composed of all D-amino acids (rrdykvevrr-NH 2 ) that contains a central sequence designed to emulates a specific domain of C-kinase potentiated protein phosphatase-1 inhibitor-17 kDa (CPI-17) surrounded by positively-charged amino acids that provide a cell penetrating peptide (CPP)-like character. Here, we examine compositional requirements of PIP 640 with regard to its actions on MLC phosphorylation, its intracellular localization to TJ structures, and its interactions with MLC phosphatase (MLCP) elements that correlate with enhanced solute uptake. These studies showed that a glutamic acid and tyrosine within this peptide are critical for PIP 640 to retain its ability to increase MLC-pS 19 levels and enhance the permeability of macromolecular solutes of the size range of therapeutic peptides without detectable cytotoxicity. On the other hand, exchange of the aspartic acid for alanine and then arginine resulted in an increasingly greater bias toward protein phosphatase-1 (PP1) relative to MLCP inhibition, an outcome that resulted in increased paracellular permeability for solutes in the size range of therapeutic peptides, but with a significant increase in cytotoxicity. Together, these data further our understanding of the composition requirements of PIP 640 with respect to the desired goal of transiently altering the intestinal epithelial cell paracellular barrier properties through an endogenous mechanism, providing a novel approach to enhance the oral bioavailability of
Vasoactive intestinal peptide and secretin: effects of combined and separate intravenous infusions on bile secretion in man
International Nuclear Information System (INIS)
Nyberg, B.; Sonnenfeld, T.; Einarsson, K.
The effects of intravenously administered vasoactive intestinal peptide (VIP) and secretin on bile secretion were studied in 12 patients with complete biliary fistulas. The two peptides were administered both simultaneously and separately. During VIP infusion, bile volume increased by 60%, and during the combined VIP and secretin infursion bile volume increased by another 70%. VIP increased bile bicarbonate concentration by some 30%. Although secretin did not increase the concentration, bicarbonate output increased threefold during secretin infusion but only twofold during VIP infusion. The outputs of bile acids were not significantly affected by the two peptides, whereas the concentration decreased by 40% and 70% after VIP and secretin, respectively. The canalicular bile flow, measured by [ 14 C]erythritol, was unaffected by VIP infusion, whereas secretin alone and the combination of the two peptides increased the canalicular clearance by 80%. The choleretic effect of VIP thus seems to occur only at the ductular level. Secretin exerts its effect at the ductular level and possibly also at the canalicular level. It is concluded that the two peptides have additive effects on the ductular bile flow.. 32 refs., 5 figs., 5 tabs
Electrical stimulation of the isolated rat intestine in the presence of nutrient stimulus enhances glucagon-like peptide-1 release
International Nuclear Information System (INIS)
Schwartz, Ann; Ort, Tatiana; Kajekar, Radhika; Hornby, Pamela J; Wade, Paul R
The release of small intestinal hormones by constituents of ingested food, such as fatty acids, is integral to post-prandial responses that reduce food intake. Recent evidence suggests that small intestinal electrical stimulation reduces food intake, although the mechanism of action is debated. To test the hypothesis that intestinal stimulation directly alters hormone release locally we used isolated rat distal ileum and measured glucagon-like peptide-1 (GLP-1) released in the presence or absence of linoleic acid (LA) and electrical field stimulation (EFS). Intact segments were oriented longitudinally between bipolar stimulating electrodes in organ bath chambers containing modified Krebs–Ringers bicarbonate (KRB) buffer including protease inhibitors. Incubation in LA (3 mg ml −1 ) for 45 min increased GLP-1 concentration (21.9 ± 2.6 pM versus KRB buffer alone 3.6 ± 0.1 pM). Eleven electrical stimulation conditions were tested. In the presence of LA none of the stimulation conditions inhibited LA-evoked GLP-1 release, whereas two high frequency short pulse widths (14 V, 20 Hz, 5 ms and 14 V, 40 Hz, 5 ms) and one low frequency long pulse width (14 V, 0.4 Hz, 300 ms) EFS conditions enhanced LA-evoked GLP-1 release by >250%. These results are consistent with a local effect of intestinal electrical stimulation to enhance GLP-1 release in response to luminal nutrients in the intestines. Enhancing hormone release could improve the efficacy of intestinal electrical stimulation and provide a potential treatment for obesity and metabolic conditions
Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats.
Lai, Sarah W; de Heuvel, Elaine; Wallace, Laurie E; Hartmann, Bolette; Holst, Jens J; Brindle, Mary E; Chelikani, Prasanth K; Sigalet, David L
To determine the effects of exogenous glucagon-like peptide-2 (GLP-2), with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats. GLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS). However, the effects of exogenous GLP-2 and SBS on enteric neurons are unclear. Sprague Dawley rats were randomized to four treatments: Transected Bowel (TB) (n = 8), TB + GLP-2 (2.5 nmol/kg/h, n = 8), SBS (n = 5), or SBS + GLP-2 (2.5 nmol/kg/h, n = 9). SBS groups underwent a 60% jejunoileal resection with cecectomy and jejunocolic anastomosis. All rats were maintained on parenteral nutrition for 7 d. Parameters measured included gut morphometry, qPCR for hexose transporter (SGLT-1, GLUT-2, GLUT-5) and GLP-2 receptor mRNA, whole mount immunohistochemistry for neurons (HuC/D, VIP, nNOS), plasma glucose, gut hormones, and body composition. Resection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2 therapy. Exogenous GLP-2 increased jejunal mucosal surface area without affecting enteric VIP or nNOS neuronal immunopositivity, attenuated resection-induced reductions in jejunal hexose transporter abundance (SGLT-1, GLUT-2), increased plasma amylin and decreased peptide YY concentrations. Exogenous GLP-2 attenuated resection-induced increases in blood glucose and body fat loss. Exogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy of further study.
Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats.
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Sarah W Lai
Full Text Available To determine the effects of exogenous glucagon-like peptide-2 (GLP-2, with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats.GLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS. However, the effects of exogenous GLP-2 and SBS on enteric neurons are unclear.Sprague Dawley rats were randomized to four treatments: Transected Bowel (TB (n = 8, TB + GLP-2 (2.5 nmol/kg/h, n = 8, SBS (n = 5, or SBS + GLP-2 (2.5 nmol/kg/h, n = 9. SBS groups underwent a 60% jejunoileal resection with cecectomy and jejunocolic anastomosis. All rats were maintained on parenteral nutrition for 7 d. Parameters measured included gut morphometry, qPCR for hexose transporter (SGLT-1, GLUT-2, GLUT-5 and GLP-2 receptor mRNA, whole mount immunohistochemistry for neurons (HuC/D, VIP, nNOS, plasma glucose, gut hormones, and body composition.Resection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2 therapy. Exogenous GLP-2 increased jejunal mucosal surface area without affecting enteric VIP or nNOS neuronal immunopositivity, attenuated resection-induced reductions in jejunal hexose transporter abundance (SGLT-1, GLUT-2, increased plasma amylin and decreased peptide YY concentrations. Exogenous GLP-2 attenuated resection-induced increases in blood glucose and body fat loss.Exogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy of further study.
Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats
de Heuvel, Elaine; Wallace, Laurie E.; Hartmann, Bolette; Holst, Jens J.; Brindle, Mary E.; Chelikani, Prasanth K.; Sigalet, David L.
Objective To determine the effects of exogenous glucagon-like peptide-2 (GLP-2), with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats. Background GLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS). However, the effects of exogenous GLP-2 and SBS on enteric neurons are unclear. Methods Sprague Dawley rats were randomized to four treatments: Transected Bowel (TB) (n = 8), TB + GLP-2 (2.5 nmol/kg/h, n = 8), SBS (n = 5), or SBS + GLP-2 (2.5 nmol/kg/h, n = 9). SBS groups underwent a 60% jejunoileal resection with cecectomy and jejunocolic anastomosis. All rats were maintained on parenteral nutrition for 7 d. Parameters measured included gut morphometry, qPCR for hexose transporter (SGLT-1, GLUT-2, GLUT-5) and GLP-2 receptor mRNA, whole mount immunohistochemistry for neurons (HuC/D, VIP, nNOS), plasma glucose, gut hormones, and body composition. Results Resection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2 therapy. Exogenous GLP-2 increased jejunal mucosal surface area without affecting enteric VIP or nNOS neuronal immunopositivity, attenuated resection-induced reductions in jejunal hexose transporter abundance (SGLT-1, GLUT-2), increased plasma amylin and decreased peptide YY concentrations. Exogenous GLP-2 attenuated resection-induced increases in blood glucose and body fat loss. Conclusions Exogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy
Bone resorption is decreased postprandially by intestinal factors and glucagon-like peptide-2 is a possible candidate
DEFF Research Database (Denmark)
Holst, Jens Juul; Hartmann, Bolette; Gottschalck, Ida B
-bowel syndrome (SBS) or total gastrectomy in order to elucidate whether the signal for the meal-induced reduction of bone resorption is initiated from the stomach or the intestine. MATERIAL AND METHODS: Bone resorption was assessed from the serum concentration of collagen type I C-telopeptide cross-links (s......OBJECTIVE: Food intake inhibits bone resorption by a mechanism thought to involve gut hormones, and the intestinotrophic glucagon-like peptide 2 (GLP-2) is a candidate because exogenous GLP-2 inhibits bone resorption in humans. The purpose of the study was to investigate patients with short...
Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats
DEFF Research Database (Denmark)
Lai, Sarah W; de Heuvel, Elaine; Wallace, Laurie E
mount immunohistochemistry for neurons (HuC/D, VIP, nNOS), plasma glucose, gut hormones, and body composition. RESULTS: Resection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2......-2 attenuated resection-induced increases in blood glucose and body fat loss. CONCLUSIONS: Exogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2......OBJECTIVE: To determine the effects of exogenous glucagon-like peptide-2 (GLP-2), with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats. BACKGROUND: GLP-2 is a gut hormone known to be trophic for small bowel mucosa...
Deficiency of the intestinal growth factor, glucagon-like peptide 2, in the colon of SCID mice with inflammatory bowel disease induced by transplantation of CD4+ T cells
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Schmidt, P T; Hartmann, B; Bregenholt, S
Glucagon-like peptide 2 (GLP-2) is produced in endocrine L-cells of the intestinal mucosa. Recently, GLP-2 was found to stimulate intestinal mucosal growth. Our objective was to study the content of GLP-2 in the large intestine in a murine model of T-cell-induced inflammatory bowel disease....
Vasoactive intestinal polypeptide and peptide histidine methionine. Presence in human follicular fluid and effects on DNA synthesis and steroid secretion in cultured human granulosa/lutein cells
DEFF Research Database (Denmark)
Gräs, S; Ovesen, Per Glud; Andersen, A N
Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) originate from the same precursor molecule, prepro VIP. In the present study we examined the concentrations of VIP and PHM in human follicular fluid and their effects on cultured human granulosa/lutein cells. Follicula...
Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas
DEFF Research Database (Denmark)
Holst, J J; Poulsen, Steen Seier
We developed specific antibodies and RIAs for glucagon-like peptides 1 and 2 (GLP-1 and GLP-2), two predicted products of the glucagon gene, and studied the occurrence, nature, and secretion of immunoreactive GLP-1 and GLP-2 in pig pancreas and small intestine. Immunoreactive GLP-1 and GLP-2 were...
[Substance P and vasoactive intestinal peptide in patients with progressive scleroderma. Determination of plasma level before and after autogenic training].
Haustein, U F; Weber, B; Seikowski, K
In 12 patients suffering from systemic sclerosis (SSc) the influence of autogenic training on the plasma level of the neuropeptides substance P and vasoactive intestinal peptide (VIP) was studied. Compared with healthy controls the SSc patients exhibited significantly elevated levels of substance P (mean +/- SD: 7.1 +/- 3.2 pmol/l vs 1.6 +/- 1.6 pmol/l). Apart from variations the VIP plasma concentration did not significantly differ from that in healthy controls (mean +/- SD 10.7 +/- 7.1 pmol/l versus 12.0 +/- 5.3 pmol/l). Autogenic training did not bring about any significant changes in the plasma levels of neuropeptides.
Phorbol esters alter adenylate cyclase responses to vasoactive intestinal peptide and forskolin in the GH cell line
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Summers, S.; Florio, T.; Cronin, M.
Activation of protein kinase C with phorbol ester modifies cyclic AMP production in several anterior pituitary cell systems. In the GH cell line from a rat pituitary tumor, exposure to phorbol 12-myristate 13-acetate (PMA: 100 nM) for 30 minutes significantly reduces vasoactive intestinal peptide (VIP: 100 nM) stimulated adenylate cyclase (AC) activity in subsequent membrane preparations to 62 + 4% of control (n = 6 independent studies). In contrast, these same membrane preparations respond to forskolin (1 ..mu..M) with significantly more activity, 130 +/- 6% of controls (n = 6 independent studies). Finally, phorbol ester does not block an inhibitory hormone input into the AC system; somatostatin (100 nM) reduction of VIP-stimulated AC activity is not significantly different in membrane preparations from PMA treated and control cells (n = 3 independent studies). These other findings lead the authors to propose that protein kinase C can modify several sites in the AC complex in anterior pituitary cells.
Naturally occurring glucagon-like peptide-2 (GLP-2) receptors in human intestinal cell lines.
Sams, Anette; Hastrup, Sven; Andersen, Marie; Thim, Lars
Although clinical trials with GLP-2 receptor agonists are currently ongoing, the mechanisms behind GLP-2-induced intestinal epithelial growth remain to be understood. To approach the GLP-2 mechanism of action this study aimed to identify intestinal cell lines endogenously expressing the GLP-2 receptor. Here we report the first identification of a cell line endogenously expressing functional GLP-2 receptors. The human intestinal epithelial cell line, FHC, expressed GLP-2 receptor encoding mRNA (RT-PCR) and GLP-2 receptor protein (Western blot). In cultured FHC cells, GLP-2 induced concentration dependent cAMP accumulation (pEC(50)=9.7+/-0.04 (mean+/-S.E.M., n=4)). In addition, a naturally occurring human intestinal fibroblast cell line, 18Co, endogenously expressing GLP-2 receptor encoding mRNA (RT-PCR) and protein (Western blot) was identified. No receptor functionality (binding or G-protein signalling) could be demonstrated in 18Co cells. The identified gut-relevant cell lines provide tools for future clarification of the mechanisms underlying GLP-2-induced epithelial growth.
Vasoactive intestinal peptide (VIP) labelling with iodine-131 by direct method; Marcacao do peptideo intestinal vasoativo (VIP) com iodo-131 por metodo direto
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Colturato, M.T.; Silva, C.P.G. da; Araujo, E.B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil). Centro de Radiofarmacia
The Vasoactive Intestinal Peptide (VIP) is a 28-amino acid polypeptide with a great numbers of receptors in tumoral cells, including adenocarcinomas and pancreatic and colon carcinomas. The VIP molecule contains two tyrosine residues, in positions 10 and 22, that are theoretically equally susceptible to iodination, The VIP was labeled with 131-iodine by direct method using Iodogen as oxidant agent: 15.03 mmol VIP + 0.10 nmol KI + [{sup 131} I]NaI + 13.9 mmol Iodogen; the final volume was adjust to 100 {mu}L using 0.2 M phosphate buffer, pH 7.5 and the reaction proceed with stirring for 30 minutes at room temperature. The radiochemical purity was determined by electrophoresis (Whatman 1MM paper; 0.05 M barbital buffer; pH 8.6; 150 V; 40 minutes) that indicates low percent of free 131-iodine. The high performance liquid chromatography (HPLC) system using RPC{sup 18}, 10 {mu}m, 4 x 250mm column, was able to separate the different radiochemical species, only when an isocratic mixture of acetonitrile: 0.1% trifluoroacetic acid (27:73) was used, with 0.5 mL/min. flux. (author)
Vasoactive intestinal peptide binding sites and fibers in the brain of the pigeon Columba livia: An autoradiographic and immunohistochemical study
International Nuclear Information System (INIS)
Hof, P.R.; Dietl, M.M.; Charnay, Y.; Martin, J.L.; Bouras, C.; Palacios, J.M.; Magistretti, P.J.
The distribution of vasoactive intestinal peptide (VIP) binding sites in the pigeon brain was examined by in vitro autoradiography on slide-mounted sections. A fully characterized monoiodinated form of VIP, which maintains the biological activity of the native peptide, was used throughout this study. The highest densities of binding sites were observed in the hyperstriatum dorsale, archistriatum, auditory field L of neostriatum, area corticoidea dorsolateralis and temporo-parieto-occipitalis, area parahippocampalis, tectum opticum, nucleus dorsomedialis anterior thalami, and in the periventricular area of the hypothalamus. Lower densities of specific binding occurred in the neostriatum, hyperstriatum ventrale and nucleus septi lateralis, dorsolateral area of the thalamus, and lateral and posteromedial hypothalamus. Very low to background levels of VIP binding were detected in the ectostriatum, paleostriatum primitivum, paleostriatum augmentatum, lobus parolfactorius, nucleus accumbens, most of the brainstem, and the cerebellum. The distribution of VIP-containing fibers and terminals was examined by indirect immunofluorescence using a polyclonal antibody against porcine VIP. Fibers and terminals were observed in the area corticoidea dorsolateralis, area parahippocampalis, hippocampus, hyperstriatum accessorium, hyperstriatum dorsale, archistriatum, tuberculum olfactorium, nuclei dorsolateralis and dorsomedialis of the thalamus, and throughout the hypothalamus and the median eminence. Long projecting fibers were visualized in the tractus septohippocampalis. In the brainstem VIP immunoreactive fibers and terminals were observed mainly in the substantia grisea centralis, fasciculus longitudinalis medialis, lemniscus lateralis, and in the area surrounding the nuclei of the 7th, 9th, and 10th cranial nerves
Enhanced Intestinal Permeability of Bufalin by a Novel Bufalin-Peptide-Dendrimer Inclusion through Caco-2 Cell Monolayer
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Chi-on Chan
Full Text Available Bufalin (BFL has excellent physiological activities such as defending tumors, improving cardiac function, and so on. However, due to its poor water-solubility and bioavailability, the clinical application of BFL remains limited. In order to improve bioavailability of BFL, in our previous research, a novel peptide-dendrimer (PD was synthesized and applied to encapsulate BFL. In the present study, we investigate the absorption property and mechanism of BFL in free form and BFL-peptide-dendrimer inclusion (BPDI delivery system by using the Caco-2 cell monolayer model in vitro. The apparent permeability coefficient (Papp values of BFL in free or BPDI form were over 1.0 × 10−6 cm/s. Meanwhile, their almost equal bi-directional transport and linear transport percentage with time and concentration course indicated that BFL in both forms was absorbed mainly through passive diffusion. The most important result is that the Papp values of BFL increased about three-fold more BPDI than those of its free form, which indicated the intestinal permeability of BFL could be improved while BFL was encapsulated in BPDI form. Therefore, PD encapsulation may be a potential delivery system to increase the bioavailability of BFL.
Effects of semielemental diet containing whey peptides on Peyer's patch lymphocyte number, immunoglobulin A levels, and intestinal morphology in mice.
Moriya, Tomoyuki; Fukatsu, Kazuhiko; Noguchi, Midori; Nishikawa, Makoto; Miyazaki, Hiromi; Saitoh, Daizoh; Ueno, Hideki; Yamamoto, Junji
Enteral nutrition (EN) is the gold standard of nutritional therapy for critically ill or severely injured patients, because EN promotes gut and hepatic immunity, thereby preventing infectious complications as compared with parenteral nutrition. However, there are many EN formulas with different protein and fat contents. Their effects on gut-associated lymphoid tissue remain unclear. Recently, semielemental diets (SEDs) containing whey peptides as a nitrogen source have been found to be beneficial in patients with malabsorption or pancreatitis. Herein, we examined the influences of various dietary formulations on gut immunity to clarify the advantages of SEDs over elemental diets. Forty-four male Institute of Cancer Research mice were randomized to four groups: chow (CH: n = 5), intragastric total parenteral nutrition (IG-TPN: n = 13), elemental diet (ED: n = 13), and SED (n = 13). The CH group received CH diet ad libitum, whereas the IG-TPN, ED (Elental, Ajinomoto, Japan), and SED (Peptino, Terumo, Japan) groups were given their respective diets for 5 day via gastrostomy. After 5 days, the mice were killed to obtain whole small intestines. Peyer's patch (PP) lymphocytes were harvested and counted. Their subpopulations were evaluated by flow cytometry. Immunoglobulin A (IgA) levels in intestinal and respiratory tract washings were measured with enzyme-linked immunosorbent assay. Villous height (VH) and crypt depth in the distal intestine were measured by light microscopy. SED increased the PP cell number and intestinal or respiratory IgA levels to those of CH mice, while ED partially restored these parameters. The IG-TPN group showed the lowest PP cell number and IgA levels among the four groups. VH was significantly greater in the CH than in the other groups. VH in the ED and SED groups also exceeded in the IG-TPN group, while being similar in these two groups. No significant crypt depth differences were observed among the four groups. SED administration
Synergistic effect of supplemental enteral nutrients and exogenous glucagon-like peptide 2 on intestinal adaptation in a rat model of short bowel syndrome
DEFF Research Database (Denmark)
Liu, Xiaowen; Nelson, David W; Holst, Jens Juul
BACKGROUND: Short bowel syndrome (SBS) can lead to intestinal failure and require total or supplemental parenteral nutrition (TPN or PN, respectively). Glucagon-like peptide 2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that stimulates intestinal adaptation. OBJECTIVE: Our...... objective was to determine whether supplemental enteral nutrients (SEN) modulate the intestinotrophic response to a low dose of GLP-2 coinfused with PN in a rat model of SBS (60% jejunoileal resection plus cecectomy). DESIGN: Rats were randomly assigned to 8 treatments by using a 2 x 2 x 2 factorial design...
Lateralized hippocampal effects of vasoactive intestinal peptide on learning and memory in rats in a model of depression.
Ivanova, Margarita; Belcheva, Stiliana; Belcheva, Iren; Negrev, Negrin; Tashev, Roman
Findings of pharmacological studies revealed that vasoactive intestinal peptide (VIP) plays a modulatory role in learning and memory. A role of the peptide in the neurobiological mechanisms of affective disorders was also suggested. The objectives are to study the involvement of VIP in learning and memory processes after unilateral and bilateral local application into hippocampal CA1 area in rats with a model of depression (bilateral olfactory bulbectomy--OBX) and to test whether VIP receptors could affect cognition. VIP (50 ng) and combination (VIP(6-28) 10 ng + VIP 50 ng) microinjected bilaterally or into the right CA1 area improved the learning and memory of OBX rats in shuttle-box and step-through behavioral tests as compared to the saline-treated OBX controls. Left-side VIP microinjections did not affect the number of avoidances (shuttle box) and learning criteria (step through) as compared to the left-side saline-treated OBX controls. The administration of the combination into left CA1 influenced positively the performance in the step-through task. VIP antagonist (VIP(6-28), 10 ng) did not affect learning and memory of OBX rats. These findings suggest asymmetric effect of VIP on cognitive processes in hippocampus of rats with OBX model of depression. Our results point to a lateralized modulatory effect of VIP injected in the hippocampal CA1 area on the avoidance deficits in OBX rats. The right CA1 area was predominantly involved in the positive effect of VIP on learning and memory. A possible role of the PAC1 receptors is suggested.
The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60 on the intestinal barrier function and gut peptides in breast cancer patients: an observational study
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Russo Francesco
Full Text Available Abstract Background Several GI peptides linked to intestinal barrier function could be involved in the modification of intestinal permeability and the onset of diarrhea during adjuvant chemotherapy. The aim of the study was to evaluate the circulating levels of zonulin, glucagon-like peptide-2 (GLP-2, epidermal growth factor (EGF and ghrelin and their relationship with intestinal permeability and chemotherapy induced diarrhea (CTD. Methods Sixty breast cancer patients undergoing an FEC60 regimen were enrolled, 37 patients completed the study. CTD(+ patients were discriminated by appropriate questionnaire and criteria. During chemotherapy, intestinal permeability was assessed by lactulose/mannitol urinary test on day 0 and day 14. Zonulin, GLP-2, EGF and ghrelin circulating levels were evaluated by ELISA tests at five time-points (days 0, 3, 10, 14, and 21. Results During FEC60 administration, the lactulose/mannitol ratio was significantly higher on day 14 than at baseline. Zonulin levels were not affected by chemotherapy, whereas GLP-2 and EGF levels decreased significantly. GLP-2 levels on day 14 were significantly lower than those on day 0 and day 3, while EGF values were significantly lower on day 10 than at the baseline. In contrast, the total concentrations of ghrelin increased significantly at day 3 compared to days 0 and 21, respectively. Ten patients (27% suffered from diarrhea. On day 14 of chemotherapy, a significant increase of the La/Ma ratio occurred in CTD(+ patients compared to CTD(− patients. With regards to circulating gut peptides, the AUCg of GLP-2 and ghrelin were significantly lower and higher in CTD(+ patients than CTD(− ones, respectively. Finally in CTD(+ patients a significant and inverse correlation between GLP-2 and La/Ma ratio was found on day 14. Conclusions Breast cancer patients undergoing FEC60 showed alterations in the intestinal permeability, which was associated with modifications in the levels of GLP-2
The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study.
Russo, Francesco; Linsalata, Michele; Clemente, Caterina; D'Attoma, Benedetta; Orlando, Antonella; Campanella, Giovanna; Giotta, Francesco; Riezzo, Giuseppe
Several GI peptides linked to intestinal barrier function could be involved in the modification of intestinal permeability and the onset of diarrhea during adjuvant chemotherapy. The aim of the study was to evaluate the circulating levels of zonulin, glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF) and ghrelin and their relationship with intestinal permeability and chemotherapy induced diarrhea (CTD). Sixty breast cancer patients undergoing an FEC60 regimen were enrolled, 37 patients completed the study. CTD(+) patients were discriminated by appropriate questionnaire and criteria. During chemotherapy, intestinal permeability was assessed by lactulose/mannitol urinary test on day 0 and day 14. Zonulin, GLP-2, EGF and ghrelin circulating levels were evaluated by ELISA tests at five time-points (days 0, 3, 10, 14, and 21). During FEC60 administration, the lactulose/mannitol ratio was significantly higher on day 14 than at baseline. Zonulin levels were not affected by chemotherapy, whereas GLP-2 and EGF levels decreased significantly. GLP-2 levels on day 14 were significantly lower than those on day 0 and day 3, while EGF values were significantly lower on day 10 than at the baseline. In contrast, the total concentrations of ghrelin increased significantly at day 3 compared to days 0 and 21, respectively. Ten patients (27%) suffered from diarrhea. On day 14 of chemotherapy, a significant increase of the La/Ma ratio occurred in CTD(+) patients compared to CTD(-) patients. With regards to circulating gut peptides, the AUCg of GLP-2 and ghrelin were significantly lower and higher in CTD(+) patients than CTD(-) ones, respectively. Finally in CTD(+) patients a significant and inverse correlation between GLP-2 and La/Ma ratio was found on day 14. Breast cancer patients undergoing FEC60 showed alterations in the intestinal permeability, which was associated with modifications in the levels of GLP-2, ghrelin and EGF. In CTD(+) patients, a different GI peptide
A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and intestinal function in pediatric patients
DEFF Research Database (Denmark)
Sigalet, David L; Kravarusic, Dragan; Butzner, Decker
[± SD] age 15.3 ± 1.3 years) and 10 controls (10.3 ± 1.6 years) were studied. In patients with active disease, fasting levels of GLP-2 remained stable but postprandial levels were reduced. Patients with active disease exhibited reduced glucose absorption and increased lactulose⁄mannitol recovery; all...... BACKGROUND⁄/OBJECTIVES: The relationship between the enteroendocrine hormone glucagon-like peptide 2 (GLP-2) and intestinal inflammation is unclear. GLP-2 promotes mucosal growth, decreases permeability and reduces inflammation in the intestine; physiological stimulation of GLP-2 release...... of the small intestine) with a disease activity index >150. Fasting and postprandial GLP-2 levels and quantitative urinary recovery of orally administered 3-O-methyl-glucose (active transport) and lactulose⁄mannitol (passive) were quantified during the acute and remission phases. RESULTS: Seven patients (mean...
Inulin-enriched pasta improves intestinal permeability and modifies the circulating levels of zonulin and glucagon-like peptide 2 in healthy young volunteers.
Russo, Francesco; Linsalata, Michele; Clemente, Caterina; Chiloiro, Marisa; Orlando, Antonella; Marconi, Emanuele; Chimienti, Guglielmina; Riezzo, Giuseppe
Apart from the intestinal environment, inulin induces physiological effects, which includes a reduction in glucose and lipid concentrations and modulation of gastrointestinal motility through the release of different peptides. We hypothesized that inulin-enriched pasta may also improve small intestine permeability in relation to zonulin and glucagon-like peptide 2 (GLP-2) levels in healthy young subjects. Twenty healthy, young male volunteers completed a randomized, double-blind crossover study consisting of a 2-week run-in period and two 5-week study periods (11% inulin-enriched or control pasta), with an 8-week washout period in between. The intestinal barrier function was assessed by lactulose-mannitol excretion in urine. Zonulin values and GLP-2 release were evaluated by enzyme-linked immunosorbent assay. In the inulin group, the urinary lactulose recovery was significantly lower than the other 2 groups. There were no significant differences in urinary mannitol levels between groups. Accordingly, the lactulose-mannitol excretion ratio was significantly decreased in the inulin-enriched pasta group compared with the other 2 groups. The inulin-enriched pasta group had significantly lower zonulin serum values and significantly higher GLP-2 basal values when compared with the baseline and control pasta groups. The dietary use of inulin-enriched pasta preserves intestinal mucosal barrier functioning and modulates circulating levels of zonulin and GLP-2, suggesting that prebiotics could be used in the prevention of gastrointestinal diseases and metabolic disorders. Copyright © 2012 Elsevier Inc. All rights reserved.
Dysbiosis of Intestinal Microbiota and Decreased Antimicrobial Peptide Level in Paneth Cells during Hypertriglyceridemia-Related Acute Necrotizing Pancreatitis in Rats
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Chunlan Huang
Full Text Available Hypertriglyceridemia (HTG aggravates the course of acute pancreatitis (AP. Intestinal barrier dysfunction is implicated in the pathogenesis of AP during which dysbiosis of intestinal microbiota contributes to the dysfunction in intestinal barrier. However, few studies focus on the changes in intestine during HTG-related acute necrotizing pancreatitis (ANP. Here, we investigated the changes in intestinal microbiota and Paneth cell antimicrobial peptides (AMPs in HTG-related ANP (HANP in rats. Rats fed a high-fat diet to induce HTG and ANP was induced by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct. Rats were sacrificed at 24 and 48 h, respectively. Pancreatic and ileal injuries were evaluated by histological scores. Intestinal barrier function was assessed by plasma diamine oxidase activity and D-lactate level. Systemic and intestinal inflammation was evaluated by tumor necrosis factor alpha (TNFα, interleukin (IL-1β, and IL-17A expression. 16S rRNA high throughput sequencing was used to investigate changes in intestinal microbiota diversity and structure. AMPs (α-defensin5 and lysozyme expression was measured by real-time polymerase chain reaction (PCR and immunofluorescence. The results showed that compared with those of normal-lipid ANP (NANP groups, the HANP groups had more severe histopathological injuries in pancreas and distal ileum, aggravated intestinal barrier dysfunction and increased TNFα, IL-1β, and IL-17A expression in plasma and distal ileum. Principal component analysis showed structural segregation between the HANP and NANP group. α-Diversity estimators in the HANP group revealed decreased microbiota diversity compared with that in NANP group. Taxonomic analysis showed dysbiosis of intestinal microbiota structure. In the HANP group, at phyla level, Candidatus_Saccharibacteria and Tenericutes decreased significantly, whereas Actinobacteria increased. At genus level, Allobaculum, Bifidobacterium
Influence of nitric oxide on histamine and carbachol – induced ...
African Journals Online (AJOL)
The study aimed to determine the influence of nitric oxide (NO) on the action of histamine and carbachol on acid secretion in the common African toad – Bufo regularis. Gastric acidity was determined by titration method. The acid secretion was determined when nitric oxide was absent following administration of NO synthase ...
The Noncaloric Sweetener Rebaudioside A Stimulates Glucagon-Like Peptide 1 Release and Increases Enteroendocrine Cell Numbers in 2-Dimensional Mouse Organoids Derived from Different Locations of the Intestine
van der Wielen, Nikkie; Ten Klooster, Jean Paul; Muckenschnabl, Susanne; Pieters, Raymond; Hendriks, Henk Fj; Witkamp, Renger F; Meijerink, Jocelijn
BACKGROUND: Glucagon-like peptide 1 (GLP-1) contributes to satiety and plays a pivotal role in insulin secretion and glucose homeostasis. Similar to GLP-1, peptide YY (PYY) and cholecystokinin also influence food intake. The secretion of these hormones by enteroendocrine cells along the intestine is
The noncaloric sweetener rebaudioside a stimulates glucagon-like peptide 1 release and increases enteroendocrine cell numbers in 2-dimensional mouse organoids derived from different locations of the intestine
Wielen, van der Nikkie; Klooster, ten Jean Paul; Muckenschnabl, Susanne; Pieters, Raymond; Hendriks, Henk F.J.; Witkamp, Renger F.; Meijerink, Jocelijn
Background: Glucagon-like peptide 1 (GLP-1) contributes to satiety and plays a pivotal role in insulin secretion and glucose homeostasis. Similar to GLP-1, peptide YY (PYY) and cholecystokinin also influence food intake. The secretion of these hormones by enteroendocrine cells along the intestine
Oral peptide specific egg antibody to intestinal sodium-dependent phosphate co-transporter-2b is effective at altering phosphate transport in vitro and in vivo.
Bobeck, Elizabeth A; Hellestad, Erica M; Sand, Jordan M; Piccione, Michelle L; Bishop, Jeff W; Helvig, Christian; Petkovich, Martin; Cook, Mark E
Hyperimmunized hens are an effective means of generating large quantities of antigen specific egg antibodies that have use as oral supplements. In this study, we attempted to create a peptide specific antibody that produced outcomes similar to those of the human pharmaceutical, sevelamer HCl, used in the treatment of hyperphosphatemia (a sequela of chronic renal disease). Egg antibodies were generated against 8 different human intestinal sodium-dependent phosphate cotransporter 2b (NaPi2b) peptides, and hNaPi2b peptide egg antibodies were screened for their ability to inhibit phosphate transport in human intestinal Caco-2 cell line. Antibody produced against human peptide sequence TSPSLCWT (anti-h16) was specific for its peptide sequence, and significantly reduced phosphate transport in human Caco-2 cells to 25.3±11.5% of control nonspecific antibody, when compared to nicotinamide, a known inhibitor of phosphate transport (P≤0.05). Antibody was then produced against the mouse-specific peptide h16 counterpart (mouse sequence TSPSYCWT, anti-m16) for further analysis in a murine model. When anti-m16 was fed to mice (1% of diet as dried egg yolk powder), egg yolk immunoglobulin (IgY) was detected using immunohistochemical staining in mouse ileum, and egg anti-m16 IgY colocalized with a commercial goat anti-NaPi2b antibody. The effectiveness of anti-m16 egg antibody in reducing serum phosphate, when compared to sevelamer HCl, was determined in a mouse feeding study. Serum phosphate was reduced 18% (Pegg yolk powder) and 30% (Pegg immunoglobulin. The methods described and the findings reported show that oral egg antibodies are useful and easy to prepare reagents for the study and possible treatment of select diseases. © 2015 Poultry Science Association Inc.
Intra-Amniotic Administration (Gallus gallus) of Cicer arietinum and Lens culinaris Prebiotics Extracts and Duck Egg White Peptides Affects Calcium Status and Intestinal Functionality.
Hou, Tao; Kolba, Nikolai; Glahn, Raymond P; Tako, Elad
Calcium (Ca) is one of the most abundant inorganic elements in the human body and has many important physiological roles. Prebiotics and bioactive peptides are two important substances used to promote calcium uptake. However, the difference in mechanisms of the calcium uptake from these two supplements is not clear. By using the Gallus gallus model and the intra-amniotic administration procedure, the aim of this study was to investigate whether Ca status, intestinal functionality, and health-promoting bacterial populations were affected by prebiotics extracted from chickpea and lentil, and duck egg white peptides (DPs). Eleven groups (non-injected; 18 MΩ H₂O; 4 mmol/L CaCl₂; 50 mg/mL chickpea + 4 mmol/L CaCl₂; 50 mg/mL lentil + 4 mmol/L CaCl₂; 40 mg/mL DPs + 4 mmol/L CaCl₂; 5 mg/mL Val-Ser-Glu-Glu (VSEE) + 4 mmol/L CaCl₂; 50 mg/mL chickpea; 50 mg/mL lentil; 40 mg/mL DPs; 5 mg/mL VSEE) were utilized. Upon hatch, blood, cecum, small intestine, liver and bone were collected for assessment of serum bone alkaline phosphate level (BALP), the relative abundance of intestinal microflora, expression of Ca-related genes, brush border membrane (BBM) functional genes, and liver and bone mineral levels, respectively. The BALP level increased in the presence of lentil, DPs and VSEE ( p Prebiotics and DPs beneficially affected the intestinal microflora and duodenal villus surface area. This research expands the understanding of the prebiotics' properties of chickpea and lentil extracts, and peptides' effects on calcium metabolism and gut health.
Nutrient-intake-level-dependent regulation of intestinal development in newborn intrauterine growth-restricted piglets via glucagon-like peptide-2.
Liu, J; Liu, Z; Gao, L; Chen, L; Zhang, H
The objective of the present study was to investigate the intestinal development of newborn intrauterine growth-restricted (IUGR) piglets subjected to normal nutrient intake (NNI) or restricted nutrient intake (RNI). Newborn normal birth weight (NBW) and IUGR piglets were allotted to NNI or RNI levels for 4 weeks from day 8 postnatal. IUGR piglets receiving NNI had similar growth performance compared with that of NBW piglets. Small intestine length and villous height were greater in IUGR piglets fed the NNI than that of piglets fed the RNI. Lactase activity was increased in piglets fed the NNI compared with piglets fed the RNI. Absorptive function, represented by active glucose transport by the Ussing chamber method and messenger RNA (mRNA) expressions of two main intestinal glucose transporters, Na+-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), were greater in IUGR piglets fed the NNI compared with piglets fed the RNI regimen. The apoptotic process, characterized by caspase-3 activity (a sign of activated apoptotic cells) and mRNA expressions of p53 (pro-apoptotic), bcl-2-like protein 4 (Bax) (pro-apoptotic) and B-cell lymphoma-2 (Bcl-2) (anti-apoptotic), were improved in IUGR piglets fed the NNI regimen. To test the hypothesis that improvements in intestinal development of IUGR piglets fed NNI might be mediated through circulating glucagon-like peptide-2 (GLP-2), GLP-2 was injected subcutaneously to IUGR piglets fed the RNI from day 8 to day 15 postnatal. Although the intestinal development of IUGR piglets fed the RNI regimen was suppressed compared with those fed the NNI regimen, an exogenous injection of GLP-2 was able to bring intestinal development to similar levels as NNI-fed IUGR piglets. Collectively, our results demonstrate that IUGR neonates that have NNI levels could improve intestinal function via the regulation of GLP-2.
Ghrelin suppresses cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) in the intestine, and attenuates the anorectic effects of CCK, PYY and GLP-1 in goldfish (Carassius auratus).
Blanco, Ayelén Melisa; Bertucci, Juan Ignacio; Valenciano, Ana Isabel; Delgado, María Jesús; Unniappan, Suraj
Ghrelin is an important gut-derived hormone with an appetite stimulatory role, while most of the intestinal hormones, including cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1), are appetite-inhibitors. Whether these important peptides with opposing roles on food intake interact to regulate energy balance in fish is currently unknown. The aim of this study was to characterize the putative crosstalk between ghrelin and CCK, PYY and GLP-1 in goldfish (Carassius auratus). We first determined the localization of CCK, PYY and GLP-1 in relation to ghrelin and its main receptor GHS-R1a (growth hormone secretagogue 1a) in the goldfish intestine by immunohistochemistry. Colocalization of ghrelin/GHS-R1a and CCK/PYY/GLP-1 was found primarily in the luminal border of the intestinal mucosa. In an intestinal explant culture, a significant decrease in prepro-cck, prepro-pyy and proglucagon transcript levels was observed after 60min of incubation with ghrelin, which was abolished by preincubation with the GHS-R1a ghrelin receptor antagonist [D-Lys3]-GHRP-6 (except for proglucagon). The protein expression of PYY and GLP-1 was also downregulated by ghrelin. Finally, intraperitoneal co-administration of CCK, PYY or GLP-1 with ghrelin results in no modification of food intake in goldfish. Overall, results of the present study show for the first time in fish that ghrelin exerts repressive effects on enteric anorexigens. It is likely that these interactions mediate the stimulatory effects of ghrelin on feeding and metabolism in fish. Copyright © 2017 Elsevier Inc. All rights reserved.
Vasodilatory effect of the stable vasoactive intestinal peptide analog RO 25-1553 in murine and rat lungs.
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Jun Yin
Full Text Available Stable analogs of vasoactive intestinal peptide (VIP have been proposed as novel line of therapy in chronic obstructive pulmonary disease (COPD based on their bronchodilatory and anti-inflammatory effects. We speculated that VIP analogs may provide additional benefits in that they exert vasodilatory properties in the lung, and tested this hypothesis in both ex vivo and in vivo models.In isolated perfused mouse lungs and in an in vivo rat model, pulmonary blood vessels were preconstricted by hypoxia and hemodynamic changes in response to systemic (ex vivo or inhaled (in vivo administration of the cyclic VIP analog RO 25-1553 were determined.In mouse lungs, RO 25-1553 reduced intrinsic vascular resistance at normoxia, and attenuated the increase in pulmonary artery pressure in response to acute hypoxia. Consistently, inhalation of RO 25-1553 (1 mg · mL(-1 for 3 min caused an extensive and sustained (> 60 min inhibition of the pulmonary arterial pressure increase in response to hypoxia in vivo that was comparable to the effects of inhaled sildenafil. This effect was not attributable to systemic cardiovascular effects of RO 25-1553, but to a lung specific reduction in pulmonary vascular resistance, while cardiac output and systemic arterial hemodynamics remained unaffected. No adverse effects of RO 25-1553 inhalation on pulmonary gas exchange, ventilation-perfusion matching, or lung fluid content were detected.Our findings demonstrate that inhaled delivery of the stable VIP analog RO 25-1553 induces a potent and sustained vasodilatory effect in the pulmonary circulation with no detectable adverse effects. Therapeutic inhalation of RO 25-1553 may provide vascular benefits in addition to its reported anti-inflammatory and bronchodilatory effects in COPD, yet caution is warranted given the overall poor results of vasodilator therapies for pulmonary hypertension secondary to COPD in a series of recent clinical trials.
Intracerebroventricular Infusion of Vasoactive Intestinal Peptide (VIP Rescues the Luteinizing Hormone Surge in Middle-Aged Female Rats
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Yan eSun
Full Text Available Reproductive aging is characterized by delayed and attenuated luteinizing hormone (LH surges apparent in middle-aged rats. The suprachiasmatic nucleus (SCN contains the circadian clock that is responsible for the timing of diverse neuroendocrine rhythms. Electrophysiological studies suggest vasoactive intestinal peptide (VIP originating from the SCN excites gonadotropin-releasing hormone (GnRH neurons and affects daily patterns of GnRH-LH release. Age-related LH surge dysfunction correlates with reduced VIP mRNA expression in the SCN and fewer GnRH neurons with VIP contacts expressing c-fos, a marker of neuronal activation, on the day of the LH surge. To determine if age-related LH surge dysfunction reflects reduced VIP availability or altered VIP responsiveness under estradiol positive feedback conditions, we assessed the effect of intracerebroventricular (icv VIP infusion on c-fos expression in GnRH neurons and on LH release in ovariohysterectomized, hormone-primed young and middle-aged rats. Icv infusion of VIP between 1300 and 1600 h significantly advanced the time of peak LH release, increased total and peak LH release, and increased the number of GnRH neurons expressing c-fos on the day of the LH surge in middle-aged rats. Surprisingly, icv infusion of VIP in young females significantly reduced the number of GnRH neurons expressing c-fos and delayed and reduced the LH surge. These observations suggest that a critical balance of VIP signaling is required to activate GnRH neurons for an appropriately timed and robust LH surge in young and middle-aged females. Age-related LH surge changes may, in part, result from decreased availability and reduced VIP-mediated neurotransmission under estradiol positive feedback conditions.
Steviol Glycoside Rebaudioside A Induces Glucagon-like Peptide-1 and Peptide YY Release in a Porcine ex Vivo Intestinal Model
Ripken, D.; Wielen, N. van der; Wortelboer, H.M.; Meijerink, J.; Witkamp, R.F.; Hendriks, H.F.J.
Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are hormones important for satiation and are involved in the process called "ileal brake". The aim of this study was to investigate the GLP-1- and PYY-stimulating efficacy of rebaudioside A, casein, and sucrose. This was studied using tissue
Steviol glycoside rebaudioside A induces glucagon-like peptide-1 and peptide YY release in a porcine ex vivo intestinal model
Ripken, D.; Wielen, van der N.; Wortelboer, H.M.; Meijerink, J.; Witkamp, R.F.; Hendriks, H.F.
Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are hormones important for satiation and are involved in the process called "ileal brake". The aim of this study was to investigate the GLP-1- and PYY-stimulating efficacy of rebaudioside A, casein, and sucrose. This was studied using tissue
Vasoactive intestinal polypeptide and peptide histidine methionine. Presence in human follicular fluid and effects on DNA synthesis and steroid secretion in cultured human granulosa/lutein cells
DEFF Research Database (Denmark)
Gräs, S; Ovesen, P; Andersen, A N
Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) originate from the same precursor molecule, prepro VIP. In the present study we examined the concentrations of VIP and PHM in human follicular fluid and their effects on cultured human granulosa/lutein cells. Follicular....../l, respectively. VIP at a concentration of 10 nmol/l caused a significant increase in [3H]thymidine incorporation, and at 1000 nmol/l a significant increase in oestradiol secretion was observed. VIP had no effect on progesterone secretion. PHM at the concentrations tested did not influence any of the activities...
Watery diarrhea syndrome in an adult with ganglioneuroma-pheochromocytoma: identification of vasoactive intestinal peptide, calcitonin, and catecholamines and assessment of their biologic activity.
Trump, D L; Livingston, J N; Baylin, S B
A case of adult ganglioneuroma-pheochromocytoma with an associated watery diarrhea syndrome is reported. High levels of vasoactive intestinal peptide (VIP) were found in preoperative serum and in tumor tissue. The serum VIP levels fell to normal, and the watery diarrhae syndrome completely ceased following removal of the tumor. In addition to containing VIP, the tumor was rich in catecholamines, and calcitonin. Peptide hormone-containing extracts and catecholamine extracts from the tumor both activated the adenyl cyclase system and increased lipolytic activity in a preparation of isolated rat fat cells. The findings in this patient further link VIP with neural crest tissues, and suggest the importance of determining catecholamine levels in patients with the watery diarrhea syndrome.
The effect of active immunization against vasoactive intestinal peptide (VIP) and inhibin on reproductive performance of aging White Leghorn roosters.
Avital-Cohen, N; Heiblum, R; Argov, N; Rosenstrauch, A; Chaiseha, Y; Mobarkey, N; Rozenboim, I
Decreasing fertility in aging domestic roosters is a well-known phenomenon. Aging is manifested by a decrease in plasma testosterone level, testis function, and spermatogenesis, resulting in a low level of fertility. The roles of vasoactive intestinal peptide (VIP) and testicular inhibin in this aging process are not clear. The effects of active immunization against VIP, inhibin, or the combination of both hormones on the reproduction of aging White Leghorn (WL) roosters were assayed. In experiment 1a, 60 White Leghorn roosters (67 wk of age) were divided into 4 groups (n = 15/group). The first group was actively immunized against VIP, the second against inhibin, the third against VIP and inhibin, and the fourth served as a control. Active immunization against VIP decreased semen quality parameters, plasma steroid levels, and gene expression of gonadotropin-releasing hormone-I (GnRH-I), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH receptor, VIP, and prolactin (Prl). Immunization against inhibin increased some of the semen quality parameters and FSH mRNA gene expression but decreased inhibin gene expression. In experiment 1b, at 94 wk of age, we took the actively immunized against VIP group and the control group and divided them into 2 subgroups (n = 7 or 8): the first group was injected with 1 mg of ovine Prl (oPrl) daily for 7 d, and the second group served as a control. Administration of oPrl to previously VIP-immunized birds significantly elevated semen quality parameters. We suggest that VIP, Prl, and inhibin have an important effect on the reproductive axis in aging roosters. Active immunization against VIP-depressed reproductive activity and Prl administration restored their reproduction, indicating that both VIP and Prl are essential for reproduction in aging roosters. Immunization against inhibin improved FSH mRNA gene expression, suggesting a negative role of inhibin on FSH secretion in aging roosters. Not all semen quality parameters
The intestinotrophic peptide, glp-2, counteracts intestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, gefitinib
DEFF Research Database (Denmark)
Hare, Kristine Juul; Hartmann, Bolette; Kissow, Hannelouise
of the segments of the gastrointestinal tract were determined, and histologic sections were analyzed by morphometric methods. RESULTS: A significant atrophy of the small-intestinal wall was observed after treatment with gefitinib because both intestinal weight and morphometrically estimated villus height...
Vasoactive intestinal peptide test
... release of hormones from the pancreas, gut, and hypothalamus, and increasing the amount of water and electrolytes ... the A.D.A.M. Editorial team. Pancreatic Cancer Read more NIH MedlinePlus Magazine Read more Health ...
A chimeric peptide of intestinal trefoil factor containing cholesteryl ester transfer protein B cell epitope significantly inhibits atherosclerosis in rabbits after oral administration.
Qi, Gaofu; Li, Jingjing; Wang, Shengying; Xin, Shanshan; Du, Peng; Zhang, Qingye; Zhao, Xiuyun
Vaccination against cholesteryl ester transfer protein (CETP) is proven to be effective for inhibiting atherosclerosis in animal models. In this study, the proteases-resistant intestinal trefoil factor (TFF3) was used as a molecular vehicle to construct chimeric TFF3 (cTFF3) containing CETP B cell epitope and tetanus toxin helper T cell epitope. It was found that cTFF3 still preserved a trefoil structure, and can resist proteases digestion in vitro. After oral immunization with cTFF3, the CETP-specific IgA and IgG could be found in intestine lavage fluid and serum, and the anti-CETP antibodies could inhibit partial CETP activity to increase high-density lipoprotein cholesterol, decrease low-density lipoprotein cholesterol, and inhibit atherosclerosis in animals. Therefore, TFF3 is a potential molecular vehicle for developing oral peptide vaccines. Our research highlights a novel strategy for developing oral peptide vaccines in the future. Copyright © 2010 Elsevier Inc. All rights reserved.
Vasoactive intestinal polypeptide excites medial pontine reticular formation neurons in the brainstem rapid eye movement sleep-induction zone
DEFF Research Database (Denmark)
Kohlmeier, Kristi Anne; Reiner, P B
Although it has long been known that microinjection of the cholinergic agonist carbachol into the medial pontine reticular formation (mPRF) induces a state that resembles rapid eye movement (REM) sleep, it is likely that other transmitters contribute to mPRF regulation of behavioral states. A key...... candidate is the peptide vasoactive intestinal polypeptide (VIP), which innervates the mPRF and induces REM sleep when injected into this region of the brainstem. To begin understanding the cellular mechanisms underlying this phenomenon, we examined the effects of VIP on mPRF cells using whole-cell patch...... conclude that VIP excites mPRF neurons by activation of a sodium current. This effect is mediated at least in part by G-protein stimulation of adenylyl cyclase, cAMP, and protein kinase A. These data suggest that VIP may play a physiological role in REM induction by its actions on mPRF neurons....
Exogenous glucagon-like peptide-1 attenuates glucose absorption and reduces blood glucose concentration after small intestinal glucose delivery in critical illness.
Miller, Asaf; Deane, Adam M; Plummer, Mark P; Cousins, Caroline E; Chapple, Lee-Anne S; Horowitz, Michael; Chapman, Marianne J
To evaluate the effect of exogenous glucagonlike peptide-1 (GLP-1) on small intestinal glucose absorption and blood glucose concentrations during critical illness. A prospective, blinded, placebo-controlled, cross-over, randomised trial in a mixed medical-surgical adult intensive care unit, with 12 mechanically ventilated critically ill patients, who were suitable for receiving small intestinal nutrient. On consecutive days, in a randomised order, participants received intravenous GLP-1 (1.2 pmol/ kg/min) or placebo (0.9% saline) as a continuous infusion over 270 minutes. After 6 hours of fasting, intravenous infusions of GLP-1 or placebo began at T = -30 min (in which T = time), with the infusion maintained at a constant rate until study completion at T = 240 min. At T = 0 min, a 100 mL bolus of mixed liquid nutrient meal (1 kcal/mL) containing 3 g of 3-O-methyl-D-gluco-pyranose (3-OMG), a marker of glucose absorption, was administered directly into the small intestine, via a post-pyloric catheter, over 6 minutes. Blood samples were taken at regular intervals for the measurement of plasma glucose and 3-OMG concentrations. Intravenous GLP-1 attenuated initial small intestinal glucose absorption (mean area under the curve [AUC] 0-30 for 3-OMG: GLP-1 group, 4.4 mmol/L/min [SEM, 0.9 mmol/L/min] v placebo group, 6.5 mmol/L/min [SEM, 1.0 mmol/L/min]; P = 0.01), overall small intestinal glucose absorption (mean AUC 0-240 for 3-OMG: GLP-1, 68.2 mmol/L/ min [SEM, 4.7 mmol/L/min] v placebo, 77.7 mmol/L/min [SEM, 4.4 mmol/lLmin]; P = 0.02), small intestinal glucose absorption and overall blood glucose concentration (mean AUC 0-240 for blood glucose: GLP-1, 2062 mmol/L/min [SEM, 111 mmol/L/min] v placebo 2328 mmol/L/min [SEM, 145 mmol/L/min]; P = 0.005). Short-term administration of exogenous GLP-1 reduces small intestinal glucose absorption for up to 4 hours during critical illness. This is likely to be an additional mechanism for the glucose-lowering effect of this agent.
DEFF Research Database (Denmark)
Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen
Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2, wh...
Orlistat inhibition of intestinal lipase acutely increases appetite and attenuates postprandial glucagon-like peptide-1-(7-36)-amide-1, cholecystokinin, and peptide YY concentrations
DEFF Research Database (Denmark)
Ellrichmann, Mark; Kapelle, Mario; Ritter, Peter R
of Orlistat or placebo. Gastric emptying, gallbladder volume and the plasma levels of CCK, PYY, GLP-1, and ghrelin were determined and appetite sensations were measured using visual analogue scales. RESULTS: Gastric emptying was accelerated by Orlistat administration (P emptying.......0001), whereas appetite and prospective food consumption increased (P gastric and gallbladder emptying and reduces...... whether Orlistat alters the secretion of glucagon-like peptide-1-(7-36)-amide (GLP-1), cholecystokinin (CCK), peptide YY (PYY), and ghrelin as well as postprandial appetite sensations. METHODS: Twenty-five healthy human volunteers were examined with a solid-liquid test meal after the oral administration...
Somatostatin, substance P and calcitonin gene-related peptide-positive intramural nerve structures of the human large intestine affected by carcinoma.
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Jerzy Kaleczyc
Full Text Available The aim of this study was to investigate the arrangement and chemical coding of enteric nerve structures in the human large intestine affected by cancer. Tissue samples comprising all layers of the intestinal wall were collected during surgery form both morphologically unchanged and pathologically altered segments of the intestine (n=15, and fixed by immersion in buffered paraformaldehyde solution. The cryostat sections were processed for double-labelling immunofluorescence to study the distribution of the intramural nerve structures (visualized with antibodies against protein gene-product 9.5 and their chemical coding using antibodies against somatostatin (SOM, substance P (SP and calcitonin gene-related peptide (CGRP. The microscopic observations revealed distinct morphological differences in the enteric nerve system structure between the region adjacent to the cancer invaded area and the intact part of the intestine. In general, infiltration of the cancer tissue resulted in the gradual (depending on the grade of invasion first decomposition and reduction to final partial or complete destruction and absence of the neuronal elements. A comparative analysis of immunohistochemically labeled sections (from the unchanged and pathologically altered areas revealed a statistically significant decrease in the number of CGRP-positive neurons and nerve fibres in both submucous and myenteric plexuses in the transitional zone between morphologically unchanged and cancer-invaded areas. In this zone, a decrease was also observed in the density of SP-positive nerve fibres in all intramural plexuses. Conversely, the investigations demonstrated statistically insignificant differences in number of SP- and SOM-positive neurons and a similar density of SOM-positive nerve fibres in the plexuses of the intact and pathologically changed areas. The differentiation between the potential adaptive changes in ENS or destruction of its elements by cancer invasion should be
123I labelled vasoactive intestinal peptide: Optimization of the radioiodination method, in vivo and in vitro assays
International Nuclear Information System (INIS)
Pozzi, O.R.; Sajaroff, E.O.; Edreira, M.; Gomez, S.I.; Manzini, A.
In the framework of the CRP, our country has worked on the optimization of synthesis, quality control, in vitro and in vivo evaluation of 123 I radiopharmaceuticals based on peptides. We have worked on selective labelling procedures using prosthetic groups with the goal to create a strong carbon-halogen bond, which will be resistant to in vivo dehalogenation and other catabolic processes. The method utilizes the labelling agent, reactive with ε-amino lysine groups, N-succinimidyl 3-iodobenzoate. This conjugation agent was radiolabelled by using an organometallic intermediate to facilitate the reaction. The organometallic N-succinimidyl 3-(tri-nbutylstannyl) benzoate (ATE) was made in a three-step synthesis pathway. The yields for the reactions of this synthetic pathway were: 56.4% for the first reaction, 67% for the second, and 58% for the ATE (469 mg, 0.92 mmol). Because of only 0.1 μmol of ATE is needed for the labelling of peptides, from one batch of organic synthesis we obtained ATE to make more than 9000 labelling. The N-succinimidyl 3-(tri-n-butylstannyl) benzoate (ATE) was radiolabelled in 55-85% radiochemical yield to obtain the N-succinimidyl 3-iodobenzoate ( [ 131 I]SIB ). Parameters like reactive concentration and isolation method of the labelling agent were studied. The labelling agent [ 131 I]SIB was subsequently conjugated to a human IgG and a peptide. A chemotactic peptide was used as a model peptide. A potent chemotactic peptide N-formyl-norleucyl-leucyl-phenylalanyl-norleucyltyrosyl- lysine (fNleLFNleYK) was derivatized by reaction with the labelling agent in 59-75% of radiochemical yield. This derivatized peptide bound specifically to human polymorphonuclear leukocytes in vitro and exhibited biological activity in a superoxide production assay. Binding affinity IC 50 : 36 nM, in the displacing of [ 3 H]fMLF binding, and IC 50 : 68 nM, in the displacing of the fNleLFNleYK-[ 131 I]SIB conjugate, for the derivatized peptide were obtained. Because
Enhanced Intestinal Permeability of Bufalin by a Novel Bufalin-Peptide-Dendrimer Inclusion through Caco-2 Cell Monolayer
Chi-on Chan; Jing Jing; Wei Xiao; Zhexu Tan; Qiuyue Lv; Jingyu Yang; Sibao Chen
Bufalin (BFL) has excellent physiological activities such as defending tumors, improving cardiac function, and so on. However, due to its poor water-solubility and bioavailability, the clinical application of BFL remains limited. In order to improve bioavailability of BFL, in our previous research, a novel peptide-dendrimer (PD) was synthesized and applied to encapsulate BFL. In the present study, we investigate the absorption property and mechanism of BFL in free form and BFL-peptide-dendrim...
Seizures induced by carbachol, morphine, and leucine-enkephalin: a comparison.
Snead, O C
The electrical, behavioral, and pharmacological properties of seizures induced by morphine, leucine-enkephalin, and the muscarinic cholinergic agonist carbachol were examined and compared. Low-dose carbachol given intracerebroventricularly (ICV) produced seizures similar electrically to those produced by ICV morphine and leucine-enkephalin, although there was some difference in site of subcortical origin of onset. Carbachol and morphine were similar in that they had the same anticonvulsant profile, produced similar behavioral changes, caused generalized absence seizures in low doses and generalized convulsive seizures in high doses, and were capable of chemical kindling. However, opiate-induced seizures were not overcome by cholinergic antagonists, nor were carbachol seizures blocked by opiate antagonists. These data suggest that there may be a common noncholinergic, nonopiatergic system involved in mediating carbachol- and morphine-induced seizures but not enkephalin seizures.
Exogenous glucagon-like peptide-2 (GLP-2) prevents chemotherapy-induced mucositis in rat small intestine
DEFF Research Database (Denmark)
Kissow, Hannelouise; Viby, Niels-Erik; Hartmann, Bolette
was analysed for weight loss, morphometric estimates and proliferation. Study 2 Rats were treated with GLP-2 or control vehicle 2 days before a single injection of 5-FU or saline. The treatments continued until kill 2 days after. The intestine was investigated for influx of myeloperoxidase (MPO)-positive cells...... and morphometric estimates, such as villus height, as a marker of mucositis. RESULTS STUDY 1: Two days after chemotherapy, there was a rise in endogenous GLP-2, followed by a marked increase in proliferation. Study 2 Exogenous GLP-2 was able to protect the intestine from severe weight loss and completely prevented...
Short Bowel Patients Treated for Two Years with Glucagon-Like Peptide 2: Effects on Intestinal Morphology and Absorption, Renal Function, Bone and Body Composition, and Muscle Function
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P. B. Jeppesen
Full Text Available Background and aims. In a short-term study, Glucagon-like peptide 2 (GLP-2 has been shown to improve intestinal absorption in short bowel syndrome (SBS patients. This study describes longitudinal changes in relation to GLP-2 treatment for two years. Methods. GLP-2, 400 micrograms, s.c.,TID, were offered, to eleven SBS patients keeping parenteral support constant. 72-hour nutritional balance studies were performed at baseline, weeks 13, 26, 52 during two years intermitted by an 8-week washout period. In addition, mucosal morphometrics, renal function (by creatinine clearance, body composition and bone mineral density (by DEXA, biochemical markers of bone turnover (by s-CTX and osteocalcin, PTH and vitamin D, and muscle function (NMR, lungfunction, exercise test were measured. Results. GLP-2 compliance was >93%. Three of eleven patients did not complete the study. In the remaining 8 patients, GLP-2 significantly reduced the fecal wet weight from approximately 3.0 to approximately 2.0 kg/day. This was accompanied by a decline in the oral wet weight intake, maintaining intestinal wet weight absorption and urinary weight constant. Renal function improved. No significant changes were demonstrated in energy intake or absorption, and GLP-2 did not significantly affect mucosal morphology, body composition, bone mineral density or muscle function. Conclusions. GLP-2 treatment reduces fecal weight by approximately 1000 g/d and enables SBS patients to maintain their intestinal fluid and electrolyte absorption at lower oral intakes. This was accompanied by a 28% improvement in creatinine clearance.
Giardia co-infection promotes the secretion of antimicrobial peptides beta-defensin 2 and trefoil factor 3 and attenuates attaching and effacing bacteria-induced intestinal disease.
Manko, Anna; Motta, Jean-Paul; Cotton, James A; Feener, Troy; Oyeyemi, Ayodele; Vallance, Bruce A; Wallace, John L; Buret, Andre G
Our understanding of polymicrobial gastrointestinal infections and their effects on host biology remains incompletely understood. Giardia duodenalis is an ubiquitous intestinal protozoan parasite infecting animals and humans. Concomitant infections with Giardia and other gastrointestinal pathogens commonly occur. In countries with poor sanitation, Giardia infection has been associated with decreased incidence of diarrheal disease and fever, and reduced serum inflammatory markers release, via mechanisms that remain obscure. This study analyzed Giardia spp. co-infections with attaching and effacing (A/E) pathogens, and assessed whether and how the presence of Giardia modulates host responses to A/E enteropathogens, and alters intestinal disease outcome. In mice infected with the A/E pathogen Citrobacter rodentium, co-infection with Giardia muris significantly attenuated weight loss, macro- and microscopic signs of colitis, bacterial colonization and translocation, while concurrently enhancing the production and secretion of antimicrobial peptides (AMPs) mouse β-defensin 3 and trefoil factor 3 (TFF3). Co-infection of human intestinal epithelial cells (Caco-2) monolayers with G. duodenalis trophozoites and enteropathogenic Escherichia coli (EPEC) enhanced the production of the AMPs human β-defensin 2 (HBD-2) and TFF3; this effect was inhibited with treatment of G. duodenalis with cysteine protease inhibitors. Collectively, these results suggest that Giardia infections are capable of reducing enteropathogen-induced colitis while increasing production of host AMPs. Additional studies also demonstrated that Giardia was able to directly inhibit the growth of pathogenic bacteria. These results reveal novel mechanisms whereby Giardia may protect against gastrointestinal disease induced by a co-infecting A/E enteropathogen. Our findings shed new light on how microbial-microbial interactions in the gut may protect a host during concomitant infections.
Lactobacillus reuteri I5007 Modulates Intestinal Host Defense Peptide Expression in the Model of IPEC-J2 Cells and Neonatal Piglets
Liu, Hongbin; Hou, Chengli; Wang, Gang; Jia, Hongmin; Yu, Haitao; Zeng, Xiangfang; Thacker, Philip A.; Zhang, Guolong; Qiao, Shiyan
Modulation of the synthesis of endogenous host defense peptides (HDPs) by probiotics represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections in human and animals. However, the extent of HDP modulation by probiotics is species dependent and strain specific. In the present study, The porcine small intestinal epithelial cell line (IPEC-J2) cells and neonatal piglets were used as in-vitro and in-vivo models to test whether Lactobacillus reuteri I5007 could modulate intestinal HDP expression. Gene expressions of HDPs, toll-like receptors, and fatty acid receptors were determined, as well as colonic short chain fatty acid concentrations and microbiota. Exposure to 108 colony forming units (CFU)/mL of L. reuteri I5007 for 6 h significantly increased the expression of porcine β-Defensin2 (PBD2), pBD3, pBD114, pBD129, and protegrins (PG) 1-5 in IPEC-J2 cells. Similarly, L. reuteri I5007 administration significantly increased the expression of jejunal pBD2 as well as colonic pBD2, pBD3, pBD114, and pBD129 in neonatal piglets (p reuteri I5007 in the piglets did not affect the colonic microbiota structure. Our findings suggested that L. reuteri I5007 could modulate intestinal HDP expression and improve the gut health of neonatal piglets, probably through the increase in colonic butyric acid concentration and the up-regulation of the downstream molecules of butyric acid, PPAR-γ and GPR41, but not through modifying gut microbiota structure. PMID:28561758
Carbachol does not down-regulate substance P receptors in pancreatic acini.
Patto, R J; Vinayek, R; Jensen, R T; Gardner, J D
In a previous study, we found that first incubating guinea pig pancreatic acini with carbachol caused desensitization of the enzyme secretory response to cholecystokinin-octapeptide (CCK-8), bombesin, and carbachol but not that to substance P. This carbachol-induced desensitization could be accounted for by carbachol-induced down-regulation of receptors for CCK-8, bombesin, and carbachol. Although carbachol did not desensitize the enzyme secretory response to substance P, an effect of carbachol on substance P receptors was not examined. In the present study, in dispersed acini from guinea pig pancreas, substance P caused a twofold increase in amylase secretion. Stimulation was half-maximal at 0.7 nM and was maximal at 10 nM. Analysis of the ability of substance P to inhibit binding of 125I-substance P to substance P receptors indicated that acini possess a single class of receptors for substance P (Kd = 0.8 +/- 0.1 nM; Bmax = 1,037 +/- 145 fmol/mg of DNA). There was a close correlation between the relative potency with which substance P stimulated amylase secretion (0.7 nM) and the potency for inhibiting binding of 125I-substance P (Kd = 0.8 nM). First incubating pancreatic acini with carbachol did not alter either substance P-stimulated enzyme secretion or binding of 125I-substance P to substance P receptors, whereas in the same experiments, carbachol reduced binding of 125I-CCK-8 to cholecystokinin receptors by 50% and decreased in CCK-8-stimulated enzyme secretion by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
The glucagon-like peptide 2 receptor is expressed in enteric neurons and not in the epithelium of the intestine
DEFF Research Database (Denmark)
Pedersen, Jens; B. Pedersen, Nis; Brix, Sophie W.
fibrillary acidic protein in these isolated tissue fractions was quantified with qRT-PCR. Expression of the Glp2r was confined to compartments containing enteric neurons and receptor expression was absent in the epithelium. Our findings provide evidence for the expression of the GLP-2R in intestinal...... compartments rich in enteric neurons and, importantly they exclude significant expression in the epithelium of rat jejunal mucosa....
Carbachol as miotic agent in intra-ocular lens implant surgery
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Agarwal Jitendra
Full Text Available The intra cameral use of 0.025% carbachol as a miotic agent in anterior chamber intraocular lens im-plant surgery us reported in 15 cases. Carbachol produced prompt and effective moisis and was found to be harmless and non-irritating to the anterior chamber structures. A rebound dialatation of the pipit was noticed in the post operative period in 3 of our first 5 cases where only carbachol was used. For prolonged miosis instillation of a more powerful miotic like pilocarpine is recommended at the completion of surgery:
Anti-allergic effects of a nonameric peptide isolated from the intestine gastrointestinal digests of abalone (Haliotis discus hannai) in activated HMC-1 human mast cells.
Ko, Seok-Chun; Lee, Dae-Sung; Park, Won Sun; Yoo, Jong Su; Yim, Mi-Jin; Qian, Zhong-Ji; Lee, Chang-Min; Oh, Junghwan; Jung, Won-Kyo; Choi, Il-Whan
The aim of the present study was to examine whether the intestine gastrointestinal (GI) digests of abalone [Haliotis discus hannai (H. discus hannai)] modulate inflammatory responses and to elucidate the mechanisms involved. The GI digests of the abalone intestines were fractionated into fractions I (>10 kDa), II (5-10 kDa) and Ⅲ (abalone intestine GI digests (AIGIDs), fraction Ⅲ inhibited the passive cutaneous anaphylaxis (PCA) reaction in mice. Subsequently, a bioactive peptide [abalone intestine GI digest peptide (AIGIDP)] isolated from fraction Ⅲ was determined to be 1175.2 Da, and the amino acid sequence was found to be PFNQGTFAS. We noted that the purified nonameric peptide (AIGIDP) attenuated the phorbol‑12‑myristate 13-acetate plus calcium ionophore A23187 (PMACI)-induced histamine release and the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in human mast cells (HMC-1 cells). In addition, we also noted that AIGIDP inhibited the PMACI‑induced activation of nuclear factor‑κB (NF-κB) by suppressing IκBα phosphorylation and that it suppressed the production of cytokines by decreasing the phosphorylation of JNK. The findings of our study indicate that AIGIDP exerts a modulatory, anti-allergic effect on mast cell-mediated inflammatory diseases.
Lack of effects of a single high-fat meal enriched with vegetable n-3 or a combination of vegetable and marine n-3 fatty acids on intestinal peptide release and adipokines in healthy female subjects
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Ingunn Naverud
Full Text Available Peptides released from the small intestine and colon regulate short-term food intake by suppressing appetite and inducing satiety. Intake of marine omega-3 (n-3 fatty acids from fish and fish oils is associated with beneficial health effects, whereas the relation between intake of the vegetable n-3 fatty acid α-linolenic acid and diseases is less clear. The aim of the present study was to investigate the postprandial effects of a single high-fat meal enriched with vegetable n-3 or a combination of vegetable and marine n-3 fatty acids with their different unsaturated fatty acid composition on intestinal peptide release and the adipose tissue. Fourteen healthy lean females consumed three test meals with different fat quality in a fixed order. The test meal consisted of three cakes enriched with coconut fat, linseed oil and a combination of linseed and cod liver oil. The test days were separated by two weeks. Fasting and postprandial blood samples at three and six hours after intake were analysed. A significant postprandial effect was observed for cholecystokinin, peptide YY, glucose-dependent insulinotropic polypeptide, amylin and insulin which increased, while leptin decreased postprandially independent of the fat composition in the high-fat meal. In conclusion, in healthy, young, lean females, an intake of a high-fat meal enriched with n-3 fatty acids from different origin stimulates intestinal peptide release without any difference between the different fat compositions.
Carbachol-mediated pigment granule dispersion in retinal pigment epithelium requires Ca2+ and calcineurin.
Johnson, Adam S; García, Dana M
Inside bluegill (Lepomis macrochirus) retinal pigment epithelial cells, pigment granules move in response to extracellular signals. During the process of aggregation, pigment motility is directed toward the cell nucleus; in dispersion, pigment is directed away from the nucleus and into long apical processes. A number of different chemicals have been found to initiate dispersion, and carbachol (an acetylcholine analog) is one example. Previous research indicates that the carbachol-receptor interaction activates a Gq-mediated pathway which is commonly linked to Ca2+ mobilization. The purpose of the present study was to test for involvement of calcium and to probe calcium-dependent mediators to reveal their role in carbachol-mediated dispersion. Carbachol-induced pigment granule dispersion was blocked by the calcium chelator BAPTA. In contrast, the calcium channel antagonist verapamil, and incubation in Ca2+-free medium failed to block carbachol-induced dispersion. The calcineurin inhibitor cypermethrin blocked carbachol-induced dispersion; whereas, two protein kinase C inhibitors (staurosporine and bisindolylmaleimide II) failed to block carbachol-induced dispersion, and the protein kinase C activator phorbol 12-myristate 13-acetate failed to elicit dispersion. A rise in intracellular calcium is necessary for carbachol-induced dispersion; however, the Ca2+ requirement is not dependent on extracellular sources, implying that intracellular stores are sufficient to enable pigment granule dispersion to occur. Calcineurin is a likely Ca2+-dependent mediator involved in the signal cascade. Although the pathway leads to the generation of diacylglycerol and calcium (both required for the activation of certain PKC isoforms), our evidence does not support a significant role for PKC.
Carbachol-mediated pigment granule dispersion in retinal pigment epithelium requires Ca2+ and calcineurin
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García Dana M
Full Text Available Abstract Background Inside bluegill (Lepomis macrochirus retinal pigment epithelial cells, pigment granules move in response to extracellular signals. During the process of aggregation, pigment motility is directed toward the cell nucleus; in dispersion, pigment is directed away from the nucleus and into long apical processes. A number of different chemicals have been found to initiate dispersion, and carbachol (an acetylcholine analog is one example. Previous research indicates that the carbachol-receptor interaction activates a Gq-mediated pathway which is commonly linked to Ca2+ mobilization. The purpose of the present study was to test for involvement of calcium and to probe calcium-dependent mediators to reveal their role in carbachol-mediated dispersion. Results Carbachol-induced pigment granule dispersion was blocked by the calcium chelator BAPTA. In contrast, the calcium channel antagonist verapamil, and incubation in Ca2+-free medium failed to block carbachol-induced dispersion. The calcineurin inhibitor cypermethrin blocked carbachol-induced dispersion; whereas, two protein kinase C inhibitors (staurosporine and bisindolylmaleimide II failed to block carbachol-induced dispersion, and the protein kinase C activator phorbol 12-myristate 13-acetate failed to elicit dispersion. Conclusion A rise in intracellular calcium is necessary for carbachol-induced dispersion; however, the Ca2+ requirement is not dependent on extracellular sources, implying that intracellular stores are sufficient to enable pigment granule dispersion to occur. Calcineurin is a likely Ca2+-dependent mediator involved in the signal cascade. Although the pathway leads to the generation of diacylglycerol and calcium (both required for the activation of certain PKC isoforms, our evidence does not support a significant role for PKC.
Effects of dietary supplementation with an expressed fusion peptide bovine lactoferricin-lactoferrampin on performance, immune function and intestinal mucosal morphology in piglets weaned at age 21 d.
Tang, Zhiru; Yin, Yulong; Zhang, Youming; Huang, Ruilin; Sun, Zhihong; Li, Tiejun; Chu, Wuying; Kong, Xiangfeng; Li, Lili; Geng, Meimei; Tu, Qiang
Lactoferrin has antimicrobial activity associated with peptide fragments lactoferricin (LFC) and lactoferrampin (LFA) released on digestion. These two fragments have been expressed in Photorhabdus luminescens as a fusion peptide linked to protein cipB. The construct cipB-LFC-LFA was tested as an alternative to antimicrobial growth promoters in pig production. Sixty piglets with an average live body weight of 5.42 (sem 0.59) kg were challenged with enterotoxigenic Escherichia coli and randomly assigned to four treatment groups fed a maize-soyabean meal diet containing either no addition (C), cipB at 100 mg/kg (C+B), cipB-LFC-LFA at 100 mg/kg (C+L) or colistin sulfate at 100 mg/kg (C+CS) for 3 weeks. Compared with C, dietary supplementation with C+L for 3 weeks increased daily weight gain by 21 %, increased recovery from diarrhoea, enhanced serum glutathione peroxidase (GPx), peroxidase (POD) and total antioxidant content (T-AOC), liver GPx, POD, superoxide dismutase and T-AOC, Fe, total Fe-binding capacity, IgA, IgG and IgM levels (P < 0.05), decreased the concentration of E. coli in the ileum, caecum and colon (P < 0.05), increased the concentration of lactobacilli and bifidobacteria in the ileum, caecum and colon (P < 0.05), and promoted development of the villus-crypt architecture of the small intestine. Growth performance was similar between C+L- and C+CS-supplemented pigs. The present results indicate that LFC-LFA is an effective alternative to the feed antibiotic CS for enhancing growth performance in piglets weaned at age 21 d.
Specific efficacy of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced neuroendocrine tumours of the small intestine
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Sabet, Amir; Dautzenberg, Kristina; Haslerud, Torjan; Aouf, Anas; Sabet, Amin; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Simon, Birgit [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)
Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with {sup 177}Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1-2 stage IV treated with {sup 177}Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2 %). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1 %), minor response in 19 (31.1 %), stable disease in 29 (47.5 %) and progressive disease in 5 (8.2 %) patients. The disease control rate was 91.8 %. Median progression-free survival (PFS) and overall survival (OS) was 33 [95 % confidence interval (CI) 25-41] and 61 months (95 % CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were
Prodrugs of purine and pyrimidine analogues for the intestinal di/tri-peptide transporter PepT1
DEFF Research Database (Denmark)
Thomsen, Anne Engelbrecht; Friedrichsen, Gerda Marie; Sørensen, Arne Hagsten
, novel L-Glu-Sar and D-Glu-Ala ester prodrugs of acyclovir and 1-(2-hydroxyethyl)-linked thymine were synthesized and their affinities for hPepT1 in Caco-2 cells were determined. Furthermore, the degradation of the prodrugs was investigated in various aqueous and biological media and compared...... to the corresponding hydrolysis of the prodrug valaciclovir. Affinity studies showed that the L-Glu-Sar prodrugs had high affinity for hPepT1 (K(i) approximately 0.2-0.3 mM), whereas the D-Glu-Ala prodrugs had poor affinity (K(i) approximately 50 mM). The pH-rate profiles of the prodrugs D-Glu[1-(2-hydroxyethyl......)thymine]-Ala and L-Glu[acyclovir]-Sar showed specific base catalyzed degradation at pH above 4.5 and 5.5, respectively. This implicates that the degradation rates at pH approximately 7.4 (t(1/2) approximately 3.5 and 5.5 h) are approximately 25 times faster than at upper small intestinal pH approximately 6.0. In 10...
Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure
Brinkman, Adam S.; Murali, Sangita G.; Hitt, Stacy; Solverson, Patrick M.; Holst, Jens J.
Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg−1·day−1), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral reference group. Animals underwent massive distal bowel resection followed by jejunocolic anastomosis and placement of jugular catheters. Starting on postoperative day 4, rats in the EN groups were allowed ad libitum access to EN. Groups provided PN + EN + GLP-2 had their rate of PN reduced by 0.25 ml/day starting on postoperative day 6. Groups provided PN + EN + GLP-2 demonstrated significantly greater body weight gain with similar energy intake and a safe 80% reduction in PN compared with TPN ± GLP-2. Groups provided PN + EN + GLP-2 for 7 or 18 days showed similar body weight gain, residual jejunal length, and digestive capacity. Groups provided PN + EN + GLP-2 showed increased jejunal GLP-2 receptor (GLP-2R), insulin-like growth factor-I (IGF-I), and IGF-binding protein-5 (IGFBP-5) expression. Treatment with TPN + GLP-2 demonstrated increased jejunal expression of epidermal growth factor. Cessation of GLP-2 after 7 days with continued EN sustained the majority of intestinal adaption and significantly increased expression of colonic proglucagon compared with PN + EN + GLP-2 for 18 days, and increased plasma GLP-2 concentrations compared with TPN alone. In summary, EN potentiate the intestinotrophic actions of GLP-2 by improving body weight gain allowing for a safe 80% reduction in PN with increased jejunal expression of GLP-2R, IGF-I, and IGFBP-5 following distal bowel
Increasing proportions of tyrosine hydroxylase-immunoreactive interneurons colocalize with choline acetyltransferase or vasoactive intestinal peptide in the developing rat cerebral cortex
Asmus, Stephen E.; Cocanougher, Benjamin T.; Allen, Donald L.; Boone, John B.; Brooks, Elizabeth A.; Hawkins, Sarah M.; Hench, Laura A.; Ijaz, Talha; Mayfield, Meredith N.
Cortical interneurons are critical for information processing, and their dysfunction has been implicated in neurological disorders. One subset of this diverse cell population expresses tyrosine hydroxylase (TH) during postnatal rat development. Cortical TH-immunoreactive neurons appear at postnatal day (P) 16. The number of TH cells sharply increases between P16 and P20 and subsequently decreases to adult values. The absence of apoptotic markers in these cells suggests that the reduction in cell number is not due to cell death but is due to a decline in TH production. Cortical TH cells lack all additional catecholaminergic enzymes, and many coexpress GABA and calretinin, but little else is known about their phenotype or function. Because interneurons containing choline acetyltransferase (ChAT) or vasoactive intestinal peptide (VIP) share characteristics with cortical TH neurons, the coexpression of TH with ChAT or VIP was examined throughout the neocortex at P16, P20, and P30. The proportions of TH cell profiles double-labeled for ChAT or VIP significantly increased between P16 and P30. Based on their proximity to blood vessels, intrinsic cholinergic and VIPergic cells have been hypothesized to regulate cortical microcirculation. Labeling with the gliovascular marker aquaporin-4 revealed that at least half of the TH cells were apposed to microvessels at these ages, and many of these cells contained ChAT or VIP. Cortical TH neurons did not coproduce nitric oxide synthase. These results suggest that increasing proportions of cortical TH neurons express ChAT or VIP developmentally and that a subset of these TH neurons may regulate local blood flow. PMID:21295554
Differential Effects of Statins on Inflammatory Interleukin-8 and Antimicrobial Peptide Human Β-Defensin 2 Responses in Salmonella-Infected Intestinal Epithelial Cells
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Fu-Chen Huang
Full Text Available Alternative therapies are needed to reduce the use of antibiotics and incidence of drug-resistant Salmonellosis. Previous studies have revealed important roles of statins in regulating innate immunity. Therefore, we investigated the effects of statins on innate immunity in Salmonella-infected intestinal epithelial cells (IECs, which are involved in mucosal innate immunity. SW480 cells and Akt siRNA- or vitamin D receptor (VDR siRNA-transfected SW480 cells were infected by wild-type S. Typhimurium strain SL1344 in the presence or absence of statins. The mRNA or protein expression was analyzed by real-time quantitative PCR or western blot analysis, respectively. Simvastatin or fluvastatin caused IL-8 (interleukin-8 suppression, but increased hBD-2 mRNA expression in Salmonella-infected SW480 cells. Both statins enhanced phosphorylated Akt and VDR expressions. Akt or VDR knockdown by siRNA counteracted the suppressive effect of simvastatin on IL-8 expression, whereas VDR knockdown diminished the enhanced hBD-2 expression in Salmonella-infected SW480 cells. Therefore, we observed differential regulation of statins on inflammatory IL-8 and anti-microbial hBD-2 expressions in Salmonella-infected IECs via PI3K/Akt signaling and VDR protein expression, respectively. The enhanced activity of antimicrobial peptides by statins in Salmonella-infected IECs could protect the host against infection, and modulation of pro-inflammatory responses could prevent the detrimental effects of overwhelming inflammation in the host.
Temperature effect on carbachol-induced depression of spontaneous quantal transmitter release in frog neuromuscular junction
Czech Academy of Sciences Publication Activity Database
Strunsky, E. G.; Borisover, M. D.; Nikolsky, E. E.; Vyskočil, František
Roč. 26, 8-9 (2001), s. 891-897 ISSN 0364-3190 R&D Projects: GA AV ČR IAA7011902; GA MŠk OK 267 Grant - others:RFBR(RU) 99-04-48286; EU(XX) Nesting Institutional research plan: CEZ:AV0Z5011922 Keywords : carbachol * temperature * acetylcholine release Subject RIV: ED - Physiology Impact factor: 1.638, year: 2001
Carbachol-mediated pigment granule dispersion in retinal pigment epithelium requires Ca2+ and calcineurin
Johnson, Adam S; Garc?a, Dana M
Abstract Background Inside bluegill (Lepomis macrochirus) retinal pigment epithelial cells, pigment granules move in response to extracellular signals. During the process of aggregation, pigment motility is directed toward the cell nucleus; in dispersion, pigment is directed away from the nucleus and into long apical processes. A number of different chemicals have been found to initiate dispersion, and carbachol (an acetylcholine analog) is one example. Previous research indicates that the ca...
Glucose and carbachol activate phospholipase C in digitonin-permeabilized islets
International Nuclear Information System (INIS)
Wolf, B.A.; Florholmen, J.; Turk, J.; McDaniel, M.L.
Stimulation of intact islets with D-glucose, the major insulin secretagogue, or with carbachol, a muscarinic agonist, results in the accumulation of inositoltrisphosphate (IP 3 ) suggesting that activation of phospholipase C (PLC) has a major role in stimulus-secretion coupling. Carbachol activation of PLC is an example of receptor-mediated activation in islets, whereas, the mechanism of glucose activation of PLC is controversial since a glucose receptor has not been identified. They have measured PLC activity in digitonin-permeabilized islets. Islets were labeled with 3 H-inositol, permeabilized and IP 3 accumulation measured by HPLC. Carbachol, in the presence of ATP, GTP and 1 μM free Ca 2+ released two-fold more Ins 1,3,4-P 3 than control in a time-dependent manner. Glucose, under the same conditions also significantly released more Ins 1,3,4-P 3 than control. This effect was not due to metabolism of glucose nor to an effect on the IP 3 -phosphomonoesterase. Preliminary Ca 2+ -dependency studies indicate that PLC is not activated by Ca 2+ in the submicromolar range. In conclusion, these studies show that Ca 2+ does not activate PLC, and furthermore, that D-glucose may be recognized directly by PLC
... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...
Acute effects of the Glucagon-Like Peptide 2 analogue, teduglutide, on intestinal adaptation in newborn pigs with short bowel syndrome
DEFF Research Database (Denmark)
Thymann, Thomas; Stoll, Barbara; Mecklenburg, Lars
Neonatal short bowel syndrome following massive gut resection associates with malabsorption of nutrients. The intestinotrophic factor glucagon-like peptide 2 (GLP-2) improves gut function in adult short bowel patients, but its effect in pediatric patients remains unknown. Our objective was to test...
C-fos expression in the pons and medulla of the cat during carbachol-induced active sleep.
Yamuy, J; Mancillas, J R; Morales, F R; Chase, M H
Microinjection of carbachol into the rostral pontine tegmentum of the cat induces a state that is comparable to naturally occurring active (REM, rapid eye movement) sleep. We sought to determine, during this pharmacologically induced behavioral state, which we refer to as active sleep-carbachol, the distribution of activated neuron within the pons and medulla using c-fos immunocytochemistry as a functional marker. Compared with control cats, which were injected with saline, active sleep-carbachol cats exhibited higher numbers of c-fos-expressing neurons in (1) the medial and portions of the lateral reticular formation of the pons and medulla, (2) nuclei in the dorsolateral rostral pons, (3) various raphe nuclei, including the dorsal, central superior, magnus, pallidus, and obscurus, (4) the medial and lateral vestibular, prepositus hypoglossi, and intercalatus nuclei, and (5) the abducens nuclei. On the other hand, the mean number of c-fos-expressing neurons found in the masseter, facial, and hypoglossal nuclei was lower in carbachol-injected than in control cats. The data indicate that c-fos expression can be employed as a marker of state-dependent neuronal activity. The specific sites in which there were greater numbers of c-fos-expressing neurons during active sleep-carbachol are discussed in relation to the state of active sleep, as well as the functional role that these sites play in generating the various physiological patterns of activity that occur during this state.
In vitro evaluation of N-methyl amide tripeptidomimetics as substrates for the human intestinal di-/tri-peptide transporter hPEPT1
DEFF Research Database (Denmark)
Andersen, Rikke; Nielsen, Carsten Uhd; Begtrup, Mikael
application of N-methyl amide bioisosteres as peptide bond replacements in tripeptides in order to decrease degradation by peptidases and yet retain affinity for and transport via hPEPT1. Seven structurally diverse N-methyl amide tripeptidomimetics were selected based on a principal component analysis...... of structural properties of 6859 N-methyl amide tripeptidomimetics. In vitro extracellular degradation of the selected tripeptidomimetics as well as affinity for and transepithelial transport via hPEPT1 were investigated in Caco-2 cells. Decreased apparent degradation was observed for all tripeptidomimetics...... to be substrates for hPEPT1 than tripeptidomimetics with charged side chains. The results of the present study indicate that the N-methyl amide peptide bond replacement approach for increasing bioavailability of tripeptidomimetic drug candidates is not generally applicable to all tripeptides. Nevertheless...
Labeling of vasoactive intestinal peptide (VIP) and VIP 10-28 fragment with radioiodine by direct method. Comparative study of the kinetics biodistribution and affinity for neuroendocrine tumor cells
International Nuclear Information System (INIS)
Colturato, Maria Tereza
In the progress of the Nuclear Medicine, many protein based radiopharmaceuticals have been developed in the last years using antibodies and, more recently, biologically active natural peptides or similar synthetic peptides. In the search for agents with specificity for the target tissue in tumors detection, it was verified that small sequences of amino acids may interact with selective sites, with homogenous distribution, fast accumulation in tissues and fast blood clearance when compared to the antibodies. Among the peptides used in the diagnosis of tumors, Vasoactive Intestinal Peptide (VIP) has been studied. VIP labeled with iodine-123 is applied in the images of intestinal adenocarcinoma and endocrine tumors. The molecule of VIP contains two tyrosine residues, in the positions 10 and 22 that are, theoretically, equally susceptible to radioiodination for direct method. The objective of this work was to produce VIP labeled with radioiodine (iodine-123), in order to introduce to the brazilian medical class this radiopharmaceutical of interest for the diagnosis and recurrence of tumors that express specific receptors. In an unpublished way, the work studied the labeling and the kinetic distribution of the VIP fragment (VIP 10-28) and verified its potential as radiopharmaceutical applied in the identification of tumors that express VIP receptors. After the choice of the appropriated technique for labeling VIP and VIP 10-28 with radioiodine, using Ceremonial T as oxidant agent and sodium metabisulfite as reducing agent, the quality control procedures were accomplished (electrophoresis and high performance liquid chromatography, HPLC) for radiochemical purity determination as well as the separation of the radiochemical species obtained. Labeling and quality control procedures applied were efficient and accurate. [ 131 I]VIP and [ 131 l]VIP 10-28 were obtained with high radiochemical purity (> 95%). The purification studies to remove free radioiodine in the labeling
Amebiasis intestinal Intestinal amebiasis
Directory of Open Access Journals (Sweden)
Full Text Available Entamoeba histolytica es el patógeno intestinal más frecuente en nuestro medio -después de Giardia lamblia-, una de las principales causas de diarrea en menores de cinco años y la cuarta causa de muerte en el mundo debida a infección por protozoarios. Posee mecanismos patogénicos complejos que le permiten invadir la mucosa intestinal y causar colitis amebiana. El examen microscópico es el método más usado para su identificación pero la existencia de dos especies morfológicamente iguales, una patógena ( E. histolytica y una no patógena ( Entamoeba dispar, ha llevado al desarrollo de otros métodos de diagnóstico. El acceso al agua potable y los servicios sanitarios adecuados, un tratamiento médico oportuno y el desarrollo de una vacuna, son los ejes para disminuir la incidencia y mortalidad de esta entidad.Entamoeba histolytica is the most frequent intestinal pathogen seen in our country, after Giardia lamblia, being one of the main causes of diarrhea in children younger than five years of age, and the fourth leading cause of death due to infection for protozoa in the world. It possesses complex pathogenic mechanisms that allow it to invade the intestinal mucosa, causing amoebic colitis. Microscopy is the most used method for its identification, but the existence of two species morphologically identical, the pathogen one ( E. histolytica, and the non pathogen one ( E. dispar, have taken to the development of other methods of diagnosis. The access to drinkable water and appropriate sanitary services, an opportune medical treatment, and the development of a vaccine are the axes to diminish the incidence and mortality of this entity.
Acylation of Therapeutic Peptides
DEFF Research Database (Denmark)
Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard
) , which promotes intestinal growth and is used to treat bowel disorders such as inflammatory bowel diseases and short bowel syndrome, and the 32 amino acid salmon calcitonin (sCT), which lowers blood calcium and is employed in the treatment of post-menopausal osteoporosis and hypercalcemia. The two...... peptides are similar in size and structure, but oppositely charged at physiological pH. Both peptides were acylated with linear acyl chains of systematically increasing length, where sCT was furthermore acylated at two different positions on the peptide backbone. For GLP-2, we found that increasing acyl...... remained optimal overall. The results indicate that rational acylation of GLP-2 can increase its in vitro intestinal absorption, alone or in combination with permeation enhancers, and are consistent with the initial project hypothesis. For sCT, an unpredicted effect of acylation largely superseded...
... Overview of Crohn Disease Additional Content Medical News Intestinal Lymphangiectasia (Idiopathic Hypoproteinemia) By Atenodoro R. Ruiz, Jr., MD, ... Overview of Malabsorption Bacterial Overgrowth Syndrome Celiac Disease Intestinal ... Intolerance Short Bowel Syndrome Tropical Sprue Whipple ...
... Colostomy ) is required to relieve an obstruction. Understanding Colostomy In a colostomy, the large intestine (colon) is cut. The part ... 1 What Causes Intestinal Strangulation? Figure 2 Understanding Colostomy Gastrointestinal Emergencies Overview of Gastrointestinal Emergencies Abdominal Abscesses ...
Vasoactive intestinal peptide (VIP) binds to guinea pig peritoneal eosinophils: A single class of binding sites with low affinity and high capacity
International Nuclear Information System (INIS)
Sakakibara, H.; Shima, K.; Takamatsu, J.; Said, S.I.
VIP binds to specific receptors on lymphocytes and mononuclear cells and exhibits antiinflammatory properties. Eosinophils (Eos) contribute to inflammatory reactions but the regulation of Eos function is incompletely understood. The authors examined the binding of monoradioiodinated VIP, [Tyr( 125 I) 10 ] VIP ( 125 I-VIP), to Eos in guinea pigs. The interaction of 125 i-VIP with Eos was rapid, reversible, saturable and linearly dependent on the number of cells. At equilibrium the binding was competitively inhibited by native peptide or by the related peptide helodermin. Scatchard analysis suggested the presence of a single class of VIP binding sites with a low affinity and a high capacity. In the presence of isobutyl-methylxanthine, VIP, PHI or helodermin did not stimulate cyclic AMP accumulation in intact Eos, while PGE 2 or 1-isoproterenol did. VIP also did not inhibit superoxide anion generation from Eos stimulated by phorbol myristate acetate. The authors conclude that: (1) VIP binds to low-affinity, specific sites on guinea pig peritoneal eosinophils; (2) this binding is not coupled to stimulation of adenylate cyclase; and (3) the possible function of these binding sites is at present unknown
Labeling of vasoactive intestinal peptide (VIP) and VIP 10-28 fragment with radioiodine by direct method. Comparative study of the kinetics biodistribution and affinity for neuroendocrine tumor cells; Marcacao do peptideo intestinal vasoativo (VIP) e do fragmento VIP10-28 com radioiodo por metodo direto. Estudo comparativo da cinetica de biodistribuicao e da afinidade por celulas de tumor neuroendocrino
Energy Technology Data Exchange (ETDEWEB)
Colturato, Maria Tereza
In the progress of the Nuclear Medicine, many protein based radiopharmaceuticals have been developed in the last years using antibodies and, more recently, biologically active natural peptides or similar synthetic peptides. In the search for agents with specificity for the target tissue in tumors detection, it was verified that small sequences of amino acids may interact with selective sites, with homogenous distribution, fast accumulation in tissues and fast blood clearance when compared to the antibodies. Among the peptides used in the diagnosis of tumors, Vasoactive Intestinal Peptide (VIP) has been studied. VIP labeled with iodine-123 is applied in the images of intestinal adenocarcinoma and endocrine tumors. The molecule of VIP contains two tyrosine residues, in the positions 10 and 22 that are, theoretically, equally susceptible to radioiodination for direct method. The objective of this work was to produce VIP labeled with radioiodine (iodine-123), in order to introduce to the brazilian medical class this radiopharmaceutical of interest for the diagnosis and recurrence of tumors that express specific receptors. In an unpublished way, the work studied the labeling and the kinetic distribution of the VIP fragment (VIP 10-28) and verified its potential as radiopharmaceutical applied in the identification of tumors that express VIP receptors. After the choice of the appropriated technique for labeling VIP and VIP 10-28 with radioiodine, using Ceremonial T as oxidant agent and sodium metabisulfite as reducing agent, the quality control procedures were accomplished (electrophoresis and high performance liquid chromatography, HPLC) for radiochemical purity determination as well as the separation of the radiochemical species obtained. Labeling and quality control procedures applied were efficient and accurate. [{sup 131}I]VIP and [{sup 131}l]VIP 10-28 were obtained with high radiochemical purity (> 95%). The purification studies to remove free radioiodine in the
Evidence that morphine and opioid peptides do not share a common pathway with adenosine in inhibiting acetylcholine release from isolated intestine.
Vizi, E S; Somogyi, G T; Magyar, K
1 The release of acetylcholine from guinea-pig ileal isolated longitudinal muscle strip with intact Auerbach's plexus was measured by bioassay and by a radioisotope technique. 2 Normorphine (5 x 10(-7)M) and D-Met2, Pro5-enkephalinamide (D-Met, Pro-EA) reduced the release of acetylcholine. Theophylline, an adenosine antagonist, failed to prevent the inhibitory effect of normorphine or D-Met, Pro-EA. 3 Theophylline (1.7 x 10(-4)M) by itself enhanced the twitch responses to field stimulation (0.1 Hz) but did not prevent the inhibitory effect of normorphine and D-Met, Pro-EA. 4 From the results it can be concluded that morphine and opioid peptides do not share a common pathway with adenosine in inhibiting acetylcholine release from axon terminals of Auerbach's plexus.
Vasoactive intestinal peptide-induced neurite remodeling in human neuroblastoma SH-SY5Y cells implicates the Cdc42 GTPase and is independent of Ras-ERK pathway
International Nuclear Information System (INIS)
Alleaume, Celine; Eychene, Alain; Harnois, Thomas; Bourmeyster, Nicolas; Constantin, Bruno; Caigneaux, Evelyne; Muller, Jean-Marc; Philippe, Michel
Vasoactive intestinal peptide (VIP) is known to regulate proliferation or differentiation in normal and tumoral cells. SH-SY5Y is a differentiated cell subclone derived from the SK-N-SH human neuroblastoma cell line and possess all the components for an autocrine action of VIP. In the present study, we investigated the morphological changes and intracellular signaling pathways occurring upon VIP treatment of SH-SY5Y cells. VIP induced an early remodeling of cell projections: a branched neurite network spread out and prominent varicosities developed along neurites. Although activated by VIP, the Ras/ERK pathway was not required for the remodeling process. In contrast, pull-down experiments revealed a strong Cdc42 activation by VIP while expression of a dominant-negative Cdc42 prevented the VIP-induced neurite changes, suggesting an important role for this small GTPase in the process. These data provide the first evidence for a regulation of the activity of Rho family GTPases by VIP and bring new insights in the signaling pathways implicated in neurite remodeling process induced by VIP in neuroblastoma cells
Vasoactive Intestinal Peptide Protects Salivary Glands against Structural Injury and Secretory Dysfunction via IL-17A and AQP5 Regulation in a Model of Sjögren Syndrome.
Li, Chengyin; Zhu, Fenglin; Wu, Bin; Wang, Yue
Sjögren syndrome (SS) is an autoimmune disease involving exocrine glands. Currently, drugs that can improve both abnormal immunity and exocrine gland function are needed. The study aimed to investigate the effect and mechanism of vasoactive intestinal peptide (VIP) on the immune response and exocrine gland function in SS. We investigated the effects of VIP on the immune response and secretory function of submandibular glands using NOD mice, and analyzed the expression of IL-17A and AQP5 (aquaporin 5). The submandibular gland cells from healthy 8-day-old Sprague-Dawley rats were used to observe the influence of VIP on AQP5 expression. Our study shows that treatment with VIP in an SS mouse model could not only reduce the immune injury to exocrine glands but also improve the secretory function of these glands. Furthermore, VIP was shown to improve the abnormal immune status by downregulating IL-17A expression in the exocrine glands. It also enhanced the secretory function of exocrine glands by upregulating AQP5 expression. Using a model of SS, we found that VIP could not only modulate the immune response but also affect exocrine gland function, and that these therapeutic effects were associated with IL-17A and AQP5 regulation. © 2018 S. Karger AG, Basel.
Investigation of carbachol and PACAP38 in a human model of migraine
DEFF Research Database (Denmark)
Schytz, Henrik Winther
and VIP in migraine and head pain. In study I-III we investigated acetylcholine, via the analogue carbachol, and PACAP38 in a human model of migraine. In study IV we studied if PACAP38 and VIP might induce central sensitization, neurogenic inflammation and mast cell degranulation in a cutaneous model...... in migraine patients as well as sustained dilatation of cephalic vessels. In study IV VIP and PACAP38 evoked skin pain, central sensitization, neurogenic inflammation and mast cell degranulation, but VIP showed to be more potent than PACAP38 in inducing neurogenic inflammation and mast cell degranulation...... that neurogenic inflammation and mast cell degranulation are unlikely to cause PACAP38 induced migraine. The present thesis contributes to our knowledge on migraine pathophysiology and suggests PAC1 receptor antagonism as a new target for migraine treatment....
Desrochers, André; Anderson, David E
A wide variety of disorders affecting the intestinal tract in cattle may require surgery. Among those disorders the more common are: intestinal volvulus, jejunal hemorrhage syndrome and more recently the duodenal sigmoid flexure volvulus. Although general principles of intestinal surgery can be applied, cattle has anatomical and behavior particularities that must be known before invading the abdomen. This article focuses on surgical techniques used to optimize outcomes and discusses specific disorders of small intestine. Diagnoses and surgical techniques presented can be applied in field conditions. Copyright © 2016 Elsevier Inc. All rights reserved.
Smooth muscle adaptation after intestinal transection and resection.
Thompson, J S; Quigley, E M; Adrian, T E
Changes in motor function occur in the intestinal remnant after intestinal resection. Smooth muscle adaptation also occurs, particularly after extensive resection. The time course of these changes and their interrelationship are unclear. Our aim was to evaluate changes in canine smooth muscle structure and function during intestinal adaptation after transection and resection. Twenty-five dogs underwent either transection (N = 10), 50% distal resection (N = 10), or 50% proximal resection (N = 5). Thickness and length of the circular (CM) and longitudinal (LM) muscle layers were measured four and 12 weeks after resection. In vitro length-tension properties and response to a cholinergic agonist were studied in mid-jejunum and mid-ileum. Transection alone caused increased CM length in the jejunum proximal to the transection but did not affect LM length or muscle thickness. A 50% resection resulted in increased length of CM throughout the intestine and thickening of CM and LM near the anastomosis. Active tension of jejunal CM increased transiently four weeks after resection. Active tension in jejunal LM was decreased 12 weeks after transection and resection. Sensitivity of CM to carbachol was similar after transection and resection. It is concluded that: (1) Structural adaptation of both circular and longitudinal muscle occurs after intestinal resection. (2) This process is influenced by the site of the intestinal remnant. (3) Only minor and transient changes occur in smooth muscle function after resection. (4) Factors other than muscle adaptation are likely involved in the changes in motor function seen following massive bowel resection.
Guanylin peptides: cyclic GMP signaling mechanisms
Directory of Open Access Journals (Sweden)
Forte L.R.
Full Text Available Guanylate cyclases (GC serve in two different signaling pathways involving cytosolic and membrane enzymes. Membrane GCs are receptors for guanylin and atriopeptin peptides, two families of cGMP-regulating peptides. Three subclasses of guanylin peptides contain one intramolecular disulfide (lymphoguanylin, two disulfides (guanylin and uroguanylin and three disulfides (E. coli stable toxin, ST. The peptides activate membrane receptor-GCs and regulate intestinal Cl- and HCO3- secretion via cGMP in target enterocytes. Uroguanylin and ST also elicit diuretic and natriuretic responses in the kidney. GC-C is an intestinal receptor-GC for guanylin and uroguanylin, but GC-C may not be involved in renal cGMP pathways. A novel receptor-GC expressed in the opossum kidney (OK-GC has been identified by molecular cloning. OK-GC cDNAs encode receptor-GCs in renal tubules that are activated by guanylins. Lymphoguanylin is highly expressed in the kidney and heart where it may influence cGMP pathways. Guanylin and uroguanylin are highly expressed in intestinal mucosa to regulate intestinal salt and water transport via paracrine actions on GC-C. Uroguanylin and guanylin are also secreted from intestinal mucosa into plasma where uroguanylin serves as an intestinal natriuretic hormone to influence body Na+ homeostasis by endocrine mechanisms. Thus, guanylin peptides control salt and water transport in the kidney and intestine mediated by cGMP via membrane receptors with intrinsic guanylate cyclase activity.
Directory of Open Access Journals (Sweden)
Tadeja Pintar
Conclusion: Intestine transplantation is reserved for patients with irreversible intestinal failure due to short gut syndrome requiring total paranteral nutrition with no possibility of discontinuation and loss of venous access for patient maintenance. In these patients complications of underlying disease and long-term total parenteral nutrition are present.
Histamine, carbachol, and serotonin induce hyperresponsiveness to ATP in guinea pig tracheas: involvement of COX-2 pathway.
Montaño, Luis M; Carbajal, Verónica; Vargas, Mario H; García-Hernández, Luz M; Díaz-Hernández, Verónica; Checa, Marco; Barajas-López, Carlos
Extracellular ATP promotes an indirect contraction of airway smooth muscle via the secondary release of thromboxane A2 (TXA2) from airway epithelium. Our aim was to evaluate if common contractile agonists modify this response to ATP. Tracheas from sensitized guinea pigs were used to evaluate ATP-induced contractions before and after a transient contraction produced by histamine, carbachol, or serotonin. Epithelial mRNA for COX-1 and COX-2 was measured by RT-PCR and their expression assessed by immunohistochemistry. Compared with the initial response, ATP-induced contraction was potentiated by pretreatment with histamine, carbachol, or serotonin. Either suramin (antagonist of P2X and P2Y receptors) plus RB2 (antagonist of P2Y receptors) or indomethacin (inhibitor of COX-1 and COX-2) annulled the ATP-induced contraction, suggesting that it was mediated by P2Y receptor stimulation and TXA2 production. When COX-2 was inhibited by SC-58125 or thromboxane receptors were antagonized by SQ-29548, just the potentiation was abolished, leaving the basal response intact. Airway epithelial cells showed increased COX-2 mRNA after stimulation with histamine or carbachol, but not serotonin, while COX-1 mRNA was unaffected. Immunochemistry corroborated this upregulation of COX-2. In conclusion, we showed for the first time that histamine and carbachol cause hyperresponsiveness to ATP by upregulating COX-2 in airway epithelium, which likely increases TXA2 production. Serotonin-mediated hyperresponsiveness seems to be independent of COX-2 upregulation, but nonetheless is TXA2 dependent. Because acetylcholine, histamine, and serotonin can be present during asthmatic exacerbations, their potential interactions with ATP might be relevant in its pathophysiology.
Epidermal Growth Factor and Intestinal Barrier Function
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Xiaopeng Tang
Full Text Available Epidermal growth factor (EGF is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health.
... most often found when a person has an upper gastrointestinal (GI) endoscopy or colonoscopy for another reason. Rarely, these tumors can cause bleeding, blockage or rupture of the intestines If this ...
The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice
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Ogawa, Eiichi [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Hosokawa, Masaya [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Faculty of Human Sciences, Tezukayama Gakuin University, Osaka (Japan); Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Tsukiyama, Katsushi; Yamada, Yuichiro [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Department of Internal Medicine, Division of Endocrinology, Diabetes and Geriatric Medicine, Akita University School of Medicine, Akita (Japan); Seino, Yutaka [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Kansai Electric Power Hospital, Osaka (Japan); Inagaki, Nobuya, E-mail: email@example.com [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); CREST of Japan Science and Technology Cooperation (JST), Kyoto (Japan)
Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin
The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice
International Nuclear Information System (INIS)
Ogawa, Eiichi; Hosokawa, Masaya; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Seino, Yutaka; Inagaki, Nobuya
Research highlights: → Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. → Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. → The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic β cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [ 14 C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [ 14 C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather
... disease Crohn's disease Infections Intestinal cancer Intestinal obstruction Irritable bowel syndrome Ulcers, such as peptic ulcer Treatment of disorders of the small intestine depends on the cause.
Fos and serotonin immunoreactivity in the raphe nuclei of the cat during carbachol-induced active sleep: a double-labeling study.
Yamuy, J; Sampogna, S; López-Rodríguez, F; Luppi, P H; Morales, F R; Chase, M H
The microinjection of carbachol into the nucleus pontis oralis produces a state which is polygraphically and behaviorally similar to active sleep (rapid eye movement sleep). In the present study, using double-labeling techniques for serotonin and the protein product of c-fos (Fos), we sought to examine whether immunocytochemically identified serotonergic neurons of the raphe nuclei of the cat were activated, as indicated by their expression of c-fos, during this pharmacologically-induced behavioral state (active sleep-carbachol). Compared with control cats, which were injected with saline, active sleep-carbachol cats exhibited a significantly greater number of c-fos-expressing neurons in the raphe dorsalis, magnus and pallidus. Whereas most of the c-fos-expressing neurons in the raphe dorsalis were small, those in the raphe magnus were medium-sized and in the raphe pallidus they were small and medium-sized. The mean number of serotonergic neurons that expressed c-fos (i.e. double-labeled cells) was similar in control and active sleep-carbachol cats. These data indicate that there is an increased number of non-serotonergic, c-fos-expressing neurons in the raphe dorsalis, magnus and pallidus during the carbachol-induced state.(ABSTRACT TRUNCATED AT 250 WORDS)
Czech Academy of Sciences Publication Activity Database
Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan
Roč. 11, - (2005), 757-788 ISSN 1075-2617 R&D Projects: GA ČR(CZ) GA203/03/1362 Institutional research plan: CEZ:AV0Z40550506 Keywords : multiple antigen peptides * peptide dendrimers * synthetic vaccine * multipleantigenic peptides Subject RIV: CC - Organic Chemistry Impact factor: 1.803, year: 2005
Pancreatic and intestinal processing of proglucagon in man
DEFF Research Database (Denmark)
Holst, J J; Poulsen, Steen Seier
We developed antisera and radioimmunoassays against synthetic replicas of glucagon-like peptide-1 (1-36) and -2, predicted products of the glucagon precursor, and against glucagon-like peptide-1 (7-36) identical to the sequence of glucagon-like peptide-1, but lacking its first six N-terminal amino...... acids. With these tools, we studied the localisation and molecular nature of glucagon-like immunoreactivity in human pancreas, small intestine and plasma. By immunohistochemistry glucagon-like peptide-1, and glucagon-like peptide-2 immunoreactivity coexisted with glucagon in pancreatic islet cells...
Responses of mRNA expression of PepT1 in small intestine to ...
African Journals Online (AJOL)
To study the effect of circulation small peptides concentration on mRNA expression in small intestine, graded amount of soybean small peptides (SSP) were infused into lactating goats through duodenal fistulas. Peptide-bound amino acid (PBAA) concentration in arterial plasma and the mRNA expression of PepT1 was ...
Whipple, G. H.; Stone, H. B.; Bernheim, B. M.
Closed duodenal loops may be made in dogs by ligatures placed just below the pancreatic duct and just beyond the duodenojejunal junction, together with a posterior gastro-enterostomy. These closed duodenal loop dogs die with symptoms like those of patients suffering from volvulus or high intestinal obstruction. This duodenal loop may simulate closely a volvulus in which there has been no vascular disturbance. Dogs with closed duodenal loops which have been washed out carefully survive a little longer on the average than animals with unwashed loops. The duration of life in the first instance is one to three days, with an average of about forty-eight hours. The dogs usually lose considerable fluid by vomiting and diarrhea. A weak pulse, low blood pressure and temperature are usually conspicuous in the last stages. Autopsy shows more or less splanchnic congestion which may be most marked in the mucosa of the upper small intestine. The peritoneum is usually clear and the closed loop may be distended with thin fluid, or collapsed, and contain only a small amount of pasty brown material. The mucosa of the loop may show ulceration and even perforation, but in the majority of cases it is intact and exhibits only a moderate congestion. Simple intestinal obstruction added to a closed duodenal loop does not modify the result in any manner, but it may hasten the fatal outcome. The liver plays no essential role as a protective agent against this poison, for a dog with an Eck fistula may live three days with a closed loop. A normal dog reacts to intraportal injection and to intravenous injection of the toxic substance in an identical manner. Drainage of this loop under certain conditions may not interfere with the general health over a period of weeks or months. Excision of the part of the duodenum included in this loop causes no disturbance. The material from the closed duodenal loops contains no bile, pancreatic juice, gastric juice, or split products from the food. It can be
Intestinal Colonization Dynamics of Vibrio cholerae.
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Salvador Almagro-Moreno
Full Text Available To cause the diarrheal disease cholera, Vibrio cholerae must effectively colonize the small intestine. In order to do so, the bacterium needs to successfully travel through the stomach and withstand the presence of agents such as bile and antimicrobial peptides in the intestinal lumen and mucus. The bacterial cells penetrate the viscous mucus layer covering the epithelium and attach and proliferate on its surface. In this review, we discuss recent developments and known aspects of the early stages of V. cholerae intestinal colonization and highlight areas that remain to be fully understood. We propose mechanisms and postulate a model that covers some of the steps that are required in order for the bacterium to efficiently colonize the human host. A deeper understanding of the colonization dynamics of V. cholerae and other intestinal pathogens will provide us with a variety of novel targets and strategies to avoid the diseases caused by these organisms.
Chicken antimicrobial peptides: biological functions and possible applications
Dijk, Albert van
Farm animals often suffer from diseases of the gastro-intestinal tract. Modulation of natural defence mechanisms by dietary additives may be one way to improve intestinal health and food safety. In mammals, antimicrobial peptides (AMPs) play an important role in the host defence of skin and mucosal
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U S Udgaonkar
Full Text Available Purpose: Intestinal myiasis is a condition when the fly larvae inhabit the gastrointestinal tract and are passed out in faeces. This type of infestation results when eggs or larvae of the fly, deposited on food are inadvertently taken by man. They survive the unfavourable conditions within the gastrointestinal tract and produce disturbances, which may vary from mild to severe. The condition is not uncommon and is often misdiagnosed as pinworm infestation. Correct diagnosis by the clinical microbiologist is important to avoid unnecessary treatment. Materials and Methods: We had 7 cases of intestinal myiasis. In 2 cases the larvae were reared to adult fly in modified meat and sand medium (developed by Udgaonkar. This medium is simple and can be easily prepared in the laboratory. Results: Of the 7 larvae, 5 were Sarcophaga haemorrhoidalis, 1 Megaselia species and 1 was identified as Muscina stabulans. Conclusions: S. haemorrhoidalis was the commonest maggot involved. A high index of suspicion is required for clinical diagnosis when the patient complains of passing wriggling worms in faeces for a long period without any response to antihelminthics. The reason for long duration of illness and recurrence of infestation is baffling. The nearest to cure was colonic wash. We feel prevention is of utmost importance, which is to avoid eating food articles with easy access to flies.
Udgaonkar, U S; Dharamsi, R; Kulkarni, S A; Shah, S R; Patil, S S; Bhosale, A L; Gadgil, S A; Mohite, R S
Intestinal myiasis is a condition when the fly larvae inhabit the gastrointestinal tract and are passed out in faeces. This type of infestation results when eggs or larvae of the fly, deposited on food are inadvertently taken by man. They survive the unfavourable conditions within the gastrointestinal tract and produce disturbances, which may vary from mild to severe. The condition is not uncommon and is often misdiagnosed as pinworm infestation. Correct diagnosis by the clinical microbiologist is important to avoid unnecessary treatment. We had 7 cases of intestinal myiasis. In 2 cases the larvae were reared to adult fly in modified meat and sand medium (developed by Udgaonkar). This medium is simple and can be easily prepared in the laboratory. Of the 7 larvae, 5 were Sarcophaga haemorrhoidalis, 1 Megaselia species and 1 was identified as Muscina stabulans. S. haemorrhoidalis was the commonest maggot involved. A high index of suspicion is required for clinical diagnosis when the patient complains of passing wriggling worms in faeces for a long period without any response to antihelminthics. The reason for long duration of illness and recurrence of infestation is baffling. The nearest to cure was colonic wash. We feel prevention is of utmost importance, which is to avoid eating food articles with easy access to flies.
Acute effects of continuous infusions of glucagon-like peptide (GLP)-1, GLP-2 and the combination (GLP-1+GLP-2) on intestinal absorption in short bowel syndrome (SBS) patients. A placebo-controlled study
DEFF Research Database (Denmark)
Madsen, K B; Askov-Hansen, C; Naimi, R M
The ileocolonic brake is impaired in short bowel syndrome (SBS) patients with distal bowel resections. An attenuated meal-stimulated hormone secretion may cause gastric hypersecretion, rapid gastric and intestinal transit and a poor adaptation. Attempting to restore this ileocolonic brake...
Guanine nucleotide-dependent, pertussis toxin-insensitive, stimulation of inositol phosphate formation by carbachol in a membrane preparation from astrocytoma cells
International Nuclear Information System (INIS)
Hepler, J.R.; Harden, T.K.
Formation of the inositol phosphates (InsP), InsP 3 , InsP 2 , and InsP 1 was increased in a concentration dependent manner (K/sub 0.5/ ∼ 5 μM) by GTPΣS in washed membranes prepared from 3 H-inositol-prelabelled 1321N1 human astrocytoma cells. Both GTPγS and GppNHp stimulated InsP formation by 2-3 fold over control; GTP and GDP were much less efficacious and GMP had no effect. Although the muscarinic cholinergic receptor agonist carbachol had no effect in the absence of guanine nucleotide, in the presence of 10 μM GTPγS, carbachol stimulated (K/sub 0.5/ ∼ 10 μ M) the formation of InsP above the level achieved with GTPγS alone. The effect of carbachol was completely blocked by atropine. The order of potency for a series of nucleotides for stimulation of InsP formation in the presence of 500 μM carbachol was GTPγS > GppNHp > GTP = GDP. Pertussis toxin, at concentrations that fully ADP-ribosylate and functionally inactivate G/sub i/, had no effect on InsP formation in the presence of GTPγS or GTPγS plus carbachol. Histamine and bradykinin also stimulated InsP formation in the presence of GTPγS in washed membranes from 1321N1 cells. These data are consistent with the idea that a guanine nucleotide regulatory protein that is not G/sub i/ is involved in receptor-mediated stimulation of InsP formation in 1321N1 human astrocytoma cells
Circulating levels of vasoactive peptides in patients with acute bacterial meningitis
DEFF Research Database (Denmark)
Berg, Ronan M G; Strauss, Gitte Irene; Tofteng, Flemming
PURPOSE: The underlying mechanisms for cerebral blood flow (CBF) abnormalities in acute bacterial meningitis (ABM) are largely unknown. Putative mediators include vasoactive peptides, e.g. calcitonin-gene related peptide (CGRP), vasoactive intestinal peptide (VIP), and endothelin-1 (ET-1), all...
Administration of a dipeptidyl peptidase IV inhibitor enhances the intestinal adaptation in a mouse model of short bowel syndrome
DEFF Research Database (Denmark)
Okawada, Manabu; Holst, Jens Juul; Teitelbaum, Daniel H
Glucagon-like peptide-2 induces small intestine mucosal epithelial cell proliferation and may have benefit for patients who suffer from short bowel syndrome. However, glucagon-like peptide-2 is inactivated rapidly in vivo by dipeptidyl peptidase IV. Therefore, we hypothesized that selectively inh...... inhibiting dipeptidyl peptidase IV would prolong the circulating life of glucagon-like peptide-2 and lead to increased intestinal adaptation after development of short bowel syndrome....
[Adult intestinal malrotation associated with intestinal volvulus].
Hernando-Almudí, Ernesto; Cerdán-Pascual, Rafael; Vallejo-Bernad, Cristina; Martín-Cuartero, Joaquín; Sánchez-Rubio, María; Casamayor-Franco, Carmen
Intestinal malrotation is a congenital anomaly of the intestinal rotation and fixation, and usually occurs in the neonatal age. Description of a clinical case associated with acute occlusive symptoms. A case of intestinal malrotation is presented in a previously asymptomatic woman of 46 years old with an intestinal obstruction, with radiology and surgical findings showing an absence of intestinal rotation. Intestinal malrotation in adults is often asymptomatic, and is diagnosed as a casual finding during a radiological examination performed for other reasons. Infrequently, it can be diagnosed in adults, associated with an acute abdomen. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.
Ambe, Peter C; Kurz, Nadja Rebecca; Nitschke, Claudia; Odeh, Siad F; Möslein, Gabriela; Zirngibl, Hubert
About 100 000 ostomy carriers are estimated to live in Germany today. The creation of an ostomy represents a major life event that can be associated with impaired quality of life. Optimal ostomy creation and proper ostomy care are crucially important determinants of the success of treatment and of the patients' quality of life. This article is based on pertinent publications retrieved by a selective search in PubMed, GoogleScholar, and Scopus, and on the authors' experience. Intestinal stomata can be created using either the small or the large bowel. More than 75% of all stomata are placed as part of the treatment of colorectal cancer. The incidence of stoma-related complications is reported to be 10-70%. Skin irritation, erosion, and ulceration are the most common early complications, with a combined incidence of 25-34%, while stoma prolapse is the most common late complication, with an incidence of 8-75%. Most early complications can be managed conservatively, while most late complications require surgical revision. In 19% of cases, an ostomy that was initially planned to be temporary becomes permanent. Inappropriate stoma location and inadequate ostomy care are the most common causes of early complications. Both surgical and patient-related factors influence late complications. Every step from the planning of a stoma to its postoperative care should be discussed with the patient in detail. Preoperative marking is essential for an optimal stoma site. Optimal patient management with the involvement of an ostomy nurse increases ostomy acceptance, reduces ostomy-related complications, and improves the quality of life of ostomy carriers.
International Nuclear Information System (INIS)
Rozenshtraukh, L.S.
Roentgenoanatomy and physiology of the small intestine are described. Indications for radiological examinations and their possibilities in the diagnosis of the small intestine diseases are considered.Congenital anomalies and failures in the small intestine development, clinical indications and diagnosis methods for the detection of different aetiology enteritis are described. Characteristics of primary malabsorption due to congenital or acquired inferiority of the small intestine, is provided. Radiological picture of intestinal allergies is described. Clinical, morphological, radiological pictures of Crohn's disease are considered in detail. Special attention is paid to the frequency of primary and secondary tuberculosis of intestinal tract. The description of clinical indications and frequency of benign and malignant tumours of the small intestine, methods for their diagnosis are given. Radiological pictures of parasitogenic and rare diseases of the small intestine are presented. Changes in the small intestine as a result of its reaction to pathological processes, developing in other organs and systems of the organism, are described
The biphasic effect of extracellular glucose concentration on carbachol-induced fluid secretion from mouse submandibular glands.
Terachi, Momomi; Hirono, Chikara; Kitagawa, Michinori; Sugita, Makoto
Cholinergic agonists evoke elevations of the cytoplasmic free-calcium concentration ([Ca 2+ ] i ) to stimulate fluid secretion in salivary glands. Salivary flow rates are significantly reduced in diabetic patients. However, it remains elusive how salivary secretion is impaired in diabetes. Here, we used an ex vivo submandibular gland perfusion technique to characterize the dependency of salivary flow rates on extracellular glucose concentration and activities of glucose transporters expressed in the glands. The cholinergic agonist carbachol (CCh) induced sustained fluid secretion, the rates of which were modulated by the extracellular glucose concentration in a biphasic manner. Both lowering the extracellular glucose concentration to less than 2.5 mM and elevating it to higher than 5 mM resulted in decreased CCh-induced fluid secretion. The CCh-induced salivary flow was suppressed by phlorizin, an inhibitor of the sodium-glucose cotransporter 1 (SGLT1) located basolaterally in submandibular acinar cells, which is altered at the protein expression level in diabetic animal models. Our data suggest that SGLT1-mediated glucose uptake in acinar cells is required to maintain the fluid secretion by sustaining Cl - secretion in real-time. High extracellular glucose levels may suppress the CCh-induced secretion of salivary fluid by altering the activities of ion channels and transporters downstream of [Ca 2+ ] i signals. © 2018 Eur J Oral Sci.
... Staying in bed for long periods of time (bedridden). Taking drugs that slow intestinal movements. These include ... be tried: Colonoscopy may be used to remove air from the large intestine. Fluids can be given ...
An Investigation into the Gastrointestinal Stability of Exenatide in the Presence of Pure Enzymes, Everted Intestinal Rings and Intestinal Homogenates.
Sun, Yanan; Wang, Mengshu; Sun, Bingxue; Li, Feng; Liu, Shubo; Zhang, Yong; Zhou, Yan; Chen, Yan; Kong, Wei
The purpose of this study was to investigate the gastrointestinal stability of exenatide to determine the key factor(s) contributing to peptide degradation during the oral delivery process. The effects of pH and various digestive enzymes on the degradation kinetics of exenatide were determined. Moreover, the degradation clearances of peptide were also examined using rat everted intestinal rings and intestinal homogenates from various intestinal locations. Exenatide was comparatively stable within a pH range of 1.2-8. However, obvious degradation was observed in the presence of digestive enzymes. The order of enzymes, in terms of ability to degradate exenatide, was chymotrypsin>aminopeptidase N>carboxypeptidase A>trypsin>pepsin. Chymotrypsin showed the greatest ability to degrade exenatide (half-life t1/2, 5.784×10(-2) h), whereas aminopeptidase N and carboxylpeptidase A gave t1/2 values of 3.53 and 10.16 h, respectively. The degradation of exenatide was found to be peptide concentration- and intestinal site-dependent, with a lower clearance in the upper part of the duodenum and the lower part of the ileum. When using intestinal homogenates as enzyme sources, the order, in terms of peptide degradation ability, was ileum>jejunum>duodenum. However, no significant difference was observed in the remaining peptide concentrations throughout 2 h of incubation, which may be due to the involvement of cytosolic enzymes. These results revealed key factors contributing to peptide degradation, and suggest that the inhibition of chymotrypsin and site-specific delivery of exenatide might be advantageous in overcoming metabolic obstacles during its oral delivery.
Peptide chemistry toolbox - Transforming natural peptides into peptide therapeutics.
Erak, Miloš; Bellmann-Sickert, Kathrin; Els-Heindl, Sylvia; Beck-Sickinger, Annette G
The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market. Copyright © 2018 Elsevier Ltd. All rights reserved.
Does liver-intestine significantly degrade circulating endogenous substance P in man?
DEFF Research Database (Denmark)
Henriksen, Jens Henrik Sahl; Schaffalitzky de Muckadell, O B; Bülow, J B
Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P was determi......Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P....... The results indicate that degradation of circulating endogenous substance P in man is not confined to liver-intestine or kidney but may take place in many tissues....
Glucagon-like peptide-1 (GLP-1) receptor agonism or DPP-4 inhibition does not accelerate neoplasia in carcinogen treated mice
DEFF Research Database (Denmark)
Kissow, Hannelouise; Hartmann, Bolette; Holst, Jens Juul
Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are secreted in parallel from the intestinal endocrine cells after nutrient intake. GLP-1 is an incretin hormone and analogues are available for the treatment of type 2 diabetes mellitus (T2DM). GLP-2 is an intestinal growth horm...
The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia
Directory of Open Access Journals (Sweden)
Tomonori Yamanishi
Full Text Available The aim of this study was to compare the effect of antimuscarinic antagonists on carbachol-induced contraction of normal human bladder and detrusor overactivity associated with benign prostatic hyperplasia (DO/BPH. Samples of human bladder muscle were obtained from patients undergoing total cystectomy for bladder cancer (normal bladder, and those undergoing retropubic prostatectomy for BPH. All of the patients with DO/BPH had detrusor overactivity according to urodynamic studies. Detrusor muscle strips were mounted in 10-ml organ baths containing Krebs solution, and concentration–response curves for carbachol were obtained in the presence of antimuscarinic antagonists (4-DAMP, methoctramine, pirenzepine, tolterodine, solifenacin, trospium, propiverine, oxybutynin, and imidafenacin or vehicle. All antagonists competitively antagonized concentration–response curves to carbachol with high affinities in normal bladder. The rank order of mean pA2 values was as follows: trospium (10.1 > 4-DAMP (9.87, imidafenacin (9.3 > solifenacin (8.8 > tolterodine (8.6 > oxybutynin (8.3 > propiverine (7.7 > pirenzepine (7.4 > methoctramine (6.6. The effects of these antimuscarinic antagonists did not change when tested with DO/BPH bladder, suggesting that each antimuscarinic antagonist has a similar effect in this condition. Schild plots showed a slope corresponding to unity, except for propiverine with DO/BPH detrusor. In conclusion, M3-receptors mainly mediate contractions in human bladder strips with normal state and DO/BPH.
Gut hormones in the treatment of short-bowel syndrome and intestinal failure
DEFF Research Database (Denmark)
Jeppesen, Palle B
PURPOSE OF REVIEW: The approval of teduglutide, a recombinant analog of human glucagon-like peptide (GLP) 2, by the US Food and Drug Administration (Gattex) and the European Medicines Agency (Revestive) has illustrated the potential of selected gut hormones as treatments in patients with short......-bowel syndrome and intestinal failure. Gut hormones may improve the structural and functional intestinal adaptation following intestinal resection by decreasing a rapid gastric emptying and hypersecretion, by increasing the intestinal blood flow, and by promoting intestinal growth. This review summarizes......-1 may be less potent. Synergistic effects may be seen by co-treatment with GLP-2. SUMMARY: Gut hormones promote intestinal adaptation and absorption, decreasing fecal losses, thereby decreasing or even eliminating the need for parenteral support. This will aid the intestinal rehabilitation...
Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats.
Turan, Inci; Ozacmak, Hale Sayan; Ozacmak, V Haktan; Barut, Figen; Araslı, Mehmet
Oxidative stress and inflammatory response are major factors causing several tissue injuries in intestinal ischemia and reperfusion (I/R). Agmatine has been reported to attenuate I/R injury of various organs. The present study aims to analyze the possible protective effects of agmatine on intestinal I/R injury in rats. Four groups were designed: sham control, agmatine-treated control, I/R control, and agmatine-treated I/R groups. IR injury of small intestine was induced by the occlusion of the superior mesenteric artery for half an hour to be followed by a 3-hour-long reperfusion. Agmatine (10mg/kg) was administered intraperitoneally before reperfusion period. After 180min of reperfusion period, the contractile responses to both carbachol and potassium chloride (KCl) were subsequently examined in an isolated-organ bath. Malondialdehyde (MDA), reduced glutathione (GSH), and the activity of myeloperoxidase (MPO) were measured in intestinal tissue. Plasma cytokine levels were determined. The expression of the intestinal inducible nitric oxide synthase (iNOS) was also assessed by immunohistochemistry. The treatment with agmatine appeared to be significantly effective in reducing the MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The increases in the I/R induced expressions of iNOS, IFN-γ, and IL-1α were brought back to the sham control levels by the treatment as well. Our findings indicate that the agmatine pretreatment may ameliorate reperfusion induced injury in small intestine mainly due to reducing inflammatory response and oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.
Gastric and intestinal surgery.
Fossum, Theresa W; Hedlund, Cheryl S
Gastric surgery is commonly performed to remove foreign bodies and correct gastric dilatation-volvulus and is less commonly performed to treat gastric ulceration or erosion, neoplasia, and benign gastric outflow obstruction. Intestinal surgery, although commonly performed by veterinarians, should never be considered routine. The most common procedures of the small intestinal tract performed in dogs and cats include enterotomy and resection/anastomosis. Surgery of the large intestine is indicated for lesions causing obstruction, perforations, colonic inertia, or chronic inflammation.
New approaches to the treatments of short bowel syndrome-associated intestinal failure
DEFF Research Database (Denmark)
Jeppesen, Palle B
PURPOSE OF REVIEW: Teduglutide, a recombinant analog of human glucagon-like peptide 2, has recently been approved in the US and Europe (Gattex and Revestive, respectively) as the first targeted treatment of short bowel syndrome-associated intestinal failure (SBS-IF). Glucagon-like peptide 2...... improves structural and functional intestinal adaptation following intestinal resection by decelerating a rapid gastric emptying, by decreasing gastric hypersecretion, by increasing intestinal blood flow and by promoting intestinal growth. This review summarizes the findings from phase 2 and 3 studies...... energy losses by approximately 0.8 MJ/day (∼200 kcal/day). In two subsequent 24-week, phase 3 studies, teduglutide reduced the need for parenteral support in the same magnitude. Teduglutide had an acceptable tolerability profile, where adverse events generally were of gastrointestinal origin consistent...
Molecular characterization of covalent complexes between tissue transglutaminase and gliadin peptides
DEFF Research Database (Denmark)
Fleckenstein, Burkhard; Qiao, Shuo-Wang; Larsen, Martin Røssel
recognized by intestinal T cells from patients. Incubation of TG2 with gliadin peptides also results in the formation of covalent TG2-peptide complexes. Here we report the characterization of complexes between TG2 and two immunodominant gliadin peptides. Two types of covalent complexes were found......; the peptides are either linked via a thioester bond to the active site cysteine of TG2 or via isopeptide bonds to particular lysine residues of the enzyme. We quantified the number of gliadin peptides bound to TG2 under different conditions. After 30 min of incubation of TG2 at 1 microm with an equimolar ratio...... of peptides to TG2, approximately equal amounts of peptides were bound by thioester and isopeptide linkage. At higher peptide to TG2 ratios, more than one peptide was linked to TG2, and isopeptide bond formation dominated. The lysine residues in TG2 that act as acyl acceptors were identified by matrix...
Intestinal lymphangiectasia in children
Isa, Hasan M.; Al-Arayedh, Ghadeer G.; Mohamed, Afaf M.
Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification. PMID:26837404
Intestinal parasites and tuberculosis
Directory of Open Access Journals (Sweden)
Anuar Alonso Cedeño-Burbano
Conclusions: The available evidence was insufficient to affirm that intestinal parasites predispose to developing tuberculous. The studies carried out so far have found statistically insignificant results.
Pretreatment with remifentanil protects against the reduced-intestinal contractility related to the ischemia and reperfusion injury in rat
Directory of Open Access Journals (Sweden)
Hale Sayan-Ozacmak
Full Text Available BACKGROUND AND OBJECTIVES: Serious functional and structural alterations of gastrointestinal tract are observed in failure of blood supply, leading to gastrointestinal dismotility. Activation of opioid receptors provides cardioprotective effect against ischemia-reperfusion (I/R injury. The aim of the present study was to determine whether or not remifentanil could reduce I/R injury of small intestine. METHODS: Male Wistar Albino rats were subjected to mesenteric ischemia (30 min followed by reperfusion (3 h. Four groups were designed: sham control; remifentanil alone; I/R control; and remifentanil + I/R. Animals in remifentanil + I/R group were subjected to infusion of remifentanil (2 ug kg-1 min-1 for 60 min, half of which started before inducing ischemia. Collecting the ileum tissues, evaluation of damage was based on contractile responses to carbachol, levels of lipid peroxidation and neutrophil infiltration, and observation of histopathological features in intestinal tissue. RESULTS: Following reperfusion, a significant decrease in carbachol-induced contractile response, a remarkable increase in both lipid peroxidation and neutrophil infiltration, and a significant injury in mucosa were observed. An average contractile response of remifentanil + I/R group was significantly different from that of the I/R group. Lipid peroxidation and neutrophil infiltration were also significantly suppressed by the treatment. The tissue samples of the I/R group were grade 4 in histopathological evaluation. In remifentanil + I/R group, on the other hand, the mucosal damage was moderate, staging as grade 1. CONCLUSIONS: The pretreatment with remifentanil can attenuate the intestinal I/R injury at a remarkable degree possibly by lowering lipid peroxidation and leukocyte infiltration.
Salivaricin P, One of a Family of Two-Component Antilisterial Bacteriocins Produced by Intestinal Isolates of Lactobacillus salivarius▿
Barrett, Eoin; Hayes, Maria; O'Connor, Paula; Gardiner, Gillian; Fitzgerald, Gerald F.; Stanton, Catherine; Ross, R. Paul; Hill, Colin
Lactobacillus salivarius DPC6005, a porcine intestinal isolate, produces a two-component bacteriocin, salivaricin P, with homology to ABP-118 produced by a human probiotic L. salivarius strain. Indeed, molecular characterization revealed that while the peptides Sln1 and ABP-118α are identical, their companion peptides (Sln2 and ABP-118β, respectively) differ by two amino acids. This observation suggests that two-component bacteriocins may be a common feature of intestinal L. salivarius strains. PMID:17416691
The mRNA expression of amino acid and sugar transporters, aminopeptidase, as well as the di- and tri-peptide transporter PepT1 in the intestines of Eimeria infected broiler chickens.
Miska, K B; Fetterer, R H
Coccidiosis in chickens is caused by infection of gut epithelial cells with protozoan parasites of the genus Eimeria This disease causes losses to the poultry industry since infected birds fail to gain weight as rapidly as non-infected birds and efficiency of feed conversion is compromised. For the present study the effect of Eimeria on expression of components of amino acid and sugar uptake mechanisms was determined. Broiler chicks were infected with Eimeria maxima, which infects the jejunum; Eimeria acervulina, which infects the duodenum; or Eimeria tenella, which infects the ceca. Sections of the jejunum, duodenum, and ceca (depending on species of Eimeria) were taken at several time points between d zero and 14 post infection (PI) for mRNA expression analysis. Genes examined included one digestive enzyme, 7 peptide and amino acid transporters located on the brush border, 8 transporters located at the basolateral surface of the gut epithelium, and 5 sugar transporters. All 3 Eimeria species examined caused decrease in expression of brush border transporters particularly at d 5 to 7 PI, which corresponds to the time when pathology is greatest. The same pattern was seen in expression of sugar transporters. However, the expression of basolateral transporters differed among species. Eimeria tenella infection resulted in decreased expression of all basolateral transporters, while E. maxima infection caused increased expression of 2 genes and slight decrease in expression of the remaining 5 genes. Infection with E. acervulina resulted in increased expression at the height of infection of all but one basolateral transporter. In conclusion, Eimeria infection causes a general decrease in gene expression of sugar transporter and brush border AATs at the height of infection. However the expression of basolateral transporters is increased in E. maxima and E. acervulina infected birds. It is possible that decreased expression of brush border transporters in combination with
Model prodrugs for the intestinal oligopeptide transporter
DEFF Research Database (Denmark)
Nielsen, C U; Andersen, R; Brodin, Birger
The human intestinal di/tri-peptide carrier, hPepT1, has been suggested as a target for increasing intestinal transport of low permeability compounds by creating prodrugs designed for the transporter. Model ester prodrugs using the stabilized dipeptides D-Glu-Ala and D-Asp-Ala as pro...... with a pH of approximately 6.0, but still release the model drug at the intercellular and blood pH of approximately 7.4. Even though benzyl alcohol is not a low molecular weight drug molecule, these results indicate that the dipeptide prodrug principle is a promising drug delivery concept. However......, the physico-chemical properties such as electronegativity, solubility, and log P of the drug molecule may also have an influence on the potential of these kinds of prodrugs. The purpose of the present study is to investigate whether the model drug electronegativity, estimated as Taft substitution parameter...
Expression and characterization of preproVIP derived peptides in the human male urogenital tract
DEFF Research Database (Denmark)
Ottesen, B; Bredkjaer, H E; Ekblad, E
Expression of the gene sequence encoding vasoactive intestinal polypeptide (VIP) leads to the synthesis of a 170 amino acid precursor molecule which can be processed to five fragments: preproVIP 22-79, peptide histidine methionine (PHM), or peptide histidine valine (PHV), preproVIP 111-122, VIP...
Transmembrane transport of peptide type compounds: prospects for oral delivery
Lipka, E.; Crison, J.; Amidon, G. L.
Synthesis and delivery of potential therapeutic peptides and peptidomimetic compounds has been the focus of intense research over the last 10 years. While it is widely recognized that numerous limitations apply to oral delivery of peptides, some of the limiting factors have been addressed and their mechanisms elucidated, which has lead to promising strategies. This article will briefly summarize the challenges, results and current approaches of oral peptide delivery and give some insight on future strategies. The barriers determining peptide bioavailability after oral administration are intestinal membrane permability, size limitations, intestinal and hepatic metabolism and in some cases solubility limitations. Poor membrane permeabilities of hydrophilic peptides might be overcome by structurally modifying the compounds, thus increasing their membrane partition characteristics and/or their affinity to carrier proteins. Another approach is the site-specific delivery of the peptide to the most permeable parts of the intestine. The current view on size limitation for oral drug delivery has neglected partition considerations. Recent studies suggest that compounds with a molecular weight up to 4000 might be significantly absorbed, assuming appropriate partition behavior and stability. Metabolism, probably the most significant factor in the absorption fate of peptides, might be controlled by coadministration of competitive enzyme inhibitors, structural modifications and administration of the compound as a well absorbed prodrug that is converted into the therapeutically active agent after its absorption. For some peptides poor solubility might present a limitation to oral absorption, an issue that has been addressed by mechanistically defining and therefore improving formulation parameters. Effective oral peptide delivery requires further development in understanding these complex mechanisms in order to maximize the therapeutic potential of this class of compounds.
Primary intestinal lymphangiectasia.
Suresh, N; Ganesh, R; Sankar, Janani; Sathiyasekaran, Malathi
Primary intestinal lymphangiectasia (PIL) is a rare disease of intestinal lymphatics presenting with hypoproteinemia, bilateral lower limb edema, ascites, and protein losing enteropathy. We report a series of 4 children from Chennai, India presenting with anasarca, recurrent diarrhea, hypoproteinemia and confirmatory features of PIL on endoscopy and histopathology.
Congenital intestinal lymphangiectasia
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Popović Dušan Đ.
Full Text Available Background. Congenital intestinal lymphangiectasia is a disease which leads to protein losing enteropathy. Tortous, dilated lymphatic vessels in the intestinal wall and mesenterium are typical features of the disease. Clinical manifestations include malabsorption, diarrhea, steatorrhea, edema and effusions. Specific diet and medication are required for disease control. Case report. A 19-year old male patient was hospitalized due to diarrhea, abdominal swelling, weariness and fatigue. Physical examination revealed growth impairment, ascites, and lymphedema of the right hand and forearm. Laboratory assessment indicated iron deficiency anaemia, lymphopenia, malabsorption, inflammatory syndrome, and urinary infection. Enteroscopy and video capsule endoscopy demonstrated dilated lymphatic vessels in the small intestine. The diagnosis was confirmed by intestinal biopsy. The patient was put on high-protein diet containing medium-chain fatty acids, somatotropin and suportive therapy. Conclusion. Congenital intestinal lymphangiectasia is a rare disease, usually diagnosed in childhood. Early recognition of the disease and adequate treatment can prevent development of various complications.
[Congenital intestinal lymphangiectasia].
Popović, Dugan D j; Spuran, Milan; Alempijević, Tamara; Krstić, Miodrag; Djuranović, Srdjan; Kovacević, Nada; Damnjanović, Svetozar; Micev, Marjan
Congenital intestinal lymphangiectasia is a disease which leads to protein losing enteropathy. Tortuous, dilated lymphatic vessels in the intestinal wall and mesenterium are typical features of the disease. Clinical manifestations include malabsorption, diarrhea, steatorrhea, edema and effusions. Specific diet and medication are required for disease control. A 19-year old male patient was hospitalized due to diarrhea, abdominal swelling, weariness and fatigue. Physical examination revealed growth impairment, ascites, and lymphedema of the right hand and forearm. Laboratory assessment indicated iron deficiency anaemia, lymphopenia, malabsorption, inflammatory syndrome, and urinary infection. Enteroscopy and video capsule endoscopy demonstrated dilated lymphatic vessels in the small intestine. The diagnosis was confirmed by intestinal biopsy. The patient was put on high-protein diet containing medium-chain fatty acids, somatotropin and supportive therapy. Congenital intestinal lymphangiectasia is a rare disease, usually diagnosed in childhood. Early recognition of the disease and adequate treatment can prevent development of various complications.
Artificial neural network models for prediction of intestinal permeability of oligopeptides
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Kim Min-Kook
Full Text Available Abstract Background Oral delivery is a highly desirable property for candidate drugs under development. Computational modeling could provide a quick and inexpensive way to assess the intestinal permeability of a molecule. Although there have been several studies aimed at predicting the intestinal absorption of chemical compounds, there have been no attempts to predict intestinal permeability on the basis of peptide sequence information. To develop models for predicting the intestinal permeability of peptides, we adopted an artificial neural network as a machine-learning algorithm. The positive control data consisted of intestinal barrier-permeable peptides obtained by the peroral phage display technique, and the negative control data were prepared from random sequences. Results The capacity of our models to make appropriate predictions was validated by statistical indicators including sensitivity, specificity, enrichment curve, and the area under the receiver operating characteristic (ROC curve (the ROC score. The training and test set statistics indicated that our models were of strikingly good quality and could discriminate between permeable and random sequences with a high level of confidence. Conclusion We developed artificial neural network models to predict the intestinal permeabilities of oligopeptides on the basis of peptide sequence information. Both binary and VHSE (principal components score Vectors of Hydrophobic, Steric and Electronic properties descriptors produced statistically significant training models; the models with simple neural network architectures showed slightly greater predictive power than those with complex ones. We anticipate that our models will be applicable to the selection of intestinal barrier-permeable peptides for generating peptide drugs or peptidomimetics.
Central nervous system regulation of intestinal lipid and lipoprotein metabolism.
Farr, Sarah; Taher, Jennifer; Adeli, Khosrow
In response to nutrient availability, the small intestine and brain closely communicate to modulate energy homeostasis and metabolism. The gut-brain axis involves complex nutrient sensing mechanisms and an integration of neuronal and hormonal signaling. This review summarizes recent evidence implicating the gut-brain axis in regulating lipoprotein metabolism, with potential implications for the dyslipidemia of insulin resistant states. The intestine and brain possess distinct mechanisms for sensing lipid availability, which triggers subsequent regulation of feeding, glucose homeostasis, and adipose tissue metabolism. More recently, central receptors, neuropeptides, and gut hormones that communicate with the brain have been shown to modulate hepatic and intestinal lipoprotein metabolism via parasympathetic and sympathetic signaling. Gut-derived glucagon-like peptides appear to be particularly important in modulating the intestinal secretion of chylomicron particles via a novel brain-gut axis. Dysregulation of these pathways may contribute to postprandial diabetic dyslipidemia. Emerging evidence implicates the central and enteric nervous systems in controlling many aspects of lipid and lipoprotein metabolism. Bidirectional communication between the gut and brain involving neuronal pathways and gut peptides is critical for regulating feeding and metabolism, and forms a neuroendocrine circuit to modulate dietary fat absorption and intestinal production of atherogenic chylomicron particles.
Quantification of peptides released during in vitro digestion of cooked meat.
Sayd, T; Chambon, C; Santé-Lhoutellier, V
We aimed to identify and quantify the peptides generated during in vitro digestion of cooked meat by liquid chromatography coupled with high resolution mass spectrometer. A total of 940 non-redundant peptides in the gastric compartment and 989 non-redundant peptides in the intestinal compartment were quantified and identified. Among the 71 different proteins identified, 43 meat proteins were found in the two digestive compartments, 20 proteins were specific to the gastric compartment and 8 proteins to the intestinal compartment. In terms of estimation, the proteins involved in muscle contraction and structure were preferentially enzymatically hydrolyzed in the small intestine. The effect of cooking provided different but less clear patterns of digestion. To the best of our knowledge, this constitutes the highest number of peptides identified in beef meat digests and provides a comprehensive database for meat protein digestion associated with cooking conditions. Such quantitative and qualitative differences may have important nutritional consequences. Copyright © 2015 Elsevier Ltd. All rights reserved.
Defying the stereotype: non-canonical roles of the peptide hormones guanylin and uroguanylin
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Nirmalya eBasu
Full Text Available The peptide hormones uroguanylin and guanylin have been traditionally thought to be mediators of fluid-ion homeostasis in the vertebrate intestine. They serve as ligands for receptor guanylyl cyclase C (GC-C, and both receptor and ligands are expressed predominantly in the intestine. Ligand binding to GC-C results in increased cGMP production in the cell which governs downstream signaling. In the last decade, a significant amount of research has unraveled novel functions for this class of peptide hormones, in addition to their action as intestinal secretagogues. An additional receptor for uroguanylin, receptor guanylyl cyclase D, has also been identified. Thus, unconventional roles of these peptides in regulating renal filtration, olfaction, reproduction and cell proliferation have begun to be elucidated in detail. These varied effects suggest that these peptide hormones act in an autocrine, paracrine as well as endocrine manner to regulate diverse cellular processes.
Anxiety, Depression, and the Microbiome: A Role for Gut Peptides.
Lach, Gilliard; Schellekens, Harriet; Dinan, Timothy G; Cryan, John F
The complex bidirectional communication between the gut and the brain is finely orchestrated by different systems, including the endocrine, immune, autonomic, and enteric nervous systems. Moreover, increasing evidence supports the role of the microbiome and microbiota-derived molecules in regulating such interactions; however, the mechanisms underpinning such effects are only beginning to be resolved. Microbiota-gut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling. Given the emerging role of the gut-brain axis in a variety of brain disorders, such as anxiety and depression, it is important to understand the contribution of bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis. Indeed, the gastrointestinal tract is the largest endocrine organ in mammals, secreting dozens of different signaling molecules, including peptides. Gut peptides in the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals thereby enabling indirect gut-brain communication. Gut peptide concentrations are not only modulated by enteric microbiota signals, but also vary according to the composition of the intestinal microbiota. In this review, we will discuss the gut microbiota as a regulator of anxiety and depression, and explore the role of gut-derived peptides as signaling molecules in microbiome-gut-brain communication. Here, we summarize the potential interactions of the microbiota with gut hormones and endocrine peptides, including neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, and ghrelin in microbiome-to-brain signaling. Together, gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.
Intestinal failure in childhood
African Journals Online (AJOL)
Insulin influences intestinal structure and absorptive function.36 The favourable effect of .... lipid emulsions, micronutrients provison and cyclic infusion.3 The guidelines on PN .... Classification, epidemiology and aetiology. Best Pract Res Clin ...
Activation of intestinal epithelial Stat3 orchestrates tissue defense during gastrointestinal infection.
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Nadine Wittkopf
Full Text Available Gastrointestinal infections with EHEC and EPEC are responsible for outbreaks of diarrheal diseases and represent a global health problem. Innate first-line-defense mechanisms such as production of mucus and antimicrobial peptides by intestinal epithelial cells are of utmost importance for host control of gastrointestinal infections. For the first time, we directly demonstrate a critical role for Stat3 activation in intestinal epithelial cells upon infection of mice with Citrobacter rodentium - a murine pathogen that mimics human infections with attaching and effacing Escherichia coli. C. rodentium induced transcription of IL-6 and IL-22 in gut samples of mice and was associated with activation of the transcription factor Stat3 in intestinal epithelial cells. C. rodentium infection induced expression of several antimicrobial peptides such as RegIIIγ and Pla2g2a in the intestine which was critically dependent on Stat3 activation. Consequently, mice with specific deletion of Stat3 in intestinal epithelial cells showed increased susceptibility to C. rodentium infection as indicated by high bacterial load, severe gut inflammation, pronounced intestinal epithelial cell death and dissemination of bacteria to distant organs. Together, our data implicate an essential role for Stat3 activation in intestinal epithelial cells during C. rodentium infection. Stat3 concerts the host response to bacterial infection by controlling bacterial growth and suppression of apoptosis to maintain intestinal epithelial barrier function.
Intestinal Permeability: The Basics
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Ingvar Bjarnason
Full Text Available The authors review some of the more fundamental principles underlying the noninvasive assessment of intestinal permeability in humans, the choice of test markers and their analyses, and the practical aspects of test dose composition and how these can be changed to allow the specific assessment of regional permeability changes and other intestinal functions. The implications of increased intestinal permeability in the pathogenesis of human disease is discussed in relation to findings in patients with Crohn's disease. A common feature of increased intestinal permeability is the development of a low grade enteropathy, and while quantitatively similar changes may be found in Crohn's disease these seem to predict relapse of disease. Moreover, factors associated with relapse of Crohn's disease have in common an action to increase intestinal permeability. While increased intestinal permeability does not seem to be important in the etiology of Crohn's disease it may be a central mechanism in the clinical relapse of disease.
Intestinal lymphangiectasia in adults.
Freeman, Hugh James; Nimmo, Michael
Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial
A dose-equivalent comparison of the effects of continuous subcutaneous glucagon-like peptide 2 (GLP-2) infusions versus meal related GLP-2 injections in the treatment of short bowel syndrome (SBS) patients
DEFF Research Database (Denmark)
Naimi, R M; Madsen, K B; Askov-Hansen, C
Glucagon-like peptide 2 (GLP-2), secreted endogenously from L-cells in the distal bowel in relation to meals, modulates intestinal absorption by adjusting gastric emptying and secretion and intestinal growth. Short bowel syndrome (SBS) patients with distal intestinal resections have attenuated...
Relationship between Gastrointestinal Peptides, Intestinal Wall Compliance, and Vascular Resistance
postprandial blood level =• 200-600 pg/ml) (14,16,34), the observations of an increase in the functional exchange vessel surface area and elevations in...transcapillary fluid exchange and imposes a "vas- cular waterfall" effect (similar to that in the upright lung) on the in- testinal vasculature. Normally...8217 hormone inhibitrice de la cholecystokinine son role en pathologle biliaire et pancreatique. Rev. Franc. Etudes. Clinet , Biol. 5: 545-557, 1960. 37
Diagnosis of intestinal and extra intestinal amoebiasis
International Nuclear Information System (INIS)
Lopez, Myriam Consuelo; Quiroz, Damian Arnoldo; Pinilla, Analida Elizabeth
The objective is to carry out a review of the national and international literature as of the XXth century in order to update the advances for the diagnosis of complex odd Entamoeba histolytic / Entamoeba dispar and that of intestinal and extra intestinal amoebiasis that may be of use to the scientific community. As well as to unify the diagnostic criteria of this parasitosis known as a public health problem, and as a consequence of that, optimize the quality of population care. Data source: there was a systematic search for the scientific literature Publisher in Spanish and English since 1960 until today, this selection started on the first semester of 2006 until 2007, in the development of the line on intestinal and extra-intestinal amoebiasis of the Medical School of the National University of Colombia. A retrospective search process was carried out, systematically reviewing the most relevant articles as well as the products of this research line. In deciding how to make this article, there was a continuous search in different data bases such as Medline, SciELO and other bases in the library of the National University of Colombia, as well as other classical books related to the subject. For that purpose the terms amoebiasis, odd Entamoeba histolytic, Entamoeba, diagnosis, epidemiology, dysentery, amoebic liver abscess, were used. Studies selection: titles and abstracts were reviewed to select the original publications and the most representative ones related to this article's subject. Data extraction: the articles were classified according to the subject, the chronology and the authors according to the scientific contribution to solve the problem. Synthesis of the data: in the fi rst instance, a chronological critical analysis was carried out to order and synthesize the progress made in the diagnosis until confirmation of the experts' agreements in the field of amoebiasis was obtained throughout the world. Conclusion: this article summarizes what has taken place
Plasma levels of gastrointestinal regulatory peptides in patients receiving maintenance hemodialysis
International Nuclear Information System (INIS)
Hegbrant, J.; Thysell, H.; Ekmann, R.
The fasting plasma levels of nine gastrointestinal regulatory peptides were measured by radioimmunoassay in 13 stable patients with chronic renal failure, receiving hemodialysis treatment regularly and compared with those of ten healthy controls. The plasma concentrations of gastrin-releasing peptide, motilin, neurotensin, pancreatic polypeptide, peptide YY, somatostatin, substance P, and vasoactive intestinal peptide were increased. The plasma level of gastrin was not statistically different from that of the control (p=0.077). It is concluded that patients with chronic renal failure, receiving hemodialysis treatment regularly, have increased concentrations of eight of nine measured gastrointestinal regulatory peptides. The elevated levels of gastrointestinal peptides in patients with chronic renal failure may contribute to uremic gastrointestinal symptoms and dysfunctions. It is necessary to make a renal function evaluation before interpreting measured plasma levels of gastrointestinal regulatory peptides. 62 refs., 2 tabs
U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...
Immunoglobulin G antibodies against deamidated-gliadin-peptides outperform anti-endomysium and tissue transglutaminase antibodies in children
Mubarak, A.; Gmelig-Meyling, F. H. J.; Wolters, V. M.; ten Kate, F. J. W.; Houwen, R. H. J.
To investigate the usefulness of deamidated-gliadin-peptides-antibodies in the diagnosis of celiac disease, serology was tested in 212 children suspected with celiac disease who had undergone a small-intestinal-biopsy. For deamidated-gliadin-peptides-antibodies, two kits were tested. Positive and
125I-labeling and purification of peptide hormones and bovine serum albumin
International Nuclear Information System (INIS)
Nemeth, J; Jakab, B.; Szilvassy, Z.; Oroszi, G.; Roeth, E.; Magyarlaki, M.; Farkas, B.
The iodination and separation of various diagnostically and/or experimentally important peptides including (Tyr 1 )-somatostatin-14, rat Tyr-α-calcitonin gene-related peptide (23-37), motilin and vasoactive intestinal peptide, furthermore bovine serum albumin are described. All species were iodinated by the iodogen method. The 125 I-labeled peptide products were separated by reversed-phase HPLC, the specific activities of mono-iodinated forms are near identical with the theoretical value. The labeled bovine serum albumin was separated by Sephadex G-100 gel filtration. (author)
International Nuclear Information System (INIS)
Pomakov, P.; Risov, A.
The routine method of contrast matter passage applied to 850 patients with different gastrointestinal diseases proved inefficient to detect any small-intestinal diverticuli. The following modiffications of the method have been tested in order to improve the diagnostic possibilities of the X-ray: study at short intervals, assisted passage, enteroclysm, pharmacodynamic impact, retrograde filling of the ileum by irrigoscopy. Twelve diverticuli of the small-intestinal loops were identified: 5 Meckel's diverticuli, 2 solitary of which one of the therminal ileum, 2 double diverticuli and 1 multiple diverticulosis of the jejunum. The results show that the short interval X-ray examination of the small intestines is the method of choice for identifying local changes in them. The solitary diverticuli are not casuistic scarcity, its occurrence is about 0.5% at purposeful X-ray investigation. The assisted passage method is proposed as a method of choice for detection of the Meckel's diverticulum. 5 figs., 3 tabs. 18 refs
Chronic intestinal pseudoobstruction syndrome
Energy Technology Data Exchange (ETDEWEB)
Yeon, Kyung Mo; Seo, Jeong Kee; Lee, Yong Seok [Seoul National University Children' s Hospital, Seoul (Korea, Republic of)
Chronic intestinal pseudoobstruction syndrome is a rare clinical condition in which impaired intestinal peristalsis causes recurrent symptoms of bowel obstruction in the absence of a mechanical occlusion. This syndrome may involve variable segments of small or large bowel, and may be associated with urinary bladder retention. This study included 6 children(3 boys and 3 girls) of chronic intestinal obstruction. Four were symptomatic at birth and two were of the ages of one month and one year. All had abdominal distension and deflection difficulty. Five had urinary bladder distension. Despite parenteral nutrition and surgical intervention(ileostomy or colostomy), bowel obstruction persisted and four patients expired from sepses within one year. All had gaseous distension of small and large bowel on abdominal films. In small bowel series, consistent findings were variable degree of dilatation, decreased peristalsis(prolonged transit time) and microcolon or microrectum. This disease entity must be differentiated from congenital megacolon, ileal atresia and megacystis syndrome.
Munot, Khushboo; Kotler, Donald P
Small intestinal infections are extremely common worldwide. They may be bacterial, viral, or parasitic in etiology. Most are foodborne or waterborne, with specific etiologies differing by region and with diverse pathophysiologies. Very young, very old, and immune-deficient individuals are the most vulnerable to morbidity or mortality from small intestinal infections. There have been significant advances in diagnostic sophistication with the development and early application of molecular diagnostic assays, though these tests have not become mainstream. The lack of rapid diagnoses combined with the self-limited nature of small intestinal infections has hampered the development of specific and effective treatments other than oral rehydration. Antibiotics are not indicated in the absence of an etiologic diagnosis, and not at all in the case of some infections.
DEFF Research Database (Denmark)
Hansen, Paul Robert
To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....
PH dependent adhesive peptides
Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan
A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.
DEFF Research Database (Denmark)
A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....
DEFF Research Database (Denmark)
A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....
DEFF Research Database (Denmark)
A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....
DEFF Research Database (Denmark)
A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....
Antimicrobial Peptides in 2014
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Guangshun Wang
Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.
Small intestine aspirate and culture
Intestinal inflammatory myofibroblastic tumour
African Journals Online (AJOL)
abdominal X-ray of patients 1, 3 and 4 demonstrated dilated small bowel loops with fluid levels in keeping with intestinal ... myxoid/vascular pattern characterised by a variable admixture of capillary-calibre blood vessels, .... in the present study had a past history of abdominal trauma or surgery. Ancillary histopathological ...
Human Intestinal Spirochaetosis
Westerman, L.J.
Human intestinal spirochaetosis is a condition of the colon that is characterized by the presence of spirochaetes attached to the mucosal cells of the colon. These spirochaetes belong to the family Brachyspiraceae and two species are known to occur in humans: Brachyspira aalborgi and Brachyspira
Intestinal health in carnivores
Hagen-Plantinga, Esther A.; Hendriks, W.H.
The knowledge on the influence of gastro-intestinal (GI) microbiota on the health status of humans and animals is rapidly expanding. A balanced microbiome may provide multiple benefits to the host, like triggering and stimulation of the immune system, acting as a barrier against possible pathogenic
Intestinal Complications of IBD
... localized pocket of pus caused by infection from bacteria. More common in Crohn's than in colitis, an abscess may form in the intestinal wall—sometimes causing it to bulge out. Visible abscesses, such as those around the anus, look like boils and treatment often involves lancing. Symptoms of ...
Intestinal volvulus in cetaceans.
Begeman, L; St Leger, J A; Blyde, D J; Jauniaux, T P; Lair, S; Lovewell, G; Raverty, S; Seibel, H; Siebert, U; Staggs, S L; Martelli, P; Keesler, R I
Intestinal volvulus was recognized as the cause of death in 18 cetaceans, including 8 species of toothed whales (suborder Odontoceti). Cases originated from 11 institutions from around the world and included both captive (n = 9) and free-ranging (n = 9) animals. When the clinical history was available (n = 9), animals consistently demonstrated acute dullness 1 to 5 days prior to death. In 3 of these animals (33%), there was a history of chronic gastrointestinal illness. The pathological findings were similar to those described in other animal species and humans, and consisted of intestinal volvulus and a well-demarcated segment of distended, congested, and edematous intestine with gas and bloody fluid contents. Associated lesions included congested and edematous mesentery and mesenteric lymph nodes, and often serofibrinous or hemorrhagic abdominal effusion. The volvulus involved the cranial part of the intestines in 85% (11 of 13). Potential predisposing causes were recognized in most cases (13 of 18, 72%) but were variable. Further studies investigating predisposing factors are necessary to help prevent occurrence and enhance early clinical diagnosis and management of the condition.
Smout, André J. P. M.
PURPOSE OF REVIEW: In the past year, many studies were published in which new and relevant information on small intestinal motility in humans and laboratory animals was obtained. RECENT FINDINGS: Although the reported findings are heterogeneous, some themes appear to be particularly interesting and
Peptides reproducibly released by in vivo digestion of beef meat and trout flesh in pigs.
Bauchart, Caroline; Morzel, Martine; Chambon, Christophe; Mirand, Philippe Patureau; Reynès, Christelle; Buffière, Caroline; Rémond, Didier
Characterisation and identification of peptides (800 to 5000 Da) generated by intestinal digestion of fish or meat were performed using MS analyses (matrix-assisted laser desorption ionisation time of flight and nano-liquid chromatography electrospray-ionisation ion trap MS/MS). Four pigs fitted with cannulas at the duodenum and jejunum received a meal exclusively made of cooked Pectoralis profundus beef meat or cooked trout fillets. A protein-free meal, made of free amino acids, starch and fat, was used to identify peptides of endogenous origin. Peptides reproducibly detected in digesta (i.e. from at least three pigs) were evidenced predominantly in the first 3 h after the meal. In the duodenum, most of the fish- and meat-derived peptides were characteristic of a peptic digestion. In the jejunum, the majority of peptides appeared to result from digestion by chymotrypsin and trypsin. Despite slight differences in gastric emptying kinetics and overall peptide production, possibly in relation to food structure and texture, six and four similar peptides were released after ingestion of fish or meat in the duodenum and jejunum. A total of twenty-six different peptides were identified in digesta. All were fragments of major structural (actin, myosin) or sarcoplasmic (creatine kinase, glyceraldehyde-3-phosphate dehydrogenase and myoglobin) muscle proteins. Peptides were short ( digestion, some of them can be reproducibly observed in intestinal digesta.
Protective Effect of Wheat Peptides against Indomethacin-Induced Oxidative Stress in IEC-6 Cells
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Hong Yin
Full Text Available Recent studies have demonstrated that wheat peptides protected rats against non-steroidal anti-inflammatory drugs-induced small intestinal epithelial cells damage, but the mechanism of action is unclear. In the present study, an indomethacin-induced oxidative stress model was used to investigate the effect of wheat peptides on the nuclear factor-κB(NF-κB-inducible nitric oxide synthase-nitric oxide signal pathway in intestinal epithelial cells-6 cells. IEC-6 cells were treated with wheat peptides (0, 125, 500 and 2000 mg/L for 24 h, followed by 90 mg/L indomethacin for 12 h. Wheat peptides significantly attenuated the indomethacin-induced decrease in superoxide dismutase and glutathione peroxidase activity. Wheat peptides at 2000 mg/L markedly decreased the expression of the NF-κB in response to indomethacin-induced oxidative stress. This study demonstrated that the addition of wheat peptides to a culture medium significantly inhibited the indomethacin-induced release of malondialdehyde and nitrogen monoxide, and increased antioxidant enzyme activity in IEC-6 cells, thereby providing a possible explanation for the protective effect proposed for wheat peptides in the prevention of indomethacin-induced oxidative stress in small intestinal epithelial cells.
Cell-Penetrating Peptides as Carriers for Oral Delivery of Biopharmaceuticals
DEFF Research Database (Denmark)
Kristensen, Mie; Nielsen, Hanne Mørck
Oral delivery of biopharmaceuticals, for example peptides and proteins, constitutes a great challenge in drug delivery due to their low chemical stability and poor permeation across the intestinal mucosa, to a large extent limiting the mode of administration to injections, which is not favouring...... patient compliance. Nevertheless, cell-penetrating peptides (CPPs) have shown promising potential as carriers to overcome the epithelium, and this minireview highlights recent knowledge gained within the field of CPP-mediated transepithelial delivery of therapeutic peptides and proteins from the intestine...... is to be preferred depends on the physicochemical properties of both the specific CPP and the specific cargo. In addition to the physical epithelial barrier, a metabolic barrier must be overcome in order to obtain CPP-mediated delivery of a cargo drug from the intestine, and a number of strategies have been employed...
[Intrauterine intestinal volvulus].
Gawrych, Elzbieta; Chojnacka, Hanna; Wegrzynowski, Jerzy; Rajewska, Justyna
Intrauterine intestinal volvulus is an extremely rare case of acute congenital intestinal obstruction. The diagnosis is usually possible in the third trimester of a pregnancy. Fetal midgut volvulus is most likely to be recognized by observing a typical clockwise whirlpool sign during color Doppler investigation. Multiple dilated intestinal loops with fluid levels are usually visible during the antenatal ultrasound as well. Physical and radiographic findings in the newborn indicate intestinal obstruction and an emergency surgery is required. The authors describe intrauterine volvulus in 3 female newborns in which surgical treatment was individualized. The decision about primary or delayed anastomosis after resection of the gangrenous part of the small bowel was made at the time of the surgery and depended on the general condition of the newborn, as well as presence or absence of meconium peritonitis. Double loop jejunostomy was performed in case of two newborns, followed by a delayed end-to-end anastomosis. In case of the third newborn, good blood supply of the small intestine after untwisting and 0.25% lignocaine injections into mesentery led to the assumption that the torsion was not complete and ischemia was reversible. In the two cases of incomplete rotation the cecum was sutured to the left abdominal wall to prevent further twisting. The postoperative course was uneventful and oral alimentation caused no problems. Physical development of all these children has been normal (current age: 1-2 years) and the parents have not observed any disorders or problems regarding passage of food through the alimentary canal. Prompt antenatal diagnosis of this surgical emergency and adequate choice of intervention may greatly reduce mortality due to intrauterine volvulus.
[Plant signaling peptides. Cysteine-rich peptides].
Ostrowski, Maciej; Kowalczyk, Stanisław
Recent bioinformatic and genetic analyses of several model plant genomes have revealed the existence of a highly abundant group of signaling peptides that are defined as cysteine-rich peptides (CRPs). CRPs are usually in size between 50 and 90 amino acid residues, they are positively charged, and they contain 4-16 cysteine residues that are important for the correct conformational folding. Despite the structural differences among CRP classes, members from each class have striking similarities in their molecular properties and function. The present review presents the recent progress in research on signaling peptides from several families including: EPF/EPFL, SP11/SCR, PrsS, RALF, LURE, and some other peptides belonging to CRP group. There is convincing evidence indicating multiple roles for these CRPs as signaling molecules during the plant life cycle, ranging from stomata development and patterning, self-incompatibility, pollen tube growth and guidance, reproductive processes, and nodule formation.
Glucagon and glucagon-like peptides 1 and 2
DEFF Research Database (Denmark)
Holst, Jens Juul
amino acid precursor, proglucagon, leaving behind proglucagon fragments (PG 1-30 and PG 72-158, the so-called major proglucagon fragment (MPGF)) that are probably inactive, the intestinal processing leads to the formation of glicentin (PG 1-69; action uncertain) and glucagon-like peptides 1 (PG 78....... After their release, the hormones are eliminated mainly in the kidneys, but both GLP-2 and in particular GLP-1, but not glucagon, are metabolized both locally and in the circulation and liver by dipeptidyl peptidase 4 (DPP-4) which inactivates the peptides, suggesting that GLP-1 acts locally rather than...
Oral Administration of Probiotics Increases Paneth Cells and Intestinal Antimicrobial Activity
Directory of Open Access Journals (Sweden)
Silvia I. Cazorla
Full Text Available The huge amount of intestinal bacteria represents a continuing threat to the intestinal barrier. To meet this challenge, gut epithelial cells produce antimicrobial peptides (AMP that act at the forefront of innate immunity. We explore whether this antimicrobial activity and Paneth cells, the main intestinal cell responsible of AMP production, are influenced by probiotics administration, to avoid the imbalance of intestinal microbiota and preserve intestinal barrier. Administration of Lactobacillus casei CRL 431 (Lc 431 and L. paracasei CNCM I-1518 (Lp 1518 to 42 days old mice, increases the number of Paneth cells on small intestine, and the antimicrobial activity against the pathogens Staphylococcus aureus and Salmonella Typhimurium in the intestinal fluids. Specifically, strong damage of the bacterial cell with leakage of cytoplasmic content, and cellular fragmentation were observed in S. Typhimurium and S. aureus. Even more important, probiotics increase the antimicrobial activity of the intestinal fluids at the different ages, from weaning (21 days old to old age (180 days old. Intestinal antimicrobial activity stimulated by oral probiotics, do not influence significantly the composition of total anaerobic bacteria, lactobacilli and enterobacteria in the large intestine, at any age analyzed. This result, together with the antimicrobial activity observed against the same probiotic bacteria; endorse the regular consumption of probiotics without adverse effect on the intestinal homeostasis in healthy individuals. We demonstrate that oral probiotics increase intestinal antimicrobial activity and Paneth cells in order to strengthen epithelial barrier against pathogens. This effect would be another important mechanism by which probiotics protect the host mainly against infectious diseases.
Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure
DEFF Research Database (Denmark)
Jeppesen, Palle B; Pertkiewicz, Marek; Messing, Bernard
Teduglutide, a glucagon-like peptide 2 analogue, might restore intestinal structural and functional integrity by promoting growth of the mucosa and reducing gastric emptying and secretion. These factors could increase fluid and nutrient absorption in patients with short bowel syndrome with intest...
Small intestinal transplantation.
LENUS (Irish Health Repository)
Quigley, E M
The past few years have witnessed a considerable shift in the clinical status of intestinal transplantation. A great deal of experience has been gained at the most active centers, and results comparable with those reported at a similar stage in the development of other solid-organ graft programs are now being achieved by these highly proficient transplant teams. Rejection and its inevitable associate, sepsis, remain ubiquitous, and new immunosuppressant regimes are urgently needed; some may already be on the near horizon. The recent success of isolated intestinal grafts, together with the mortality and morbidity attendant upon the development of advanced liver disease related to total parenteral nutrition, has prompted the bold proposal that patients at risk for this complication should be identified and should receive isolated small bowel grafts before the onset of end-stage hepatic failure. The very fact that such a suggestion has begun to emerge reflects real progress in this challenging field.
Mocellin, Simone
Peptides derived from tumor associated antigens can be utilized to elicit a therapeutically effective immune response against melanoma in experimental models. However, patient vaccination with peptides - although it is often followed by the induction of melanoma- specific T lymphocytes - is rarely associated with tumor response of clinical relevance. In this review I summarize the principles of peptide design as well as the results so far obtained in the clinical setting while treating cutaneous melanoma by means of this active immunotherapy strategy. I also discuss some immunological and methodological issues that might be helpful for the successful development of peptide-based vaccines.
Antimicrobial Peptides in Reptiles
van Hoek, Monique L.
Reptiles are among the oldest known amniotes and are highly diverse in their morphology and ecological niches. These animals have an evolutionarily ancient innate-immune system that is of great interest to scientists trying to identify new and useful antimicrobial peptides. Significant work in the last decade in the fields of biochemistry, proteomics and genomics has begun to reveal the complexity of reptilian antimicrobial peptides. Here, the current knowledge about antimicrobial peptides in reptiles is reviewed, with specific examples in each of the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras), Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are presented of the major classes of antimicrobial peptides expressed by reptiles including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP-2), lysozyme, crotamine, and others. Some of these peptides have been identified and tested for their antibacterial or antiviral activity; others are only predicted as possible genes from genomic sequencing. Bioinformatic analysis of the reptile genomes is presented, revealing many predicted candidate antimicrobial peptides genes across this diverse class. The study of how these ancient creatures use antimicrobial peptides within their innate immune systems may reveal new understandings of our mammalian innate immune system and may also provide new and powerful antimicrobial peptides as scaffolds for potential therapeutic development. PMID:24918867
Does vasoactive intestinal polypeptide mediate the pathophysiology of bowel obstruction?
Basson, M D; Fielding, L P; Bilchik, A J; Zucker, K A; Ballantyne, G H; Sussman, J; Adrian, T E; Modlin, I M
We hypothesized that bioactive peptides might be released into the portal circulation and mediate pathophysiologic alterations accompanying small bowel obstruction. We studied this question in a subacute canine small bowel obstruction model using 50 percent diameter occlusion. Control animals underwent sham laparotomy. Vasoactive intestinal peptide (VIP), peptide YY, and gastrin were measured in portal and systemic plasma by specific radioimmunoassays at 24-hour intervals as the obstruction progressed to completion over 5 days. All peptides in both groups demonstrated portal and peripheral gradients. In control dogs, peptide concentrations did not change postoperatively but VIP increased markedly in obstructed dogs, demonstrating a median portal level of 95 pmol/liter at 96 hours compared with 31.5 pmol/liter in control animals. These portal VIP levels are known to cause hypersecretion and splanchnic vasodilation in experimental models. The release of vasoactive compounds such as VIP may mediate local pathophysiology in human small bowel obstruction. A similar explanation of the systemic effects is consistent with the known cardiopulmonary bioactivity of VIP.
The alpha cell expresses glucagon-like peptide-2 receptors and glucagon-like peptide-2 stimulates glucagon secretion from the rat pancreas
DEFF Research Database (Denmark)
de Heer, J; Pedersen, J; Orskov, C
AIMS/HYPOTHESIS: Glucagon-like peptide-2 (GLP-2) is a gut hormone regulating intestinal growth and nutrient absorption. Recently, GLP-2 has been reported to stimulate glucagon secretion in healthy humans. We sought to clarify the mechanism and physiological significance of this endocrine effect. ...... of the glucagonotropic action of GLP-2 in humans....
Human Milk: Bioactive Proteins/Peptides and Functional Properties.
Lönnerdal, Bo
Breastfeeding has been associated with many benefits, both in the short and in the long term. Infants being breastfed generally have less illness and have better cognitive development at 1 year of age than formula-fed infants. Later in life, they have a lower risk of obesity, diabetes and cardiovascular disease. Several components in breast milk may be responsible for these different outcomes, but bioactive proteins/peptides likely play a major role. Some proteins in breast milk are comparatively resistant towards digestion and may therefore exert their functions in the gastrointestinal tract in intact form or as larger fragments. Other milk proteins may be partially digested in the upper small intestine and the resulting peptides may exert functions in the lower small intestine. Lactoferrin, lysozyme and secretory IgA have been found intact in the stool of breastfed infants and are therefore examples of proteins that are resistant against proteolytic degradation in the gut. Together, these proteins serve protective roles against infection and support immune function in the immature infant. α-lactalbumin, β-casein, κ-casein and osteopontin are examples of proteins that are partially digested in the upper small intestine, and the resulting peptides influence functions in the gut. Such functions include stimulation of immune function, mineral and trace element absorption and defense against infection. © 2016 Nestec Ltd., Vevey/S. Karger AG, Basel.
C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...
Neural influences on human intestinal epithelium in vitro.
Krueger, Dagmar; Michel, Klaus; Zeller, Florian; Demir, Ihsan E; Ceyhan, Güralp O; Slotta-Huspenina, Julia; Schemann, Michael
We present the first systematic and, up to now, most comprehensive evaluation of the basic features of epithelial functions, such as basal and nerve-evoked secretion, as well as tissue resistance, in over 2200 surgical specimens of human small and large intestine. We found no evidence for impaired nerve-evoked epithelial secretion or tissue resistance with age or disease pathologies (stomach, pancreas or colon cancer, polyps, diverticulitis, stoma reversal). This indicates the validity of future studies on epithelial secretion or resistance that are based on data from a variety of surgical specimens. ACh mainly mediated nerve-evoked and basal secretion in the small intestine, whereas vasoactive intestinal peptide and nitric oxide were the primary pro-secretory transmitters in the large intestine. The results of the present study revealed novel insights into regional differences in nerve-mediated secretion in the human intestine and comprise the basis by which to more specifically target impaired epithelial functions in the diseased gut. Knowledge on basic features of epithelial functions in the human intestine is scarce. We used Ussing chamber techniques to record basal tissue resistance (R-basal) and short circuit currents (ISC; secretion) under basal conditions (ISC-basal) and after electrical field stimulation (ISC-EFS) of nerves in 2221 resectates from 435 patients. ISC-EFS was TTX-sensitive and of comparable magnitude in the small and large intestine. ISC-EFS or R-basal were not influenced by the patients' age, sex or disease pathologies (cancer, polyps, diverticulitis). Ion substitution, bumetanide or adenylate cyclase inhibition studies suggested that ISC-EFS depended on epithelial cAMP-driven chloride and bicarbonate secretion but not on amiloride-sensitive sodium absorption. Although atropine-sensitive cholinergic components prevailed for ISC-EFS of the duodenum, jejunum and ileum, PG97-269-sensitive [vasoactive intestinal peptide (VIP) receptor 1
Therapeutic effects of Glucagon-Like Peptide-2 on experimental radiation enteritis in rat
International Nuclear Information System (INIS)
Torres, S.
Radiation enteritis in patients treated by abdominal and pelvic radiotherapy is characterized by acute mucosal disruption and chronic intestinal fibrosis. Using a model of localized intestinal irradiation in the rat, we showed remote intestinal dysfunction outside the irradiation field along the whole gut, probably associated with perturbations in the systems regulating intestinal functions. Based on the hypothesis of consequential late effects, acute administration of Glucagon-Like Peptide-2, a growth factor with specific trophic effect on the intestinal mucosa, limited the apparition of both acute and chronic radiation enteritis. This suggests that therapeutic strategies targeting the severity of acute tissue damage may also limit chronic sequelae. The study of GLP-2 effects on epithelial cells in co-culture with either subepithelial myo-fibroblasts or enteric nervous system emphasized the problem of the modelization of complex systems in vitro, and suggested a synergic action from these different actors in vivo. (author)
Lipo sarcoma in small intestine
International Nuclear Information System (INIS)
Rodriguez Iglesias, J.; Pineyro Gutierrez, A.; Taroco Medeiros, L.; Fein Kolodny, C.; Navarrete Pedocchi, H.
A case is presented by primitive liposarcoma in small intestine , an extensive bibliographical review foreigner and national in this case. It detach the exceptional of the intestinal topography of the liposarcomas; and making stress in the relative value of the computerized tomography and ultrasonography in the diagnose of the small intestine tumors . As well as in the sarcomas of another topography, chemo and radiotherapy associated to the exeresis surgery, it can be of benefit [es
Peptide Vaccines for Leishmaniasis
Directory of Open Access Journals (Sweden)
Rory C. F. De Brito
Full Text Available Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.
Peptide Vaccines for Leishmaniasis.
De Brito, Rory C F; Cardoso, Jamille M De O; Reis, Levi E S; Vieira, Joao F; Mathias, Fernando A S; Roatt, Bruno M; Aguiar-Soares, Rodrigo Dian D O; Ruiz, Jeronimo C; Resende, Daniela de M; Reis, Alexandre B
Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.
DEFF Research Database (Denmark)
A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...
Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3.
Lammers, Karen M; Lu, Ruliang; Brownley, Julie; Lu, Bao; Gerard, Craig; Thomas, Karen; Rallabhandi, Prasad; Shea-Donohue, Terez; Tamiz, Amir; Alkan, Sefik; Netzel-Arnett, Sarah; Antalis, Toni; Vogel, Stefanie N; Fasano, Alessio
Celiac disease is an immune-mediated enteropathy triggered by gliadin, a component of the grain protein gluten. Gliadin induces an MyD88-dependent zonulin release that leads to increased intestinal permeability, a postulated early element in the pathogenesis of celiac disease. We aimed to establish the molecular basis of gliadin interaction with intestinal mucosa leading to intestinal barrier impairment. Alpha-gliadin affinity column was loaded with intestinal mucosal membrane lysates to identify the putative gliadin-binding moiety. In vitro experiments with chemokine receptor CXCR3 transfectants were performed to confirm binding of gliadin and/or 26 overlapping 20mer alpha-gliadin synthetic peptides to the receptor. CXCR3 protein and gene expression were studied in intestinal epithelial cell lines and human biopsy specimens. Gliadin-CXCR3 interaction was further analyzed by immunofluorescence microscopy, laser capture microscopy, real-time reverse-transcription polymerase chain reaction, and immunoprecipitation/Western blot analysis. Ex vivo experiments were performed using C57BL/6 wild-type and CXCR3(-/-) mouse small intestines to measure intestinal permeability and zonulin release. Affinity column and colocalization experiments showed that gliadin binds to CXCR3 and that at least 2 alpha-gliadin 20mer synthetic peptides are involved in this binding. CXCR3 is expressed in mouse and human intestinal epithelia and lamina propria. Mucosal CXCR3 expression was elevated in active celiac disease but returned to baseline levels following implementation of a gluten-free diet. Gliadin induced physical association between CXCR3 and MyD88 in enterocytes. Gliadin increased zonulin release and intestinal permeability in wild-type but not CXCR3(-/-) mouse small intestine. Gliadin binds to CXCR3 and leads to MyD88-dependent zonulin release and increased intestinal permeability.
The inhibitory effect of tiamulin on high K(+)-induced contraction in guinea pig intestinal smooth muscle.
Nakajyo, S; Fukui, T; Hara, Y; Shimizu, K; Urakawa, N
Tiamulin with an IC50 of 1.7 x 10(-6) M inhibited both the rapid and sustained contractions induced by hyperosmotically added 60 mM K+ (Hyper 60 K+) without changing the membrane potential in the intestinal muscle. Tiamulin inhibition (2 x 10(-6)-2 x 10(-5) M) of the Ca(2+)-induced contraction in depolarized muscle was competitively antagonized by raising external Ca2+. Tiamulin (2 x 10(-5) M) slightly affected the Hyper 60 K(+)-induced phasic contraction under hypoxia and the carbachol-induced phasic contraction. Moreover, tiamulin (2 x 10(-5) M) inhibited the Hyper 60 K(+)-induced contraction with decreasing [Ca2+]cyt level. Although the inhibitory effect of 10(-7)-10(-5) M monesin, an inhibitor of mitochondrial respiration, on the Hyper 60 K(+)-induced contraction was reduced under hypoxia, the effect of tiamulin (2 x 10(-7)-2 x 10(-4) M) was not modified. Tiamulin changed neither the intracellular Na+ and K+ content of the depolarized muscle nor the Ca(2+)-induced contraction in the chemically skinned preparations. These results suggest that the inhibitory action of tiamulin on the Hyper 60 K(+)-induced tonic contraction is possibly due to the competitive inhibition of Ca2+ entry through the voltage-dependent Ca2+ channel of the intestinal smooth muscle cell.
Intestinal parasites : associations with intestinal and systemic inflammation
Zavala, Gerardo A; García, Olga P; Camacho, Mariela; Ronquillo, Dolores; Campos-Ponce, Maiza; Doak, Colleen; Polman, Katja; Rosado, Jorge L
AIMS: Evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school-aged children with high rates of obesity. METHODS AND RESULTS: Plasma concentrations of CRP, leptin, TNF-α, IL-6 and IL-10 were measured as systemic inflammation markers and
Human intestinal mucus proteins isolated by transanal irrigation and proctosigmoidoscopy
Directory of Open Access Journals (Sweden)
Paola Andrea Gómez Buitrago
Full Text Available Human intestinal mucus essentially consists of a network of Mucin2 glycoproteins embedded in many lower molecular weight proteins. This paper contributes to the proteomic study of human intestinal mucus by comparing two sample collection methods (transanal irrigation and brush cytology during proctosigmoidoscopy and analysis techniques (electrophoresis and digestion in solution. The entire sample collection and treatment process is explained, including protein extraction, digestion and desalination and peptide characterisation using a nanoAcquity UPLC chromatograph coupled to an HDMS spectrometer equipped with a nanoESI source. Collecting mucus via transanal irrigation provided a larger sample volume and protein concentration from a single patient. The proctosigmoidoscopy sample could be analysed via digestion in solution after depleting albumin. The analysis indicates that a simple mucus lysis method can evaluate the electrophoresis and digestion in solution techniques. Studying human intestinal mucus complexes is important because they perform two essential survival functions for humans as the first biochemical and physical defences for the gastrointestinal tract and a habitat for intestinal microbiota, which are primarily hosted in the colon and exceeds the human genetic information and cell number 100- and 10-fold (1.
Updates in weight loss surgery and gastrointestinal peptides
DEFF Research Database (Denmark)
Svane, Maria Saur; Bojsen-Møller, Kirstine N; Madsbad, Sten
PURPOSE OF REVIEW: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy are referred to as 'metabolic surgery' due to hormonal shifts with impacts on diabetes remission and weight loss. The purpose of this review is to summarize recent findings in mechanisms underlying beneficial effects...... of weight loss surgery. RECENT FINDINGS: Importantly, gut hormone secretion is altered after RYGB and sleeve gastrectomy due to accelerated transit of nutrients to distal parts of the small intestine, leading to excessive release of L-cell peptide hormones [e.g. glucagon-like peptide-1 (GLP-1), peptide YY......; as demonstrated by relapse of impaired glucose tolerance in studies blocking the GLP-1 receptor by exendin 9-39, and later after major weight loss increased peripheral insulin sensitivity. Gut hormone secretion changes towards a more anorectic profile and is likely important for less caloric intake and weight...
Impaired intestinal proglucagon processing in mice lacking prohormone convertase 1
DEFF Research Database (Denmark)
Ugleholdt, Randi; Zhu, Xiaorong; Deacon, Carolyn F
proglucagon processing showed marked defects. Tissue proglucagon levels in null mice were elevated, and proglucagon processing to glicentin, oxyntomodulin, and glucagon-like peptide-1 and -2 (GLP-1 and GLP-2) was markedly decreased, indicating that PC1 is essential for the processing of all the intestinal...... proglucagon cleavage sites. This includes the monobasic site R(77) and, thereby, production of mature, biologically active GLP-1. We also found elevated glucagon levels, suggesting that factors other than PC1 that are capable of processing to mature glucagon are present in the secretory granules of the L cell......The neuroendocrine prohormone convertases 1 and 2 (PC1 and PC2) are expressed in endocrine intestinal L cells and pancreatic A cells, respectively, and colocalize with proglucagon in secretory granules. Mice lacking PC2 have multiple endocrinopathies and cannot process proglucagon to mature...
Small Intestine Cancer—Health Professional Version
Adenocarcinoma is the most common type of small intestine cancer. Other types of small intestine cancer are sarcomas, carcinoid tumors, gastrointestinal stromal tumors, and lymphomas. Find evidence-based information on small intestine cancer treatment, research, and statistics.
Targeting nanoparticles to M cells with non-peptidic ligands for oral vaccination
Fievez, Virginie; Plapied, Laurence; des Rieux, Anne; Pourcelle, Vincent; Freichels, Hélène; Wascotte, Valentine; Vanderhaegen, Marie-Lyse; Jérôme, Christine; Vanderplasschen, Alain; Marchand-Brynaert, Jacqueline; Préat, Véronique
The presence of RGD on nanoparticles allows the targeting of β1 integrins at the apical surface of human M cells and the enhancement of an immune response after oral immunization. To check the hypothesis that non-peptidic ligands targeting intestinal M cells or APCs would be more efficient for oral immunization than RGD, novel non-peptidic and peptidic analogs (RGD peptidomimitic (RGDp), LDV derivative (LDVd) and LDV peptidomimetic (LDVp)) as well as mannose were grafted on the PEG chain of P...
Toxicity of Biologically Active Peptides and Future Safety Aspects: An Update.
Khan, Fazlullah; Niaz, Kamal; Abdollahi, Mohammad
Peptides are fragments of proteins with significant biological activities. These peptides are encoded in the protein sequence. Initially, such peptides are inactive in their parental form, unless proteolytic enzymes are released. These peptides then exhibit various functions and play a therapeutic role in the body. Besides the therapeutic and physiological activities of peptides, the main purpose of this study was to highlight the safety aspects of peptides. We performed an organized search of available literature using PubMed, Google Scholar, Medline, EMBASE, Reaxys and Scopus databases. All the relevant citations including research and review articles about the toxicity of biologically active peptides were evaluated and gathered in this study. Biological peptides are widely used in the daily routine ranging from food production to the cosmetics industry and also they have a beneficial role in the treatment and prevention of different diseases. These peptides are manufactured by both chemical and biotechnological techniques, which show negligible toxicity, however, some naturally occurring peptides and enzymes may induce high toxicity. Depending upon the demand and expected use in the food or pharmaceutical industry, we need different approaches to acertain the safety of these peptides preferentially through in silico methods. Intestinal wall disruption, erythrocytes and lymphocytes toxicity, free radical production, enzymopathic and immunopathic tissue damage and cytotoxicity due to the consumption of peptides are the main problems in the biological system that lead to various complicated disorders. Therefore, before considering biologically active peptides for food production and for therapeutic purpose, it is first necessary to evaluate the immunogenicity and toxicities of peptides. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.com.
Hippo signalling directs intestinal fate
DEFF Research Database (Denmark)
le Bouteiller, Marie Catherine M; Jensen, Kim Bak
Hippo signalling has been associated with many important tissue functions including the regulation of organ size. In the intestinal epithelium differing functions have been proposed for the effectors of Hippo signalling, YAP and TAZ1. These are now shown to have a dual role in the intestinal...
Plasma GLP-2 levels and intestinal markers in the juvenile pig during intestinal adaptation
DEFF Research Database (Denmark)
Paris, Monique C; Fuller, Peter J; Carstensen, Bendix
) or supplemented either with fiber (n = 6) or with bovine colostrum protein concentrate (CPC; n = 10) for 8 weeks until sacrifice. Plasma GLP-2 levels were measured at weeks 0, 2, 4, and 8 postoperatively. In addition, end-stage parameters were studied at week 8 including weight gain, ileal villus height, crypt......Adaptation of the residual small bowel following resection is dependent on luminal and humoral factors. We aimed to establish if circulating levels of glucagon-like peptide (GLP-2) change under different dietary regimens following resection and to determine if there is a relationship between plasma...... GLP-2 levels and markers of intestinal adaptation. Four-week-old piglets underwent a 75% proximal small bowel resection (n = 31) or transection (n = 14). Postoperatively they received either pig chow (n = 14), nonpolymeric (elemental) infant formula (n = 7), or polymeric infant formula alone (n = 8...
Effects of chronic glucagon-like peptide-2 therapy during weaning in neonatal pigs
DEFF Research Database (Denmark)
Sigalet, David L; de Heuvel, Elaine; Wallace, Laurie
BACKGROUND: The enteroendocrine hormone glucagon like peptide-2 (GLP-2) and its ligands are under development as therapeutic agents for a variety of intestinal pathologies. A number of these conditions occur in neonates and infants, and thus a detailed understanding of the effects of GLP-2 during...
Expression of receptors for gut peptides in human pancreatic adenocarcinoma and tumour-free pancreas
Tang, C.; Biemond, I.; Offerhaus, G. J.; Verspaget, W.; Lamers, C. B.
Gut hormones that modulate the growth of normal pancreas may also modulate the growth of cancers originating from pancreas. This study visualized and compared the receptors for cholecystokinin (CCK), bombesin (BBS), secretin and vasoactive intestinal peptide (VIP) in tumour-free tissue sections of
Neural regulation of glucagon-like peptide-1 secretion in pigs
DEFF Research Database (Denmark)
Hansen, Lene; Lampert, Sarah; Mineo, Hitoshi
Glucagon-like peptide (GLP)-1 is secreted rapidly from the intestine postprandially. We therefore investigated its possible neural regulation. With the use of isolated perfused porcine ileum, GLP-1 secretion was measured in response to electrical stimulation of the mixed, perivascular nerve supply...
Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves
International Nuclear Information System (INIS)
Wang Junru; Zheng Huaien; Kulkarni, Ashwini; Ou Xuemei; Hauer-Jensen, Martin
Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor β immunoreactivity). In mast cell-deficient rats, capsaicin treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent
Identification and Relative Quantification of Bioactive Peptides Sequentially Released during Simulated Gastrointestinal Digestion of Commercial Kefir.
Liu, Yufang; Pischetsrieder, Monika
Health-promoting effects of kefir may be partially caused by bioactive peptides. To evaluate their formation or degradation during gastrointestinal digestion, we monitored changes of the peptide profile in a model of (1) oral, (2) gastric, and (3) small intestinal digestion of kefir. Matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy analyses revealed clearly different profiles between digests 2/3 and kefir/digest 1. Subsequent ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry identified 92 peptides in total (25, 25, 43, and 30, partly overlapping in kefir and digests 1, 2, and 3, respectively), including 16 peptides with ascribed bioactivity. Relative quantification in scheduled multiple reaction monitoring mode showed that many bioactive peptides were released by simulated digestion. Most prominently, the concentration of angiotensin-converting enzyme inhibitor β-casein 203-209 increased approximately 10 000-fold after combined oral, gastric, and intestinal digestion. Thus, physiological digestive processes may promote bioactive peptide formation from proteins and oligopeptides in kefir. Furthermore, bioactive peptides present in certain compartments of the gastrointestinal tract may exert local physiological effects.
Differential proteiomic analysis of mouse intestinal epithelium irradiated by γ-ray
International Nuclear Information System (INIS)
Zhang Bo; Su Yongping; Liu Xiaohong; Ai Guoping; Ran Xinze; Wei Yongjiang; Wang Junping; Cheng Tianmin
Objective: For elucidating the molecular mechanism of reconstruction of intestinal epithelium damaged by ionizing radiation, the proteomes of murine intestinal epithelium from normal and irradiated mice were compared by 2-D electrophoresis. Methods: Histopathologic sections of whole small intestine made from BALB/c mice 3 h and 72 h after total-body irradiation were stained with hematoxylin-eosin. Intestinal epithelial cells were isolated from normal and irradiated mice. The total protein samples prepared by one-step method were used in 2-D electrophoresis, the protein maps were compared and the differential spots were detected with PDQuest analysis software. Twenty-eight different spots were cut off from the gels, digested in gel with trypsin, measured with MALDI-TOF-MS and searched in database. Results: Small intestinal epithelium was damaged as early as 3 h after irradiation, and reconstructed 72 h later. After Coomassie-staining, the 2-DE image analysis by PDQuest software detected 638 ± 39 protein spots in normal mice group, 566 ± 32 spots in 3 hours post irradiation group, and 591 ± 29 spots in 3 days post irradiation group. The 2-DE images showed that proteomes of intestinal epithelium were altered with γ-irradiation. The proteins identified by peptide mass fingerprinting involved in cellular events, including signal transduction, metabolism and oxidative stress responses. Conclusions: Gamma-irradiation can induce the protein expression of intestinal epithelium. The technique of 2-D electrophoresis is a useful tool in the study of molecular mechanism of radiation damage
Diversity-oriented peptide stapling
DEFF Research Database (Denmark)
Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias
as a powerful method for peptide stapling. However, to date CuAAC stapling has not provided a simple method for obtaining peptides that are easily diversified further. In the present study, we report a new diversity-oriented peptide stapling (DOPS) methodology based on CuAAC chemistry. Stapling of peptides...
Oral delivery of peptides and proteins using lipid-based drug delivery systems
DEFF Research Database (Denmark)
Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette
INTRODUCTION: In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism...... by which intestinal absorption of peptides and proteins is promoted. AREAS COVERED: The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two...... and proteins. EXPERT OPINION: Lipid-based DDS are safe and suitable for oral delivery of peptides and proteins. Significant progress has been made in this area with several technologies on clinical trials. However, a better understanding of the mechanism of action in vivo is needed in order to improve...
[Treatment of children with intestinal failure: intestinal rehabilitation, home parenteral nutrition or small intestine transplantation?
Neelis, E.G.; Oers, H.A. van; Escher, J.C.; Damen, G.M.; Rings, E.H.; Tabbers, M.M.
Intestinal failure is characterised by inadequate absorption of food or fluids, which is caused by insufficient bowel surface area or functioning. Children with chronic intestinal failure are dependent on parenteral nutrition (PN), which can be provided at home (HPN). In the Netherlands, HPN for
DEFF Research Database (Denmark)
Koch, T.; Næsby, M.; Wittung, P.
Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....
Directory of Open Access Journals (Sweden)
Tambet eTeesalu
Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is
Peptide aldehyde inhibitors of bacterial peptide deformylases.
Durand, D J; Gordon Green, B; O'Connell, J F; Grant, S K
Bacterial peptide deformylases (PDF, EC 220.127.116.11) are metalloenzymes that cleave the N-formyl groups from N-blocked methionine polypeptides. Peptide aldehydes containing a methional or norleucinal inhibited recombinant peptide deformylase from gram-negative Escherichia coli and gram-positive Bacillus subtilis. The most potent inhibitor was calpeptin, N-CBZ-Leu-norleucinal, which was a competitive inhibitor of the zinc-containing metalloenzymes, E. coli and B. subtilis PDF with Ki values of 26.0 and 55.6 microM, respectively. Cobalt-substituted E. coli and B. subtilis deformylases were also inhibited by these aldehydes with Ki values for calpeptin of 9.5 and 12.4 microM, respectively. Distinct spectral changes were observed upon binding of calpeptin to the Co(II)-deformylases, consistent with the noncovalent binding of the inhibitor rather than the formation of a covalent complex. In contrast, the chelator 1,10-phenanthroline caused the time-dependent inhibition of B. subtilis Co(II)-PDF activity with the loss of the active site metal. The fact that calpeptin was nearly equipotent against deformylases from both gram-negative and gram-positive bacterial sources lends further support to the idea that a single deformylase inhibitor might have broad-spectrum antibacterial activity. Copyright 1999 Academic Press.
Gastrointestinal Endogenous Proteins as a Source of Bioactive Peptides - An In Silico Study
Dave, Lakshmi A.; Montoya, Carlos A.; Rutherfurd, Shane M.; Moughan, Paul J.
Dietary proteins are known to contain bioactive peptides that are released during digestion. Endogenous proteins secreted into the gastrointestinal tract represent a quantitatively greater supply of protein to the gut lumen than those of dietary origin. Many of these endogenous proteins are digested in the gastrointestinal tract but the possibility that these are also a source of bioactive peptides has not been considered. An in silico prediction method was used to test if bioactive peptides could be derived from the gastrointestinal digestion of gut endogenous proteins. Twenty six gut endogenous proteins and seven dietary proteins were evaluated. The peptides present after gastric and intestinal digestion were predicted based on the amino acid sequence of the proteins and the known specificities of the major gastrointestinal proteases. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified. After gastrointestinal digestion (based on the in silico simulation), the total number of bioactive peptides predicted to be released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins. Within the intact proteins and after simulated gastrointestinal digestion, angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most frequently observed in both the dietary and endogenous proteins. Among the dietary proteins, after in silico simulated gastrointestinal digestion, myosin was found to have the highest number of ACE-inhibitory peptide sequences (49 peptides), while for the gut endogenous proteins, mucin-5AC had the greatest number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins may be an important source of bioactive peptides in the gut particularly since gut endogenous proteins represent a quantitatively large and consistent source of protein. PMID:24901416
Gastrointestinal endogenous proteins as a source of bioactive peptides--an in silico study.
Dave, Lakshmi A; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J
Dietary proteins are known to contain bioactive peptides that are released during digestion. Endogenous proteins secreted into the gastrointestinal tract represent a quantitatively greater supply of protein to the gut lumen than those of dietary origin. Many of these endogenous proteins are digested in the gastrointestinal tract but the possibility that these are also a source of bioactive peptides has not been considered. An in silico prediction method was used to test if bioactive peptides could be derived from the gastrointestinal digestion of gut endogenous proteins. Twenty six gut endogenous proteins and seven dietary proteins were evaluated. The peptides present after gastric and intestinal digestion were predicted based on the amino acid sequence of the proteins and the known specificities of the major gastrointestinal proteases. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified. After gastrointestinal digestion (based on the in silico simulation), the total number of bioactive peptides predicted to be released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins. Within the intact proteins and after simulated gastrointestinal digestion, angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most frequently observed in both the dietary and endogenous proteins. Among the dietary proteins, after in silico simulated gastrointestinal digestion, myosin was found to have the highest number of ACE-inhibitory peptide sequences (49 peptides), while for the gut endogenous proteins, mucin-5AC had the greatest number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins may be an important source of bioactive peptides in the gut particularly since gut endogenous proteins represent a quantitatively large and consistent source of protein.
Compartmentalised expression of meprin in small intestinal mucosa: enhanced expression in lamina propria in coeliac disease.
Lottaz, Daniel; Buri, Caroline; Monteleone, Giovanni; Rösmann, Sandra; Macdonald, Thomas T; Sanderson, Ian R; Sterchi, Erwin E
Epithelial cells in the human small intestine express meprin, an astacin-like metalloprotease, which accumulates normally at the brush border membrane and in the gut lumen. Therefore, meprin is targeted towards luminal components. In coeliac disease patients, peptides from ingested cereals trigger mucosal inflammation in the small intestine, disrupting epithelial cell differentiation and function. Using in situ hybridisation on duodenal tissue sections, we observed a marked shift of meprin mRNA expression from epithelial cells, the predominant expression site in normal mucosa, to lamina propria leukocytes in coeliac disease. Meprin thereby gains access to the substrate repertoire present beneath the epithelium.
Intestinal transplantation: The anesthesia perspective.
Dalal, Aparna
Intestinal transplantation is a complex and challenging surgery. It is very effective for treating intestinal failure, especially for those patients who cannot tolerate parenteral nutrition nor have extensive abdominal disease. Chronic parental nutrition can induce intestinal failure associated liver disease (IFALD). According to United Network for Organ Sharing (UNOS) data, children with intestinal failure affected by liver disease secondary to parenteral nutrition have the highest mortality on a waiting list when compared with all candidates for solid organ transplantation. Intestinal transplant grafts can be isolated or combined with the liver/duodenum/pancreas. Organ Procurement and Transplantation Network (OPTN) has defined intestinal donor criteria. Living donor intestinal transplant (LDIT) has the advantages of optimal timing, short ischemia time and good human leukocyte antigen matching contributing to lower postoperative complications in the recipient. Thoracic epidurals provide excellent analgesia for the donors, as well as recipients. Recipient management can be challenging. Thrombosis and obstruction of venous access maybe common due to prolonged parenteral nutrition and/or hypercoaguability. Thromboelastography (TEG) is helpful for managing intraoperative product therapy or thrombosis. Large fluid shifts and electrolyte disturbances may occur due to massive blood loss, dehydration, third spacing etc. Intestinal grafts are susceptible to warm and cold ischemia and ischemia-reperfusion injury (IRI). Post-reperfusion syndrome is common. Cardiac or pulmonary clots can be monitored with transesophageal echocardiography (TEE) and treated with recombinant tissue plasminogen activator. Vasopressors maybe used to ensure stable hemodynamics. Post-intestinal transplant patients may need anesthesia for procedures such as biopsies for surveillance of rejection, bronchoscopy, endoscopy, postoperative hemorrhage, anastomotic leaks, thrombosis of grafts etc. Asepsis
Multiple Factors Related to the Secretion of Glucagon-Like Peptide-1
Directory of Open Access Journals (Sweden)
XingChun Wang
Full Text Available The glucagon-like peptide-1 is secreted by intestinal L cells in response to nutrient ingestion. It regulates the secretion and sensitivity of insulin while suppressing glucagon secretion and decreasing postprandial glucose levels. It also improves beta-cell proliferation and prevents beta-cell apoptosis induced by cytotoxic agents. Additionally, glucagon-like peptide-1 delays gastric emptying and suppresses appetite. The impaired secretion of glucagon-like peptide-1 has negative influence on diabetes, hyperlipidemia, and insulin resistance related diseases. Thus, glucagon-like peptide-1-based therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors are now well accepted in the management of type 2 diabetes. The levels of glucagon-like peptide-1 are influenced by multiple factors including a variety of nutrients. The component of a meal acts as potent stimulants of glucagon-like peptide-1 secretion. The levels of its secretion change with the intake of different nutrients. Some drugs also have influence on GLP-1 secretion. Bariatric surgery may improve metabolism through the action on GLP-1 levels. In recent years, there has been a great interest in developing effective methods to regulate glucagon-like peptide-1 secretion. This review summarizes the literature on glucagon-like peptide-1 and related factors affecting its levels.
Impact of Intestinal Microbiota on Intestinal Luminal Metabolome
Matsumoto, Mitsuharu; Kibe, Ryoko; Ooga, Takushi; Aiba, Yuji; Kurihara, Shin; Sawaki, Emiko; Koga, Yasuhiro; Benno, Yoshimi
Low–molecular-weight metabolites produced by intestinal microbiota play a direct role in health and disease. In this study, we analyzed the colonic luminal metabolome using capillary electrophoresis mass spectrometry with time-of-flight (CE-TOFMS) —a novel technique for analyzing and differentially displaying metabolic profiles— in order to clarify the metabolite profiles in the intestinal lumen. CE-TOFMS identified 179 metabolites from the colonic luminal metabolome and 48 metabolites were present in significantly higher concentrations and/or incidence in the germ-free (GF) mice than in the Ex-GF mice (p metabolome and a comprehensive understanding of intestinal luminal metabolome is critical for clarifying host-intestinal bacterial interactions. PMID:22724057
Megacystis microcolon intestinal hypoperistalsis syndrome
Hiradfar, Mehran; Shojaeian, Reza; Dehghanian, Paria; Hajian, Sara
Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a multisystemic disorder in which impaired intestinal motor activity causes recurrent symptoms of intestinal obstruction in the absence of mechanical occlusion, associated with bladder distention without distal obstruction of the urinary tract. MMIHS and prune belly syndrome may overlap in most of the clinical features and discrimination of these two entities is important because the prognosis, management and consulting with parents are completely different. MMIHS outcome is very poor and in this article we present two neonates with MMIHS that both died in a few days. PMID:23729700
Antibiotic concentrations in intestinal mucosa.
Malmborg, A S
The concentrations in the intestinal mucosa after the initial dose of cefoxitin, piperacillin and clindamycin have been studied. The antibiotics were given at the induction of anesthesia as prophylaxis to patients undergoing elective colorectal surgery. The concentrations of the antibiotics in serum and intestinal mucosa taken during the operation were determined by the microbiological agar diffusion method. Therapeutic concentrations in intestinal mucosa were maintained during the major part of the operation period. The mean mucosa/serum concentration ratios were for cefoxitin 0.4, for piperacillin 0.5 and for clindamycin 1.2.
Directory of Open Access Journals (Sweden)
N.I. Ursova
Full Text Available The article analyzes modern data on infants' intestinal colics. Peculiarities of nutrition, intestinal microbiocenose in healthy infants, methods of colcs' correction are discussed. Author describes the principles of probiotics choice based on their clinical effectiveness in infants. Milk formula «Nan Comfort» can be useful in prophylaxis and treatment of functional disorders of gastrointestinal tract in children.Key words: infants, gastrointestinal tract, anatomy, physiology, intestinal colics, nutrition, probiotics.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 125–131
Bioactive dietary peptides and amino acids in inflammatory bowel disease.
Zhang, Hua; Hu, Chien-An A; Kovacs-Nolan, Jennifer; Mine, Yoshinori
Inflammatory bowel disease (IBD), most commonly ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammation of the gastrointestinal tract. Patients affected with IBD experience symptoms including abdominal pain, persistent diarrhea, rectal bleeding, and weight loss. There is no cure for IBD; thus treatments typically focus on preventing complications, inducing and maintaining remission, and improving quality of life. During IBD, dysregulation of the intestinal immune system leads to increased production of pro-inflammatory cytokines, such as TNF-α and IL-6, and recruitment of activated immune cells to the intestine, causing tissue damage and perpetuating the inflammatory response. Recent biological therapies targeting specific inflammatory cytokines or pathways, in particular TNF-α, have shown promise, but not all patients respond to treatment, and some individuals become intolerant to treatment over time. Dietary peptides and amino acids (AAs) have been shown to modulate intestinal immune functions and influence inflammatory responses, and may be useful as alternative or ancillary treatments in IBD. This review focuses on dietary interventions for IBD treatment, in particular the role of dietary peptides and AAs in reducing inflammation, oxidative stress, and apoptosis in the gut, as well as recent advances in the cellular mechanisms responsible for their anti-inflammatory activity.
The novel β3-adrenoceptor agonist mirabegron reduces carbachol-induced contractile activity in detrusor tissue from patients with bladder outflow obstruction with or without detrusor overactivity
DEFF Research Database (Denmark)
Svalø, Julie; Nordling, Jørgen; Bouchelouche, Kirsten
preparations from patients with bladder outflow obstruction (BOO) with and without detrusor overactivity (DO), and from patients with normal bladder function. We compared the effects to those of isoprenaline, a non-selective β-adrenoceptor agonist. Detrusor specimens were obtained from patients with benign...... carbachol-induced tone in tissues from all groups. Isoprenaline decreased tension with higher potency than mirabegron in normal, BOO and BOO+DO detrusor strips with pIC(50) values of 7.49 ± 0.16 vs. 6.23 ± 0.26 (P=0.0002), 6.89 ± 0.34 vs. 6.04 ± 0.31 (P=0.01), and 6.57 ± 0.20 vs. 5.41 ± 0.08 (P...), respectively. The maximal relaxant effect of isoprenaline and mirabegron in the normal, BOO and BOO+DO detrusor was 37.7 ± 14.4% and 36.1 ± 23.3%, 14.4 ± 12.2% vs. 33.4 ± 21.0% and 18.3 ± 10.0% vs. 28.3 ± 12.2% (n=4, P>0.05), respectively. Mirabegron and isoprenaline reduced carbachol-induced tone in both...
Common occurrence of antibacterial agents in human intestinal microbiota
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Fatima eDrissi
Full Text Available Laboratory experiments have revealed many active mechanisms by which bacteria can inhibit the growth of other organisms. Bacteriocins are a diverse group of natural ribosomally-synthesized antimicrobial peptides produced by a wide range of bacteria and which seem to play an important role in mediating competition within bacterial communities. In this study, we have identified and established the structural classification of putative bacteriocins encoded by 317 microbial genomes in the human intestine. On the basis of homologies to available bacteriocin sequences, mainly from lactic acid bacteria, we report the widespread occurrence of bacteriocins across the gut microbiota: 175 bacteriocins were found to be encoded in Firmicutes, 79 in Proteobacteria, 34 in Bacteroidetes and 25 in Actinobacteria. Bacteriocins from gut bacteria displayed wide differences among phyla with regard to class distribution, net positive charge, hydrophobicity and secondary structure, but the α-helix was the most abundant structure. The peptide structures and physiochemical properties of bacteriocins produced by the most abundant bacteria in the gut, the Firmicutes and the Bacteroidetes, seem to ensure low antibiotic activity and participate in permanent intestinal host defence against the proliferation of harmful bacteria. Meanwhile, the potentially harmful bacteria, including the Proteobacteria, displayed highly effective bacteriocins, probably supporting the virulent character of diseases. These findings highlight the eventual role played by bacteriocins in gut microbial competition and their potential place in antibiotic therapy.
Intestinal Failure (Short Bowel Syndrome)
... at the beginning to maintain nutrition and good hydration although it is hoped that the small intestine ... life. For more information or to locate a pediatric gastroenterologist in your area please visit our website ...
African Journals Online (AJOL)
Hymenolepis nana and Dentostomella ... worms (H. nana and D. translucida) were observed in the lumen of the intestine with severe cellular infiltration .... helminthosis and Balantidosis in Red monkey (Erythrocebus patas) in Ibadan Nigeria Nigerian ...
Telescoping Intestine in an Adult
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Khaldoon Shaheen
Full Text Available Protrusion of a bowel segment into another (intussusception produces severe abdominal pain and culminates in intestinal obstruction. In adults, intestinal obstruction due to intussusception is relatively rare phenomenon, as it accounts for minority of intestinal obstructions in this population demographic. Organic lesion is usually identifiable as the cause of adult intussusceptions, neoplasms account for the majority. Therefore, surgical resection without reduction is almost always necessary and is advocated as the best treatment of adult intussusception. Here, we describe a rare case of a 44-year-old male with a diffuse large B-cell lymphoma involving the terminal ileum, which had caused ileocolic intussusception and subsequently developed intestinal obstruction requiring surgical intervention. This case emphasizes the importance of recognizing intussusception as the initial presentation for bowel malignancy.
Handelman, Amir; Lapshina, Nadezda; Apter, Boris; Rosenman, Gil
Bio-nanophotonics is a wide field in which advanced optical materials, biomedicine, fundamental optics, and nanotechnology are combined and result in the development of biomedical optical chips. Silk fibers or synthetic bioabsorbable polymers are the main light-guiding components. In this work, an advanced concept of integrated bio-optics is proposed, which is based on bioinspired peptide optical materials exhibiting wide optical transparency, nonlinear and electrooptical properties, and effective passive and active waveguiding. Developed new technology combining bottom-up controlled deposition of peptide planar wafers of a large area and top-down focus ion beam lithography provides direct fabrication of peptide optical integrated circuits. Finding a deep modification of peptide optical properties by reconformation of biological secondary structure from native phase to β-sheet architecture is followed by the appearance of visible fluorescence and unexpected transition from a native passive optical waveguiding to an active one. Original biocompatibility, switchable regimes of waveguiding, and multifunctional nonlinear optical properties make these new peptide planar optical materials attractive for application in emerging technology of lab-on-biochips, combining biomedical photonic and electronic circuits toward medical diagnosis, light-activated therapy, and health monitoring. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Antimicrobial Peptides from Plants
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James P. Tam
Full Text Available Plant antimicrobial peptides (AMPs have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic, lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms.
Intestinal actinomycosis: a case report
International Nuclear Information System (INIS)
Loureiro, C.M.; Labrunie, E.; Pannaim, V.L.N.; Santos, A.A.S. dos; Pereira, A.A.
Intestinal actinomycosis: a case report. The authors describe a case of intestinal actinomycosis, which was manisfestated by abdominal mass and suggested, clinical and radiologically, a bowel carcinoma. They discuss the pathogenesis, and the clinical and radiological manisfestations of this disease, and its differential diagnosis. This is an infrequent disease which must be considered whenever suggestive clinical aspects are associated with a radiological ''malignant pattern'' of a bowel lesion. (author) [pt
Human antimicrobial peptides and cancer.
Jin, Ge; Weinberg, Aaron
Antimicrobial peptides (AMPs) have long been a topic of interest for entomologists, biologists, immunologists and clinicians because of these agents' intriguing origins in insects, their ubiquitous expression in many life forms, their capacity to kill a wide range of bacteria, fungi and viruses, their role in innate immunity as microbicidal and immunoregulatory agents that orchestrate cross-talk with the adaptive immune system, and, most recently, their association with cancer. We and others have theorized that surveillance through epithelial cell-derived AMPs functions to keep the natural flora of microorganisms in a steady state in different niches such as the skin, the intestines, and the mouth. More recently, findings related to specific activation pathways of some of these AMPs have led investigators to associate them with pro-tumoral activity; i.e., contributing to a tumorigenic microenvironment. This area is still in its infancy as there are intriguing yet contradictory findings demonstrating that while some AMPs have anti-tumoral activity and are under-expressed in solid tumors, others are overexpressed and pro-tumorigenic. This review will introduce a new paradigm in cancer biology as it relates to AMP activity in neoplasia to address the following questions: Is there evidence that AMPs contribute to tumor promoting microenvironments? Can an anti-AMP strategy be of use in cancer therapy? Do AMPs, expressed in and released from tumors, contribute to compositional shifting of bacteria in cancerous lesions? Can specific AMP expression characteristics be used one day as early warning signs for solid tumors? Copyright © 2018 Elsevier Ltd. All rights reserved.
Parenteral Nutrition and Intestinal Failure.
Bielawska, Barbara; Allard, Johane P
Severe short bowel syndrome (SBS) is a major cause of chronic (Type 3) intestinal failure (IF) where structural and functional changes contribute to malabsorption and risk of micronutrient deficiencies. Chronic IF may be reversible, depending on anatomy and intestinal adaptation, but most patients require long-term nutritional support, generally in the form of parenteral nutrition (PN). SBS management begins with dietary changes and pharmacologic therapies taking into account individual anatomy and physiology, but these are rarely sufficient to avoid PN. New hormonal therapies targeting intestinal adaptation hold promise. Surgical options for SBS including intestinal transplant are available, but have significant limitations. Home PN (HPN) is therefore the mainstay of treatment for severe SBS. HPN involves chronic administration of macronutrients, micronutrients, fluid, and electrolytes via central venous access in the patient's home. HPN requires careful clinical and biochemical monitoring. Main complications of HPN are related to venous access (infection, thrombosis) and metabolic complications including intestinal failure associated liver disease (IFALD). Although HPN significantly impacts quality of life, outcomes are generally good and survival is mostly determined by the underlying disease. As chronic intestinal failure is a rare disease, registries are a promising strategy for studying HPN patients to improve outcomes.
Primary intestinal lymphangiectasia: Minireview
Ingle, Sachin B; Hinge (Ingle), Chitra R
Primary idiopathic intestinal lymphangiectasia is an unusual disease featured by the presence of dilated lymphatic channels which are located in the mucosa, submucosa or subserosa leading to protein loosing enteropathy.Most often affected were children and generally diagnosed before third year of life but may be rarely seen in adults too. Bilateral pitting oedema of lower limb is the main clinical manifestation mimicking the systemic disease and posing a real diagnostic dilemma to the clinicians to differentiate it from other common systemic diseases like Congestive cardiac failure, Nephrotic Syndrome, Protein Energy Malnutrition, etc. Diagnosis can be made on capsule endoscopy which can localise the lesion but unable to take biopsy samples. Thus, recently double-balloon enteroscopy and biopsy in combination can be used as an effective diagnostic tool to hit the correct diagnosis. Patients respond dramatically to diet constituting low long chain triglycerides and high protein content with supplements of medium chain triglyceride. So early diagnosis is important to prevent untoward complications related to disease or treatment for the sake of accurate pathological diagnosis. PMID:25325063
[Malaria and intestinal protozoa].
Rojo-Marcos, Gerardo; Cuadros-González, Juan
Malaria is life threatening and requires urgent diagnosis and treatment. Incidence and mortality are being reduced in endemic areas. Clinical features are unspecific so in imported cases it is vital the history of staying in a malarious area. The first line treatments for Plasmodium falciparum are artemisinin combination therapies, chloroquine in most non-falciparum and intravenous artesunate if any severity criteria. Human infections with intestinal protozoa are distributed worldwide with a high global morbid-mortality. They cause diarrhea and sometimes invasive disease, although most are asymptomatic. In our environment populations at higher risk are children, including adopted abroad, immune-suppressed, travelers, immigrants, people in contact with animals or who engage in oral-anal sex. Diagnostic microscopic examination has low sensitivity improving with antigen detection or molecular methods. Antiparasitic resistances are emerging lately. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Haemorrhage and intestinal lymphoma
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Attilia M. Pizzini
Full Text Available Background: The prevalence of coeliac disease is around 1% in general population but this is often unrecognised. The classical presentation of adult coeliac disease is characterized by diarrhoea and malabsorption syndrome, but atypical presentations are probably more common and are characterized by iron deficiency anaemia, weight loss, fatigue, infertility, arthralgia, peripheral neuropathy and osteoporosis. Unusual are the coagulation disorders (prevalence 20% and these are due to vitamin K malabsorption (prolonged prothrombin time. Clinical case: A 64-year-old man was admitted to our Department for an extensive spontaneous haematoma of the right leg. He had a history of a small bowel resection for T-cell lymphoma, with a negative follow-up and he didn't report any personal or familiar history of bleeding. Laboratory tests showed markedly prolonged prothrombin (PT and partial-thromboplastin time (PTT, corrected by mixing studies, and whereas platelet count and liver tests was normal. A single dose (10 mg of intravenous vitamin K normalized the PT. Several days before the patient had been exposed to a superwarfarin pesticide, but diagnostic tests for brodifacoum, bromadiolone or difenacoum were negative. Diagnosis of multiple vitamin K-dependent coagulationfactor deficiencies (II, VII, IX, X due to intestinal malabsorption was made and coeliac disease was detected. Therefore the previous lymphoma diagnosis might be closely related to coeliac disease. Conclusions: A gluten free diet improves quality of life and restores normal nutritional and biochemical status and protects against these complications.
Energy Technology Data Exchange (ETDEWEB)
Davidson, J., E-mail: firstname.lastname@example.com [Salford Royal Hospital, Salford (United Kingdom); Plumb, A.; Burnett, H. [Salford Royal Hospital, Salford (United Kingdom)
Intestinal failure (IF) is the inability of the alimentary tract to digest and absorb sufficient nutrition to maintain normal fluid balance, growth, and health. It commonly arises from disease affecting the mesenteric root. Although severe IF is usually managed in specialized units, it lies at the end of a spectrum with degrees of nutritional compromise being widely encountered, but commonly under-recognized. Furthermore, in the majority of cases, the initial enteric insult occurs in non-specialist IF centres. The aim of this article is to review the common causes of IF, general principles of its management, some commoner complications, and the role of radiology in the approach to a patient with severe IF. The radiologist has a crucial role in helping provide access for feeding solutions (both enteral and parenteral) and controlling sepsis (via drainage of collections) in an initial restorative phase of treatment, whilst simultaneously mapping bowel anatomy and quality, and searching for disease complications to assist the clinicians in planning a later, restorative phase of therapy.
Effect of Da-Cheng-Qi Decoction on Pancreatitis-Associated Intestinal Dysmotility in Patients and in Rat Models
Directory of Open Access Journals (Sweden)
Jianlei Zhao
Full Text Available The impairment of intestinal motility and related infectious complications are the predominant clinical phenomenon in patients with severe acute pancreatitis (SAP. We aimed to investigate the effects of Da-Cheng-Qi decoction (DCQD on the gastrointestinal injury in SAP patients and the potential mechanism involved in rats. DCQD was enema administered to 70 patients for 7 days in West China Hospital. Mortality and organ failure during admission were observed and blood samples for laboratory analysis were collected. We also experimentally examined plasma inflammatory cytokines in rat serum and carried the morphometric studies of the gut. Intestinal propulsion index and serum and tissue vasoactive intestinal peptide (VIP were also detected. Though DCQD did not affect the overall incidence of organ failure, it shortened the average time of paralytic intestinal obstruction and decreased the morbidity of infectious complications in patients with SAP. Compared with untreated rats, the DCQD lowered the levels of proinflammatory cytokine and decreased the mean pathological intestinal lesion scores. The VIP level in intestinal tissue or serum in DCQD group was obviously lowered and intestinal propulsion index was significantly improved. In conclusion, DCQD has good effect on pancreatitis-associated intestinal dysmotility in patients and in rat models.
Plasma endocannabinoid levels in lean, overweight and obese humans: relationships with intestinal permeability markers, inflammation and incretin secretion.
Little, Tanya J; Cvijanovic, Nada; DiPatrizio, Nicholas V; Argueta, Donovan A; Rayner, Christopher K; Feinle-Bisset, Christine; Young, Richard L
Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation, however little is known of these effects in humans. This study aimed to: (i) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl-sn-glycerol (2-AG) and OEA in humans, and (ii) examine relationships with intestinal permeability, inflammation markers and incretin hormone secretion. 20 lean, 18 overweight and 19 obese participants underwent intraduodenal Intralipid® infusion (2 kcal/min) with collection of endoscopic duodenal biopsies and blood. Plasma AEA, 2-AG, and OEA (HPLC/tandem mass spectrometry), tumour necrosis factor-α (TNF-α), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) (multiplex), and duodenal expression of occludin, zona-occludin-1 (ZO-1), intestinal-alkaline-phosphatase (IAP), and toll-like receptor-4 (TLR4) (RT-PCR), were assessed. Fasting plasma AEA was increased in obese, compared with lean and overweight (Plean (Plean and overweight. The relationships between plasma AEA with duodenal ZO-1 and IAP, and GIP, suggest that altered endocannabinoid signalling may contribute to changes in intestinal permeability, inflammation and incretin release in human obesity.
Therapeutic HIV Peptide Vaccine
DEFF Research Database (Denmark)
Fomsgaard, Anders
Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...
Descriptors for antimicrobial peptides
DEFF Research Database (Denmark)
Jenssen, Håvard
of these are currently being used in quantitative structure--activity relationship (QSAR) studies for AMP optimization. Additionally, some key commercial computational tools are discussed, and both successful and less successful studies are referenced, illustrating some of the challenges facing AMP scientists. Through...... examples of different peptide QSAR studies, this review highlights some of the missing links and illuminates some of the questions that would be interesting to challenge in a more systematic fashion. Expert opinion: Computer-aided peptide QSAR using molecular descriptors may provide the necessary edge...
Intestinal barrier integrity and inflammatory bowel disease
DEFF Research Database (Denmark)
Holmberg, Fredrik Eric Olof; Pedersen, Jannie; Jørgensen, Peter
Disruption of normal barrier function is a fundamental factor in the pathogenesis of inflammatory bowel disease, which includes increased epithelial cell death, modified mucus configuration, altered expression and distribution of tight junction-proteins, along with a decreased expression of antim......Disruption of normal barrier function is a fundamental factor in the pathogenesis of inflammatory bowel disease, which includes increased epithelial cell death, modified mucus configuration, altered expression and distribution of tight junction-proteins, along with a decreased expression...... of antimicrobial peptides. Inflammatory bowel disease is associated with life-long morbidity for affected patients, and both the incidence and prevalence is increasing globally, resulting in substantial economic strain for society. Mucosal healing and re-establishment of barrier integrity is associated......, novel treatment strategies to accomplish mucosal healing and to re-establish normal barrier integrity in inflammatory bowel disease are warranted, and luminal stem cell-based approaches might have an intriguing potential. Transplantation of in vitro expanded intestinal epithelial stem cells derived...
The cell-specific pattern of cholecystokinin peptides in endocrine cells versus neurons is governed by the expression of prohormone convertases 1/3, 2, and 5/6
DEFF Research Database (Denmark)
Bundgaard, J.R.; Hannibal, J.; Zhu, X.
Most peptide hormone genes are, in addition to endocrine cells, also expressed in neurons. The peptide hormone cholecystokinin (CCK) is expressed in different molecular forms in cerebral neurons and intestinal endocrine cells. To understand this difference, we examined the roles of the neuroendoc...
Antimicrobial Peptides: An Introduction.
Haney, Evan F; Mansour, Sarah C; Hancock, Robert E W
The "golden era" of antibiotic discovery has long passed, but the need for new antibiotics has never been greater due to the emerging threat of antibiotic resistance. This urgency to develop new antibiotics has motivated researchers to find new methods to combat pathogenic microorganisms resulting in a surge of research focused around antimicrobial peptides (AMPs; also termed host defense peptides) and their potential as therapeutics. During the past few decades, more than 2000 AMPs have been identified from a diverse range of organisms (animals, fungi, plants, and bacteria). While these AMPs share a number of common features and a limited number of structural motifs; their sequences, activities, and targets differ considerably. In addition to their antimicrobial effects, AMPs can also exhibit immunomodulatory, anti-biofilm, and anticancer activities. These diverse functions have spurred tremendous interest in research aimed at understanding the activity of AMPs, and various protocols have been described to assess different aspects of AMP function including screening and evaluating the activities of natural and synthetic AMPs, measuring interactions with membranes, optimizing peptide function, and scaling up peptide production. Here, we provide a general overview of AMPs and introduce some of the methodologies that have been used to advance AMP research.
Primary intestinal lymphangiectasia (Waldmann's disease).
Vignes, Stéphane; Bellanger, Jérôme
Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool alpha1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective
Primary intestinal lymphangiectasia (Waldmann's disease
Directory of Open Access Journals (Sweden)
Bellanger Jérôme
Full Text Available Abstract Primary intestinal lymphangiectasia (PIL is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other
Regulatory peptides in the upper respiratory system and oral cavity of man. An immunocytochemical and radioimmunological study
International Nuclear Information System (INIS)
Hauser-Kronberger, C.
In the present study a dense network of peptide-immunoreactive nerve fibres in the upper respiratory system and the oral cavity of man was investigated. The occurrence, distribution and concentrations of regulatory peptide immunoreactivities in human nasal mucosa, soft palate, ventricular fold, vocal cord, epiglottis, subglottis, glandula submandibularis and glandula parotis were investigated using highly efficient immunocytochemical and radio-immunological methods. In the tissues investigated vasoactive intestinal polypeptide (VIP) and other derivatives from the VIP-precursor (peptide histidine methionine = PHM), prepro VIP (111-122)), neuropeptide tyrosine (NPY) and its C-flanking peptide (CPON), calcitonin gene-related peptide (CGRP), substance P, neurokinin A, bombesin-flanking peptide and somatostatin were detected. The regulatory peptides demonstrated also included the recently isolated peptides helospectin and pituitary adenylate cyclase activating peptide (PACAP). Single endocrine-like cells were for the first time demonstrated within the respiratory epithelium and in the lamina propria of the nasal mucosa and soft palate and in groups within ducts. Ultrastructural immunelectronmicroscopy was performed using an ABC-pre-embedding method. In addition, semithin Epon resin sections were immunostained. The concentrations of VIP, NPY, CGRP, substance P and neurokinin A were measured using radioimmunological methods. The peptide immunoreactivities demonstrated in a dense network of neuronal structures and endocrine cells give indication for the presence of a complex regulatory system with potent physiological mechanisms in the upper respiratory system and allocated tissues of man
Isotopic identification of intestinal strangulation
International Nuclear Information System (INIS)
Anderson, M.C.; Selby, J.B.
A small series of eleven dogs prepared with a strangulating segment of jejunum demonstrated that a radionuclide, 99 mTc-labelled albumin, concentrates in the lumen and bowel wall of the affected intestinal segment. Modern scanning equipment accurately localized the strangulating loop. This technique has the potential of identifying patients with intestinal obstruction, in whom strangulation is a factor, prior to the development of impaired arterial inflow and frank gangrene. These findings confirmed earlier obstructions that were reported when nuclear scanning instrumentation was less sophisticated. Identification of patients at risk for intestinal strangulation requires a high index of suspicion. Excruciating cramping abdominal pain out of proportion to physical findings, roentgenogram evidence, and laboratory studies should alert the physician to the possibility of intestinal ischemia and closed loop obstruction. Radionuclide scanning in such cases may be of assistance in defining or excluding the diagnosis of a strangulating mechanism. The test is simple, relatively economical, and represents a low risk procedure to patients. It would have no place when the classic physical and laboratory findings of intestinal infarction are present
Intestinal circulation during inhalation anesthesia
International Nuclear Information System (INIS)
Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.
This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86 Rb and 9-microns spheres labeled with 141 Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO 2 ) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines
[Primary intestinal lymphangiectasia (Waldmann's disease)].
Vignes, S; Bellanger, J
Primary intestinal lymphangiectasia (PIL), Waldmann's disease, is a rare disorder of unknown etiology characterized by dilated intestinal lacteals leading to lymph leakage into the small-bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. The main symptom is bilateral lower limb edema. Edema may be moderate to severe including pleural effusion, pericarditis or ascites. Protein-losing enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance and diagnosis by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of biopsies. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Several B-cell lymphomas of the gastrointestinal tract or with extra-intestinal localizations were reported in PIL patients. A long-term strictly low-fat diet associated with medium-chain triglyceride and liposoluble vitamin supplementation is the cornerstone of PIL medical management. Octreotide, a somatostatin analog, have been proposed with an inconsistent efficacy in association with diet. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. A prolonged clinical and biological follow-up is recommended. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.
Parenteral nutrition in intestinal failure
Directory of Open Access Journals (Sweden)
Kurkchubasche AG
Full Text Available Arlet G Kurkchubasche,1 Thomas J Herron,2 Marion F Winkler31Department of Surgery and Pediatrics, 2Department of Surgery, Alpert Medical School of Brown University, 3Department of Surgery/Nutritional Support Service, Rhode Island Hospital, Providence, RI, USAAbstract: Intestinal failure is a consequence of extensive surgical resection resulting in anatomic loss and/or functional impairment in motility or absorptive capacity. The condition is clinically characterized by the inability to maintain fluid, energy, protein, electrolyte, or micronutrient balance when on a conventionally accepted, normal diet. Parenteral nutrition (PN is the cornerstone of management until intestinal adaptation returns the patient to a PN-independent state. Intestinal length, residual anatomic segments and motility determine the need for and duration of parenteral support. The goals of therapy are to provide sufficient nutrients to enable normal growth and development in children, and support a healthy functional status in adults. This review addresses indications for PN, the formulation of the PN solution, patient monitoring, and considerations for prevention of PN-associated complications. With the ultimate goal of achieving enteral autonomy, the important role of diet, pharmacologic interventions, and surgery is discussed.Keywords: intestinal failure, short-bowel syndrome, parenteral nutrition, home nutrition support, intestinal rehabilitation
Small intestinal sulphoxidation of albendazole.
Villaverde, C; Alvarez, A I; Redondo, P; Voces, J; Del Estal, J L; Prieto, J G
1. The in vitro sulphoxidation of Albendazole (ABZ) by rat intestinal microsomes has been examined. The results revealed intestinal sulphoxidation of ABZ by intestinal microsomes in a NADPH-dependent enzymatic system. The kinetic constants for sulphoxidase activity were Vmax = 46 pmol/min/mg protein and Michaelis constant Km = 6.8 microM. 2. The possible effect of inducers (Arochlor 1254 and ABZ pretreatment) and inhibitors (erythromycin, methimazole, carbon monoxide and fenbendazole), was also studied. In rat pretreated with Arochlor 1254, Vmax was 52 pmol/min/mg protein, whereas oral administration of ABZ increased the intestinal sulphoxidation of the drug, Vmax being 103 pmol/min/mg protein. 3. Erythromycin did not change the enzymatic bioconversion of ABZ, but methimazole and carbon monoxide inhibited the enzyme activity by approximately 60 and 30% respectively. Fenbendazole (a structural analogue of ABZ) was a competitive inhibitor of the sulphoxidation process, characterized by a Ki or 69 microM. 4. These data demonstrate that the intestinal enzymes contributing to the initial sulphoxidation of ABZ may be similar to the hepatic enzymes involved in the biotransformation process by the P450 and FMO systems, a conclusion that needs to be further established.
Isotopic identification of intestinal strangulation
Energy Technology Data Exchange (ETDEWEB)
Anderson, M.C.; Selby, J.B.
A small series of eleven dogs prepared with a strangulating segment of jejunum demonstrated that a radionuclide, /sup 99/mTc-labelled albumin, concentrates in the lumen and bowel wall of the affected intestinal segment. Modern scanning equipment accurately localized the strangulating loop. This technique has the potential of identifying patients with intestinal obstruction, in whom strangulation is a factor, prior to the development of impaired arterial inflow and frank gangrene. These findings confirmed earlier obstructions that were reported when nuclear scanning instrumentation was less sophisticated. Identification of patients at risk for intestinal strangulation requires a high index of suspicion. Excruciating cramping abdominal pain out of proportion to physical findings, roentgenogram evidence, and laboratory studies should alert the physician to the possibility of intestinal ischemia and closed loop obstruction. Radionuclide scanning in such cases may be of assistance in defining or excluding the diagnosis of a strangulating mechanism. The test is simple, relatively economical, and represents a low risk procedure to patients. It would have no place when the classic physical and laboratory findings of intestinal infarction are present.
The Relationship between Glucagon-Like Peptide 2 and Feeding Intolerance in Preterm Infants
DEFF Research Database (Denmark)
Ozer, Esra Arun; Holst, Jens Juul; Duman, Nuray
Glucagon-like peptide 2 (GLP-2) is a hormone produced primarily in the distal intestine, stimulated by enteral nutrients, and playing diverse roles in the intestinal adaptation and growth. We aimed to investigate whether GLP-2 may play a role in the development of feeding intolerance which is a c...... with low levels of GLP-2 carry a risk for development of feeding intolerance. It may, therefore, be of relevance to investigate the therapeutic and prophylactic effects of GLP-2 administration in the preterm babies.......Glucagon-like peptide 2 (GLP-2) is a hormone produced primarily in the distal intestine, stimulated by enteral nutrients, and playing diverse roles in the intestinal adaptation and growth. We aimed to investigate whether GLP-2 may play a role in the development of feeding intolerance which...... is a common problem in preterm newborns resulting from the intestinal immaturity. The study included 20 term and 28 preterm neonates. Of preterm babies, 13 showed feeding intolerance fulfilling at least one of the following criteria: abdominal distension, increased gastric residual volume and presence of bile...
Exploitation of starch industry liquid by-product to produce bioactive peptides from rice hydrolyzed proteins.
Dei Piu', Lucilla; Tassoni, Annalisa; Serrazanetti, Diana Isabella; Ferri, Maura; Babini, Elena; Tagliazucchi, Davide; Gianotti, Andrea
Small peptides show higher antioxidant capacity than native proteins and may be absorbed in the intestine without further digestion. In our study, a protein by-product from rice starch industry was hydrolyzed with commercial proteolytic enzymes (Alcalase, Neutrase, Flavourzyme) and microbial whole cells of Bacillus spp. and the released peptides were tested for antioxidant activity. Among enzymes, Alcalase was the most performing, while microbial proteolytic activity was less efficient. Conversely, the antioxidant activity was higher in the samples obtained by microbial hydrolysis and particularly with Bacillus pumilus AG1. The sequences of low molecular weight antioxidant peptides were determined and analyzed for aminoacidic composition. The results obtained so far suggest that the hydrolytic treatment of this industrial by-product, with selected enzymes and microbial systems, can allow its exploitation for the production of functional additives and supplements rich in antioxidant peptides, to be used in new food formulas for human consumption. Copyright © 2014 Elsevier Ltd. All rights reserved.
Orally active-targeted drug delivery systems for proteins and peptides.
Li, Xiuying; Yu, Miaorong; Fan, Weiwei; Gan, Yong; Hovgaard, Lars; Yang, Mingshi
In the past decade, extensive efforts have been devoted to designing 'active targeted' drug delivery systems (ATDDS) to improve oral absorption of proteins and peptides. Such ATDDS enhance cellular internalization and permeability of proteins and peptides via molecular recognition processes such as ligand-receptor or antigen-antibody interaction, and thus enhance drug absorption. This review focuses on recent advances with orally ATDDS, including ligand-protein conjugates, recombinant ligand-protein fusion proteins and ligand-modified carriers. In addition to traditional intestinal active transport systems of substrates and their corresponding receptors, transporters and carriers, new targets such as intercellular adhesion molecule-1 and β-integrin are also discussed. ATDDS can improve oral absorption of proteins and peptides. However, currently, no clinical studies on ATDDS for proteins and peptides are underway, perhaps due to the complexity and limited knowledge of transport mechanisms. Therefore, more research is warranted to optimize ATDDS efficiency.
Glucagon-like peptide-1 analogues: An overview
Directory of Open Access Journals (Sweden)
Vishal Gupta
Full Text Available Abnormalities of the incretin axis have been implicated in the pathogenesis of type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1 and gastroinhibitory intestinal peptide constitutes >90% of all the incretin function. Augmentation of GLP-1 results in improvement of beta cell health in a glucose-dependant manner (post-prandial hyperglycemia and suppression of glucagon (fasting hyperglycemia, amongst other beneficial pleiotropic effects. Native GLP-1 has a very short plasma half-life and novel methods have been developed to augment its half life, such that its anti-hyperglycemic effects can be exploited. They can be broadly classified as exendin-based therapies (exenatide, exenatide once weekly, DPP-4-resistant analogues (lixisenatide, albiglutide, and analogues of human GLP-1 (liraglutide, taspoglutide. Currently, commercially available analogues are exenatide, exenatide once weekly, and liraglutide. This review aims to provide an overview of most GLP-1 analogues.
The physiology of glucagon-like peptide 1
DEFF Research Database (Denmark)
Holst, Jens Juul
Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in these cells. The current knowledge regarding regulation of proglucagon gene expression in the gut...... and in the brain and mechanisms responsible for the posttranslational processing are reviewed. GLP-1 is released in response to meal intake, and the stimuli and molecular mechanisms involved are discussed. GLP-1 is extremely rapidly metabolized and inactivated by the enzyme dipeptidyl peptidase IV even before...... postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the "ileal brake" mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these actions, GLP-1 or GLP-1 receptor agonists...
Enhancing bioactive peptide release and identification using targeted enzymatic hydrolysis of milk proteins.
Nongonierma, Alice B; FitzGerald, Richard J
Milk proteins have been extensively studied for their ability to yield a range of bioactive peptides following enzymatic hydrolysis/digestion. However, many hurdles still exist regarding the widespread utilization of milk protein-derived bioactive peptides as health enhancing agents for humans. These mostly arise from the fact that most milk protein-derived bioactive peptides are not highly potent. In addition, they may be degraded during gastrointestinal digestion and/or have a low intestinal permeability. The targeted release of bioactive peptides during the enzymatic hydrolysis of milk proteins may allow the generation of particularly potent bioactive hydrolysates and peptides. Therefore, the development of milk protein hydrolysates capable of improving human health requires, in the first instance, optimized targeted release of specific bioactive peptides. The targeted hydrolysis of milk proteins has been aided by a range of in silico tools. These include peptide cutters and predictive modeling linking bioactivity to peptide structure [i.e., molecular docking, quantitative structure activity relationship (QSAR)], or hydrolysis parameters [design of experiments (DOE)]. Different targeted enzymatic release strategies employed during the generation of milk protein hydrolysates are reviewed herein and their limitations are outlined. In addition, specific examples are provided to demonstrate how in silico tools may help in the identification and discovery of potent milk protein-derived peptides. It is anticipated that the development of novel strategies employing a range of in silico tools may help in the generation of milk protein hydrolysates containing potent and bioavailable peptides, which in turn may be used to validate their health promoting effects in humans. Graphical abstract The targeted enzymatic hydrolysis of milk proteins may allow the generation of highly potent and bioavailable bioactive peptides.
Effects of gastric inhibitory polypeptide, glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists on Bone Cell Metabolism
DEFF Research Database (Denmark)
Hansen, Morten S S; Tencerova, Michaela; Frølich, Jacob
The relationship between gut and skeleton is increasingly recognised as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibi......-clinical investigations, clinical trials are needed to clarify if similar effects are present and clinically relevant in humans. This article is protected by copyright. All rights reserved....
[Distiller Yeasts Producing Antibacterial Peptides].
Klyachko, E V; Morozkina, E V; Zaitchik, B Ts; Benevolensky, S V
A new method of controlling lactic acid bacteria contamination was developed with the use of recombinant Saccharomyces cerevisiae strains producing antibacterial peptides. Genes encoding the antibacterial peptides pediocin and plantaricin with codons preferable for S. cerevisiae were synthesized, and a system was constructed for their secretory expression. Recombinant S. cerevisiae strains producing antibacterial peptides effectively inhibit the growth of Lactobacillus sakei, Pediacoccus pentasaceus, Pediacoccus acidilactici, etc. The application of distiller yeasts producing antibacterial peptides enhances the ethanol yield in cases of bacterial contamination. Recombinant yeasts producing the antibacterial peptides pediocin and plantaricin can successfully substitute the available industrial yeast strains upon ethanol production.
Glucagon-like peptide-1 and its class B G Protein-coupled receptors: A long march to therapeutic successes.
de Graaf, C.; Donnely, D.; Wootten, D.; Lau, J.; Sexton, P.M.; Miller, L.J.; Ahn, J.M.; Liao, J.; Fletcher, M.M.; Yang, D.; Brown, A.J.; Zhou, C.; Deng, J.; Wang, M.W.
Theglucagon-likepeptide (GLP)-1receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secretedfromthreemajor tissues inhumans,enteroendocrine L cells in the distal intestine, a cells in the pancreas, and the central nervous system, which
Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice
DEFF Research Database (Denmark)
Hartmann, B; Thulesen, J; Kissow, Hannelouise
Glucagon-like peptide-2 (GLP-2) induces intestinal growth in mice; but in normal rats, it seems less potent, possibly because of degradation of GLP-2 by the enzyme dipeptidyl peptidase IV (DPP-IV). The purpose of this study was to investigate the survival and effect of GLP-2 in rats and mice afte...
The effects of variations in dose and method of administration on glucagon like peptide-2 activity in the rat
DEFF Research Database (Denmark)
Kaji, Tatsuru; Tanaka, Hiroaki; Holst, Jens Juul
Glucagon-like peptide-2 (GLP-2) is a potent, intestinal-specific trophic hormone. However, the relationship between the dose and timing of GLP-2 administration and these trophic effects is not clear. We investigated the effects of variations in the dose and timing of GLP-2 administration on its...
Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon
DEFF Research Database (Denmark)
Jeppesen, P B; Hartmann, B; Thulesen, J
Glucagon-like peptide 2 (GLP-2) is intestinotrophic, antisecretory, and transit-modulating in rodents, and it is mainly secreted from the intestinal mucosa of the terminal ileum and colon after food ingestion. We assessed the effect of GLP-2 on the gastrointestinal function in patients without a ...
Ligand-regulated peptide aptamers.
Miller, Russell A
The peptide aptamer approach employs high-throughput selection to identify members of a randomized peptide library displayed from a scaffold protein by virtue of their interaction with a target molecule. Extending this approach, we have developed a peptide aptamer scaffold protein that can impart small-molecule control over the aptamer-target interaction. This ligand-regulated peptide (LiRP) scaffold, consisting of the protein domains FKBP12, FRB, and GST, binds to the cell-permeable small-molecule rapamycin and the binding of this molecule can prevent the interaction of the randomizable linker region connecting FKBP12 with FRB. Here we present a detailed protocol for the creation of a peptide aptamer plasmid library, selection of peptide aptamers using the LiRP scaffold in a yeast two-hybrid system, and the screening of those peptide aptamers for a ligand-regulated interaction.
Biosynthesis of cardiac natriuretic peptides
DEFF Research Database (Denmark)
Goetze, Jens Peter
Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...... peptides has only been elucidated during the last decade. The cellular synthesis including amino acid modifications and proteolytic cleavages has proven considerably more complex than initially perceived. Consequently, the elimination phase of the peptide products in circulation is not yet well....... An inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...
Radiolabelled peptides for oncological diagnosis
Energy Technology Data Exchange (ETDEWEB)
Laverman, Peter; Boerman, Otto C.; Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Sosabowski, Jane K. [Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, London (United Kingdom)
Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of research in nuclear medicine. The {sup 111}In-labelled somatostatin analogue octreotide (OctreoScan trademark) is the most successful radiopeptide for tumour imaging, and was the first to be approved for diagnostic use. Based on the success of these studies, other receptor-targeting peptides such as cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin (BN), chemokine receptor CXCR4 targeting peptides, and RGD peptides are currently under development or undergoing clinical trials. In this review, we discuss some of these peptides and their analogues, with regard to their potential for radionuclide imaging of tumours. (orig.)
Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases
Opazo, Maria C.; Ortega-Rocha, Elizabeth M.; Coronado-Arrázola, Irenice; Bonifaz, Laura C.; Boudin, Helene; Neunlist, Michel; Bueno, Susan M.; Kalergis, Alexis M.; Riedel, Claudia A.
The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases. PMID:29593681
Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases
Directory of Open Access Journals (Sweden)
Maria C. Opazo
Full Text Available The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases.
Gintonin absorption in intestinal model systems
Directory of Open Access Journals (Sweden)
Byung-Hwan Lee
Conclusion: The present study shows that gintonin could be absorbed in the intestine through transcellular and paracellular diffusion, and active transport. In addition, the lipid component of gintonin might play a key role in its intestinal absorption.
Therapeutic hypothermia reduces intestinal ischemia/reperfusion ...
African Journals Online (AJOL)
The detached intestinal epithelial cells in hypothermia group showed ... of apoptosis than those in normothermia group at 4 h (17.30 ± 2.56 vs. ... intestinal ischemia/reperfusion (IR) injury, which could be attenuated by therapeutic hypothermia.
Immunohistochemical study on the ontogenetic development of the regional distribution of peptide YY, pancreatic polypeptide, and glucagon-like peptide 1 endocrine cells in bovine gastrointestinal tract.
Pyarokhil, Asadullah Hamid; Ishihara, Miyuki; Sasaki, Motoki; Kitamura, Nobuo
The regional distribution and relative frequency of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and glucagon-like peptide 1 (GLP-1)-immunoreactive (IR) cells were determined immunohistochemically in the gastrointestinal tract at seven ontogenetic stages in pre- and postnatal cattle. Different frequencies of PYY-, PP-, and GLP-1-IR cells were found in the intestines at all stages; they were not found in the esophagus and stomach. The frequencies varied depending on the intestinal segment and the developmental stage. The frequencies of PYY- and PP-IR cells were lower in the small intestine and increased from ileum to rectum, whereas GLP-1-IR cells were more numerous in duodenum and jejunum, decreased in ileum and cecum, and increased again in colon and rectum. The frequencies also varied according to pre- and postnatal stages. All three cell types were most numerous in fetus, and decreased in calf and adult groups, indicating that the frequencies of these three types of endocrine cells decrease with postnatal development. The results suggest that these changes vary depending on feeding habits and adaptation of growth, secretion, and motility of intestine at different ontogenetic stages of cattle. Copyright © 2011 Elsevier B.V. All rights reserved.
Update on small intestinal stem cells
Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio
Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to id...
Intestinal epithelium in inflammatory bowel disease
DEFF Research Database (Denmark)
Coskun, Mehmet
The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs) that are crucial in maintaining intestinal...... of inflammatory bowel disease (IBD). Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets....
Directory of Open Access Journals (Sweden)
Mehrzad Sadredinamin
Full Text Available Antimicrobial peptides (AMPs are extensive group of molecules that produced by variety tissues of invertebrate, plants, and animal species which play an important role in their immunity response. AMPs have different classifications such as; biosynthetic machines, biological sources, biological functions, molecular properties, covalent bonding patterns, three dimensional structures, and molecular targets.These molecules have multidimensional properties including antimicrobial activity, antiviral activity, antifungal activity, anti-parasite activity, biofilm control, antitumor activity, mitogens activity and linking innate to adaptive immunity that making them promising agents for therapeutic drugs. In spite of this advantage of AMPs, their clinical developments have some limitation for commercial development. But some of AMPs are under clinical trials for the therapeutic purpose such as diabetic foot ulcers, different bacterial infections and tissue damage. In this review, we emphasized on the source, structure, multidimensional properties, limitation and therapeutic applications of various antimicrobial peptides.
Exercise and the gastro-intestinal tract
African Journals Online (AJOL)
on perfonnance and me value of cardiovascular training in improving performance in aerobic sports is well recognised. The role of me gastro-intestinal tracr, bom as a limiting and sustaining facror in aerobic exercises, is less well appreciared. Gastro-intestinal symptoms. The spectrum of gastro-intestinal effecrs of exercise ...
The mucosal firewalls against commensal intestinal microbes.
Macpherson, Andrew J; Slack, Emma; Geuking, Markus B; McCoy, Kathy D
Mammals coexist with an extremely dense microbiota in the lower intestine. Despite the constant challenge of small numbers of microbes penetrating the intestinal surface epithelium, it is very unusual for these organisms to cause disease. In this review article, we present the different mucosal firewalls that contain and allow mutualism with the intestinal microbiota.
Peptide degradation and the role of DPP-4 inhibitors in the treatment of type 2 diabetes
DEFF Research Database (Denmark)
Deacon, Carolyn F
-1 is an intestinal hormone with potent insulinotropic and glucagonostatic effects and can normalise blood glucose levels in patients with type 2 diabetes, but the native peptide is not therapeutically useful because of its inherent metabolic instability. Using the GLP-1/DPP-4 system and type 2...... diabetes as an example, this review summarises how knowledge of a peptide's biological effects coupled with an understanding of the pathways involved in its metabolic clearance can be exploited in a rational, step-by-step manner to develop a therapeutic agent, which is effective and well tolerated, and any...
The role of the physiologic barrier function of the small bowel and its possible role in health and disease has attracted much attention over the past decade. The intestinal mucosal barrier for luminal macromolecules and microorganism is the result of non-immunologic and immunologic defense
Drug Transporters in the Intestine
DEFF Research Database (Denmark)
Steffansen, Bente
to the intestinal exsorptive DTs. An example is the API sulfasalazine, which is a substrate for breast cancer resistance protein (BCRP)/ABCG2. Sulfasalazine absorption is found to increase when human volunteers are administered high concentrations together with the inhibitor and spice curcumin. In conclusion...
Radiology of the small intestine
International Nuclear Information System (INIS)
Trueber, E.; Engelbrecht, V.
The book presents the state of the art in radiology of the small intestine, discussing diagnostic fundamentals in the general, introductory chapter and continuing with the specific modalities available and applicable for diagnostic evaluation of the various symptoms and lesions. (orig./CB) [de
Circadian disorganization alters intestinal microbiota.
Directory of Open Access Journals (Sweden)
Robin M Voigt
Full Text Available Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases.
Milk products and intestinal health
Van der Meer, R; Bovee-Oudenhoven, IMJ; Sesink, ALA; Kleibeuker, JH
Milk products may improve intestinal health by means of the cytoprotective effects of their high calcium phosphate (CaPi) content. We hypothesized that this cytoprotection may increase host defenses against bacterial infections as well as decrease colon cancer risk. This paper summarizes our studies
Hirschsprung's disease - Postsurgical intestinal dysmotility
Romaneli, Mariana Tresoldi das Neves; Ribeiro, Antonio Fernando; Bustorff-Silva, Joaquim Murray; de Carvalho, Rita Barbosa; Lomazi, Elizete Aparecida
Abstract Objective: To describe the case of an infant with Hirschsprung's disease presenting as total colonic aganglionosis, which, after surgical resection of the aganglionic segment persisted with irreversible functional intestinal obstruction; discuss the difficulties in managing this form of congenital aganglionosis and discuss a plausible pathogenetic mechanism for this case. Case description: The diagnosis of Hirschsprung's disease presenting as total colonic aganglionosis was establi...
Intestinal Volvulus in Idiopathic Steatorrhea
Warner, H. A.; Kinnear, D. G.; Cameron, D. G.
Volvulus of the intestine has recently been observed in three patients with idiopathic steatorrhea in relapse. Two patients gave a history of intermittent abdominal pain, distension and obstipation. Radiographic studies during these attacks revealed obstruction at the level of the sigmoid colon. Reduction under proctoscopic control was achieved in one instance, spontaneous resolution occurring in the other. The third patient presented as a surgical emergency and underwent operative reduction of a small intestinal volvulus. Persistence of diarrhea and weight loss postoperatively led to further investigation and a diagnosis of idiopathic steatorrhea. In all cases, treatment resulted in clinical remission with a coincident disappearance of obstructive intestinal symptoms. The pathogenesis of volvulus in sprue is poorly understood. Atonicity and dilatation of the bowel and stretching of the mesentery likely represent important factors. The symptoms of recurrent abdominal pain and distension in idiopathic steatorrhea necessitate an increased awareness of intestinal volvulus as a complication of this disease. ImagesFig. 1Fig. 2Fig. 3Figs. 4 and 5Fig. 6 PMID:13998948
Diversity of insect intestinal microflora
Czech Academy of Sciences Publication Activity Database
Mrázek, Jakub; Štrosová, Lenka; Fliegerová, Kateřina; Kott, T.; Kopečný, Jan
Roč. 53, č. 3 (2008), s. 229-233 ISSN 0015-5632 R&D Projects: GA ČR GA303/06/0974 Institutional research plan: CEZ:AV0Z50450515 Keywords : insect intestinal microflora Subject RIV: EE - Microbiology, Virology Impact factor: 1.172, year: 2008
Microcontainers for Intestinal Drug Delivery
DEFF Research Database (Denmark)
Tentor, Fabio; Mazzoni, Chiara; Keller, Stephan Sylvest
Among all the drug administration routes, the oral one is the most preferred by the patients being less invasive, faster and easier. Oral drug delivery systems designed to target the intestine are produced by powder technology and capsule formulations. Those systems including micro- and nano...
NOD-Like Receptors in Intestinal Homeostasis and Epithelial Tissue Repair
Parlato, Marianna; Yeretssian, Garabet
The intestinal epithelium constitutes a dynamic physical barrier segregating the luminal content from the underlying mucosal tissue. Following injury, the epithelial integrity is restored by rapid migration of intestinal epithelial cells (IECs) across the denuded area in a process known as wound healing. Hence, through a sequence of events involving restitution, proliferation and differentiation of IECs the gap is resealed and homeostasis reestablished. Relapsing damage followed by healing of the inflamed mucosa is a hallmark of several intestinal disorders including inflammatory bowel diseases (IBD). While several regulatory peptides, growth factors and cytokines stimulate restitution of the epithelial layer after injury, recent evidence in the field underscores the contribution of innate immunity in controlling this process. In particular, nucleotide-binding and oligomerization domain-like receptors (NLRs) play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Here, we review the process of intestinal epithelial tissue repair and we specifically focus on the impact of NLR-mediated signaling mechanisms involved in governing epithelial wound healing during disease. PMID:24886810
Lymphatic deletion of calcitonin receptor–like receptor exacerbates intestinal inflammation
Davis, Reema B.; Kechele, Daniel O.; Blakeney, Elizabeth S.; Pawlak, John B.
Lymphatics play a critical role in maintaining gastrointestinal homeostasis and in the absorption of dietary lipids, yet their roles in intestinal inflammation remain elusive. Given the increasing prevalence of inflammatory bowel disease, we investigated whether lymphatic vessels contribute to, or may be causative of, disease progression. We generated a mouse model with temporal and spatial deletion of the key lymphangiogenic receptor for the adrenomedullin peptide, calcitonin receptor–like receptor (Calcrl), and found that the loss of lymphatic Calcrl was sufficient to induce intestinal lymphangiectasia, characterized by dilated lacteals and protein-losing enteropathy. Upon indomethacin challenge, Calcrlfl/fl/Prox1-CreERT2 mice demonstrated persistent inflammation and failure to recover and thrive. The epithelium and crypts of Calcrlfl/fl/Prox1-CreERT2 mice exhibited exacerbated hallmarks of disease progression, and the lacteals demonstrated an inability to absorb lipids. Furthermore, we identified Calcrl/adrenomedullin signaling as an essential upstream regulator of the Notch pathway, previously shown to be critical for intestinal lacteal maintenance and junctional integrity. In conclusion, lymphatic insufficiency and lymphangiectasia caused by loss of lymphatic Calcrl exacerbates intestinal recovery following mucosal injury and underscores the importance of lymphatic function in promoting recovery from intestinal inflammation. PMID:28352669
Angiotensin receptors and angiotensin I-converting enzyme in rat intestine
International Nuclear Information System (INIS)
Duggan, K.A.; Mendelsohn, F.A.; Levens, N.R.
The purpose of this study was to map the distribution of angiotensin II (ANG II) receptors and ANG I-converting enzyme (ACE) in rat intestine. ANG II binding sites were visualized by in vitro autoradiography using iodinated [Sar1, Ile8]ANG II. The distribution of ACE was mapped using an iodinated derivative of lisinopril. Male Sprague-Dawley rats were killed and the interior of the whole intestine washed with ice-cold saline. Segments of duodenum, jejunum, ileum, and colon were quickly frozen in a mixture of isopentane and dry ice. Twenty-micron frozen sections were thaw-mounted onto gelatin-coated slides, incubated with either ligand, and exposed to X-ray film. After exposure and subsequent development, the films were quantitated by computerized densitometry. ANG II receptors were most dense in the colon, followed by the ileum, duodenum, and jejunum. Within each segment of intestine, specific ANG II binding sites were localized exclusively to the muscularis. In contrast, ACE was present in both the mucosa and the muscularis. The colocalization of ANG II receptors and ACE may suggest a role for locally generated ANG II in the control of intestinal function. The luminal orientation of ACE in the mucosa of the small intestine may suggest that at this site ACE serves primarily to hydrolyze dietary peptides
Epithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice.
He, Zhengxiang; Chen, Lili; Souto, Fabricio O; Canasto-Chibuque, Claudia; Bongers, Gerold; Deshpande, Madhura; Harpaz, Noam; Ko, Huaibin M; Kelley, Kevin; Furtado, Glaucia C; Lira, Sergio A
Increased expression of Interleukin (IL)-33 has been detected in intestinal samples of patients with ulcerative colitis, a condition associated with increased risk for colon cancer, but its role in the development of colorectal cancer has yet to be fully examined. Here, we investigated the role of epithelial expressed IL-33 during development of intestinal tumors. IL-33 expression was detected in epithelial cells in colorectal cancer specimens and in the Apc Min/+ mice. To better understand the role of epithelial-derived IL-33 in the intestinal tumorigenesis, we generated transgenic mice expressing IL-33 in intestinal epithelial cells (V33 mice). V33 Apc Min/+ mice, resulting from the cross of V33 with Apc Min/+ mice, had increased intestinal tumor burden compared with littermate Apc Min/+ mice. Consistently, Apc Min/+ mice deficient for IL-33 receptor (ST2), had reduced polyp burden. Mechanistically, overexpression of IL-33 promoted expansion of ST2 + regulatory T cells, increased Th2 cytokine milieu, and induced alternatively activated macrophages in the gut. IL-33 promoted marked changes in the expression of antimicrobial peptides, and antibiotic treatment of V33 Apc Min/+ mice abrogated the tumor promoting-effects of IL-33 in the colon. In conclusion, elevated IL-33 signaling increases tumor development in the Apc Min/+ mice.
In vivo analysis of intestinal permeability following hemorrhagic shock
Alsaigh, Tom; Chang, Marisol; Richter, Michael; Mazor, Rafi; Kistler, Erik B
AIM: To determine the time course of intestinal permeability changes to proteolytically-derived bowel peptides in experimental hemorrhagic shock. METHODS: We injected fluorescently-conjugated casein protein into the small bowel of anesthetized Wistar rats prior to induction of experimental hemorrhagic shock. These molecules, which fluoresce when proteolytically cleaved, were used as markers for the ability of proteolytically cleaved intestinal products to access the central circulation. Blood was serially sampled to quantify the relative change in concentration of proteolytically-cleaved particles in the systemic circulation. To provide spatial resolution of their location, particles in the mesenteric microvasculature were imaged using in vivo intravital fluorescent microscopy. The experiments were then repeated using an alternate measurement technique, fluorescein isothiocyanate (FITC)-labeled dextrans 20, to semi-quantitatively verify the ability of bowel-derived low-molecular weight molecules (< 20 kD) to access the central circulation. RESULTS: Results demonstrate a significant increase in systemic permeability to gut-derived peptides within 20 min after induction of hemorrhage (1.11 ± 0.19 vs 0.86 ± 0.07, P < 0.05) compared to control animals. Reperfusion resulted in a second, sustained increase in systemic permeability to gut-derived peptides in hemorrhaged animals compared to controls (1.2 ± 0.18 vs 0.97 ± 0.1, P < 0.05). Intravital microscopy of the mesentery also showed marked accumulation of fluorescent particles in the microcirculation of hemorrhaged animals compared to controls. These results were replicated using FITC dextrans 20 [10.85 ± 6.52 vs 3.38 ± 1.11 fluorescent intensity units (× 105, P < 0.05, hemorrhagic shock vs controls)], confirming that small bowel ischemia in response to experimental hemorrhagic shock results in marked and early increases in gut membrane permeability. CONCLUSION: Increased small bowel permeability in hemorrhagic
Prenatal intestinal volvulus: look for cystic fibrosis.
Chouikh, Taieb; Mottet, Nicolas; Cabrol, Christelle; Chaussy, Yann
Intestinal volvulus is a life-threatening emergency requiring prompt surgical management. Prenatal intestinal volvulus is rare, and most are secondary to intestinal atresia, mesenteric defect or without any underlying cause. Cystic fibrosis (CF) is known to cause digestive tract disorders. After birth, 10-15% of newborns with CF may develop intestinal obstruction within a few days of birth because of meconial ileus. 1 This obstruction is a result of dehydrated thickened meconium obstructing the intestinal lumen. We report two cases of fetuses with prenatal diagnosis of segmental volvulus in whom CF was diagnosed. 2016 BMJ Publishing Group Ltd.
Therapeutic peptides for cancer therapy. Part II - cell cycle inhibitory peptides and apoptosis-inducing peptides.
Raucher, Drazen; Moktan, Shama; Massodi, Iqbal; Bidwell, Gene L
Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that arrest the cell cycle by mimicking CDK inhibitors or induce apoptosis directly are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Inhibition of cancer cell proliferation directly using peptides that arrest the cell cycle or induce apoptosis is a promising strategy. Peptides can be designed that interact very specifically with cyclins and/or cyclin-dependent kinases and with members of apoptotic cascades. Use of these peptides is not limited by their design, as a rational approach to peptide design is much less challenging than the design of small molecule inhibitors of specific protein-protein interactions. However, the limitations of peptide therapy lie in the poor pharmacokinetic properties of these large, often charged molecules. Therefore, overcoming the drug delivery hurdles could open the door for effective peptide therapy, thus making an entirely new class of molecules useful as anticancer drugs.
Chenodeoxycholic acid reduces intestinal permeability in newly weaned piglets
DEFF Research Database (Denmark)
van der Meer, Y; Gerrits, W J J; van den Bosch, M
weaned (21 d) piglets offered a diet with or without 60 mg CDCA/kg feed (n = 24/treatment). Upon weaning, piglets were fasted for 16 h and then intragastrically dosed with 20 g test feed in 40 g water. Subsequently, a jugular blood sample was taken on 45, 90, 135, or 180 min for analysis of GLP-2......, peptide YY (PYY), and glucose. Afterwards, piglets were offered the experimental diets ad libitum. On days 3.5, 7.5, and 10.5 after weaning, serum responses to an intragastric dose of lactulose and Co-EDTA were tested at 2 h after dosing in 8 piglets per treatment. Immediately thereafter, piglets were...... to newly weaned piglets, implying that CDCA deserves further study as a means for improving intestinal health. The positive correlation found between Co-EDTA and lactulose indicates that both marker molecules measure similar change in permeability....
A etiological factors in mechanical intestinal obstruction
International Nuclear Information System (INIS)
Asad, S.; Khan, H.; Khan, I.A.; Ghaffar, S.; Rehman, Z.U.
Background: Intestinal obstruction occurs when the normal flow of intestinal contents is interrupted. The most frequent causes of intestinal obstruction are postoperative adhesions and hernias, which cause extrinsic compression of the intestine. Less frequently, tumours or strictures of the bowel can cause intrinsic blockage. Objective of the study was to find out the various a etiological factors of mechanical intestinal obstruction and to evaluate the morbidity and mortality in adult patients presenting to Surgical 'A' unit of Ayub teaching hospital with mechanical intestinal obstruction. Methods: This cross-sectional study was conducted from March 2009 to September, 2009. All patients presenting with intestinal obstruction and were above the age of 12 years were included in the study. Patients with non-mechanical obstruction were excluded from the study and those who responded to conservative measures were also excluded. Results: A total of 36 patients with age ranging from 12 to 80 years (Mean age 37.72+-19.74 years) and male to female ratio of 1.77:1, were treated for mechanical intestinal obstruction. The most common cause for mechanical intestinal obstruction was adhesions (36.1%). Intestinal tuberculosis was the second most common cause (19.4%), while hernias and sigmoid volvulus affected 13.9% patients each. Malignancies were found in 5.6% cases. Conclusion: Adhesions and Tuberculosis are the leading causes of mechanical intestinal obstruction in Pakistan. Although some patients can be treated conservatively, a substantial portion requires immediate surgical intervention. (author)
Intestinal perfusion in the study of intestinal absorption
International Nuclear Information System (INIS)
Baker, S.J.
Several techniques for studying absorption by means of intestinal perfusion have been developed. While the principle is simple, the practice is complicated by absorption of the solvent and by excretion of fluid into the lumen. To improve reliability a ''marker'' is incorporated into the system; it should behave as nearly as possible like the nutrient of interest, except that it should be unabsorbable. A great many markers, including several labelled with radionuclides, have been developed for use with numerous nutrients, and perfusion methods using double or triple tubes or occlusive balloons have been tested. The perfusion technique is too complicated for routine diagnostic use, but it offers at present the only possibility of studying the function of defined sections of the small intestine in the intact human. (author)
The CT signs of intestinal volvulus
International Nuclear Information System (INIS)
Ji Jiansong; Wang Zufei; Xu Zhaolong; Lv Guijian; Xu Min; Zhao Zhongwei; Su Jinliang; Zhou Limin
Objective: To improve the accuracy rate of spiral CT diagnosing intestinal volvulus. Methods: To analysis the CT findings of 9 cases of intestinal volvulus proved by operation, the main reconstruction techniques were multiplanar reformation (MPR) and sliding thin-slab maximum intensity projection (STS-MIP). Results: All the 9 cases were diagnosed accurately, the main signs were 'whirlpool' of intestine (6 cases) and vessels (9 cases),'target loop' (2 cases),'beak'(6 cases). Conclusion: 'Whirlpool' of vessels is a specific sign to diagnose intestinal volvulus, 'target loop', reduced enhancement of intestinal wall and ascites are the reliable signs to strangulated intestinal obstruction. Spiral CT and reconstructions have important value to diagnose the intestinal volvulus. (authors)
DEFF Research Database (Denmark)
Jensen, Knud Jørgen
This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective.......This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective....
Improving Peptide Applications Using Nanotechnology.
Narayanaswamy, Radhika; Wang, Tao; Torchilin, Vladimir P
Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology.
Human Milk Hyaluronan Enhances Innate Defense of the Intestinal Epithelium*
Hill, David R.; Rho, Hyunjin K.; Kessler, Sean P.; Amin, Ripal; Homer, Craig R.; McDonald, Christine; Cowman, Mary K.; de la Motte, Carol A.
Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human β-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human β-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine Hβ D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn. PMID:23950179
Anticancer peptides from bacteria
Directory of Open Access Journals (Sweden)
Tomasz M. Karpiński
Full Text Available Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data regarding the properties, action and anticancer activity of listed peptides.
The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology.
Yu, Huimin; Hasan, Nesrin M; In, Julie G; Estes, Mary K; Kovbasnjuk, Olga; Zachos, Nicholas C; Donowitz, Mark
The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow "mini-intestines" ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases. However, this model is reductionist and lacks many of the complexities of normal intestine. Consequently, it is not yet possible to predict how great the advances using this model will be for understanding human physiology and pathophysiology, nor how the model will be modified to include multiple other intestinal cell types and physical forces necessary to more closely approximate normal intestine. This review describes recent studies using mini-intestines, which have readdressed previously established models of normal intestinal transport physiology and newly examined intestinal pathophysiology. The emphasis is on studies with human enteroids grown either as three-dimensional spheroids or two-dimensional monolayers. In addition, comments are provided on mouse studies in cases when human studies have not yet been described.
Intestinal permeability and nutritional status in developmental disorders.
Souza, Nilian Carla Silva; Mendonca, Jacqueline Nakau; Portari, Guilherme Vannucchi; Jordao Junior, Alceu Afonso; Marchini, Julio Sergio; Chiarello, Paula Garcia
Autism is a developmental disorder with a possible connection between dietary components and triggering or worsening of symptoms. An altered intestinal permeability might allow absorption of incompletely digested peptides (gluten and casein) that could produce opioid-like activity on the brain, causing significant changes in behavior. To assess the intestinal permeability and nutritional status of participants with developmental disorders to determine if changes in the intestinal mucosal barrier and/or injury to the intercellular junctions have occurred that might justify application of further dietary modifications. To assess intestinal permeability, the research team analyzed participants urine under fasting conditions, using gas chromatography to determine chromatographic peaks. To assess nutritional status, the team determined participants heights and weights and performed a bioelectric bioimpedance examination at least 4 hours after their most recent meal. In addition, the team determined food intake using three diet diaries. They asked participants and caregivers to register each food consumed during 2 nonconsecutive weekdays and 1 weekend day. The study occurred at the Ribeirao Preto School of Medicine, Sao Paulo University. Seven participants aged 9 to 23 years with developmental disorders (the developmental group, DG) completed the study. The research team recruited them through the Association of Friends of the Autistic Persons of Ribeirao Preto in Ribeirao Preto, Brazil. The control group (CG) consisted of nonsmoking healthy volunteers in the general population who were similar in age to the experimental group and did not suffer from diseases that potentially could influence nutritional status and intestinal function. To assess intestinal permeability, participants ingested 150 mL of an isosmolar solution of the sugars mannitol (2 g) and lactulose (7.5 g) under fasting conditions and the researchers collected all voided urine over a period of 5 hours
Influence of ionizing radiation on gastrointestinal peptide levels
Energy Technology Data Exchange (ETDEWEB)
Wysocki, J.; Esposito, V.; Linard, C. [CEA Fontenay-aux-Roses, 92 (France). Inst. de Protection et de Surete Nucleaire
Exposure of the gut to ionising radiation may induce gastrointestinal damage and dysfunction. Early effects such as nausea, vomiting and diarrhea, anorexia may be observed within the first 24 h after irradiation. Such symptoms are seen even with doses as low as 1 Gy. later effects and the onset of the gastrointestinal syndrome are seen at higher doses (10 Gy) and include gastric emptying inhibition, intestinal hemorrhages, disturbances in water and electrolytes balance and septicemia. The severity of which depends on the nature, dose and dose rate received. The mechanism underlying these changes was unclear; it has long been known that exposure to ionising radiation affects intestinal morphology usually because of inhibition of mitotic activity at the level of the crypt enterocyst. The various physiological functions of the gastrointestinal tract are controlled by a wide variety of agents as neurotransmitters, neuropeptides. Radiation induces alterations in hormonal release and response. The present study carried out in the rat focuses on Gastrin Releasing Peptide (GRP), a gastrointestinal neuropeptide present in the central nervous system and in the gut endocrine cells were released into blood. The GRP controls food intake, pancreatic enzyme secretions, gastric emptying, intestinal motility and cellular proliferation. The aim was to investigate the effects of gamma and neutron/gamma on plasma and gastrointestinal tissue levels of GRP
Ultrasonographic Demonstration of Intestinal Obstruction
International Nuclear Information System (INIS)
Lee, Dong Hoo; Choi, Hyae Seoun; Kim, S. K.; Han, S.U.; Park, K. S.; Park, H. N.
The cardinal feature of intestinal obstruction is the intraluminal fluid accumulation within the bowel segments. The presence of air simply makes it easier to find dilated fluid-filled bowel loop on plain radiographic films. Distended fluid-filed loop, however, may be obscure on X-ray film when gas is absent, secondary to vomiting, or to cessation of air swallowing. furthermore, in closed loop obstruction, air cannot enter the involved bowel, and thereby in this situation gray scale ultrasonography may be a useful device in making a rapid diagnosis. By sonographic confirmations of intestinal obstruction, a tonic, fluid-filled bowel loops usually were revealed as multiple, circular or cylindrical cystic structures with a finely irregular wall. Valvulae connivente sexhibit a characteristic key-board appearance when they project into the fluid-filled lumen
The intestinal microenvironment in sepsis.
Fay, Katherine T; Ford, Mandy L; Coopersmith, Craig M
The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients. Published by Elsevier B.V.
Gliadin peptides induce tissue transglutaminase activation and ER-stress through Ca2+ mobilization in Caco-2 cells.
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Ivana Caputo
Full Text Available BACKGROUND: Celiac disease (CD is an intestinal inflammatory condition that develops in genetically susceptible individuals after exposure to dietary wheat gliadin. The role of post-translational modifications of gliadin catalyzed by tissue transglutaminase (tTG seems to play a crucial role in CD. However, it remains to be established how and where tTG is activated in vivo. We have investigated whether gliadin peptides modulate intracellular Ca(2+ homeostasis and tTG activity. METHODS/PRINCIPAL FINDINGS: We studied Ca(2+ homeostasis in Caco-2 cells by single cell microfluorimetry. Under our conditions, A-gliadin peptides 31-43 and 57-68 rapidly mobilized Ca(2+ from intracellular stores. Specifically, peptide 31-43 mobilized Ca(2+ from the endoplasmic reticulum (ER and mitochondria, whereas peptide 57-68 mobilized Ca(2+ only from mitochondria. We also found that gliadin peptide-induced Ca(2+ mobilization activates the enzymatic function of intracellular tTG as revealed by in situ tTG activity using the tTG substrate pentylamine-biotin. Moreover, we demonstrate that peptide 31-43, but not peptide 57-68, induces an increase of tTG expression. Finally, we monitored the expression of glucose-regulated protein-78 and of CCAAT/enhancer binding protein-homologous protein, which are two biochemical markers of ER-stress, by real-time RT-PCR and western blot. We found that chronic administration of peptide 31-43, but not of peptide 57-68, induces the expression of both genes. CONCLUSIONS: By inducing Ca(2+ mobilization from the ER, peptide 31-43 could promote an ER-stress pathway that may be relevant in CD pathogenesis. Furthermore, peptides 31-43 and 57-68, by activating intracellular tTG, could alter inflammatory key regulators, and induce deamidation of immunogenic peptides and gliadin-tTG crosslinking in enterocytes and specialized antigen-presenting cells.
Vitamin D signaling in intestinal innate immunity and homeostasis.
Dimitrov, Vassil; White, John H
The lumen of the gut hosts a plethora of microorganisms that participate in food assimilation, inactivation of harmful particles and in vitamin synthesis. On the other hand, enteric flora, a number of food antigens, and toxins are capable of triggering immune responses causing inflammation, which, when unresolved, may lead to chronic conditions such as inflammatory bowel disease (IBD). It is important, therefore, to contain the gut bacteria within the lumen, control microbial load and composition, as well as ensure adequate innate and adaptive immune responses to pathogenic threats. There is growing evidence that vitamin D signaling has impacts on all these aspects of intestinal physiology, contributing to healthy enteric homeostasis. VD was first discovered as the curative agent for nutritional rickets, and its classical actions are associated with calcium absorption and bone health. However, vitamin D exhibits a number of extra-skeletal effects, particularly in innate immunity. Notably, it stimulates production of pattern recognition receptors, anti-microbial peptides, and cytokines, which are at the forefront of innate immune responses. They play a role in sensing the microbiota, in preventing excessive bacterial overgrowth, and complement the actions of vitamin D signaling in enhancing intestinal barrier function. Vitamin D also favours tolerogenic rather than inflammogenic T cell differentiation and function. Compromised innate immune function and overactive adaptive immunity, as well as defective intestinal barrier function, have been associated with IBD. Importantly, observational and intervention studies support a beneficial role of vitamin D supplementation in patients with Crohn's disease, a form of IBD. This review summarizes the effects of vitamin D signaling on barrier integrity and innate and adaptive immunity in the gut, as well as on microbial load and composition. Collectively, studies to date reveal that vitamin D signaling has widespread effects
Colon in acute intestinal infection.
Guarino, Alfredo; Buccigrossi, Vittoria; Armellino, Carla
The colon is actively implicated in intestinal infections not only as a target of enteric pathogens and their products but also as a target organ for treatment. In the presence of diarrhea, both of osmotic and secretory nature, the colon reacts with homeostatic mechanisms to increase ion absorption. These mechanisms can be effectively exploited to decrease fluid discharge. A model of intestinal infections using rotavirus (RV) in colonic cells was set up and used to define a dual model of secretory and osmotic diarrhea in sequence. Using this model, antidiarrheal drugs were tested, namely zinc and the enkephalinase inhibitor racecadotril. Zinc was able to decrease the enterotoxic activity responsible for secretory diarrhea. It also inhibited the cytotoxic effect of RV. The mechanism of zinc was related at least in part to the activation of MAPK activity, but also a direct antiviral effect was observed. Racecadotril showed a potent and selective inhibition of active secretion, being particularly effective in the first phase of RV diarrhea. The use of drugs active at the colonic level, therefore, offers effective options to treat intestinal infections in childhood. In addition, the colon is the natural site of colonic microflora, a target of probiotic therapy, which is the first line of approach recommended by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition to treat infectious diarrhea.
Radiological manifestations of intestinal tuberculosis
International Nuclear Information System (INIS)
Im, Jae Hoon
Radiological findings of 87 cases of intestinal tuberculosis are analyzed and presented. The diagnosis was based on histopathology in 29 cases, and on clinical ground and radiological findings in 58 cases. The radio of male and female patients was 4:6, and peak incidence is between 10 and 30. Abdominal pain, diarrhea, weight loss, fever and general weakness are frequent symptoms, and tenderness of abdomen, ascites with abdominal distension, malnutrition and emaciation are frequent signs of the patients. Laboratory investigation reveal anemia, raised ESR, hypoalbuminaemia and positive occult blood reaction in the stool in most of the patients. Chest film show activity pulmonary tuberculosis in only 1/3 patients. There is no pathognomonic radiological findings in intestinal tuberculosis and their manifestations are protean, and differentiation from other inflammatory diseases and malignant tumors in gastrointestinal tract is very difficult on radiological ground alone. However, in patients with complaining vague abdominal symptoms and signs, the radiological diagnosis is most certain means in the decision of existence of organic lesion and suggestion of tuberculosis in the gastrointestinal tract and its extent as yet. Multiplicity of the lesion, involvement of adjacent organ such as peritoneum or mesenteric lymph nodes, typical nodularity or irregularity of mesenteric border and existence of active pulmonary tuberculosis are the suggestive findings of intestinal tuberculosis. In the diagnosis of inflammatory disease or malignant tumor of gastrointestinal tract, the possibility of tuberculosis should be borne in mind, and vice versa
Directory of Open Access Journals (Sweden)
Maria do Carmo Friche PASSOS
Full Text Available ABSTRACT BACKGROUND In recent years, especially after the development of sophisticated metagenomic studies, research on the intestinal microbiota has increased, radically transforming our knowledge about the microbiome and its association with health maintenance and disease development in humans. Increasing evidence has shown that a permanent alteration in microbiota composition or function (dysbiosis can alter immune responses, metabolism, intestinal permeability, and digestive motility, thereby promoting a proinflammatory state. Such alterations can mainly impair the host's immune and metabolic functions, thus favoring the onset of diseases such as diabetes, obesity, digestive, neurological, autoimmune, and neoplastic diseases. This comprehensive review is a compilation of the available literature on the formation of the complex intestinal ecosystem and its impact on the incidence of diseases such as obesity, non-alcoholic steatohepatitis, irritable bowel syndrome, inflammatory bowel disease, celiac disease, and digestive neoplasms. CONCLUSION: Alterations in the composition and function of the gastrointestinal microbiota (dysbiosis have a direct impact on human health and seem to have an important role in the pathogenesis of several gastrointestinal diseases, whether inflammatory, metabolic, or neoplastic ones.
Radiological manifestations of intestinal tuberculosis
Energy Technology Data Exchange (ETDEWEB)
Im, Jae Hoon [Seoul National University College of Medicine, Seoul (Korea, Republic of)
Radiological findings of 87 cases of intestinal tuberculosis are analyzed and presented. The diagnosis was based on histopathology in 29 cases, and on clinical ground and radiological findings in 58 cases. The radio of male and female patients was 4:6, and peak incidence is between 10 and 30. Abdominal pain, diarrhea, weight loss, fever and general weakness are frequent symptoms, and tenderness of abdomen, ascites with abdominal distension, malnutrition and emaciation are frequent signs of the patients. Laboratory investigation reveal anemia, raised ESR, hypoalbuminaemia and positive occult blood reaction in the stool in most of the patients. Chest film show activity pulmonary tuberculosis in only 1/3 patients. There is no pathognomonic radiological findings in intestinal tuberculosis and their manifestations are protean, and differentiation from other inflammatory diseases and malignant tumors in gastrointestinal tract is very difficult on radiological ground alone. However, in patients with complaining vague abdominal symptoms and signs, the radiological diagnosis is most certain means in the decision of existence of organic lesion and suggestion of tuberculosis in the gastrointestinal tract and its extent as yet. Multiplicity of the lesion, involvement of adjacent organ such as peritoneum or mesenteric lymph nodes, typical nodularity or irregularity of mesenteric border and existence of active pulmonary tuberculosis are the suggestive findings of intestinal tuberculosis. In the diagnosis of inflammatory disease or malignant tumor of gastrointestinal tract, the possibility of tuberculosis should be borne in mind, and vice versa.
[Intestinal parasitic diseases in children].
Mare, Anca; Man, A; Toma, Felicia; Székely, Edit; Lôrinczi, Lilla; Sipoş, Anca
To compare the incidence of intestinal parasitosis between children with residence in urban and rural areas: to compare the efficacy of parasitologic diagnostic methods. In our study we included two lots of children. The first lot consisted in 74 children from rural areas from which we collected 44 samples of feces and 55 samples for the "Scotch tape" test. The second lot consisted in 214 children from urban areas from which we collected 44 samples of feces. We examined each sample of feces by three different methods. The study was performed between April to June 2006. The incidence of intestinal parasitosis increases in children from urban areas towards rural areas, and in children between 5 and 10 years. Ascariasis is the most frequent disease in both urban and rural areas. By examination of each fecal sample by three different methods, the number of positive cases increased. The residence in rural areas and age between 5 to 10 years are risk factors for intestinal parasitosis. The "Scotch tape" test was more efficient in Enterobius vermicularis infection than the methods performed from feces. We recommend using at the same time three diagnostic methods for feces examination to improve the diagnostic sensibility.
Safety concerns over the use of intestinal permeation enhancers: A mini-review.
McCartney, Fiona; Gleeson, John P; Brayden, David J
Intestinal permeation enhancers (PEs) are key components in ∼12 oral peptide formulations in clinical trials for a range of molecules, primarily insulin and glucagon-like-peptide 1 (GLP-1) analogs. The main PEs comprise medium chain fatty acid-based systems (sodium caprate, sodium caprylate, and N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC)), bile salts, acyl carnitines, and EDTA. Their mechanism of action is complex with subtle differences between the different molecules. With the exception of SNAC and EDTA, most PEs fluidize the plasma membrane causing plasma membrane perturbation, as well as enzymatic and intracellular mediator changes that lead to alteration of intestinal epithelial tight junction protein expression. The question arises as to whether PEs can cause irreversible epithelial damage and tight junction openings sufficient to permit co-absorption of payloads with bystander pathogens, lipopolysaccharides and its fragment, or exo- and endotoxins that may be associated with sepsis, inflammation and autoimmune conditions. Most PEs seem to cause membrane perturbation to varying extents that is rapidly reversible, and overall evidence of pathogen co-absorption is generally lacking. It is unknown however, whether the intestinal epithelial damage-repair cycle is sustained during repeat-dosing regimens for chronic therapy.
Actinidin enhances protein digestion in the small intestine as assessed using an in vitro digestion model.
Kaur, Lovedeep; Rutherfurd, Shane M; Moughan, Paul J; Drummond, Lynley; Boland, Mike J
This paper describes an in vitro study that tests the proposition that actinidin from green kiwifruit influences the digestion of proteins in the small intestine. Different food proteins, from sources including soy, meat, milk, and cereals, were incubated in the presence or absence of green kiwifruit extract (containing actinidin) using a two-stage in vitro digestion system consisting of an incubation with pepsin at stomach pH (simulating gastric digestion) and then with added pancreatin at small intestinal pH, simulating upper tract digestion in humans. The digests from the small intestinal stage (following the gastric digestion phase) were subjected to gel electrophoresis (SDS-PAGE) to assess loss of intact protein and development of large peptides during the in vitro simulated digestion. Kiwifruit extract influenced the digestion patterns of all of the proteins to various extents. For some proteins, actinidin had little impact on digestion. However, for other proteins, the presence of kiwifruit extract resulted in a substantially greater loss of intact protein and different peptide patterns from those seen after digestion with pepsin and pancreatin alone. In particular, enhanced digestion of whey protein isolate, zein, gluten, and gliadin was observed. In addition, reverse-phase HPLC (RP-HPLC) analysis showed that a 2.5 h incubation of sodium caseinate with kiwifruit extract alone resulted in approximately 45% loss of intact protein.
Synthetic peptides for antibody production
Zegers, N.D.
Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the
Synthetic peptides for antibody production
N.D. Zegers (Netty)
textabstractSynthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps
Peptide radiopharmaceuticals in nuclear medicine
International Nuclear Information System (INIS)
Blok, D.; Vermeij, P.; Feitsma, R.I.J.; Pauwels, E.J.K.
This article reviews the labelling of peptides that are recognised to be of interest for nuclear medicine or are the subject of ongoing nuclear medicine research. Applications and approaches to the labelling of peptide radiopharmaceuticals are discussed, and drawbacks in their development considered. (orig.)
Role of luminal nutrients and endogenous GLP-2 in intestinal adaptation to mid-small bowel resection
DEFF Research Database (Denmark)
Dahly, Elizabeth M; Gillingham, Melanie B; Guo, Ziwen
To elucidate the role of luminal nutrients and glucagon-like peptide-2 (GLP-2) in intestinal adaptation, rats were subjected to 70% midjejunoileal resection or ileal transection and were maintained with total parenteral nutrition (TPN) or oral feeding. TPN rats showed small bowel mucosal hyperpla......To elucidate the role of luminal nutrients and glucagon-like peptide-2 (GLP-2) in intestinal adaptation, rats were subjected to 70% midjejunoileal resection or ileal transection and were maintained with total parenteral nutrition (TPN) or oral feeding. TPN rats showed small bowel mucosal...... rats was associated with a significant positive correlation between increases in plasma bioactive GLP-2 and proglucagon mRNA expression in the colon of TPN rats and ileum of orally fed rats. These data support a significant role for endogenous GLP-2 in the adaptive response to mid-small bowel resection...
Structure of protein emulsion in food impacts intestinal microbiota, caecal luminal content composition and distal intestine characteristics in rats.
Beaumont, Martin; Jaoui, Daphné; Douard, Véronique; Mat, Damien; Koeth, Fanny; Goustard, Bénédicte; Mayeur, Camille; Mondot, Stanislas; Hovaghimian, Anais; Le Feunteun, Steven; Chaumontet, Catherine; Davila, Anne-Marie; Tomé, Daniel; Souchon, Isabelle; Michon, Camille; Fromentin, Gilles; Blachier, François; Leclerc, Marion
Few studies have evaluated in vivo the impact of food structure on digestion, absorption of nutrients and on microbiota composition and metabolism. In this study we evaluated in rat the impact of two structures of protein emulsion in food on gut microbiota, luminal content composition, and intestinal characteristics. Rats received for 3 weeks two diets of identical composition but based on lipid-protein matrices of liquid fine (LFE) or gelled coarse (GCE) emulsion. LFE diet led to higher abundance, when compared to the GCE, of Lactobacillaceae (Lactobacillus reuteri) in the ileum, higher β-diversity of the caecum mucus-associated bacteria. In contrast, the LFE diet led to a decrease in Akkermansia municiphila in the caecum. This coincided with heavier caecum content and higher amount of isovalerate in the LFE group. LFE diet induced an increased expression of (i) amino acid transporters in the ileum (ii) glucagon in the caecum, together with an elevated level of GLP-1 in portal plasma. However, these intestinal effects were not associated with modification of food intake or body weight gain. Overall, the structure of protein emulsion in food affects the expression of amino acid transporters and gut peptides concomitantly with modification of the gut microbiota composition and activity. Our data suggest that these effects of the emulsion structure are the result of a modification of protein digestion properties. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
DEFF Research Database (Denmark)
Bundgaard, Louise; Jacobsen, Stine; Sørensen, Mette Aamand
Progress in MS-based methods for veterinary research and diagnostics is lagging behind compared to the human research, and proteome data of domestic animals is still not well represented in open source data repositories. This is particularly true for the equine species. Here we present a first...... Equine PeptideAtlas encompassing high-resolution tandem MS analyses of 51 samples representing a selection of equine tissues and body fluids from healthy and diseased animals. The raw data were processed through the Trans-Proteomic Pipeline to yield high quality identification of proteins and peptides....... The current release comprises 24 131 distinct peptides representing 2636 canonical proteins observed at false discovery rates of 0.2% at the peptide level and 1.4% at the protein level. Data from the Equine PeptideAtlas are available for experimental planning, validation of new datasets, and as a proteomic...
Vascular targeting with peptide libraries
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Pasqualini, R. [La Jolla Cancer Research Center The Burnham Inst., La Jolla CA (United States)
The authors have developed an 'in vivo' selection system in which phage capable of selective homing to different tissues are recovered from a phage display peptide library following intravenous administration. Using this strategy, they have isolate several organ and tumor-homing peptides. They have shown that each of those peptides binds of different receptors that are selectively expressed on the vasculature of the target tissue. The tumor-homing peptides bind to receptors that are up regulated in tumor angiogenic vasculature. Targeted delivery of doxorubicin to angiogenic vasculature using these peptides in animals models decrease toxicity and increased the therapeutic efficacy of the drug. Vascular targeting may facilitate the development of other treatment strategies that rely on inhibition of angio genesis and lead to advances to extend the potential for targeting of drugs, genes and radionuclides in the context of many diseases.
Natriuretic peptides and cerebral hemodynamics
DEFF Research Database (Denmark)
Guo, Song; Barringer, Filippa; Zois, Nora Elisabeth
Natriuretic peptides have emerged as important diagnostic and prognostic tools for cardiovascular disease. Plasma measurement of the bioactive peptides as well as precursor-derived fragments is a sensitive tool in assessing heart failure. In heart failure, the peptides are used as treatment...... in decompensated disease. In contrast, their biological effects on the cerebral hemodynamics are poorly understood. In this mini-review, we summarize the hemodynamic effects of the natriuretic peptides with a focus on the cerebral hemodynamics. In addition, we will discuss its potential implications in diseases...... where alteration of the cerebral hemodynamics plays a role such as migraine and acute brain injury including stroke. We conclude that a possible role of the peptides is feasible as evaluated from animal and in vitro studies, but more research is needed in humans to determine the precise response...
Maize Bioactive Peptides against Cancer
Díaz-Gómez, Jorge L.; Castorena-Torres, Fabiola; Preciado-Ortiz, Ricardo E.; García-Lara, Silverio
Cancer is one of the main chronic degenerative diseases worldwide. In recent years, consumption of whole-grain cereals and their derived food products has been associated with reduction risks of various types of cancer. Cereals main biomolecules includes proteins, peptides, and amino acids present in different quantities within the grain. The nutraceutical properties associated with peptides exerts biological functions that promote health and prevent this disease. In this review, we report the current status and advances on maize peptides regarding bioactive properties that have been reported such as antioxidant, antihypertensive, hepatoprotective, and anti-tumour activities. We also highlighted its biological potential through which maize bioactive peptides exert anti-cancer activity. Finally, we analyse and emphasize the possible areas of application for maize peptides.
Role of intestinal brush border peptidases in the simulated digestion of milk proteins.
Picariello, Gianluca; Miralles, Beatriz; Mamone, Gianfranco; Sánchez-Rivera, Laura; Recio, Isidra; Addeo, Francesco; Ferranti, Pasquale
This study aimed to assess the impact of the "often neglected" intestinal brush border membranes (BBMs) hydrolases on dietary peptides, exploring the possibility that the disintegration of proteins progressed in the small intestine up to a "core" of intrinsically stable oligopeptides, persisting independently on the up-stream breakdown. Samples of sodium caseinate, skim milk powder, and whey protein isolate were submitted to in vitro simulated gastropancreatic digestion using two different procedures: (i) a simplified model involving the main compartmental specific proteases; (ii) a static digestion method based on a frameset of parameters inferred from in vivo. The gastroduodenal digesta were further hydrolyzed with peptidases from porcine jejunal BBM. The peptidomes arising from the two digestion models, characterized by combined HPLC and MS techniques, differed to some extent. However, only specific protein domains survived digestion, among which are potential bioactive or immunogenic (food allergy) peptides. The degree of hydrolysis (DH) after BBM digestion (70-77%) practically did not differ between the digestion models and significantly increased the DH after duodenal steps. Any in vitro digestion model should be supplemented with a jejunal phase to realistically determine the bioaccessibility and bioavailability of dietary peptides. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Immunogold staining procedure for the localisation of regulatory peptides.
Varndell, I M; Tapia, F J; Probert, L; Buchan, A M; Gu, J; De Mey, J; Bloom, S R; Polak, J M
The use of protein A- and IgG-conjugated colloidal gold staining methods for the immuno-localisation of peptide hormones and neurotransmitters at light- and electron microscope level are described and discussed. Bright-field and dark-ground illumination modes have been used to visualise the gold-labelled antigenic sites at the light microscope level. Immunogold staining procedures at the ultrastructural level using region-specific antisera have been adopted to localise specific molecular forms of peptides including gastrin (G17 and G34), glucagon and pro-glucagon, insulin and pro-insulin, in normal tissue and in tumours of the gastroenteropancreatic system. Similar methods have been used to demonstrate the heterogeneity of p-type nerves in the enteric nervous system. Vasoactive intestinal polypeptide (VIP) has been localised to granular sites (mean +/- S.D. granule diameter = 98 +/- 19 nm) in nerve terminals of the enteric plexuses and in tumour cells of diarrhoeogenic VIP-producing neoplasias (mean +/- S.D. granule diameter = 126 +/- 37 nm) using immunogold procedures applied to ultraviolet-cured ultrathin sections. Co-localisation of amines and peptides in carotid body type I cells and in chromaffin cells of normal adrenal medulla and phaeochromocytomas has also been demonstrated. Advantages of the immunogold procedures over alternative immunocytochemical techniques are discussed.
Metabolism of aspartame by human and pig intestinal microvillar peptidases.
Hooper, N M; Hesp, R J; Tieku, S
The artificial sweetener aspartame (N-L-alpha-aspartyl-L-phenyl-alanine-1-methyl ester; Nutrasweet), its decomposition product alpha Asp-Phe and the related peptide alpha Asp-PheNH2 were rapidly hydrolysed by microvillar membranes prepared from human duodenum, jejunum and ileum, and from pig duodenum and kidney. The metabolism of aspartame by the human and pig intestinal microvillar membrane preparations was inhibited significantly (> 78%) by amastatin or 1,10-phenanthroline, and partially (> 38%) by actinonin or bestatin, and was activated 2.9-4.5-fold by CaCl2. The inhibition by amastatin and 1,10-phenanthroline, and the activation by CaCl2 are characteristic of the cell-surface ectoenzyme aminopeptidase A (EC 22.214.171.124) and a purified preparation of this enzyme hydrolysed aspartame with a Km of 0.25 mM and a Vmax of 126 mumol/min per mg. A purified preparation of aminopeptidase W (EC 126.96.36.199) also hydrolysed aspartame but with a Km of 4.96 mM and a Vmax of 110 mumol/min per mg. However, rentiapril, an inhibitor of aminopeptidase W, caused only slight inhibition (maximally 19%) of the hydrolysis of aspartame by the microvillar membrane preparations. Similar patterns of inhibition and kinetic parameters were observed for alpha Asp-Phe and alpha Asp-PheNH2. Two other decomposition products of aspartame, beta Asp-PheMe and cyclo-Asp-Phe, were essentially resistant to hydrolysis by both the human and pig intestinal microvillar membrane preparations and the purified preparations of aminopeptidases A and W. Although the relatively selective inhibitor of aminopeptidase N (EC 126.96.36.199), actinonin, partially inhibited the metabolism of aspartame, alpha Asp-Phe and alpha Asp-PheNH2 by the human and pig intestinal microvillar membrane preparations, these peptides were not hydrolysed by a purified preparation of aminopeptidase N. Membrane dipeptidase (EC 220.127.116.11) only hydrolysed the unblocked dipeptide, alpha Asp-Phe, but the selective inhibitor of this enzyme, cilastatin
An intestinal Trojan horse for gene delivery.
Peng, Haisheng; Wang, Chao; Xu, Xiaoyang; Yu, Chenxu; Wang, Qun
The intestinal epithelium forms an essential element of the mucosal barrier and plays a critical role in the pathophysiological response to different enteric disorders and diseases. As a major enteric dysfunction of the intestinal tract, inflammatory bowel disease is a genetic disease which results from the inappropriate and exaggerated mucosal immune response to the normal constituents in the mucosal microbiota environment. An intestine targeted drug delivery system has unique advantages in the treatment of inflammatory bowel disease. As a new concept in drug delivery, the Trojan horse system with the synergy of nanotechnology and host cells can achieve better therapeutic efficacy in specific diseases. Here, we demonstrated the feasibility of encapsulating DNA-functionalized gold nanoparticles into primary isolated intestinal stem cells to form an intestinal Trojan horse for gene regulation therapy of inflammatory bowel disease. This proof-of-concept intestinal Trojan horse will have a wide variety of applications in the diagnosis and therapy of enteric disorders and diseases.
Intestinal epithelium in inflammatory bowel disease
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Mehmet eCoskun
Full Text Available The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs that are crucial in maintaining intestinal homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of inflammatory bowel disease (IBD. Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets.
Oral delivery of peptides and proteins using lipid-based drug delivery systems.
Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette
In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism by which intestinal absorption of peptides and proteins is promoted. The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two most important barriers (extensive enzymatic degradation and poor transmucosal permeability). This paper also gives a clear-cut idea about advantages and drawbacks of using different lipidic colloidal carriers ((micro)emulsions, solid lipid core particles and liposomes) for oral delivery of peptides and proteins. Lipid-based DDS are safe and suitable for oral delivery of peptides and proteins. Significant progress has been made in this area with several technologies on clinical trials. However, a better understanding of the mechanism of action in vivo is needed in order to improve the design and development of lipid-based DDS with the desired bioavailability and therapeutic profile.
Disturbed release of gastrointestinal peptides in anorexia nervosa and in obesity.
Baranowska, B; Radzikowska, M; Wasilewska-Dziubinska, E; Roguski, K; Borowiec, M
It is commonly accepted that some neuropeptides play an important role in the control of appetite and hormonal secretion. Several gastrointestinal peptides may affect on central control of appetite via vagal and spinal nerves. The aim of this study was to evaluate the release of gastrointestinal peptides in anorexia nervosa and in obesity, because in these diseases the disturbances in the control of appetite and hormonal secretion were found. Material consisted of 30 women with anorexia nervosa aged 16-29 years (mean 22 years) and 23 women with obesity aged 19-33 years (mean 29 years) and 25 lean women of control group. In women with anorexia nervosa as compared with control group we observed a significant increase of plasma vasoactive intestinal peptide (VIP) levels (p anorexia nervosa. These findings suggests that dysfunction of brain-gut axis may be also an important factor in the abnormal control of appetite axcept of hypothalamic dysfunction.
Purification and use of E. coli peptide deformylase for peptide deprotection in chemoenzymatic peptide synthesis
Di Toma, Claudia; Sonke, Theo; Quaedflieg, Peter J.; Janssen, Dick B.
Peptide deformylases (PDFs) catalyze the removal of the formyl group from the N-terminal methionine residue in nascent polypeptide chains in prokaryotes. Its deformylation activity makes PDF an attractive candidate for the biocatalytic deprotection of formylated peptides that are used in
Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation
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Acar, Handan [Institute; Department; Samaeekia, Ravand [Institute; Department; Schnorenberg, Mathew R. [Institute; Department; Medical; Sasmal, Dibyendu K. [Institute; Huang, Jun [Institute; Tirrell, Matthew V. [Institute; Institute; LaBelle, James L. [Department
Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation, and PA monomers are internalized via endocytosis. However, endocytotic sequestration and steric hindrance from the lipid tail are two major mechanisms that limit PA efficacy to target intracellular PPIs. To address these problems, we have constructed a PA platform consisting of cathepsin-B cleavable PAs in which a selective p53-based inhibitory peptide is cleaved from its lipid tail within endosomes, allowing for intracellular peptide accumulation and extracellular recycling of the lipid moiety. We monitor for cleavage and follow individual PA components in real time using a resonance energy transfer (FRET)-based tracking system. Using this platform, components in real time using a Forster we provide a better understanding and quantification of cellular internalization, trafficking, and endosomal cleavage of PAs and of the ultimate fates of each component.
Milk bioactive peptides and beta-casomorphins induce mucus release in rat jejunum.
Trompette, Aurélien; Claustre, Jean; Caillon, Fabienne; Jourdan, Gérard; Chayvialle, Jean Alain; Plaisancié, Pascale
Intestinal mucus is critically involved in the protection of the mucosa. An enzymatic casein hydrolysate and beta-casomorphin-7, a mu-opioid peptide generated in the intestine during bovine casein digestion, markedly induce mucus discharge. Because shorter mu-opioid peptides have been described, the effects of the opioid peptides in casein, beta-casomorphin-7, -6, -4, -4NH2 and -3, and of opioid neuropeptides met-enkephalin, dynorphin A and (D-Ala2,N-Me-Phe4,glycinol5)enkephalin (DAMGO) on intestinal mucus secretion were investigated. The experiments were conducted with isolated perfused rat jejunum. Mucus secretion under the influence of beta-casomorphins and opioid neuropeptides administered intraluminally or intra-arterially was evaluated using an ELISA for rat intestinal mucus. Luminal administration of beta-casomorphin-7 (1.2 x 10(-4) mol/L) provoked a mucus discharge (500% of controls) that was inhibited by naloxone, a specific opiate receptor antagonist. Luminal beta-casomorphin-6, -4 and -4NH2 did not modify basal mucus secretion, whereas intra-arterial administration of beta-casomorphin-4 (1.2 x 10(-6) mol/L) induced a mucus discharge. In contrast, intra-arterial administration of the nonopioid peptide beta-casomorphin-3 did not release mucus. Among the opioid neuropeptides, intra-arterial infusion of Met-enkephalin or dynorphin-A did not provoke mucus secretion. In contrast, beta-endorphin (1.2 x 10(-8) to 1.2 x 10(-6) mol/L) induced a dose-dependent release of mucus (maximal response at 500% of controls). DAMGO (1.2 x 10(-6) mol/L), a mu-receptor agonist, also evoked a potent mucus discharge. Our findings suggest that mu-opioid neuropeptides, as well as beta-casomorphins after absorption, modulate intestinal mucus discharge. Milk opioid-derived peptides may thus be involved in defense against noxious agents and could have dietary and health applications.
Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse
Arrieta, M C; Madsen, K; Doyle, J; Meddings, J
Background: Defects in the small intestinal epithelial barrier have been associated with inflammatory bowel disease but their role in the causation of disease is still a matter of debate. In some models of disease increased permeability appears to be a very early event. The interleukin 10 (IL10) gene-deficient mouse spontaneously develops colitis after 12 weeks of age. These mice have been shown to have increased small intestinal permeability that appears early in life. Furthermore, the development of colitis is dependent upon luminal agents, as animals do not develop disease if raised under germ-free conditions. Aims: To determine if the elevated small bowel permeability can be prevented, and if by doing so colonic disease is prevented or attenuated. Methods: IL10 gene-deficient (IL10−/−) mice) were treated with AT-1001 (a zonulin peptide inhibitor), a small peptide previously demonstrated to reduce small intestinal permeability. Small intestinal permeability was measured, in vivo, weekly from 4 to 17 weeks of age. Colonic disease was assessed at 8 weeks in Ussing chambers, and at 17 weeks of age inflammatory cytokines and myeloperoxidase were measured in the colon. Colonic permeability and histology were also endpoints. Results: Treated animals showed a marked reduction in small intestinal permeability. Average area under the lactulose/mannitol time curve: 5.36 (SE 0.08) in controls vs 3.97 (SE 0.07) in the high-dose AT-1001 group, p<0.05. At 8 weeks of age there was a significant reduction of colonic mucosal permeability and increased electrical resistance. By 17 weeks of age, secretion of tumour necrosis factor α (TNFα) from a colonic explant was significantly lower in the treated group (25.33 (SE 4.30) pg/mg vs 106.93 (SE 17.51) pg/ml in controls, p<0.01). All other markers also demonstrated a clear reduction of colitis in the treated animals. Additional experiments were performed which demonstrated that AT-1001 was functionally active only in the small
Update on small intestinal stem cells.
Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio
Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to identify the integrating signals from the surrounding niche, supporting a model whereby distinct cell populations facilitate homeostatic vs injury-induced regeneration.
Impaired neutrophil function in intestinal lymphangiectasia.
Bolton, R P; Cotter, K L; Losowsky, M S
Impaired neutrophil chemotaxis and phagocytosis were shown in three patients with intestinal lymphangiectasia. Abnormalities in cell associated and serum derived activity occurred, and possible mechanisms are suggested.
Lymphangiectasia of small intestine presenting as intussusception
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Katoch Pervez
Full Text Available Intussusception is defined as telescoping of a segment of gastrointestinal tract into an adjacent one. In small children, it is the commonest cause of intestinal obstruction. More than 90% of childhood intussusceptions are idiopathic. We report a rare case of localized small intestinal lymphangiectasia, presenting as intussusception in a 6-month-old male child. The child presented with features of acute intestinal obstruction for which he was later operated. The gross examination of excised ileocecal mass revealed intussusception. Histopathologic examination revealed lymphangiectasia of small intestine, which acted as a lead point for ileocecal intussusception. Postoperative period was uneventful.
Lymphangiectasia of small intestine presenting as intussusception.
Katoch, Pervez; Bhardwaj, Subhash
Intussusception is defined as telescoping of a segment of gastrointestinal tract into an adjacent one. In small children, it is the commonest cause of intestinal obstruction. More than 90% of childhood intussusceptions are idiopathic. We report a rare case of localized small intestinal lymphangiectasia, presenting as intussusception in a 6-month-old male child. The child presented with features of acute intestinal obstruction for which he was later operated. The gross examination of excised ileocecal mass revealed intussusception. Histopathologic examination revealed lymphangiectasia of small intestine, which acted as a lead point for ileocecal intussusception. Postoperative period was uneventful.
Bile acids in regulation of intestinal physiology.
LENUS (Irish Health Repository)
Keating, Niamh
In addition to their roles in facilitating lipid digestion and absorption, bile acids are recognized as important regulators of intestinal function. Exposure to bile acids can dramatically influence intestinal transport and barrier properties; in recent years, they have also become appreciated as important factors in regulating cell growth and survival. Indeed, few cells reside within the intestinal mucosa that are not altered to some degree by exposure to bile acids. The past decade saw great advances in the knowledge of how bile acids exert their actions at the cellular and molecular levels. In this review, we summarize the current understanding of the role of bile acids in regulation of intestinal physiology.
Candida utilis and Chlorella vulgaris counteract intestinal inflammation in Atlantic salmon (Salmo salar L..
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Fabian Grammes
Full Text Available Intestinal inflammation, caused by impaired intestinal homeostasis, is a serious condition in both animals and humans. The use of conventional extracted soybean meal (SBM in diets for Atlantic salmon and several other fish species is known to induce enteropathy in the distal intestine, a condition often referred to as SBM induced enteropathy (SBMIE. In the present study, we investigated the potential of different microbial ingredients to alleviate SBMIE in Atlantic salmon, as a model of feed-induced inflammation. The dietary treatments consisted of a negative control based on fish meal (FM, a positive control based on 20% SBM, and four experimental diets combining 20% SBM with either one of the three yeasts Candida utilis (CU, Kluyveromyces marxianus (KM, Saccharomyces cerevisiae (SC or the microalgae Chlorella vulgaris (CV. Histopathological examination of the distal intestine showed that all fish fed the SC or SBM diets developed characteristic signs of SBMIE, while those fed the FM, CV or CU diets showed a healthy intestine. Fish fed the KM diet showed intermediate signs of SBMIE. Corroborating results were obtained when measuring the relative length of PCNA positive cells in the crypts of the distal intestine. Gene set enrichment analysis revealed decreased expression of amino acid, fat and drug metabolism pathways as well as increased expression of the pathways for NOD-like receptor signalling and chemokine signalling in both the SC and SBM groups while CV and CU were similar to FM and KM was intermediate. Gene expression of antimicrobial peptides was reduced in the groups showing SBMIE. The characterisation of microbial communities using PCR-DGGE showed a relative increased abundance of Firmicutes bacteria in fish fed the SC or SBM diets. Overall, our results show that both CU and CV were highly effective to counteract SBMIE, while KM had less effect and SC had no functional effects.
SPAK Dependent Regulation of Peptide Transporters PEPT1 and PEPT2
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Jamshed Warsi
Full Text Available Background/Aims: SPAK (STE20-related proline/alanine-rich kinase is a powerful regulator of renal tubular ion transport and blood pressure. Moreover, SPAK contributes to the regulation of cell volume. Little is known, however, about a role of SPAK in the regulation or organic solutes. The present study thus addressed the influence of SPAK on the peptide transporters PEPT1 and PEPT2. Methods: To this end, cRNA encoding PEPT1 or PEPT2 were injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type, SPAK, WNK1 insensitive inactive T233ASPAK, constitutively active T233ESPAK, and catalytically inactive D212ASPAK. Electrogenic peptide (glycine-glycine transport was determined by dual electrode voltage clamp and PEPT2 protein abundance in the cell membrane by chemiluminescence. Intestinal electrogenic peptide transport was estimated from peptide induced current in Ussing chamber experiments of jejunal segments isolated from gene targeted mice expressing SPAK resistant to WNK-dependent activation (spaktg/tg and respective wild-type mice (spak+/+. Results: In PEPT1 and in PEPT2 expressing oocytes, but not in oocytes injected with water, the dipeptide gly-gly (2 mM generated an inward current, which was significantly decreased following coexpression of SPAK. The effect of SPAK on PEPT1 was mimicked by T233ESPAK, but not by D212ASPAK or T233ASPAK. SPAK decreased maximal peptide induced current of PEPT1. Moreover, SPAK decreased carrier protein abundance in the cell membrane of PEPT2 expressing oocytes. In intestinal segments gly-gly generated a current, which was significantly higher in spaktg/tg than in spak+/+ mice. Conclusion: SPAK is a powerful regulator of peptide transporters PEPT1 and PEPT2.
Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure
Korpela, K.; Mutanen, A.; Salonen, A.; Savilahti, E.; Vos, de W.M.; Pakarinen, M.P.
BACKGROUND: Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. METHODS: We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent
Gluten-degrading bacteria are present in the human small intestine of healthy volunteers and celiac patients.
Herrán, Alexandra R; Pérez-Andrés, Jénifer; Caminero, Alberto; Nistal, Esther; Vivas, Santiago; Ruiz de Morales, José María; Casqueiro, Javier
Gluten is the only known environmental factor that triggers celiac disease. Several studies have described an imbalance between the intestinal microbiota of different individuals based on diagnoses. Moreover, recent studies have suggested that human bacteria may play an important role in gluten hydrolysis. However, there has been no research focusing on the small intestine. This study aimed to characterize the adult small intestine microbiota possibly implicated in gluten hydrolysis. Duodenal biopsies from different diagnosed individuals were cultured in a gluten-containing medium, and the grown microbiota was analyzed by culture dependent/independent methods. Results showed that gluten-degrading bacteria can be found in the human small intestine. Indeed, 114 bacterial strains belonging to 32 species were isolated; 85 strains were able to grow in a medium containing gluten as the sole nitrogen source, 31 strains showed extracellular proteolytic activity against gluten protein and 27 strains showed peptidolytic activity towards the 33 mer peptide, an immunogenic peptide for celiac disease patients. We found that there are no differences based on the diagnosis, but each individual has its own population of gluten-hydrolyzing bacteria. These bacteria or their gluten-degrading enzymes could help to improve the quality of life of celiac disease patients'. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
Radiopharmaceutical development of radiolabelled peptides
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Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)
Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin
Intestinal Lymphangiectasia Secondary to Neuroblastoma
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RM Reifen
Full Text Available An eight month-old infant presented with a 10-day history of vomiting and diarrhea, and a one-week history of swelling of the lower extremities. Laboratory evaluations revealed hypoproteinemia and lymphocytopenia due to protein-losing enteropathy. Peroral small bowel biopsy showed intestinal lymphangiectasia. Subsequent onset of unexplained ecchymosis and obstructive jaundice resulted in additional studies which revealed an omental neuroblastoma as the underlying etiology of the infant's symptoms. This report emphasizes the importance of considering secondary, obstructive causes for lymphangiectasia and protein-losing enteropathy.
The DNA Sensor AIM2 Maintains Intestinal Homeostasis via Regulation of Epithelial Antimicrobial Host Defense
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Shuiqing Hu
Full Text Available Microbial pattern molecules in the intestine play immunoregulatory roles via diverse pattern recognition receptors. However, the role of the cytosolic DNA sensor AIM2 in the maintenance of intestinal homeostasis is unknown. Here, we show that Aim2−/− mice are highly susceptible to dextran sodium sulfate-induced colitis that is associated with microbial dysbiosis as represented by higher colonic burden of commensal Escherichia coli. Colonization of germ-free mice with Aim2−/− mouse microbiota leads to higher colitis susceptibility. In-depth investigation of AIM2-mediated host defense responses reveals that caspase-1 activation and IL-1β and IL-18 production are compromised in Aim2−/− mouse colons, consistent with defective inflammasome function. Moreover, IL-18 infusion reduces E. coli burden as well as colitis susceptibility in Aim2−/− mice. Altered microbiota in inflammasome-defective mice correlate with reduced expression of several antimicrobial peptides in intestinal epithelial cells. Together, these findings implicate DNA sensing by AIM2 as a regulatory mechanism for maintaining intestinal homeostasis.
Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers.
Shrestha, Neha; Shahbazi, Mohammad-Ali; Araújo, Francisca; Zhang, Hongbo; Mäkilä, Ermei M; Kauppila, Jussi; Sarmento, Bruno; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A
Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (P(app)) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane. Copyright © 2014 Elsevier Ltd. All rights reserved.
Loss of Sonic hedgehog leads to alterations in intestinal secretory cell maturation and autophagy.
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Jessica Gagné-Sansfaçon
Full Text Available BACKGROUND: Intestinal epithelial cells express the Sonic and Indian hedgehog ligands. Despite the strong interest in gut hedgehog signaling in GI diseases, no studies have specifically addressed the singular role of intestinal epithelial cell Sonic hedgehog signaling. The aim of this study was to investigate the specific role of Sonic hedgehog in adult ileal epithelial homeostasis. METHODOLOGY/PRINCIPAL FINDINGS: A Sonic hedgehog intestinal epithelial conditional knockout mouse model was generated. Assessment of ileal histological abnormalities, crypt epithelial cell proliferation, epithelial cell fate, junctional proteins, signaling pathways, as well as ultrastructural analysis of intracellular organelles were performed in control and mutant mice. Mice lacking intestinal epithelial Sonic Hedgehog displayed decreased ileal crypt/villus length, decreased crypt proliferation as well as a decrease in the number of ileal mucin-secreting goblet cells and antimicrobial peptide-secreting Paneth cells during adult life. These secretory cells also exhibited disruption of their secretory products in mutant mice. Ultrastructural microscopy analysis revealed a dilated ER lumen in secretory cells. This phenotype was also associated with a decrease in autophagy. CONCLUSIONS/SIGNIFICANCE: Altogether, these findings indicate that the loss of Sonic hedgehog can lead to ileal secretory cell modifications indicative of endoplasmic reticulum stress, accompanied by a significant reduction in autophagy.
Chitosan-based scaffolds for the support of smooth muscle constructs in intestinal tissue engineering
Zakhem, Elie; Raghavan, Shreya; Gilmont, Robert R; Bitar, Khalil N
Intestinal tissue engineering is an emerging field due to a growing demand for intestinal lengthening and replacement procedures secondary to massive resections of the bowel. Here, we demonstrate the potential use of a chitosan/collagen scaffold as a 3D matrix to support the bioengineered circular muscle constructs maintain their physiological functionality. We investigated the biocompatibility of chitosan by growing rabbit colonic circular smooth muscle cells (RCSMCs) on chitosan-coated plates. The cells maintained their spindle-like morphology and preserved their smooth muscle phenotypic markers. We manufactured tubular scaffolds with central openings composed of chitosan and collagen in a 1:1 ratio. Concentrically-aligned 3D circular muscle constructs were bioengineered using fibrin-based hydrogel seeded with RCSMCs. The constructs were placed around the scaffold for 2 weeks, after which they were taken off and tested for their physiological functionality. The muscle constructs contracted in response to Acetylcholine (Ach) and potassium chloride (KCl) and they relaxed in response to vasoactive intestinal peptide (VIP). These results demonstrate that chitosan is a biomaterial possibly suitable for intestinal tissue engineering applications. PMID:22483012
[Nutrient sensing by the gastro-intestinal nervous system and control of energy homeostasis].
Gilles, Mithieux
The gastrointestinal nerves are crucial in the sensing of nutrients and hormones and its translation in terms of control of food intake. Major macronutrients like glucose and proteins are sensed by the extrinsic nerves located around the portal vein walls, which signal to the brain and account for the satiety phenomenon they promote. Glucose is sensed in the portal vein by neurons expressing the glucose receptor SGLT3, which activates the main regions of the brain involved in the control of food intake. Proteins indirectly act on food intake by inducing intestinal gluconeogenesis and its sensing by the portal glucose sensor. The mechanism involves a prior antagonism by peptides of the μ-opioid receptors present in the portal vein nervous system and a reflex arc with the brain inducing intestinal gluconeogenesis. In a comparable manner, short chain fatty acids produced from soluble fibers act via intestinal gluconeogenesis to exert anti-obesity and anti-diabetic effects. In the case of propionate, the mechanism involves a prior activation of the free fatty acid receptor FFAR3 present in the portal nerves and a reflex arc initiating intestinal gluconeogenesis. © Société de Biologie, 2016.
Short-term administration of glucagon-like peptide-2. Effects on bone mineral density and markers of bone turnover in short-bowel patients with no colon
DEFF Research Database (Denmark)
Haderslev, K V; Jeppesen, P B; Hartmann, B
Glucagon-like peptide 2 (GLP-2) is a newly discovered intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment improved the intestinal absorptive capacity of short-bowel patients with no colon. Additionally, GLP-2 treatment was associated with changes in body composition ...
GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans
DEFF Research Database (Denmark)
Schjoldager, B T; Mortensen, P E; Christiansen, J
Glucagon-like peptide 1 amide (GLP-1 amide), a predicted product of the glucagon gene (proglucagon 72-107-amide), and truncated GLP-1 (proglucagon 78-107-amide), recently isolated from porcine small intestine, were infused in doses of 100 and 400 ng/kg/hr and 12.5 and 50 ng/kg/hr, respectively...
Glucagon-like peptide-2 (GLP-2) increases net amino acid utilization by the portal-drained viscera of ruminating calves
DEFF Research Database (Denmark)
Taylor-Edwards, C C; Burrin, D G; Kristensen, Niels Bastian
Glucagon-like peptide-2 (GLP-2) increases small intestinal mass and blood flow in ruminant calves, but its impact on nutrient metabolism across the portal-drained viscera (PDV) and liver is unknown. Eight Holstein calves with catheters in the carotid artery, mesenteric vein, portal vein and hepat...
Peptide-LNA oligonucleotide conjugates
DEFF Research Database (Denmark)
Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte
properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...
New vasoactive peptides in cirrhosis
DEFF Research Database (Denmark)
Kimer, Nina; Goetze, Jens Peter; Bendtsen, Flemming
BACKGROUND: Patients with cirrhosis have substantial circulatory imbalance between vasoconstrictive and vasodilating forces. The study of circulatory vasoactive peptides may provide important pathophysiological information. This study aimed to assess concentrations, organ extraction and relations...... to haemodynamic changes in the pro-peptides copeptin, proadrenomedullin and pro-atrial natriuretic peptide (proANP) in patients with cirrhosis. MATERIALS AND METHODS: Fifty-four cirrhotic patients and 15 controls were characterized haemodynamically during a liver vein catheterization. Copeptin, proadrenomedullin...... pressure (R=0·32, P0·31, Ppeptide is elevated in cirrhosis. Copeptin, proadrenomedullin and proANP are related to portal pressure and seem associated with systemic haemodynamics. These propeptides may...
The Role of Sphingolipids on Innate Immunity to Intestinal Salmonella Infection.
Huang, Fu-Chen
Salmonella spp. remains a major public health problem for the whole world. To reduce the use of antimicrobial agents and drug-resistant Salmonella , a better strategy is to explore alternative therapy rather than to discover another antibiotic. Sphingolipid- and cholesterol-enriched lipid microdomains attract signaling proteins and orchestrate them toward cell signaling and membrane trafficking pathways. Recent studies have highlighted the crucial role of sphingolipids in the innate immunity against infecting pathogens. It is therefore mandatory to exploit the role of the membrane sphingolipids in the innate immunity of intestinal epithelia infected by this pathogen. In the present review, we focus on the role of sphingolipids in the innate immunity of intestinal epithelia against Salmonella infection, including adhesion, autophagy, bactericidal effect, barrier function, membrane trafficking, cytokine and antimicrobial peptide expression. The intervention of sphingolipid-enhanced foods to make our life healthy or pharmacological agents regulating sphingolipids is provided at the end.
Intestinal subepithelial myofibroblasts support in vitro and in vivo growth of human small intestinal epithelium.
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Nicholas Lahar
Full Text Available The intestinal crypt-niche interaction is thought to be essential to the function, maintenance, and proliferation of progenitor stem cells found at the bases of intestinal crypts. These stem cells are constantly renewing the intestinal epithelium by sending differentiated cells from the base of the crypts of Lieberkühn to the villus tips where they slough off into the intestinal lumen. The intestinal niche consists of various cell types, extracellular matrix, and growth factors and surrounds the intestinal progenitor cells. There have recently been advances in the understanding of the interactions that regulate the behavior of the intestinal epithelium and there is great interest in methods for isolating and expanding viable intestinal epithelium. However, there is no method to maintain primary human small intestinal epithelium in culture over a prolonged period of time. Similarly no method has been published that describes isolation and support of human intestinal epithelium in an in vivo model. We describe a technique to isolate and maintain human small intestinal epithelium in vitro from surgical specimens. We also describe a novel method to maintain human intestinal epithelium subcutaneously in a mouse model for a prolonged period of time. Our methods require various growth factors and the intimate interaction between intestinal sub-epithelial myofibroblasts (ISEMFs and the intestinal epithelial cells to support the epithelial in vitro and in vivo growth. Absence of these myofibroblasts precluded successful maintenance of epithelial cell formation and proliferation beyond just a few days, even in the presence of supportive growth factors. We believe that the methods described here can be used to explore the molecular basis of human intestinal stem cell support, maintenance, and growth.
Prematurity reduces functional adaptation to intestinal resection in piglets
DEFF Research Database (Denmark)
Aunsholt, Lise; Thymann, Thomas; Qvist, Niels
Background: Necrotizing enterocolitis and congenital gastrointestinal malformations in infants often require intestinal resection, with a subsequent risk of short bowel syndrome (SBS). We hypothesized that immediate intestinal adaptation following resection of the distal intestine with placement ...
Bioactive Milk for Intestinal Maturation in Preterm Neonates
DEFF Research Database (Denmark)
Li, Yanqi
The fetal small intestine grows dramatically fast during the second and third trimester of human pregnancy. Many intestinal functions are therefore affected by preterm birth, including gastrointestinal motility, digestive and absorptive function, mucosal barrier function, and the intestinal...
Redistribution of intestinal microcirculatory oxygenation during acute hemodilution in pigs
Schwarte, Lothar A.; Fournell, Artur; van Bommel, Jasper; Ince, Can
Acute normovolemic hemodilution (ANH) compromizes intestinal microcirculatory oxygenation; however, the underlying mechanisms are incompletely understood. We hypothesized that contributors herein include redistribution of oxygen away from the intestines and shunting of oxygen within the intestines.
International Nuclear Information System (INIS)
Cardenas, Rene; Haro, Elfa
The paper present the diagnosic sensitivit of gastro esophagic scintigraphy (GCE) in children with suspiction of gastro esophagic reflux (RGE), as well as to evidence bronchial aspiratin in cases with suspected RGE. There was studied two groups of children: group A: Include 73 childs with documented diagnosis of RGE, by meas of cine esophagography. Group B: Include 22 children with symptoms of suspiction of. (The author)
Characterization of synthetic peptides by mass spectrometry
DEFF Research Database (Denmark)
Prabhala, Bala Krishna; Mirza, Osman Asghar; Højrup, Peter
Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI......-TOF-MS and LC-MS of synthetic peptides....
Lymphoma Caused by Intestinal Microbiota
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Mitsuko L. Yamamoto
Full Text Available The intestinal microbiota and gut immune system must constantly communicate to maintain a balance between tolerance and activation: on the one hand, our immune system should protect us from pathogenic microbes and on the other hand, most of the millions of microbes in and on our body are innocuous symbionts and some can even be beneficial. Since there is such a close interaction between the immune system and the intestinal microbiota, it is not surprising that some lymphomas such as mucosal-associated lymphoid tissue (MALT lymphoma have been shown to be caused by the presence of certain bacteria. Animal models played an important role in establishing causation and mechanism of bacteria-induced MALT lymphoma. In this review we discuss different ways that animal models have been applied to establish a link between the gut microbiota and lymphoma and how animal models have helped to elucidate mechanisms of microbiota-induced lymphoma. While there are not a plethora of studies demonstrating a connection between microbiota and lymphoma development, we believe that animal models are a system which can be exploited in the future to enhance our understanding of causation and improve prognosis and treatment of lymphoma.
Chronic intestinal pseudo-obstruction.
Gabbard, Scott L; Lacy, Brian E
Chronic intestinal pseudo-obstruction (CIP) is a rare and serious disorder of the gastrointestinal (GI) tract characterized as a motility disorder with the primary defect of impaired peristalsis; symptoms are consistent with a bowel obstruction, although mechanical obstruction cannot be identified. CIP is classified as a neuropathy, myopathy, or mesenchymopathy; it is a neuropathic process in the majority of patients. The natural history of CIP is generally that of a progressive disorder, although occasional patients with secondary CIP note significant symptomatic improvement when the underlying disorder is identified and treated. Symptoms vary from patient to patient depending on the location of the luminal GI tract involved and the degree of involvement; however, the small intestine is nearly always involved. Common symptoms include dysphagia, gastroesophageal reflux, abdominal pain, nausea, vomiting, bloating, abdominal distension, constipation or diarrhea, and involuntary weight loss. Unfortunately, these symptoms are nonspecific, which can contribute to misdiagnosis or a delay in diagnosis and treatment. Since many of the symptoms and signs suggest a mechanical bowel obstruction, diagnostic tests typically focus on uncovering a mechanical obstruction, although routine tests do not identify an obstructive process. Nutrition supplementation is required for many patients with CIP due to symptoms of dysphagia, nausea, vomiting, and weight loss. This review discusses the epidemiology, etiology, pathogenesis, diagnosis, and treatment of patients with CIP, with an emphasis on nutrition assessment and treatment options for patients with nutrition compromise.
Exogenous glucagon-like peptide-2 (GLP-2) augments GLP-2 receptor mRNA and maintains proglucagon mRNA levels in resected rats
DEFF Research Database (Denmark)
Koopmann, Matthew C; Nelson, David W; Murali, Sangita G
BACKGROUND: Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent proglucagon-derived hormone that stimulates intestinal adaptive growth. Our aim was to determine whether exogenous GLP-2 increases resection-induced adaptation without diminishing endogenous proglucagon and GLP-2 receptor express...... augments adaptive growth and digestive capacity of the residual small intestine in a rat model of mid-small bowel resection by increasing plasma GLP-2 concentrations and GLP-2 receptor expression without diminishing endogenous proglucagon expression.......BACKGROUND: Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent proglucagon-derived hormone that stimulates intestinal adaptive growth. Our aim was to determine whether exogenous GLP-2 increases resection-induced adaptation without diminishing endogenous proglucagon and GLP-2 receptor...
Marine Peptides: Bioactivities and Applications
Directory of Open Access Journals (Sweden)
Randy Chi Fai Cheung
Full Text Available Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant, immunomodulatory, analgesic, anxiolytic anti-diabetic, appetite suppressing and neuroprotective activities have attracted the attention of the pharmaceutical industry, which attempts to design them for use in the treatment or prevention of various diseases. Some marine peptides or their derivatives have high commercial values and had reached the pharmaceutical and nutraceutical markets. A large number of them are already in different phases of the clinical and preclinical pipeline. This review highlights the recent research in marine peptides and the trends and prospects for the future, with special emphasis on nutraceutical and pharmaceutical development into marketed products.
Cardioprotective peptides from marine sources.
Harnedy, Padraigín A; FitzGerald, Richard J
Elevated blood pressure or hypertension is one of the fastest growing health problems worldwide. Although the etiology of essential hypertension has a genetic component, dietary factors play an important role. With the high costs and adverse side-effects associated with synthetic antihypertensive drugs and the awareness of the link between diet and health there has been increased focus on identification of food components that may contribute to cardiovascular health. In recent years special interest has been paid to the cardioprotective activity of peptides derived from food proteins including marine proteins. These peptides are latent within the sequence of the parent protein and only become active when released by proteolytic digestion during gastrointestinal digestion or through food processing. Current data on antihypertensive activity of marine-derived protein hydrolysates/peptides in animal and human studies is reviewed herein. Furthermore, products containing protein hydrolysates/peptides from marine origin with antihypertensive effects are discussed.
Antimicrobial peptides from Capsicum sp.
African Journals Online (AJOL)
ajl yemi
Dec 30, 2011 ... Key words: Antimicrobial peptides, Capsicum sp, Capsicum chinense, chili pepper, agronomical options, ..... of this human activity is resumed by the simple phrase: produce .... It will be interesting to scale the AMPs extraction.
Production and characterization of peptide antibodies
DEFF Research Database (Denmark)
Trier, Nicole Hartwig; Hansen, Paul Robert; Houen, Gunnar
Proteins are effective immunogens for generation of antibodies. However, occasionally the native protein is known but not available for antibody production. In such cases synthetic peptides derived from the native protein are good alternatives for antibody production. These peptide antibodies...... are powerful tools in experimental biology and are easily produced to any peptide of choice. A widely used approach for production of peptide antibodies is to immunize animals with a synthetic peptide coupled to a carrier protein. Very important is the selection of the synthetic peptide, where factors......, including solid-phase peptide-carrier conjugation and peptide-carrier conjugation in solution. Upon immunization, adjuvants such as Al(OH)(3) are added together with the immunogenic peptide-carrier conjugate, which usually leads to high-titred antisera. Following immunization and peptide antibody...
FMRFamide- and neurotensin-immunoreactive elements in the intestine of some polyclad and triclad flatworms (Turbellaria).
Punin MYu; Markosova, T G
By means of immunohistochemistry with antisera to tetrapeptide FMRFamide and regulatory peptides neurotensin and calcitonin intestines of marine turbellarians Notoplana atomata, N. humilis (Polycladida) and Procerodes littoralis (Tricladida) were investigated. In all flatworms polymorphous cells and processes reacting with antibodies to FMRFamide and neurotensin but not with calcitonin were revealed. These cell elements are localized both in the epithelium and beneath it. FMRFamide-immunoreactive cells and processes of investigated turbellarians and neurotensin-immunoreactive elements in P. littoralis obviously belong to the nervous system, while intraepithelial neurotensin-immunoreactive cells of polyclads share some morphological features with endocrine-like cells.
Release of PYY from pig intestinal mucosa; luminal and neural regulation
DEFF Research Database (Denmark)
Sheikh, S P; Holst, J J; Orskov, C
in release of PYY into the circulation. Stimulation of the splanchnic nerves did not affect the basal release of PYY. PYY-immunoreactivity extracted from ileal tissue or released to plasma or perfusate from the ileum was indistinguishable from synthetic porcine PYY by gel filtration and reverse phase HPLC...... of PYY was observed in isolated perfused pig ileum in response to luminal stimulation with glucose and vascular administration of the neuropeptide gastrin-releasing peptide (GRP). Electrical stimulation of the vagus nerve supply to the distal small intestine in intact anaesthetized pigs resulted...
Conformational restrictions in ligand binding to the human intestinal di-/tripeptide transporter
DEFF Research Database (Denmark)
Våbenø, Jon; Nielsen, Carsten Uhd; Steffansen, Bente
The aim of the present study was to develop a computational method aiding the design of dipeptidomimetic pro-moieties targeting the human intestinal di-/tripeptide transporter hPEPT1. First, the conformation in which substrates bind to hPEPT1 (the bioactive conformation) was identified...... to change the peptide backbone conformation (DeltaE(bbone)) from the global energy minimum conformation to the identified bioactive conformation was calculated for 20 hPEPT1 targeted model prodrugs with known K(i) values. Quantitatively, an inverse linear relationship (r(2)=0.81, q(2)=0.80) was obtained...
Is nonoperative management of adhesive intestinal obstruction ...
African Journals Online (AJOL)
Background: Nonoperative management of adhesive intestinal obstruction gives good results in adults but there are scant studies on its outcome in children. This study reports outcomes and experiences with nonoperative and operative management of adhesive intestinal obstruction in children in a resource-poor country.
Haricharan; Murali Krishna; Koti Reddy; Nara Hari
INTRODUCTION: Adhesive intestinal obstruction is an inevitable complication of abdominal surgeries. It has high morbidity with associated poor quality of life and predisposition to repeated hospitalization. Commonest cause of bowel obstruction in developed countries is postoperative adhesions with extrinsic compression of the intestine. Most of them can be managed conservatively. METHODS: A retrospective study of 30 patients admit...
Intestinal lymphangiectasia mimicking primary peritoneal carcinoma.
Steines, Jennifer C; Larson, Joshua H; Wilkinson, Neal; Kirby, Patricia; Goodheart, Michael J
Intestinal lymphangiectasia is an obstruction of the lymphatic system. We report on a patient with mesenteric adenopathy and an elevated CA125 level, which were suspicious for peritoneal carcinoma. Further evaluation and bowel resection identified intestinal lymphangiectasia. This disease should be considered in patients with mesenteric adenopathy and a small bowel mass. Copyright © 2010 Mosby, Inc. All rights reserved.
Intestinal cholesterol secretion: future clinical implications
Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.
Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues
Intestinal cholesterol secretion : future clinical implications
Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.
Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues
Radiodiagnosis of diseases of the small intestine
International Nuclear Information System (INIS)
Roentgenological image of diseases, development anomalies, various diseases of the small intestine is presented. Roentgenological semiotics of chronic enterocolotis, absorption failure syndrome, Crohn's disease, tuberculosis, abdominal actinomycosis, carcenoid, benign tumors, small intestine cancer, is given. To state final correct diagnosis a complex investigation, comprising angiography, computer tomography and ultrasound diagnosis, is necessary
Ruminal and Intestinal Digestibility of Leucaena Foliage
African Journals Online (AJOL)
Dec 30, 2013 ... Keywords: Intestinal digestibility, protein fodder, mobile nylon bag, a three-step technique ... A potential strategy for increasing the quality and availability of feed for small ruminants in the dry ... to measure intestinal disappearance of DM and CP using the mobile bag method described by De Boer et al.
Ectoparasites and intestinal helminths of speckled pigeon ...
African Journals Online (AJOL)
Ectoparasites and intestinal helminths of speckled pigeon ( Columba guinea Hartlaub and Finsch 1870) in Zaria, Nigeria. ... Science World Journal ... A total of 30 (20 males and 10 females) Speckled Pigeons trapped from the wild in Zaria and its environs, Nigeria, were examined for ectoparasites and intestinal helminths, ...
Laparoscopic Treatment of Intestinal Malrotation in Children
Ooms, N.; Matthyssens, L.E.; Draaisma, J.M.T.; Blaauw, I. de; Wijnen, M.H.
Purpose Intestinal malrotation is a congenital intestinal rotation anomaly, which can be treated by either laparotomy or laparoscopy. Our hypothesis is that laparoscopic treatment leads to less small bowel obstruction because of the fewer adhesions in comparison to laparotomy, without increasing the
Monozygotic twins with discordant intestinal rotation
International Nuclear Information System (INIS)
Smith, Vance L.; Nwomeh, Benedict C.; Long, Frederick
Previous case reports have suggested a strong concordance of intestinal malrotation among identical twins. This has led to the recommendation that the asymptomatic twin undergo screening when malrotation is discovered in the identical sibling. We present a case of monozygotic twins in which one twin presented with intestinal malrotation with midgut volvulus while the other twin was found to have normal gastrointestinal anatomy. (orig.)
Monozygotic twins with discordant intestinal rotation
Energy Technology Data Exchange (ETDEWEB)
Smith, Vance L.; Nwomeh, Benedict C. [Ohio State University College of Medicine and Public Health, Department of Pediatric Surgery, Columbus Children' s Hospital, Columbus, OH (United States); Long, Frederick [Ohio State University College of Medicine and Public Health, Department of Radiology, Columbus Children' s Hospital, Columbus, OH (United States)
Previous case reports have suggested a strong concordance of intestinal malrotation among identical twins. This has led to the recommendation that the asymptomatic twin undergo screening when malrotation is discovered in the identical sibling. We present a case of monozygotic twins in which one twin presented with intestinal malrotation with midgut volvulus while the other twin was found to have normal gastrointestinal anatomy. (orig.)
Intestinal malrotation and volvulus in adult life
Haak, Bastiaan W.; Bodewitz, Sander T.; Kuijper, Caroline F.; de Widt-Levert, Louise M.
Midgut volvulus due to intestinal malrotation is a rare cause of intestinal obstruction when occurring in adult life. This paper documents the difficulties in reaching an early diagnosis. We describe the case of an 85-year-old man with non-specific abdominal complaints for 20 years, who presented
Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.
Mehta, M K; Garde, S V; Sheth, A R
To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. These regulatory peptides may be involved in the pathophysiology of the testes.
Energy Technology Data Exchange (ETDEWEB)
Bachovchin, W.W.; Unkefer, C.J.
Advances in magnetic resonance and vibrational spectroscopy make it possible to derive detailed structural information about biomolecular structures in solution. These techniques are critically dependent on the availability of labeled compounds. For example, NMR techniques used today to derive peptide and protein structures require uniformity {sup 13}C-and {sup 15}N-labeled samples that are derived biosynthetically from (U-6-{sup 13}C) glucose. These experiments are possible now because, during the 1970s, the National Stable Isotope Resource developed algal methods for producing (U-6-{sup 13}C) glucose. If NMR techniques are to be used to study larger proteins, we will need sophisticated labelling patterns in amino acids that employ a combination of {sup 2}H, {sup 13}C, and {sup 15}N labeling. The availability of these specifically labeled amino acids requires a renewed investment in new methods for chemical synthesis of labeled amino acids. The development of new magnetic resonance or vibrational techniques to elucidate biomolecular structure will be seriously impeded if we do not see rapid progress in labeling technology. Investment in labeling chemistry is as important as investment in the development of advanced spectroscopic tools.
Matrix-assisted peptide synthesis on nanoparticles.
Khandadash, Raz; Machtey, Victoria; Weiss, Aryeh; Byk, Gerardo
We report a new method for multistep peptide synthesis on polymeric nanoparticles of differing sizes. Polymeric nanoparticles were functionalized via their temporary embedment into a magnetic inorganic matrix that allows multistep peptide synthesis. The matrix is removed at the end of the process for obtaining nanoparticles functionalized with peptides. The matrix-assisted synthesis on nanoparticles was proved by generating various biologically relevant peptides. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
Regional specialization within the intestinal immune system
DEFF Research Database (Denmark)
Mowat, Allan M.; Agace, William Winston
The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly...... implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout...... the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease...
Multispectral tissue characterization for intestinal anastomosis optimization
Cha, Jaepyeong; Shademan, Azad; Le, Hanh N. D.; Decker, Ryan; Kim, Peter C. W.; Kang, Jin U.; Krieger, Axel
Intestinal anastomosis is a surgical procedure that restores bowel continuity after surgical resection to treat intestinal malignancy, inflammation, or obstruction. Despite the routine nature of intestinal anastomosis procedures, the rate of complications is high. Standard visual inspection cannot distinguish the tissue subsurface and small changes in spectral characteristics of the tissue, so existing tissue anastomosis techniques that rely on human vision to guide suturing could lead to problems such as bleeding and leakage from suturing sites. We present a proof-of-concept study using a portable multispectral imaging (MSI) platform for tissue characterization and preoperative surgical planning in intestinal anastomosis. The platform is composed of a fiber ring light-guided MSI system coupled with polarizers and image analysis software. The system is tested on ex vivo porcine intestine tissue, and we demonstrate the feasibility of identifying optimal regions for suture placement.
Directory of Open Access Journals (Sweden)
A.N. Surkov
Full Text Available Acute intestinal infections are quite common among children. Their clinical presentations include intoxication syndrome (drowsiness, low appetite, fever etc, infectious toxic syndrome (toxicosis with exicosis, neurotoxicosi, hypovolemic or infectious-toxic shockand diarrhea syndrome. Sometimes intestinal infections can be quite severe and even lethal. However disease duration and outcome depend on timelines and adequacy of prescribed treatment. Main guidelines of intestinal infections treatment include probiotics. That is why the right choice of probiotics is important for a pediatrician. The article contains basic information upon etiopathogenesis, classification, diagnostic criteria and acute pediatric intestinal infections treatment guidelines.Key words: acute intestinal infections, etiopathogenesis, diagnostic criteria, treatment, probiotics, children. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (6: 141–147
Material Binding Peptides for Nanotechnology
Directory of Open Access Journals (Sweden)
Urartu Ozgur Safak Seker
Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.
The preferred substrates for transglutaminase 2 in a complex wheat gluten digest are Peptide fragments harboring celiac disease T-cell epitopes.
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Siri Dørum
Full Text Available BACKGROUND: Celiac disease is a T-cell mediated chronic inflammatory disorder of the gut that is induced by dietary exposure to gluten proteins. CD4+ T cells of the intestinal lesion recognize gluten peptides in the context of HLA-DQ2.5 or HLA-DQ8 and the gluten derived peptides become better T-cell antigens after deamidation catalyzed by the enzyme transglutaminase 2 (TG2. In this study we aimed to identify the preferred peptide substrates of TG2 in a heterogeneous proteolytic digest of whole wheat gluten. METHODS: A method was established to enrich for preferred TG2 substrates in a complex gluten peptide mixture by tagging with 5-biotinamido-pentylamine. Tagged peptides were isolated and then identified by nano-liquid chromatography online-coupled to tandem mass spectrometry, database searching and final manual data validation. RESULTS: We identified 31 different peptides as preferred substrates of TG2. Strikingly, the majority of these peptides were harboring known gluten T-cell epitopes. Five TG2 peptide substrates that were predicted to bind to HLA-DQ2.5 did not contain previously characterized sequences of T-cell epitopes. Two of these peptides elicited T-cell responses when tested for recognition by intestinal T-cell lines of celiac disease patients, and thus they contain novel candidate T-cell epitopes. We also found that the intact 9mer core sequences of the respective epitopes were not present in all peptide substrates. Interestingly, those epitopes that were represented by intact forms were frequently recognized by T cells in celiac disease patients, whereas those that were present in truncated versions were infrequently recognized. CONCLUSION: TG2 as well as gastrointestinal proteolysis play important roles in the selection of gluten T-cell epitopes in celiac disease.
The Preferred Substrates for Transglutaminase 2 in a Complex Wheat Gluten Digest Are Peptide Fragments Harboring Celiac Disease T-Cell Epitopes
Dørum, Siri; Arntzen, Magnus Ø.; Qiao, Shuo-Wang; Holm, Anders; Koehler, Christian J.; Thiede, Bernd; Sollid, Ludvig M.; Fleckenstein, Burkhard
Background Celiac disease is a T-cell mediated chronic inflammatory disorder of the gut that is induced by dietary exposure to gluten proteins. CD4+ T cells of the intestinal lesion recognize gluten peptides in the context of HLA-DQ2.5 or HLA-DQ8 and the gluten derived peptides become better T-cell antigens after deamidation catalyzed by the enzyme transglutaminase 2 (TG2). In this study we aimed to identify the preferred peptide substrates of TG2 in a heterogeneous proteolytic digest of whole wheat gluten. Methods A method was established to enrich for preferred TG2 substrates in a complex gluten peptide mixture by tagging with 5-biotinamido-pentylamine. Tagged peptides were isolated and then identified by nano-liquid chromatography online-coupled to tandem mass spectrometry, database searching and final manual data validation. Results We identified 31 different peptides as preferred substrates of TG2. Strikingly, the majority of these peptides were harboring known gluten T-cell epitopes. Five TG2 peptide substrates that were predicted to bind to HLA-DQ2.5 did not contain previously characterized sequences of T-cell epitopes. Two of these peptides elicited T-cell responses when tested for recognition by intestinal T-cell lines of celiac disease patients, and thus they contain novel candidate T-cell epitopes. We also found that the intact 9mer core sequences of the respective epitopes were not present in all peptide substrates. Interestingly, those epitopes that were represented by intact forms were frequently recognized by T cells in celiac disease patients, whereas those that were present in truncated versions were infrequently recognized. Conclusion TG2 as well as gastrointestinal proteolysis play important roles in the selection of gluten T-cell epitopes in celiac disease. PMID:21124911
Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis.
Pendharkar, Sayali A; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S
Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. GRP is significantly increased in patients with AGM after pancreatitis and is associated with increased levels of pro
Flanking signal and mature peptide residues influence signal peptide cleavage
Directory of Open Access Journals (Sweden)
Ranganathan Shoba
Full Text Available Abstract Background Signal peptides (SPs mediate the targeting of secretory precursor proteins to the correct subcellular compartments in prokaryotes and eukaryotes. Identifying these transient peptides is crucial to the medical, food and beverage and biotechnology industries yet our understanding of these peptides remains limited. This paper examines the most common type of signal peptides cleavable by the endoprotease signal peptidase I (SPase I, and the residues flanking the cleavage sites of three groups of signal peptide sequences, namely (i eukaryotes (Euk (ii Gram-positive (Gram+ bacteria, and (iii Gram-negative (Gram- bacteria. Results In this study, 2352 secretory peptide sequences from a variety of organisms with amino-terminal SPs are extracted from the manually curated SPdb database for analysis based on physicochemical properties such as pI, aliphatic index, GRAVY score, hydrophobicity, net charge and position-specific residue preferences. Our findings show that the three groups share several similarities in general, but they display distinctive features upon examination in terms of their amino acid compositions and frequencies, and various physico-chemical properties. Thus, analysis or prediction of their sequences should be separated and treated as distinct groups. Conclusion We conclude that the peptide segment recognized by SPase I extends to the start of the mature protein to a limited extent, upon our survey of the amino acid residues surrounding the cleavage processing site. These flanking residues possibly influence the cleavage processing and contribute to non-canonical cleavage sites. Our findings are applicable in defining more accurate prediction tools for recognition and identification of cleavage site of SPs.
Impact of human milk pasteurization on the kinetics of peptide release during in vitro dynamic term newborn digestion.
Deglaire, Amélie; De Oliveira, Samira C; Jardin, Julien; Briard-Bion, Valérie; Emily, Mathieu; Ménard, Olivia; Bourlieu, Claire; Dupont, Didier
Holder pasteurization (62.5°C, 30 min) ensures sanitary quality of donor's human milk but also denatures beneficial proteins. Understanding whether this further impacts the kinetics of peptide release during gastrointestinal digestion of human milk was the aim of the present paper. Mature raw (RHM) or pasteurized (PHM) human milk were digested (RHM, n = 2; PHM, n = 3) by an in vitro dynamic system (term stage). Label-free quantitative peptidomics was performed on milk and digesta (ten time points). Ascending hierarchical clustering was conducted on "Pasteurization × Digestion time" interaction coefficients. Preproteolysis occurred in human milk (159 unique peptides; RHM: 91, PHM: 151), mostly on β-casein (88% of the endogenous peptides). The predicted cleavage number increased with pasteurization, potentially through plasmin activation (plasmin cleavages: RHM, 53; PHM, 76). During digestion, eight clusters resumed 1054 peptides from RHM and PHM, originating for 49% of them from β-casein. For seven clusters (57% of peptides), the kinetics of peptide release differed between RHM and PHM. The parent protein was significantly linked to the clustering (p-value = 1.4 E-09), with β-casein and lactoferrin associated to clusters in an opposite manner. Pasteurization impacted selectively gastric and intestinal kinetics of peptide release in term newborns, which may have further nutritional consequences. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[Neovagina with intestine: 13 cases].
Parente, A; Molina, E; Cerdá, J; Cañizo, A; Rodriguez, A; Laín, A; Fanjul, M; Vázquez, J
The absence or hipoplasia vaginal can turn out to be isolated, associated with ambiguous genitalia, or as anatomical variant in a syndrome of sewer. The fundamental aim in the creation of a new vagina is: to obtain a good aesthetic result, to fulfil functional criteria (elasticity, sensibility, physiological inclination) and to improve the quality of life of the patients avoiding the use of molds and minimizing the morbidity of the zones donors. In this work let's sense beforehand our experience in the accomplishment of neovaginas with intestine. We analyze the clinical record of 13 patients treated surgically in the last ten years. We differentiate two groups according to the age, the diagnosis and the type of surgery: a) the first group of 8 patients present syndrome of insensibility to the androgens (4), syndrome of Rokitansky (2), extrofia of sewer (1) and mixed gonadal disgenesia (1). This group of patients were controlled in the adolescence by an average of age of 19 years (11-35 years), they fulfilling a neovagina with sigma; b) the second group of 5 patients with sewer (3), extrofia of sewer (1) and congenital suprarrenal hiperplasia (1). This group was controlled prematurely by a middle ages of one year (4 months-3 years). The intestinal segment used as neovagina was sigma (2), ileon (2) and rectum (1), and was performed during the surgical correction of her congenital malformation. Two patients have presented intestinal obstruction in the postoperatory immediate one. Four patients have needed removal of a small vaginal prolapse, and three have needed vaginal transitory expansions for introit stenosis. The long-term evolution has been favorable with an excellent aesthetic aspect. Four patients recount sexual fully satisfactory relations. We believe that the neovagina with sigma is at present the best option in patients with absence or hipoplasia vaginal. The advantages are the possibility of precocious and one time correction, a neovagina of dimensions and
Peptides and Anti-peptide Antibodies for Small and Medium Scale Peptide and Anti-peptide Affinity Microarrays: Antigenic Peptide Selection, Immobilization, and Processing.
Zhang, Fan; Briones, Andrea; Soloviev, Mikhail
This chapter describes the principles of selection of antigenic peptides for the development of anti-peptide antibodies for use in microarray-based multiplex affinity assays and also with mass-spectrometry detection. The methods described here are mostly applicable to small to medium scale arrays. Although the same principles of peptide selection would be suitable for larger scale arrays (with 100+ features) the actual informatics software and printing methods may well be different. Because of the sheer number of proteins/peptides to be processed and analyzed dedicated software capable of processing all the proteins and an enterprise level array robotics may be necessary for larger scale efforts. This report aims to provide practical advice to those who develop or use arrays with up to ~100 different peptide or protein features.
Spike Protein Fusion Peptide and Feline Coronavirus Virulence
Chang, Hui-Wen; Egberink, Herman F.; Halpin, Rebecca; Spiro, David J.
Coronaviruses are well known for their potential to change their host or tissue tropism, resulting in unpredictable new diseases and changes in pathogenicity; severe acute respiratory syndrome and feline coronaviruses, respectively, are the most recognized examples. Feline coronaviruses occur as 2 pathotypes: nonvirulent feline enteric coronaviruses (FECVs), which replicate in intestinal epithelium cells, and lethal feline infectious peritonitis viruses (FIPVs), which replicate in macrophages. Evidence indicates that FIPV originates from FECV by mutation, but consistent distinguishing differences have not been established. We sequenced the full genome of 11 viruses of each pathotype and then focused on the single most distinctive site by additionally sequencing hundreds of viruses in that region. As a result, we identified 2 alternative amino acid differences in the putative fusion peptide of the spike protein that together distinguish FIPV from FECV in >95% of cases. By these and perhaps other mutations, the virus apparently acquires its macrophage tropism and spreads systemically. PMID:22709821
Automated solid-phase peptide synthesis to obtain therapeutic peptides
Directory of Open Access Journals (Sweden)
Veronika Mäde
Full Text Available The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS offers a suitable technology to produce chemically engineered peptides. This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used. Critical issues and suggestions for the synthesis are covered. The development of automated methods from conventional to essentially improved microwave-assisted instruments is discussed. In order to improve pharmacokinetic properties of peptides, lipidation and PEGylation are described as covalent conjugation methods, which can be applied by a combination of automated and manual synthesis approaches. The synthesis and application of SPPS is described for neuropeptide Y receptor analogs as an example for bioactive hormones. The applied strategies represent innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies.
Laparoscopic intestinal derotation: original technique.
Valle, Mario; Federici, Orietta; Tarantino, Enrico; Corona, Francesco; Garofalo, Alfredo
The intestinal derotation technique, introduced by Cattel and Valdoni 40 years ago, is carried out using a laparoscopic procedure, which is described here for the first time. The method is effective in the treatment of malign lesions of the III and IV duodenum and during laparoscopic subtotal colectomy with anastomosis between the ascending colon and the rectum. Ultimately, the procedure allows for the verticalization of the duodenal C and the anterior positioning of the mesenteric vessels, facilitating biopsy and resection of the III and IV duodenal portions and allowing anastomosis of the ascending rectum, avoiding both subtotal colectomy and the risk of torsion of the right colic loop. Although the procedure calls for extensive experience with advanced video-laparoscopic surgery, it is both feasible and repeatable. In our experience we have observed no mortality or morbidity.
What peptides these deltorphins be.
Lazarus, L H; Bryant, S D; Cooper, P S; Salvadori, S
The deltorphins are a class of highly selective delta-opioid heptapeptides from the skin of the Amazonian frogs Phyllomedusa sauvagei and P. bicolor. The first of these fascinating peptides came to light in 1987 by cloning of the cDNA of from frog skins, while the other members of this family were identified either by cDNA or isolation of the peptides. The distinctive feature of deltorphins is the presence of a naturally occurring D-enantiomer at the second position in their common N-terminal sequence, Tyr-D-Xaa-Phe, comparable to dermorphin, which is the prototype of a group of mu-selective opioids from the same source. The D-amino acid and the anionic residues, either Glu or Asp, as well as their unique amino acid compositions are responsible for the remarkable biostability, high delta-receptor affinity, bioactivity and peptide conformation. This review summarizes a decade of research from many laboratories that defined which residues and substituents in the deltorphins interact with the delta-receptor and characterized pharmacological and physiological activities in vitro and in vivo. It begins with a historical description of the topic and presents general schema for the synthesis of peptide analogues of deltorphins A, B and C as a means to document the methods employed in producing a myriad of analogues. Structure activity studies of the peptides and their pharmacological activities in vitro are detailed in abundantly tabulated data. A brief compendium of the current level of knowledge of the delta-receptor assists the reader to appreciate the rationale for the design of these analogues. Discussion of the conformation of these peptides addresses how structure leads to further hypotheses regarding ligand receptor interaction. The review ends with a broad discussion of the potential applications of these peptides in clinical and therapeutic settings.
Diffused and sustained inhibitory effects of intestinal electrical stimulation on intestinal motility mediated via sympathetic pathway.
Zhao, Xiaotuan; Yin, Jieyun; Wang, Lijie; Chen, Jiande D Z
The aims were to investigate the energy-dose response effect of intestinal electrical stimulation (IES) on small bowel motility, to compare the effect of forward and backward IES, and to explore the possibility of using intermittent IES and mechanism of IES on intestinal motility. Five dogs implanted with a duodenal cannula and one pair of intestinal serosal electrodes were studied in five sessions: 1) energy-dose response study; 2) forward IES; 3) backward IES; 4) intermittent IES vs. continuous IES; 5) administration of guanethidine. The contractile activity and tonic pressure of the small intestine were recorded. The duration of sustained effect after turning off IES was manually calculated. 1) IES with long pulse energy dose dependently inhibited contractile activity and tonic pressure of the small intestine (p intestine depended on the energy of IES delivered (p intestine. 5) Guanethidine blocked the inhibitory effect of IES on intestinal motility. IES with long pulses inhibits small intestinal motility; the effect is energy-dose dependent, diffused, and sustained. Intermittent IES has the same efficacy as the continuous IES in inhibiting small intestinal motility. Forward and backward IES have similar inhibitory effects on small bowel motility. This IES-induced inhibitory effect is mediated via the sympathetic pathway. © 2013 International Neuromodulation Society.
Pharmacologic Effects in vivo in Brain by Vector-Mediated Peptide Drug Delivery
Bickel, Ulrich; Yoshikawa, Takayoshi; Landaw, Elliot M.; Faull, Kym F.; Pardridge, William M.
Pharmacologic effects in brain caused by systemic administration of neuropeptides are prevented by poor transport of the peptide through the brain vascular endothelium, which comprises the blood-brain barrier in vivo. In the present study, successful application of a chimeric peptide approach to enhance drug delivery through the blood-brain barrier for the purpose of achieving a central nervous system pharmacologic effect is described. The chimeric peptide was formed by linkage of a potent vasoactive intestinal peptide (VIP) analogue, which had been monobiotinylated, to a drug transport vector. The vector consisted of a covalent conjugate of avidin and the OX26 monoclonal antibody to the transferrin receptor. Owing to the high concentration of transferrin receptors on brain capillary endothelia, OX26 targets brain and undergoes receptor-mediated transcytosis through the blood-brain barrier. Systemic infusion of low doses (12 μg/kg) of the VIP chimeric peptide in rats resulted in an in vivo central nervous system pharmacologic effect: a 65% increase in cerebral blood flow. Biotinylated VIP analogue without the brain transport vector was ineffective.
Usefulness of antibodies to deamidated gliadin peptides in celiac disease diagnosis and follow-up.
Volta, Umberto; Granito, Alessandro; Fiorini, Erica; Parisi, Claudia; Piscaglia, Maria; Pappas, Georgios; Muratori, Paolo; Bianchi, Francesco B
The prevalence of the recently described deamidated gliadin peptide antibodies was compared with that of the routinely used antigliadin, antiendomysial, and tissue transglutaminase antibodies in the sera of 128 untreated celiac patients and 134 controls. Sensitivity and specificity for celiac disease were 83.6 and 90.3% for IgA and 84.4 and 98.5% for IgG antibodies to deamidated gliadin peptides. The new test displayed higher diagnostic accuracy than antigliadin antibodies and, although less sensitive than antiendomysial and tissue transglutaminase antibodies, showed significantly higher specificity than tissue transglutaminase antibodies (P < 0.001). Persistence of peptide antibodies after gluten withdrawal was an expression of low compliance with the diet and of the lack of improvement of the intestinal mucosa. The combined use of tissue transglutaminase and deamidated gliadin peptide antibodies seems to be a very useful tool for celiac disease diagnosis. Moreover, antibodies to deamidated gliadin peptides can be helpful in disease follow-up.
Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP
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Silva, P.; Stoff, J.S.; Solomon, R.J.; Lear, S.; Kniaz, D.; Greger, R.; Epstein, F.H.
Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters.
Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP
International Nuclear Information System (INIS)
Silva, P.; Stoff, J.S.; Solomon, R.J.; Lear, S.; Kniaz, D.; Greger, R.; Epstein, F.H.
Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters
Peptides PHI and VIP: comparison between vascular and nonvascular smooth muscle effect in rabbit uterus
International Nuclear Information System (INIS)
Bardrum, B.; Ottesen, B.; Fahrenkrug, J.
The distribution and effects of the two neuropeptides, vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine amide (PHI), on vascular and nonvascular smooth muscle in the urogenital tract of nonpregnant rabbit female, were investigated. Immunoreactive VIP and PHI were present in all regions except the ovary with the highest concentration in the uterin cervix. By using in vitro tension recordings of myometrial specimens, it was demonstrated that both peptides displayed a dose-dependent inhibition of the mechanical activity. The dose-response curves of VIP and PHI were superimposable with and ID 50 of 3 x 10 -8 mol/l, and their combined effect was additive. In addition, the influence of the two peptides on myometrial blood flow (MBF) was investigated by the xenon-133 washout technique. Both peptides were found to increase MBF with the same potency and efficacy. Their combined effect was additive. In conclusion VIP and PHI are present in the rabbit urogenital tract, and the two peptides are equipotent inhibitors of mechanical nonvascular and vascular smooth muscle activity in the uterus
Co-delivery of a hydrophobic small molecule and a hydrophilic peptide by porous silicon nanoparticles.
Liu, Dongfei; Bimbo, Luis M; Mäkilä, Ermei; Villanova, Francesca; Kaasalainen, Martti; Herranz-Blanco, Barbara; Caramella, Carla M; Lehto, Vesa-Pekka; Salonen, Jarno; Herzig, Karl-Heinz; Hirvonen, Jouni; Santos, Hélder A
Nanoparticulate drug delivery systems offer remarkable opportunities for clinical treatment. However, there are several challenges when they are employed to deliver multiple cargos/payloads, particularly concerning the synchronous delivery of small molecular weight drugs and relatively larger peptides. Since porous silicon (PSi) nanoparticles (NPs) can easily contain high payloads of drugs with various properties, we evaluated their carrier potential in multi-drug delivery for co-loading of the hydrophobic drug indomethacin and the hydrophilic human peptide YY3-36 (PYY3-36). Sequential loading of these two drugs into the PSi NPs enhanced the drug release rate of each drug and also their amount permeated across Caco-2 and Caco-2/HT29 cell monolayers. Regardless of the loading approach used, dual or single, the drug permeation profiles were in good correlation with their drug release behaviour. Furthermore, the permeation studies indicated the critical role of the mucus intestinal layer and the paracellular resistance in the permeation of the therapeutic compounds across the intestinal wall. Loading with PYY3-36 also greatly improved the cytocompatibility of the PSi NPs. Conformational analysis indicated that the PYY3-36 could still display biological activity after release from the PSi NPs and permeation across the intestinal cell monolayers. These results are the first demonstration of the promising potential of PSi NPs for simultaneous multi-drug delivery of both hydrophobic and hydrophilic compounds. Copyright © 2013 Elsevier B.V. All rights reserved.
Sequencing Cyclic Peptides by Multistage Mass Spectrometry
Mohimani, Hosein; Yang, Yu-Liang; Liu, Wei-Ting; Hsieh, Pei-Wen; Dorrestein, Pieter C.; Pevzner, Pavel A.
Some of the most effective antibiotics (e.g., Vancomycin and Daptomycin) are cyclic peptides produced by non-ribosomal biosynthetic pathways. While hundreds of biomedically important cyclic peptides have been sequenced, the computational techniques for sequencing cyclic peptides are still in their infancy. Previous methods for sequencing peptide antibiotics and other cyclic peptides are based on Nuclear Magnetic Resonance spectroscopy, and require large amount (miligrams) of purified materials that, for most compounds, are not possible to obtain. Recently, development of mass spectrometry based methods has provided some hope for accurate sequencing of cyclic peptides using picograms of materials. In this paper we develop a method for sequencing of cyclic peptides by multistage mass spectrometry, and show its advantages over single stage mass spectrometry. The method is tested on known and new cyclic peptides from Bacillus brevis, Dianthus superbus and Streptomyces griseus, as well as a new family of cyclic peptides produced by marine bacteria. PMID:21751357
Cyclic peptide therapeutics: past, present and future.
Zorzi, Alessandro; Deyle, Kaycie; Heinis, Christian
Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics. Over 40 cyclic peptide drugs are currently in clinical use and around one new cyclic peptide drug enters the market every year on average. The vast majority of clinically approved cyclic peptides are derived from natural products, such as antimicrobials or human peptide hormones. New powerful techniques based on rational design and in vitro evolution have enabled the de novo development of cyclic peptide ligands to targets for which nature does not offer solutions. A look at the cyclic peptides currently under clinical evaluation shows that several have been developed using such techniques. This new source for cyclic peptide ligands introduces a freshness to the field, and it is likely that de novo developed cyclic peptides will be in clinical use in the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.
Is the Diagnosis of Celiac Disease Possible Without Intestinal Biopsy?
Directory of Open Access Journals (Sweden)
Maha Shomaf
Full Text Available Background: Coeliac disease is defined as a state of immune-mediated hyper-responsiveness to dietary gluten from wheat, barley, or rye in genetically predisposed individuals that results in tissue damage. The diagnosis is made by microscopic examination of a small intestinal biopsy, although serological testing for antibodies against tissue transglutaminase and deamidated gliadin peptide can be of great advantage. It has been suggested that duodenal biopsy can be avoided in patients with high levels of the tissue transglutaminase antibody, since a relationship has been found to be present between tissue transglutaminase antibody titres and coeliac disease. Aims: To study the correlation between tissue transglutaminase titre and small intestinal biopsy findings in patients with coeliac disease. Study Design: Diagnostic accuracy study. Methods: Ninety-five cases of patients diagnosed with coeliac disease and with positive serum tissue transglutaminase titres were retrieved from the Jordan University Hospital archives between December 2014 and December 2015. All the cases were classified according to the Marsh classification. Results: Ninety-five cases with a positive titre for the antibody were included in this study, 73 (76.8% of them were females and 22 cases (23.2% were males. The age of the patients ranged between 4 and 75 years with a mean age ± standard deviation of 32.3±14.7. The sensitivity was the highest in Marsh IIIC and lowest in Marsh IIIA (95% versus 68% respectively. The specificity was moderate (76% for all subtypes of Marsh III. Conclusion: This study showed a positive correlation between the tissue transglutaminase titre and the degree of duodenal damage (Marsh IIIC in patients with coeliac disease. In the presence of high tissue transglutaminase levels, duodenal biopsy might not be always necessary for diagnosis, particularly in symptomatic patients
Proteomic analysis of rainbow trout (Oncorhynchus mykiss) intestinal epithelia: physiological acclimation to short-term starvation.
Baumgarner, Bradley L; Bharadwaj, Anant S; Inerowicz, Dorota; Goodman, Angela S; Brown, Paul B
The intestinal epithelia form the first line of defense against harmful agents in the gut lumen of most monogastric vertebrates, including teleost fishes. Previous investigations into the effect of starvation on the intestinal epithelia of teleost fishes have focused primarily on changes in morphological characteristics and targeted molecular analysis of specific enzymes. The goal of this study was to use a comprehensive approach to help reveal how the intestinal epithelia of carnivorous teleost fishes acclimate to short-term nutrient deprivation. We utilized two-dimensional gel electrophoresis (2-DE) to conduct the proteomic analysis of the mucosal and epithelial layer of the anterior gut intestinal tract (GIT) from satiation fed vs. 4 week starved rainbow trout (Oncorhynchus mykiss). A total of 40 proteins were determined to be differentially expressed and were subsequently picked for in-gel trypsin digestion. Peptide mass fingerprint analysis was conducted using matrix assisted laser desorption time-of-flight/time-of-flight. Nine of the 11 positively identified proteins were directly related to innate immunity. The expression of α-1 proteinase inhibitor decreased in starved vs. fed fish. Also, the concentration of one leukocyte elastase inhibitor (LEI) isomer decreased in starved fish, though the concentration of another LEI isomer increased in due to starvation. In addition, starvation promoted an increased concentration of the important xenobiotic-transporter p-glycoprotein. Finally, starvation resulted in a significant increase in type II keratin E2. Overall, our results indicate that starvation promoted a reduced capacity to inhibit enzymatic stress but increased xenobiotic resistance and paracellular permeability of epithelial cells in the anterior intestine of rainbow trout. Copyright © 2012 Elsevier Inc. All rights reserved.
The Drosophila MAPK p38c regulates oxidative stress and lipid homeostasis in the intestine.
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Sveta Chakrabarti
Full Text Available The p38 mitogen-activated protein (MAP kinase signaling cassette has been implicated in stress and immunity in evolutionarily diverse species. In response to a wide variety of physical, chemical and biological stresses p38 kinases phosphorylate various substrates, transcription factors of the ATF family and other protein kinases, regulating cellular adaptation to stress. The Drosophila genome encodes three p38 kinases named p38a, p38b and p38c. In this study, we have analyzed the role of p38c in the Drosophila intestine. The p38c gene is expressed in the midgut and upregulated upon intestinal infection. We showed that p38c mutant flies are more resistant to infection with the lethal pathogen Pseudomonas entomophila but are more susceptible to the non-pathogenic bacterium Erwinia carotovora 15. This phenotype was linked to a lower production of Reactive Oxygen Species (ROS in the gut of p38c mutants, whereby the transcription of the ROS-producing enzyme Duox is reduced in p38c mutant flies. Our genetic analysis shows that p38c functions in a pathway with Mekk1 and Mkk3 to induce the phosphorylation of Atf-2, a transcription factor that controls Duox expression. Interestingly, p38c deficient flies accumulate lipids in the intestine while expressing higher levels of antimicrobial peptide and metabolic genes. The role of p38c in lipid metabolism is mediated by the Atf3 transcription factor. This observation suggests that p38c and Atf3 function in a common pathway in the intestine to regulate lipid metabolism and immune homeostasis. Collectively, our study demonstrates that p38c plays a central role in the intestine of Drosophila. It also reveals that many roles initially attributed to p38a are in fact mediated by p38c.
The Drosophila MAPK p38c regulates oxidative stress and lipid homeostasis in the intestine.
Chakrabarti, Sveta; Poidevin, Mickaël; Lemaitre, Bruno
The p38 mitogen-activated protein (MAP) kinase signaling cassette has been implicated in stress and immunity in evolutionarily diverse species. In response to a wide variety of physical, chemical and biological stresses p38 kinases phosphorylate various substrates, transcription factors of the ATF family and other protein kinases, regulating cellular adaptation to stress. The Drosophila genome encodes three p38 kinases named p38a, p38b and p38c. In this study, we have analyzed the role of p38c in the Drosophila intestine. The p38c gene is expressed in the midgut and upregulated upon intestinal infection. We showed that p38c mutant flies are more resistant to infection with the lethal pathogen Pseudomonas entomophila but are more susceptible to the non-pathogenic bacterium Erwinia carotovora 15. This phenotype was linked to a lower production of Reactive Oxygen Species (ROS) in the gut of p38c mutants, whereby the transcription of the ROS-producing enzyme Duox is reduced in p38c mutant flies. Our genetic analysis shows that p38c functions in a pathway with Mekk1 and Mkk3 to induce the phosphorylation of Atf-2, a transcription factor that controls Duox expression. Interestingly, p38c deficient flies accumulate lipids in the intestine while expressing higher levels of antimicrobial peptide and metabolic genes. The role of p38c in lipid metabolism is mediated by the Atf3 transcription factor. This observation suggests that p38c and Atf3 function in a common pathway in the intestine to regulate lipid metabolism and immune homeostasis. Collectively, our study demonstrates that p38c plays a central role in the intestine of Drosophila. It also reveals that many roles initially attributed to p38a are in fact mediated by p38c.
Congenital intestinal lymphangiectasia. A case report
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Georgios Mitsiakos
Full Text Available Congenital intestinal lymphangiectasia, first described by Waldmann et al. in 1961, is a rare congenital malformation of the lymphatics, presented with generalized edema, hypoproteinemia and lymphopenia. Diagnosis is based on endoscopy findings and pathology.We present here a case of a male neonate, second child of an indigenous woman, delivered by caesarean section. Prenatally, multiple cystic abdominal masses were identified by ultrasound. The patient was treated successfully with enterectomy and anastomosis. Histopathology revealed primary intestinal lymphangiectasia with no features of malignancy.Intestinal lymphangiectasia is a rare pathology, which should be differentiated while exploring abdominal masses, hypoproteinemia and edema especially in neonates.
Peptide Vaccine: Progress and Challenges
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Weidang Li
Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.
Double-Stranded Peptide Nucleic Acids
DEFF Research Database (Denmark)
A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.......A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....
Growth of embryo and gene expression of nutrient transporters in the small intestine of the domestic pigeon (Columba livia)*
Chen, Ming-xia; Li, Xiang-guang; Yang, Jun-xian; Gao, Chun-qi; Wang, Bin; Wang, Xiu-qi; Yan, Hui-chao
The objective of this study was to investigate the relationship between gene expression of nutrient (amino acid, peptide, sodium and proton) transporters in the small intestine and embryonic growth in domestic pigeons (Columba livia). One hundred and twenty-five fertilized eggs were randomly assigned into five groups and were incubated under optimal conditions (temperature of 38.1 °C and relative humidity of 55%). Twenty embryos/birds from each group were sacrificed by cervical dislocation on embryonic day (E) 9, 11, 13, 15 and day of hatch (DOH). The eggs, embryos (without yolk sac), and organs (head, brain, heart, liver, lungs, kidney, gizzard, small intestine, legs, and thorax) were dissected, cleaned, and weighed. Small intestine samples were collected for RNA isolation. The mRNA abundance of intestinal nutrient transporters was evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR). We classified these ten organs into four types according to the changes in relative weight during embryonic development. In addition, the gene expression of nutrient transporters was differentially regulated by embryonic day. The mRNA abundances of b0,+AT, EAAT3, y+LAT2, PepT1, LAT4, NHE2, and NHE3 increased linearly with age, whereas mRNA abundances of CAT1, CAT2, LAT1, EAAT2, SNAT1, and SNAT2 were increased to higher levels on E9 or E11 and then decreased to lower levels until DOH. The results of correlation analysis showed that the gene expressions of b0,+AT, EAAT3, PepT1, LAT4, NHE2, NHE3, and y+LAT2 had positive correlations with body weight (0.71
Growth of embryo and gene expression of nutrient transporters in the small intestine of the domestic pigeon (Columba livia).
Chen, Ming-xia; Li, Xiang-guang; Yang, Jun-xian; Gao, Chun-qi; Wang, Bin; Wang, Xiu-qi; Yan, Hui-chao
The objective of this study was to investigate the relationship between gene expression of nutrient (amino acid, peptide, sodium and proton) transporters in the small intestine and embryonic growth in domestic pigeons (Columba livia). One hundred and twenty-five fertilized eggs were randomly assigned into five groups and were incubated under optimal conditions (temperature of 38.1 °C and relative humidity of 55%). Twenty embryos/birds from each group were sacrificed by cervical dislocation on embryonic day (E) 9, 11, 13, 15 and day of hatch (DOH). The eggs, embryos (without yolk sac), and organs (head, brain, heart, liver, lungs, kidney, gizzard, small intestine, legs, and thorax) were dissected, cleaned, and weighed. Small intestine samples were collected for RNA isolation. The mRNA abundance of intestinal nutrient transporters was evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR). We classified these ten organs into four types according to the changes in relative weight during embryonic development. In addition, the gene expression of nutrient transporters was differentially regulated by embryonic day. The mRNA abundances of b(0,+)AT, EAAT3, y(+)LAT2, PepT1, LAT4, NHE2, and NHE3 increased linearly with age, whereas mRNA abundances of CAT1, CAT2, LAT1, EAAT2, SNAT1, and SNAT2 were increased to higher levels on E9 or E11 and then decreased to lower levels until DOH. The results of correlation analysis showed that the gene expressions of b(0,+)AT, EAAT3, PepT1, LAT4, NHE2, NHE3, and y(+)LAT2 had positive correlations with body weight (0.71
Distinct Signaling Cascades Elicited by Different Formyl Peptide Receptor 2 (FPR2 Agonists
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Fabio Cattaneo
Full Text Available The formyl peptide receptor 2 (FPR2 is a remarkably versatile transmembrane protein belonging to the G-protein coupled receptor (GPCR family. FPR2 is activated by an array of ligands, which include structurally unrelated lipids and peptide/proteins agonists, resulting in different intracellular responses in a ligand-specific fashion. In addition to the anti-inflammatory lipid, lipoxin A4, several other endogenous agonists also bind FPR2, including serum amyloid A, glucocorticoid-induced annexin 1, urokinase and its receptor, suggesting that the activation of FPR2 may result in potent pro- or anti-inflammatory responses. Other endogenous ligands, also present in biological samples, include resolvins, amyloidogenic proteins, such as beta amyloid (Aβ-42 and prion protein (Prp106–126, the neuroprotective peptide, humanin, antibacterial peptides, annexin 1-derived peptides, chemokine variants, the neuropeptides, vasoactive intestinal peptide (VIP and pituitary adenylate cyclase activating polypeptide (PACAP-27, and mitochondrial peptides. Upon activation, intracellular domains of FPR2 mediate signaling to G-proteins, which trigger several agonist-dependent signal transduction pathways, including activation of phospholipase C (PLC, protein kinase C (PKC isoforms, the phosphoinositide 3-kinase (PI3K/protein kinase B (Akt pathway, the mitogen-activated protein kinase (MAPK pathway, p38MAPK, as well as the phosphorylation of cytosolic tyrosine kinases, tyrosine kinase receptor transactivation, phosphorylation and nuclear translocation of regulatory transcriptional factors, release of calcium and production of oxidants. FPR2 is an attractive therapeutic target, because of its involvement in a range of normal physiological processes and pathological diseases. Here, we review and discuss the most significant findings on the intracellular pathways and on the cross-communication between FPR2 and tyrosine kinase receptors triggered by different FPR2
Changes in Enteric Neurons of Small Intestine in a Rat Model of Irritable Bowel Syndrome with Diarrhea.
Li, Shan; Fei, Guijun; Fang, Xiucai; Yang, Xilin; Sun, Xiaohong; Qian, Jiaming; Wood, Jackie D; Ke, Meiyun
Physical and/or emotional stresses are important factors in the exacerbation of symptoms in irritable bowel syndrome (IBS). Several lines of evidence support that a major impact of stress on the gastrointestinal tract occurs via the enteric nervous system. We aimed to evaluate histological changes in the submucosal plexus (SMP) and myenteric plexus (MP) of the distal ileum in concert with the intestinal motor function in a rat model of IBS with diarrhea. The rat model was induced by heterotypic chronic and acute stress (CAS). The intestinal transit was measured by administering powdered carbon by gastric gavage. Double immunohistochemical fluorescence staining with whole-mount preparations of SMP and MP of enteric nervous system was used to assess changes in expression of choline acetyltransferase, vasoactive intestinal peptide, or nitric oxide synthase in relation to the pan neuronal marker, anti-Hu. The intestinal transit ratio increased significantly from control values of 50.8% to 60.6% in the CAS group. The numbers of enteric ganglia and neurons in the SMP were increased in the CAS group. The proportions of choline acetyltransferase- and vasoactive intestinal peptide-immunoreactive neurons in the SMP were increased (82.1 ± 4.3% vs. 76.0 ± 5.0%, P = 0.021; 40.5 ± 5.9% vs 28.9 ± 3.7%, P = 0.001), while nitric oxide synthase-immunoreactive neurons in the MP were decreased compared with controls (23.3 ± 4.5% vs 32.4 ± 4.5%, P = 0.002). These morphological changes in enteric neurons to CAS might contribute to the dysfunction in motility and secretion in IBS with diarrhea.
Dietary supplementation with bovine lactoferrampin-lactoferricin produced by Pichia pastoris fed-batch fermentation affects intestinal microflora in weaned piglets.
Tang, Xiang-Shan; Shao, Hua; Li, Tie-Jun; Tang, Zhi-Ru; Huang, Rui-Ling; Wang, Sheng-Ping; Kong, Xiang-Feng; Wu, Xin; Yin, Yu-Long
This work is aimed at investigating the effects of recombinant bovine lactoferrampin-lactoferricin (LFA-LFC) instead of chlortetracycline on intestinal microflora in weaned piglets. The high cost of peptide production from either native digestion or chemical synthesis limits the clinical application of antimicrobial peptides. The expression of recombinant peptides in yeast may be an effective alternative. In the current study, recombinant LFA-LFC was produced via fed-batch fermentation in recombinant strain Pichia pastoris (KM71) XS10. Uniform design U6(6(4)) was used to optimize the fermentation conditions. The target peptide purified via cation-exchange and size-exclusion chromatography was added into the dietary of weaned piglets. After 21 days, the Lactobacilli, Bifidobacteria, and Enterobacteria in the chyme of the gut were quantified using real-time polymerase chain reaction. The results showed that approximately 82 mg of LFA-LFC was secreted into 1 L of medium under optimized conditions. Moreover, purified peptide showed strong antimicrobial activities against all the tested microorganisms. Compared with the control group, the LFA-LFC group increased the amount of Lactobacilli and Bifidobacteria (P<0.05) in the chyme of the stomach, duodenum, jejunum, ileum, colon, and caecum. These results show that dietary supplementation with LFA-LFC can affect intestinal microflora in weaned piglets.
Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo?Obstruction in 6 Dogs
Zacuto, A.C.; Pesavento, P.A.; Hill, S.; McAlister, A.; Rosenthal, K.; Cherbinsky, O.; Marks, S.L.
Background Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo?obstruction in humans and animals. Objective To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Animals Six client?owned dogs. Methods Retrospective case series. Medical records were reviewed to de...
Structural Characterization of Peptide Antibodies
DEFF Research Database (Denmark)
Chailyan, Anna; Marcatili, Paolo
The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery....... To better understand the underlying mechanisms of antibody-antigen interaction here we present a pipeline developed by us to structurally classify immunoglobulin antigen binding sites and to infer key sequence residues and other variables that have a prominent role in each structural class....
Self-assembling peptide semiconductors
Tao, Kai; Makam, Pandeeswar; Aizen, Ruth; Gazit, Ehud
Semiconductors are central to the modern electronics and optics industries. Conventional semiconductive materials bear inherent limitations, especially in emerging fields such as interfacing with biological systems and bottom-up fabrication. A promising candidate for bioinspired and durable nanoscale semiconductors is the family of self-assembled nanostructures comprising short peptides. The highly ordered and directional intermolecular π-π interactions and hydrogen-bonding network allow the formation of quantum confined structures within the peptide self-assemblies, thus decreasing the band gaps of the superstructures into semiconductor regions. As a result of the diverse architectures and ease of modification of peptide self-assemblies, their semiconductivity can be readily tuned, doped, and functionalized. Therefore, this family of electroactive supramolecular materials may bridge the gap between the inorganic semiconductor world and biological systems. PMID:29146781
Antimicrobial Peptide Production and Purification.
Suda, Srinivas; Field, Des; Barron, Niall
Antimicrobial peptides (AMPs) are natural defense compounds which are synthesized as ribosomal gene-encoded pre-peptides and produced by all living organisms. AMPs are small peptides, usually cationic and typically have hydrophobic residues which interact with cell membranes and have either a narrow or broad spectrum of biological activity. AMPs are isolated from the natural host or heterologously expressed in other hosts such as Escherichia coli. The proto-typical lantibiotic Nisin is a widely used AMP that is produced by the food-grade organism Lactococcus lactis. Although AMP production and purification procedures require optimization for individual AMPs, the Nisin production and purification protocol outlined in this chapter can be easily applied with minor modifications for the production and purification of other lantibiotics or AMPs. While Nisin is produced and secreted into the supernatant, steps to recover Nisin from both cell-free supernatant and cell pellet are outlined in detail.
Delivery systems for antimicrobial peptides
DEFF Research Database (Denmark)
Nordström, Randi; Malmsten, Martin
Due to rapidly increasing resistance development against conventional antibiotics, finding novel approaches for the treatment of infections has emerged as a key health issue. Antimicrobial peptides (AMPs) have attracted interest in this context, and there is by now a considerable literature...... on the identification such peptides, as well as on their optimization to reach potent antimicrobial and anti-inflammatory effects at simultaneously low toxicity against human cells. In comparison, delivery systems for antimicrobial peptides have attracted considerably less interest. However, such delivery systems...... are likely to play a key role in the development of potent and safe AMP-based therapeutics, e.g., through reducing chemical or biological degradation of AMPs either in the formulation or after administration, by reducing adverse side-effects, by controlling AMP release rate, by promoting biofilm penetration...
Radioactive labelling of peptidic hormones
International Nuclear Information System (INIS)
Fromageot, P.; Pradelles, P.; Morgat, J.L.; Levine, H.
The labelling of peptidic hormones requires stability, specificity and sensitivity of the label. Introduction of a radioactive atome is one way to satisfy these criteria. Several processes have been described to prepare radioactive TRF: synthesis of the peptide with labelled aminoacids or introduction of the label into the hormone. In that approach, tritium can be substituted in the imidazole ring, via precursors activating the proper carbon. Monoiodo TRF leads essentially to tritium labelling of the 5 positions whereas monoazo TRF allows the preparation of 3 H TRF labelled in the 2 positions. Di-substituted TRF leads to labelling into the 2 and 5 carbons. Labelled analogs of TRF can be prepared with labelled iodine; further developments of peptide labelling, will be presented. In particular, the homolytic scission of the C-iodine, bond by photochemical activation. The nascent carbon radical can be stabilized by a tritiated scavenger. This approach eliminates the use of heavy metal catalysts
DEFF Research Database (Denmark)
Hesselager, Marianne Overgaard; Codrea, Marius; Sun, Zhi
Biological research of Sus scrofa, the domestic pig, is of immediate relevance for food production sciences, and for developing pig as a model organism for human biomedical research. Publicly available data repositories play a fundamental role for all biological sciences, and protein data...... repositories are in particular essential for the successful development of new proteomic methods. Cumulative proteome data repositories, including the PeptideAtlas, provide the means for targeted proteomics, system-wide observations, and cross-species observational studies, but pigs have so far been...... underrepresented in existing repositories. We here present a significantly improved build of the Pig PeptideAtlas, which includes pig proteome data from 25 tissues and three body fluid types mapped to 7139 canonical proteins. The content of the Pig PeptideAtlas reflects actively ongoing research within...
Interactions between the intestinal microbiota and innate lymphoid cells
Chen, Vincent L; Kasper, Dennis L
The mammalian intestine must manage to contain 100 trillion intestinal bacteria without inducing inappropriate immune responses to these microorganisms. The effects of the immune system on intestinal microorganisms are numerous and well-characterized, and recent research has determined that the microbiota influences the intestinal immune system as well. In this review, we first discuss the intestinal immune system and its role in containing and maintaining tolerance to commensal organisms. We next introduce a category of immune cells, the innate lymphoid cells, and describe their classification and function in intestinal immunology. Finally, we discuss the effects of the intestinal microbiota on innate lymphoid cells. PMID:24418741
Bovine pancreatic polypeptide as an antagonist of muscarinic cholinergic receptors
International Nuclear Information System (INIS)
Pan, G.Z.; Lu, L.; Qian, J.; Xue, B.G.
In dispersed acini from rat pancreas, it was found that bovine pancreatic polypeptide (BPP) and its C-fragment hexapeptide amide (PP-6), at concentrations of 0.1 and 30 μM, respectively, could significantly inhibit amylase secretion stimulated by carbachol, and this inhibition by BPP was dose dependent. 45 Ca outflux induced by carbachol was also inhibited by BPP or PP-6, but they had no effect on cholecystokinin octapeptide- (CCK-8) or A23187-stimulated 45 Ca outflux. BPP was also capable of displacing the specific binding of [ 3 H]-quinuclidinyl benzilate to its receptors, and it possessed a higher affinity (K/sub i/35nM) than carbachol (K/sub i/ 1.8 μM) in binding with M-receptors. It is concluded from this study that BPP acts as an antagonist of muscarinic cholinergic receptors in rat pancreatic acini. In addition, BPP inhibited the potentiation of amylase secretion caused by the combination of carbachol plus secretin or vasoactive intestinal peptide. This may be a possible explanation of the inhibitory effect of BPP on secretin-induced pancreatic enzyme secretion shown in vivo, since pancreatic enzyme secretion stimulated by secretin under experimental conditions may be the result of potentiation of enzyme release produced by the peptide in combination with a cholinergic stimulant
Experiencing sexuality after intestinal stoma
Directory of Open Access Journals (Sweden)
Maria Angela Boccara de Paula
Full Text Available OBJECTIVE: Identify the Social Representations (SR of ostomized people in terms of sexuality after the stoma. METHODS: An exploratory, descriptive, qualitative study using the Social Representation Theory with 15 ostomized people (8 females, mean age of 57.9 years, between August and September 2005. Data obtained from transcribed interviews were submitted to content analysis, resulting in the thematic unit "Giving new meaning to sexuality" and subthemes. RESULTS: The study demonstrated that the intestinal stoma interferes in the sexuality experience, showing that the meanings attributed to this experience are based on individual life stories, quality of personal relationships established in practice and perception of sexuality, despite the stoma. CONCLUSIONS: The Social Representations, in terms of experiencing sexuality after the stoma, are based on meanings attributed to the body, associated with daily life and present in the social imaginary. It is influenced by other factors, such as physiological changes resulting from the surgery and the fact of having or not a partner. Care taken during sexual practices provide greater security and comfort in moments of intimacy, resembling the closest to what ostomized people experienced before the stoma. The self-irrigation technique associated or not with the use of artificial occluder, has been attested by its users as a positive element that makes a difference in sexual practice after the stoma. The support to ostomized people should be comprehensive, not limited to technical care and disease, which are important, but not sufficient. The interdisciplinary health team should consider all aspects of the person, seeking a real meeting between subjects.OBJETIVO: Identificar as Representações Sociais (RS da pessoa estomizada intestinal sobre vivência da sexualidade após confecção do estoma. MÉTODOS: Estudo exploratório, descritivo, qualitativo do ponto de vista do referencial da Representa
Intestinal Iron Homeostasis and Colon Tumorigenesis
Directory of Open Access Journals (Sweden)
Yatrik M. Shah
Full Text Available Colorectal cancer (CRC is the third most common cause of cancer-related deaths in industrialized countries. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Iron is an essential nutrient for cell growth. Iron overload caused by hereditary mutations or excess dietary iron uptake has been identified as a risk factor for CRC. Intestinal iron is tightly controlled by iron transporters that are responsible for iron uptake, distribution, and export. Dysregulation of intestinal iron transporters are observed in CRC and lead to iron accumulation in tumors. Intratumoral iron results in oxidative stress, lipid peroxidation, protein modification and DNA damage with consequent promotion of oncogene activation. In addition, excess iron in intestinal tumors may lead to increase in tumor-elicited inflammation and tumor growth. Limiting intratumoral iron through specifically chelating excess intestinal iron or modulating activities of iron transporter may be an attractive therapeutic target for CRC.
Diversity and functions of intestinal mononuclear phagocytes
DEFF Research Database (Denmark)
Joeris, Thorsten; Müller-Luda, K; Agace, William Winston
The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation. In the curr......The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation....... In the current review we discuss the function of intestinal cDC and monocyte-derived MNP, highlighting how these subsets play several non-redundant roles in the regulation of intestinal immune responses. While much remains to be learnt, recent findings also underline how the various populations of MNP adapt...
Pterostilbene Prevents Intestinal Ischemia Reperfusion Injury in ...
African Journals Online (AJOL)
Methods: Male Wistar rats were divided into 4 groups as follows: Control group; intestinal .... excitation wavelength (485 nm) and emission wavelength (528 nm). The results ... Ethanolic phase of the tissue homogenate was extracted using ...
Gastro-intestinal phytobezoars in Zimbabwean Africans.
Stein, C M; Gelfand, M
The clinical features of 10 African patients with gastro-intestinal phytobezoars are described. These were similar to those described with persimmon bezoars and we postulate that the fruit of locally found trees, also of the genus Diospyros, are responsible.
Epidemiology of small intestinal atresia in Europe
DEFF Research Database (Denmark)
Best, Kate E; Tennant, Peter W G; Addor, Marie-Claude
The epidemiology of congenital small intestinal atresia (SIA) has not been well studied. This study describes the presence of additional anomalies, pregnancy outcomes, total prevalence and association with maternal age in SIA cases in Europe....
Congenital central hypoventilation syndrome and intestinal ...
African Journals Online (AJOL)
... hypoventilation syndrome (CCHS), also called 'Ondine's curse', is characterised by an abnormal ventilatory response to progressive hypercapnia and sustained hypoxaemia. Neonates with this condition experience hypoventilation or apnoea while asleep. Patients may also have congenital intestinal aganglionosis (CIA), ...
Mesenteric lipoma causing recurrent intestinal obstruction
African Journals Online (AJOL)
Jan 12, 2013 ... vomiting, constipation, and central abdominal mass. ... Mesenteric lipoma may cause abdominal pain by complete intestinal .... Kaniklides C, Frykberg T, Lundkvist K. Pediatric mesenteric lipoma: An unusual cause of repeated ...
Inflammasome in Intestinal Inflammation and Cancer
Directory of Open Access Journals (Sweden)
Tiago Nunes
Full Text Available The activation of specific cytosolic pathogen recognition receptors, the nucleotide-binding-oligomerization-domain- (NOD- like receptors (NLRs, leads to the assembly of the inflammasome, a multimeric complex platform that activates caspase-1. The caspase-1 pathway leads to the upregulation of important cytokines from the interleukin (IL-1 family, IL-1β, and IL-18, with subsequent activation of the innate immune response. In this review, we discuss the molecular structure, the mechanisms behind the inflammasome activation, and its possible role in the pathogenesis of inflammatory bowel diseases and intestinal cancer. Here, we show that the available data points towards the importance of the inflammasome in the innate intestinal immune response, being the complex involved in the maintenance of intestinal homeostasis, correct intestinal barrier function and efficient elimination of invading pathogens.
Novel Formulations for Antimicrobial Peptides
Directory of Open Access Journals (Sweden)
Ana Maria Carmona-Ribeiro
Full Text Available Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.