[Complications of hepatic hydatidosis].

[Complications of hepatic hydatidosis]. Fifty cases of complicated hydatid cyst of the liver on a total of 250 cases of hydatid cyst observed were analyzed. The Authors describe the several complications observed (compression, infection, rupture into biliary tract or into the thorax or into the peritoneal cavity, the diagnostic and therapeutic procedures. Total mortality was about 7.6% (3 cases) 2 patient died for intraperitoneal rupture and one for rupture in the biliary tract. Surgical treatment should be as radical as possible performing total or subtotal pericystectomy, hepatic resection is reserved to selected cases. Drainage by Kehr tube of biliary tract is necessary of rupture of the cyst in the biliary tract, while we limit the indication for a papillostomy to the sphincter duct stenosis.


[Aneurysms of the peripheral arteries].

[Aneurysms of the peripheral arteries]. The Authors examine aetiological, pathological, and clinical patterns of the peripheric aneurysms and emphasize the frequency with which an aneurysm, even when asymptomatic, can complicate and cause acute ischaemia of a limb with high risk of amputation. They present their personal experience of ten operated cases, some of choice, others in emergency, and report the immediate and late results.


[Acute thrombosis of the lower limbs: choice of treatment?]. The paper reports the Authors' experience of treating acute thrombotic-type ischemia of the lower limbs. It analyses the results obtained in 105 patients treated either using vascular reconstruction, loco-regional fibrinolytic therapy, or simple thrombectomy. Statistical analysis reveals a marked difference between reconstructive surgery and simple thrombectomy, whereas fibrinolysis was found to be a useful but limited method used only in patients with pallid ischemia and in circulatory compensation. In conclusion, the Authors sustain that an aggressive-type approach is currently the most reliable method to be used in all cases in which the patient's general and local conditions permit.


[Mechanical and antibiotic preparation and infections in colorectal surgery. Comparison of 2 methods of orthograde lavage]. The efficacy of two methods of orthograde lavage preparation in elective colorectal surgery was tested in 133 consecutive patients: the results obtained with whole gut irrigation (50 patients, group A) were compared with the results of oral lavage solution (83 patients, group B). All patients received a parenteral association of antibodies (clindamycin in combination with a broad spectrum antibiotic, mainly II or III generation cephalosporins). Bacterial cultures were carried out at the end of the lavage in the rectal effluent (no statistically significant differences between the two groups) and in the intraoperative aspirate from the colon (the bacterial concentration was higher in group B). The total number of infections was 12 (9%), with 6 (12%) in group A and 6 (7.2%) in group B. The infectious complications involved perineal wound in 9 cases (in 2 patients in combination with abdominal wound infection), abdominal drainage in 2 and abdominal wound in 1. The type of broad spectrum antibiotic did not affect the infection rate significantly. Perioperative and infection site bacteriological cultures grew the same type of organism only in one case. The surgeons' judgement of the adequacy of the cleansing favored whole gut irrigation, although the results of the study revealed that both methods were safe and provided equally adequate bowel cleansing.


[Surgical day hospital: technical possibilities and organizational model]. The Authors propose an organizational model for a surgical day hospital program, which is being used for a pilot day surgery unit in the I Department of Surgery of the Rome University "La Sapienza". The program requires little capital investment, as it is closely linked, geographically and administratively, to the main surgical unit, and uses the present staff, facilities and support services. The model is based on a computerized LAN (Local Area Network), providing fast recording, scheduling, management and trannsfer of medical data for each patient. The present situation is reported in detail. Data from the authors' outpatient department for 1988, have been recorded and elaborated. The results show a low use of surgical day care, limited to minor surgical procedures, and with not a single operation performed under general anesthesia. The authors hope to see a growth in the use of day surgery and a more selective use of inpatient care.


[Association of biliary calculosis and portal cavernomatosis]. This paper reports the case of a woman, who underwent surgery because of cholelithiasis, with intraoperative finding of prehepatic portal hypertension from portal vein thrombosis ("portal cavernoma") with healthy liver, later confirmed by angiographic studies. This rare pathologic association carries a higher risk of major operative complications; therefore the Authors agree with the general belief that, for these cases, biliary tract surgery should be as simple and safe as possible. In the case of preoperative diagnosis of biliary disease associated with portal cavernoma, should a surgical approach on the biliary tract be required, we agree on the advisability of performing a shunting procedure before any kind of biliary surgery. In case of variceal bleeding endoscopic sclerotherapy will be the first choice; surgical procedures (shunting) should be seen as a second choice in case of rebleeding after sclerotherapy.


[The Roux loop syndrome: a postgastrectomy syndrome. Description of 2 clinical cases]. The Roux-En-Y operation has been used to control enterogastric reflux occurring after previous distal gastric resection and it has been used extensively in the treatment of alkaline reflux. Recently a postgastrectomy syndrome characterized by chronic abdominal pain, persistent nausea and vomiting that is exacerbated by eating and that develops after the Roux-En-Y operation has been described. It has therefore been postulated that the Roux-En-Y limb acts as a functional obstruction and causes the symptoms.


[Polycystic retroperitoneal leiomyosarcoma. A clinical and anatomo-pathological contribution]. The Authors report an unusual case of retroperitoneal leiomyosarcoma, multicystic, resembling an ovarian cystoma in a patient with simultaneous subclavian-axillary thrombosis. They analyze anatomo-pathological and clinical aspects of this kind of tumor and underline the possible errors they themselves faced. To they come to the conclusion that a careful diagnostic iter of this kind of tumor must be carried out and that the surgical approach must be radical.


[A case of extrarenal angiomyolipoma with intestinal localization]. The Authors present a case of extrarenal angiomyolipoma. The tumor arose from the pericolonic fat of the sigmoid colon and, increasing in size, caused intestinal obstruction by extrinsic lesion. Extrarenal angiomyolipoma is extremely rare and to our knowledge this is the first reported case arising from the colonic wall.


[From laparotomy to pelviscopy. A new trend]. Our pelviscopic operative series from 1986 to June 1991 is reported. Nowadays our group performs 70% of female genital benign lesions by the pelviscopic technique. Infect laparotomy has been abandoned in case of benign ovarian cyst while the pelviscopic myomectomy rate is about 69%. Our results show that this kind of management is safe and also undeniable advantages such as morbidity reduction, shorter hospital stay, less social cost, quick return to work and renewing of the method make the indications more and more every day.


[Spontaneous abortion. Epidemiologic considerations]. The authors report on the incidence of spontaneous abortion, the commonest complication of the pregnancy. The period examined is from March 1989 and March 1991, in the obstetrical division of University of L'Aquila. The incidence and association between maternal age, malformations, parity, maternal cigarette smoking and alcohol are reported.


[Predictive factors of infantile cerebral lesions during pregnancy and labor]. The risks connected with children's cerebral lesions are examined by means of two different surveys related to a retrospective study over a period of about 10 years. One of these surveys is clinical and is based in the obstetric case history of children carrying psychomotor handicaps. The other survey is instrumental and concerns 100 cases of pathologic cardiotocography during labour associated with fetal suffering. The results of border surveys are discusses. For the assessment of the obstetric risk the sum of the pathologic conditions that emerged during pregnancy and delivery have to be taken into consideration. Cardiotocography is still a fundamental diagnostic examination to recognise the suffering fetus and the data collected real a close association between cardiotocography diagnosis and the conditions of the baby at the birth.


Protection by N-methyl-D-aspartate receptor antagonists against impairment of working memory in rats following transient cerebral ischemia. A 5-min period of cerebral ischemia increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) assessed by the working memory procedure applied in a three-panel runway task. The selective and competitive N-methyl-D-aspartate (NMDA) receptor antagonist CGS 19755 (3.2 and 10 mg/kg), administered i.p. immediately after blood flow reperfusion, significantly reduced the increase in errors expected to occur 24 h after 5 min of ischemia. CGS 19755 10 mg/kg had no effect on the increase in errors when injected 6 h after ischemia. The i.p. administration of the non-competitive NMDA antagonists dextrorphan 10 and 32 mg/kg and MK-801 1.0 mg/kg immediately after reperfusion decreased the increase of errors in the ischemic rats. The protective effects of NMDA antagonists suggest that the mechanism mediated by NMDA receptors during the early reperfusion phase plays a pivotal role in the postischemic impairment of working memory.


[Prophylactic use of cefotetan in gynecologic surgery]. The efficacy of prophylactic treatment with systemic antibiotics in laparotomic gynecologic surgery is well established. Lately, short-term schemes have been preferred in surgical prophylaxis for different reasons. First of all, experimental data demonstrated that the efficacy of an antibiotic is maximal when it reaches active tissue concentrations at the time of bacterial contamination. In addition with the availability of new, long-acting antibiotics, a long period of time around the operations was possibly covered. The effectiveness of a single preoperative 2 gm dose of Cefotetan was compared with a traditional treatment of 3 gm daily of Cefazolin for one week following surgery in 86 women undergoing laparotomic gynecologic surgery for benign pathology. Our results confirm that preoperative treatment with Cefotetan is able to prevent infectious disease such as 3 gm of Cefazolin per day for one week. Thus, Cefotetan can be used for this type of prophylaxis considering its broad spectrum of action and pharmacokinetic properties.


[Identification of growth hormone in human embryos and fetuses]. The authors report a study on 10 human fetuses aged between 9 and 16 weeks of gestation. A PAP technique (peroxidase-anti-peroxidase) was used to identify the time and place of growth hormone appearance. Data obtained show intense positivity for chondrocytes, obleoblasts and perichrondrium. Hepatocytes were also found to be positive. These results suggest that GH plays an important role in a number of tissues in which it conditions maturation and development.


Neuronal survival and neurite extension supported by astrocytes co-cultured in transwells. The influence of astrocytes on the development of cerebral cortical neurons was studied in a co-culture system using transwells with chemically defined medium. Cerebral cortical neurons from 15- or 16-day-old mouse embryo were cultured in the lower wells which were separated by a porous membrane from the upper transwells where cerebral cortical astrocytes from newborn mouse were cultured. Neurons co-cultured with astrocytes for 7 days formed a network-like web and maintained a slightly better survival from 4 to 7 days. However, neurons cultured in conditioned medium obtained from astrocytes did not form any network after 7 days even though they maintained a better cell survival at 4 days.


Enhancement of postsynaptic responsiveness during long-term potentiation of mossy fiber synapses in guinea pig hippocampus. The primary site responsible for the long-lasting enhancement of synaptic transmission during long-term potentiation (LTP) was examined by quantal analysis of excitatory postsynaptic potentials in thin sections of the guinea pig hippocampus. With induction of LTP in mossy fiber synapses, estimated values of quantal amplitude (q) and Pascal parameters p and r were increased significantly. No increases in quantal content (m) were detected. The magnitude of increases in q was almost equal to that of LTP. These results indicate that LTP in mossy fiber synapses results from increases in responsiveness of postsynaptic neurons.


[THe use of leuprolide in endometrial glandular hyperplasia]. Endometrial hyperplasia is a very frequent pathology during menopause and involves the risk of the malignant transformation of lesions and the onset of anemia due to concomitant clinical phenomena. Standard medical treatments often involve major collateral effects which impede their long-term use. In an attempt to avoid radical surgery for many women or the use of other invasive techniques, this paper proposes the use of Leuprolide acetate which was used to treat 30 patients with histologically confirmed symptoms of endometrial hyperplasia without atypia. This controlled-session LHRH analog was administered using an intramuscular route every 30 days for 6 months. Hysteroscopic and histological controls were carried out 30 days after the last treatment and showed the resolution of histological and clinical symptoms; this was confirmed after 3 months. Fibroma, which are the most frequently associated pathology, were considerably reduced.


Behavioral and electroencephalographic effects of a serotonin receptor agonist (5-methoxy-N,N-dimethyltryptamine) in a feline model of photosensitive epilepsy. The effects of a serotonin (5-HT) receptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), on epileptic photosensitivity were studied in the lateral geniculate-kindled cat. 5-MeODMT at 4 mg/kg significantly suppressed photically induced myoclonus, but not paroxysmal EEG activity, at 0.5-1 h after injection. This antiepileptic effect was seen in association with the appearance of behavioral signs similar to those seen in the 5-HT syndrome. The present data provide further evidence that 5-HT plays an important role in photosensitive epilepsy, and suggest that the inhibitory effect of 5-MeODMT on photosensitivity results from its agonist action at 5-HT1 receptors.


[Intravenous leiomyomatosis of the uterus. Report of a case]. A clinicopathological study of a case of intravascular leiomyomatosis was performed, recalling the rarity of this pathology and the necessity of a careful follow-up. Microscopically the intravascular tumor resembles the benign leiomyoma. Authors have taken into consideration the most likely differential diagnoses: endolymphatic stromal myosis and low-grade leiomyosarcoma, they study the problem of the so-called "benign metastasizing leiomyoma" and emphasize that intravenous leiomyomatosis is frequently underdiagnosed.


[Report of a case of autoimmune thrombocytopenic purpura in pregnancy]. A clinical report concerning a severe idiopathic thrombocytopenia during pregnancy (minimal platelet count 3000/mm3 is described). Corticosteroids and immunoglobulins were administered in preparation to elective cesarean delivery. Since the platelet count not improve significantly, 3 units of platelets from a single donor were adjunctively given using diapheresis. An elective cesarean delivery was performed at 34 weeks, without further complications. The newborn weighed 2550 g and the postnatal course was uneventful.


Onset of CGRP expression and its restriction to a subset of spinal motor neuron pools in the chick embryo is not affected by treatment with curare. Calcitonin gene-related peptide (CGRP) is expressed in and defines a subset of motor neuron pools in the lumbar spinal cord of the chick embryo. The onset of CGRP expression in individual pools coincides with both the period of the initial innervation of the leg and the beginning of naturally occurring cell death in the lumbar motor column. Administration of neuromuscular blocking agents at this time results in a striking reduction of normal motor neuron loss. It has been reported that such treatment also results in the abolition of CGRP expression at later stages of development. In this study, we have examined the effect of curare treatment on CGRP expression in motor neurons earlier in their development. We find that, in contrast to the effects reported at later stages, inhibition of neuromuscular activity does not affect either the onset of CGRP expression or its restriction to a subset of motor neuron pools. This demonstrates that the control of the onset of CGRP expression is unlikely to be linked to processes which are regulated by neuromuscular transmission including naturally-occurring cell death.


Synaptosomal plasma and mitochondrial membrane potentials during anoxia. The precise mechanism by which altered oxidative metabolism impairs neuronal function is unknown. Previous indirect studies suggest that anoxia's effects on the mitochondrial membrane potentials may underlie anoxia's actions. Twenty minutes of anoxia reduced the mitochondrial membrane potential of intact synaptosomes by 38-59 mV, but diminished the plasma membrane potential by only 4-10 mV. Anoxia did not alter the response of the plasma or mitochondrial membrane potentials to K+, nor did anoxia affect the reaction of the plasma membrane potential to valinomycin. However, anoxia diminished the response of the mitochondrial membrane potential to valinomycin by 50%. Thus, partial collapse of the mitochondrial membrane potential may be an important mediator of hypoxia-or anoxia-induced changes in neuronal function.


Amphetamine enhances extracellular concentrations of dopamine and acetylcholine in dorsolateral striatum and nucleus accumbens of freely moving rats. The effect of two consecutive administrations of amphetamine (1.5 mg/kg, s.c.; 2 h apart) on dopamine (DA) and acetylcholine (ACh) efflux in dorsolateral striatum and nucleus accumbens was studied with in vivo microdialysis in freely moving rats. Amphetamine was found to cause a more persistent increase of extracellular DA in the dorsolateral striatum than in the nucleus accumbens. The increase in DA overflow by amphetamine was accompanied by an increase of extracellular ACh in both brain areas. The results are inconsistent with the hypothesis of an amphetamine-induced inhibitory regulation by DA on ACh overflow.


Growth of axon collaterals of eclosion hormone neurons into a new release site during metamorphosis of Bombyx mori. Eclosion hormone (EH) is a peptide triggering ecdysis in insects. Injection of Lucifer dye into EH producing cells in the silkworm at various stages of adult development revealed that after pupation the EH cells produced many axon collaterals to form a new neurohaemal structure in the corpora cardiaca (CC), the corpora allata and the associated nerves of the CC. The axon collaterals may serve as a major release site of EH at adult ecdysis.


The immediate consequences of middle cerebral artery occlusion on GABA synthesis in mouse cortex and cerebellum. The effect on gamma-aminobutyric acid (GABA) synthesis of focal ischaemia in the right cortex of the mouse was investigated by performing a right middle cerebral artery (MCA) occlusion. Synthesis of GABA was determined by measurement of the rate of GABA accumulation in tissue following injection of amino oxyacetic acid (AOAA; 30 mg/kg, i.p.). Five min following the MCA occlusion, the rate of GABA synthesis in the right (ischaemic) cortex was decreased by approximately 70% compared to either the left cortex or the right cortex of untreated controls. The basal GABA concentration was however unaffected. Four hours after the occlusion the rate of GABA synthesis was similar in the right and left cortex. The rate of GABA accumulation in the cerebellum was unchanged at both times after the right MCA occlusion compared with untreated control mice. The data suggest that there is a rapid but short lasting decrease in GABA synthesis following an ischaemic insult and it is suggested that this might be associated with the EEG spiking activity that occurs at this time.


Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment. Enriched environment has been shown to enhance learning and memory and to induce morphological changes in the hippocampus. We report that rats housed in an enriched environment showed improved performance in the Morris water maze and decreased spontaneous motor activity. Exposure to behavioural tests increased expression of the mRNA that encodes brain-derived neurotrophic factor in the hippocampus. This was not seen when rats subjected to impoverished housing were tested suggesting that environmental history of the animal is of importance to induce expression of brain-derived neurotrophic factor in the hippocampus that may promote neuronal changes related to learning and memory.


Stress induces neuronal death in the hippocampus of castrated rats. Whereas loss of CA3 neurons in the hippocampus of monkeys which died of stress ulcers suggests that some structural changes may occur, there is no direct evidence that shows stress-induced irreversible changes of neurons. When rats were orchidectomized (castrated) and stressed by restraint and immersion in water for 15 min/day for 30 days, significant loss of hippocampal CA3 and CA4 neurons was observed. Furthermore, primary cultured hippocampal neurons survived shorter when treated with corticosterone. This neuronal loss was prevented by simultaneous administration of testosterone in vivo and in vitro. These findings indicate that stress can contribute to neuronal degeneration associated with hypogonadal conditions such as aging.


Interaction of vestibular and proprioceptive inputs for human self-motion perception. Human perception of horizontal self(body)-motion in space was studied during various combinations of vestibular and leg-proprioceptive stimuli in the dark. During sinusoidal rotations of the trunk relative to the stationary feet (functionally synergistic combination) the perception was almost veridical over the frequency range tested (0.025-0.4 Hz). This finding suggested a dominance of the proprioceptive over the vestibular input, since the quantitative aspects of the perception (gain, phase, and detection threshold): (a) closely resembled those of the proprioceptive foot-to-trunk perception, and (b) clearly differed from those of the vestibular self-motion perception. However, when using other combinations, the self-motion perception changed in a monotonous way as a function of the two inputs, indicating that the two inputs do interact in a linear way. In a model of these findings the interaction occurs in two stages: (1) summation of a vestibular trunk-in-space signal and a (dynamically matched) proprioceptive foot-to-trunk signal yields an internal representation of foot support motion in space; (2) superposition of the latter by an almost ideal proprioceptive trunk-to-foot signal results in a representation of trunk-in-space motion (essentially proprioception-dependent and ideal when the feet are stationary).


A lipoxygenase pathway of arachidonic acid metabolism mediates FMRFamide activation of a potassium current in an identified neuron of Helisoma. The neuropeptide FMRFamide causes a presynaptic inhibition of neurotransmitter release from neuron B5 of Helisoma. In this study we demonstrate that one of FMRFamide's actions is to activate an outwardly rectifying potassium current. Arachidonic acid also activates an outward current in B5. The phospholipase A2 inhibitor, 4-bromophenacylbromide (BPB), and nordihydroguaiaretic acid (NDGA), an inhibitor of arachidonic acid metabolism, but not indomethacin, block FMRFamide's activation of the potassium current. Taken together these data demonstrate that one of FMRFamide's presynaptic actions is to activate a potassium current through a lipoxygenase pathway of arachidonic acid metabolism.


Glutamate receptor expression in the rat retina. The expression of five genes (GluR A; B; C; D; GluR 5) encoding functional subunits of glutamate receptors was investigated in the rat retina using in situ hybridization with oligonucleotide probes. All five genes are expressed in the retina. All probes label cell bodies in the ganglion cell layer as well as somata in the inner third of the inner nuclear layer (INL), where the amacrine cells are located. In addition GluR 5, B and D, and to a lesser extent also GluR A are found in the middle and outer part of the INL, where bipolar and horizontal cells reside. Different subsets of retinal neurons may thus use glutamate receptors of different subunit composition.


Ultrastructural evidence for GABA-mediated disinhibitory circuits in the spinal cord of the cat. The synaptic relationships between gamma-aminobutyric acid (GABA)-immunoreactive and enkephalin-immunoreactive profiles in the cat spinal cord were examined using combined pre-embedding immunoperoxidase and post-embedding immunogold electron microscopic immunocytochemistry. Although colchicine was not used, enkephalin-immunoreactive somata and dendrites were detected in regions associated with nociceptive transmission, including laminae I, II, V and X. In each of these laminae, many GABA-immunoreactive terminals were found presynaptic to enkephalin-immunoreactive cell bodies and dendrites. We propose that disinhibition of opioid-containing neurons may be a common feature of pain-related circuits in the cat spinal cord.


Neuropeptide Y messenger ribonucleic acid in the magnocellular hypothalamo-neurohypophysial system of the rat is increased during osmotic stimulation. In the magnocellular hypothalamo-neurohypophysial system of the rat, levels of neuropeptide Y (NPY) mRNA were investigated by in situ hybridization histochemistry both in normal and osmotically stimulated animals. As an osmotic stimulus, animals were given 340 mM NaCl to drink for 12 days. After saline treatment, there was a very marked increase in NPY mRNA in the hypothalamic magnocellular supraoptic (SON) and paraventricular (PVN) nuclei (7600% and 3200%, resp.). These data suggest that magnocellular SON and PVN neurons synthesize NPY in response to the physiological stimulus of increased plasma osmolality.


Immunoreactivity of skate electrocytes towards monoclonal antibodies against human dystrophin and dystrophin-related (DMDL) protein. Monoclonal antibodies against human dystrophin have been used to demonstrate the existence of a dystrophin-like protein in the electrocytes of skate electric organ. This protein is also present in skate muscle and resembles that found in Torpedo electric organ. Monoclonal antibodies against a human autosomal homologue of dystrophin (DMDL protein) did not detect a similar protein in skate or Torpedo. Immunocytochemical staining of the innervated and non-innervated faces of the electrocyte membrane was obtained using the anti-dystrophin antibodies only.


Graft-derived cholinergic reinnervation of the hippocampus prevents a lasting increase of hippocampal noradrenaline concentration induced by septohippocampal damage in rats. Long-Evans female rats sustained aspirative lesions of the septohippocampal pathways and, 2 weeks later, received into the dorsal hippocampus grafts prepared from the septal area (rich in cholinergic neurons; Group Sep) or from the mesencephalic raphe (poor in cholinergic neurons; Group Rap) of rat fetuses. Lesion-only (Group Les) and virtually intact (Group Sham) rats served as controls. Between 9.5 and 10.5 months after grafting surgery, we found the lesions to decrease choline acetyltransferase activity (ChAT), high affinity synaptosomal uptake of [3H]choline (HACU) and serotonin concentration ([5-HT]), as well as to increase the noradrenaline concentration ([NA]) in the dorsal hippocampus. Raphe grafts increased [5-HT] to 456% of normal, but had only weak or no effects on the other lesion-induced modifications in brain neurochemistry. Septal grafts dramatically increased ChAT activity and HACU, enhanced [5-HT], and reduced [NA] to near-normal levels. We also found a significant negative correlation between HACU and [NA] in rats with lesions, whether grafted or not. These data show that grafts providing the denervated hippocampus with a new cholinergic innervation might be able to exert inhibitory effects on the lesion-induced increase of [NA]. Since such an increase is indicative of sympathetic sprouting, the finding of reduced [NA] in rats with graft-derived cholinergic reinnervation of the hippocampus is in line with the hypothesis that hippocampal cholinergic denervation plays a crucial role in the induction of sympathetic sprouting. However, our data do not allow to distinguish whether grafts rich in cholinergic neurons inhibited the sympathetic sprouting itself, or rather reduced the NA content of sprouted fibers.


Evidence for the presence of excitatory A2 adenosine receptors in the rat hippocampus. The A2 adenosine receptor agonist, CGS 21680 in nanomolar concentrations, reversibly increased in a concentration-dependent manner the amplitude of orthodromically-evoked population spikes recorded from the CA1 pyramidal cell layer of rat hippocampal slices. The adenosine receptor antagonist, 3,7-dimethyl-l-propargylxanthine (DMPX, 10 microM), which has selectivity for A2 adenosine receptors, prevented this excitatory effect of CGS 21680. These results suggest that A2 adenosine receptors are present in the rat hippocampus and that activation of these receptors enhance hippocampal excitability.


Recovery of distal skills after neonatal lesion of the sensorimotor cortex in the cat. The cytoarchitectonic cortical areas containing the cells of origin of the pyramidal tract were unilaterally removed from kittens during the first postnatal month. After 5 months, the distal skills of these operated animals were analyzed using a food retrieving task. After an initial deficit, cats achieved the same performance in grasping and wrist movement with the limb contralateral to the lesion as with the opposite limb. The duration of the deficit was dependent on age at the time of lesion. Recovery of distal skills after neonatal lesion is discussed with regard to the low degree of maturity of the corticospinal tract in newborn cat.


Effects of glycine antagonists on Mg(2+)- and glycine-induced [3H]N-(1-[2-thienyl]cyclohexyl)-3,4-piperidine binding. We investigated the effects of glycine antagonists, 3-amino-1-hydroxy-2- pyrrolidone (HA-966), 7-chlorokynurenic acid (7-Cl-KYNA), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 6,7-dichloro-3-hydroxy-2-quinoxalinecarboxylic acid (DHQXC), 6,7-dichloroquinoxaline-2,3-dione (DCQX), and 5-chloro-indole-2-carboxylic acid (5-Cl-I2CA), on Mg(2+)- and glycine-induced [3H]N-(1-[2-thienyl]cyclohexyl)-3,4-piperidine ([3H]TCP) binding to well-washed rat cortical membranes. Except for 5-Cl-I2CA, all the glycine antagonists completely inhibited not only glycine- but also Mg(2+)-induced [3H]TCP binding in a concentration-dependent manner. Out of all the glycine antagonists examined DHQXC most selectively inhibited Mg(2+)-induced [3H]TCP binding, while DCQX was the most selective for inhibiting glycine-induced [3H]TCP binding.


The role of swollen astrocytes in human brain lesions after edema--an immunohistochemical study using formalin-fixed paraffin-embedded sections. Swollen astrocytes (SAs) in the white matter after brain edema were immunohistochemically studied in cases with cerebral vascular events, brain tumor and protracted non-missile head injury. SAs showed a decrease in reactivity to glial fibrillary acidic protein (GFAP) and, on the other hand, were positive for laminin, an extracellular matrix glycoprotein known to be secreted by astrocytes. SAs in protracted lesions were strongly positive for both vimentin and plasma proteins including IgG, IgM, C3d and C4d. Remarkable vimentin expression in SAs, instead of GFAP, strongly suggests that SAs are not going to degenerate but are bearing up to regenerate in such circumstances. A number of vimentin-positive buttons also appeared in such protracted lesions, demonstrating disintegration of the processes of SAs. Immunohistochemical detection of plasma proteins in SAs are believed to indicate a facilitated activation in SAs to transform to macrophage-like cells and to act as phagocytes. In addition, demonstration of laminin may suggest hyperactivity of laminin production in SAs after both axonal injury and concomitant edema in order to stimulate neuritic regeneration.


Regional differences in the effect of N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) on extracellular dopamine levels: an in vivo microdialysis study. N-[1-(2-Benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) is a phencyclidine derivative highly selective for the dopamine (DA) uptake complex. Its effect on extracellular DA levels was studied by in vivo microdialysis on freely moving rats. In the striatum, BTCP induced a dose-dependent increase in DA levels, without affecting DA metabolites. In the nucleus accumbens, a lower increase in DA was observed, but with concomitant decreases in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). These experiments show that the effects of BTCP on extracellular DA levels are significantly different on extrapyramidal and mesolimbic dopaminergic terminals.


Two classes of spontaneous GABA-mediated miniature synaptic currents in cultured rat hippocampal neurons. Amplitude and time course of spontaneous gamma-aminobutyric acid (GABA)-mediated miniature postsynaptic currents (MPSCs), recorded in cultured embryonic hippocampal neurons in presence of either tetrodotoxin (TTX) or increased external [Mg2+/Ca2+] ratio, revealed that they form two classes. The distribution of the most commonly recorded MPSCs was skewed both in terms of peak amplitude and rise-time (skew-MPSCs, mode: 70-120 pS). Another, less frequent class (mode: 1-3 nS) formed bell-shaped (bell-MPSCs) amplitude and rise-time distributions. MPSC initial slope did not correlate with rise time, indicating that smaller MPSCs were not electrotonically attenuated. Bell-MPSCs did not result from the integration of skew-MPSCs and both classes appeared to be composed of subunits.


No psychological dependence after oral administration of morphine to rats. Rats subjected to forced oral self-administration of morphine solutions without or in combination with two daily i.p. injections of morphine preferred drinking water when this was offered in addition to morphine solutions. The daily intake of morphine during the terminal phase of self-administration of morphine was 50-80 mg/kg (oral application alone) or 270 mg/kg (oral and i.p. application). Morphine treated animals showed withdrawal symptoms on administration of naloxone 1 mg/kg i.p. during the period of self-administration, but not when they had started drinking exclusively water. The tail-flick test revealed no tolerance during prolonged treatment with morphine. The results indicate that no psychological dependence developed when morphine was applied orally and regularly.


Müller (glial) cells in the retina of urodeles and anurans reveal different morphology by means of freeze-fracturing. Müller (glial) cells of the retina of various species of amphibia (urodeles and anurans) were investigated by means of the freeze-fracture technique. This was done because Müller cells in anamniotes were believed to differ from those in mammals in that they should lack the so-called orthogonal arrays of particles (OAP) which are a characteristic feature of Müller cells in mammalian retina. However, as we could demonstrate previously (Berg-von der Emde and Wolburg, Glia, 2 (1989) 458), fish retinal Müller cells also contain OAP in their membranes suggesting that OAP are a general marker of Müller cells in all vertebrates. As demonstrated in this study, Müller cells of urodeles (Batrachoseps attenuatus and Pleurodeles waltlii) are OAP-positive, whereas two anurans (Rana esculenta and Xenopus laevis) do not reveal any OAP in their Müller cell membranes. Under phylogenetic aspects, it appears very interesting that frogs are as yet the only vertebrate group that deviates from all other vertebrates in terms of Müller cell membrane morphology.


Catecholamine histofluorescence depletion in the infarcted brain parenchyma but not in the adventitia of the occluded cerebral arteries in rats. The effect of acute cerebral ischemia on the catecholamine-containing nerve fibers in the brain parenchyma and in the adventitia of the cerebral arteries was studied in the rat. Unilateral cerebral ischemia was produced with an intraluminal thread technique which does not damage the adventitia of cerebral arteries. One to three days after surgery the ischemic damage of the brain was consistently observed in the territory of the middle cerebral artery of the operated side. Depletion of catecholamine histofluorescence was observed in the infarcted brain parenchyma. However, in the adventitia of the middle cerebral arteries of the operated side, catecholamine histofluorescence remained intact. No detectable changes in fluorescence were observed in the brain parenchyma or adventitia of the cerebral arteries in the contralateral side. The results indicate that the perivascular catecholamine-containing nerve fibers are not impaired by the intraluminal occlusion of the cerebral artery in the early stage of ischemia.


c-Fos protein expression in the rat subfornical organ following osmotic stimulation. To examine the role of the subfornical organ (SFO) in the osmotic activation of hypothalamic neurons, the responses of the SFO to osmotic stimulation were evaluated by using c-Fos protein immunohistochemistry. Numerous c-Fos-immunoreactive nuclei were found in the SFO of rats injected i.p. with hypertonic saline solution as early as 30 min after stimulation, and the effect lasted up to 3 h. Only a few c-Fos-positive cells were detected in the SFO of rats injected with isotonic saline. However, electrolytic lesions of the SFO did not prevent the osmotic activation of the hypothalamic paraventricular and supraoptic nuclei. These data suggest that the SFO and the hypothalamic magnocellular nuclei are simultaneously but separately activated by osmotic stress.


Distribution of neurofibrillary tangles and senile plaques in the cerebral cortex in postencephalitic parkinsonism. Postencephalitic parkinsonism is characterized neuropathologically by severe loss of pigmented neurons in the substantia nigra and the presence of high densities of neurofibrillary tangles in several brainstem structures. In 5 cases of postencephalitic parkinsonism, we observed that the neurofibrillary tangle distribution in the cerebral cortex predominated in the hippocampus and entorhinal cortex. In the prefrontal and inferior temporal cortex, neurofibrillary tangles were preferentially localized in layers II and III. This pattern contrasts with the neurofibrillary tangle distribution observed in neocortical areas of Alzheimer's disease cases, where neurofibrillary tangles are denser in layer V than in layer III. These results suggest that specific elements of the cortical circuitry might be differentially affected in postencephalitic parkinsonism as compared to Alzheimer's disease, and that cortical involvement is likely to be a common feature of this condition.


Clozapine's mechanisms of action: non-dopaminergic activity rather than anatomical selectivity. The mechanisms of clozapine's unusual actions were investigated in anesthetized rats. Sensory field potentials were recorded in the nucleus accumbens, striatum and somatosensory cortex. Both haloperidol and clozapine suppressed responses in the striatum and accumbens. Clozapine's but not haloperidol's subcortical actions were unaffected by dopamine depletion. In addition, the cortical effects of the two drugs differed. These data indicate that clozapine has non-dopaminergic activity but no particular specificity for limbic basal ganglia structures. While it is known that clozapine acts as a serotonergic and cholinergic antagonist, several considerations suggest that action on still another transmitter system, possibly glutamate, needs to be investigated.


Spontaneous perikaryal neurofilament phosphorylation in the septofimbrial nucleus of the rat. Phosphorylation of the 200 kDa neurofilament peptide NF-H usually only occurs in axons. We describe the spontaneous presence of phosphorylated NF-H in a population of small spindle-shaped neurons of the rat septofimbrial nucleus. A similar phenomenon has been observed in axotomized neurons and in human neurodegenerative diseases. Our observations, as well as previous studies by other authors, indicate that perikaryal neurofilament phosphorylation is not necessarily linked to pathological conditions.


MK-801, but not anisomycin, inhibits the induction of tolerance to ischemia in the gerbil hippocampus. We examined whether MK-801, an N-methyl-D-aspartate (NMDA)-receptor antagonist, or anisomycin, a reversible protein synthesis inhibitor, inhibits the induction of ischemic tolerance following preconditioning with sublethal ischemia in gerbil hippocampus. Preconditioning with 2 min of ischemia, which induced heat shock protein-72 immunoreactivity, prevented hippocampal CA1 neuronal damage following 3 min of ischemia produced 3 days later. MK-801, but not anisomycin, inhibited the induction of tolerance although the heat shock protein synthesis was reduced in both groups. The present result suggests that NMDA receptor activation, causing stress response, induces the ischemic tolerance.


Brainstem projections to the medial preoptic region containing the luteinizing hormone-releasing hormone perikarya in the rat. An immunohistochemical and retrograde transport study. The afferent projections to the anterior medial preoptic area (MPA) from the brainstem have been studied, in female Wistar rats, by retrograde tracing with horseradish peroxidase (HRP). The HRP was injected by iontophoresis into the preoptic region containing the luteinizing hormone-releasing hormone (LHRH) perikarya. The brain sections including the MPA were reacted with diaminobenzidine (DAB) to reveal the injection site; the LHRH cells were then immunohistochemically identified using DAB with ammonium nickel sulphate. When the injection site incorporated the LHRH cells, the brainstem sections were reacted with the DAB nickel solution to detect lysosomal HRP and then immunohistochemically processed to locate the adrenaline-synthesizing cells using DAB alone. The results confirm the brainstem projections to the MPA from the central grey matter, ventral tegmental area, subcoeruleus area, the dorsal raphe nucleus, the lateral parabrachial nucleus, the raphe pontis nucleus, the raphe obscurus nucleus, the region of the paragigantocellular nucleus and the nucleus of the solitary tract. Given the considerable evidence implicating the ascending adrenergic systems in the regulation of LHRH, we focused our attention on the afferents from the locus coeruleus, area postrema and the adrenaline-synthesizing cell groups (C1-3). The only cells which were retrogradely labelled and immunopositive for phenylethanolamine N-methyltransferase were found in C3.


Release of immunoreactive enkephalinergic substances in the periaqueductal grey of the cat during fatiguing isometric contractions. Antibody-coated microprobes were used to determine whether immunoreactive enkephalins were released in response to fatiguing isometric contractions of the hind-limb muscles in cats anesthetized with alpha-chloralose. Contractions were performed by stimulating the tibial nerve via a microprocessor-controlled stimulator. Microprobes were inserted into the periaqueductal grey (P 0.5-1.0 mm) prior to, during and following fatiguing contractions. During fatiguing contractions, mean arterial blood pressure increased by 76 +/- 9 mmHg above resting and recovery levels. Levels of immunoreactive enkephalins were elevated in the dorsolateral periaqueductal grey during the isometric contraction when compared to resting levels. It is possible that isometric muscle contraction causes the release of Met-enkephalin-like substances in the periaqueductal grey.


The effects of cortical ablation on d-amphetamine-induced changes in striatal dopamine turnover and ascorbic acid catabolism in the rat. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA) and dehydroascorbic acid (DHAA) levels were determined by HPLC in the striatal synaptosomal fraction and in the whole striatum of rats, whose fronto-parietal cortex had been bilaterally ablated, after a single injection of d-amphetamine (2.0 mg/kg i.p.). d-Amphetamine significantly increased the DHAA/AA ratio in unoperated and sham-operated rats, but failed to increase it in ablated rats, as compared to pertinent saline-treated groups. In the synaptosomal fraction, d-amphetamine significantly decreased the DHAA/AA ratio in unoperated, sham-operated and ablated rats. d-Amphetamine significantly decreased the DOPAC/DA ratio in the whole striatum and significantly increased it in the striatal synaptosomal fraction in all experimental groups. Cortical ablation greatly increased d-amphetamine-induced motor hyperactivity. We conclude that the d-amphetamine-induced increase in AA striatal oxidation requires integrity of the cortico-striatal glutamatergic pathways. Further, AA oxidation occurs in the extracellular space. The cortico-striatal glutamatergic pathways exert an inhibitory modulation on d-amphetamine behavioral effects.


Significance of nerve growth factor content levels after transient forebrain ischemia in gerbils. Involvement of nerve growth factor (NGF) in the pathogenesis of delayed neuronal death (DND) of CA1 neurons in the hippocampus has been suggested. We measured regional changes in the content of tissue NGF of the hippocampus in the Mongolian gerbil after 5 min forebrain ischemia. The NGF content was found to decrease significantly in the CA3 and dentate regions by 32% two days after ischemia. By contrast in the CA1 region, the level of NGF became significantly elevated by 50% two weeks after ischemia or later. The early reduction of NGF content in the afferent area projecting to the CA1 sector might be primarily linked to the pathogenesis of DND, whereas the delayed increase within the CA1 sector might be a secondary local response mainly of reactive astroglia.


The changing axonal distribution in white muscle of the developing catfish, Ictalurus nebulosus (Lesueur). The development of the peripheral innervation pattern of the axial white muscle fibres of the brown bullhead, Ictalurus nebulosus (Lesueur), was investigated utilizing silver impregnation. In the younger fish examined, axons were observed to run along the myoseptum and into the body of the myotome. With development, axons were gradually restricted to the myoseptal ends as is the situation in adult bullheads. Possible mechanisms for elimination of the superfluous axons observed in the white muscle of the developing brown bullhead are discussed.


Initial observations on the distribution of cannabinoid receptor binding sites in the human adult basal ganglia using autoradiography. The distribution of cannabinoid receptor binding sites has been studied in the basal ganglia of 3 human adults using the synthetic cannabinoid agonist [3H]CP55,940 and autoradiography. The [3H]CP55,940-specific labeling was found in the caudate, putamen, accumbens, substantia nigra pars reticulata, and globus pallidus. The binding was consistently higher in the medial over the lateral part of the globus pallidus.


Eating and drinking cause increased dopamine release in the nucleus accumbens and ventral tegmental area in the rat: measurement by in vivo microdialysis. Dopamine (DA) release was simultaneously monitored in the nucleus accumbens (NAC) and ventral tegmental area (VTA) of conscious rats using in vivo microdialysis. During dialysis perfusion, rats were allowed access to food or water for 20 min following a 36 h food and water deprivation period. DA release increased significantly in the NAC and VTA in response to eating and drinking. The increases in both regions continued until 20-60 min after the end of the feeding or drinking session. These results show that the mesolimbic DA pathway is activated in response to ingestive behavior, and that DA release occurs in the cell body (A10) region as well as in the mesolimbic DA nerve terminals.


Activation of hippocampal metabotropic excitatory amino acid receptors leads to seizures and neuronal damage. A role for ionotropic (NMDA, AMPA, and kainate) excitatory amino acid (EAA) receptors in seizure and seizure-related brain damage is well documented. To study the possible role of metabotropic (G-protein linked) EAA receptors in this regard, a highly selective metabotropic EAA agonist was injected into the hippocampus of halothane-anesthetized rats. This resulted in delayed-onset seizures and selective hippocampal neuronal damage that was indirectly mediated by NMDA receptors. This provides direct evidence for a novel role of metabotropic EAA receptors in the etiology of seizures and neuronal damage.


Intrathecal midazolam versus intrathecal morphine in orofacial nociception: an experimental study in rats. The antinociceptive properties of intrathecal midazolam (15 and 30 micrograms) and intrathecal morphine (30 micrograms) were compared using an adaptation of the formalin test to the orofacial region in rats. Both midazolam and morphine were effective in reducing the nociceptive response of the second phase of this biphasic pain test. Only midazolam (30 micrograms) reduced also the first phase. These results confirm the existence of analgesic properties of midazolam in the case of long-lasting pain.


Potentiation by cyclooxygenase inhibitors of the release of catecholamines from the rabbit carotid body and its reversal by prostaglandin E2. Salicylates, at the high therapeutic doses used in the treatment of rheumatoid arthritis, produce an increase in ventilation and augment the carotid body reactivity to hypoxic stimulus, leading to an exaggerated hyperventilation during hypoxia. These effects had been related to the action of salicylates as uncouplers of oxidative phosphorylation. In the present study, carried out in an in vitro preparation of the rabbit carotid body, we show that acetylsalicylic acid and indomethacin, two anti-inflammatory drugs that are also powerful inhibitors of cyclooxygenase, the prostaglandin-synthetizing enzyme, produce an increase in the [3H]catecholamine release evoked by low oxygen stimulation. The drugs did not affect basal normoxic release, a finding that suggests that at the concentration used these anti-inflammatory agents do not have uncoupling actions, and that their effects on hypoxic-induced release of [3H]catecholamines is mediated by their specific action as cyclooxygenase inhibitors. In agreement with this suggestion we found that prostaglandin E2 completely prevented the effects of both anti-inflammatory agents. In addition, our data indicate that endogenously synthetized prostaglandins are powerful modulators of chemoreceptor cell function.


Cocaine-induced disturbances of corticogenesis in the developing murine brain. Exposure of fetuses to cocaine can induce behavioral disturbances and structural modifications of the CNS. Cocaine was injected into pregnant mice from the eighth day of gestation until term and the brains of their offspring were examined at the light and EM levels. Cocaine severely disturbs neocortical architecture, disrupting horizontal and vertical lamination, and inducing abnormal array of the axonal-dendritic bundles. Cocaine also alters several steps of gliogenesis. The severity of the malformations is variable, but evident in all exposed animals.


Compartmentalization of NADPH-diaphorase staining in the developing human striatum. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) staining of striatal neuropil showed inhomogeneities in human fetal and adult brains. Highly reactive patches were seen during fetal and neonatal period, distributed in a lighter stained background matrix. In adult, zones of low NADPH-d reactivity appeared against darker background staining. NADPH-d reactive patches corresponded to and showed a similar shift in the intensity of staining during development as acetylcholinesterase (AChE) reactive striosomes.


Effects of background illuminations on the receptive field size of horizontal cells in the turtle retina are mediated by dopamine. Intracellular recordings from luminosity-type horizontal cells of the turtle retina were used to analyze the effects of steady and flickering background illumination on the size of their receptive fields. Both types of background illumination reduce the size of the receptive field to about the same extent. The reduction seems largely due an increase in the coupling resistance between horizontal cells. The effects of both types of background illumination are sensitive to the dopamine antagonist fluphenazine. This suggests that steady and flickering illuminations stimulate the release of endogenous dopamine.


An electrophysiological study of D2 dopaminergic actions in normal human retina: a tool in Parkinson's disease. A peculiar deficit of electrophysiological retinal responses to pattern reversal grating stimuli has been reported in Parkinson's disease (PD) patients. A similar abnormality has been reproduced by means of non-selective dopaminergic antagonists in normal humans. Aim of this study was to verify, by means of a selective D2 antagonist (sulpiride) administered to normal subjects, whether a D2 blockade affects the visual electrophysiological performances with the same trend as observed in PD patients. Patterns electroretinogram (PERG) responses to 1 cycle per degree (c/d) of spatial frequency at 1 (transient) and 7.5 (steady state) Hz of temporal modulation of a square-wave grating pattern reversal have been recorded in 19 healthy volunteers before and after the administration of 100 mg i.m. of sulpiride. The data are consistent for the following conclusion: a selective D2 antagonist reduces steady state and delays transient retinal responses as expected for a PD mimicking agent.


Effects of CNS stimulants on the in vivo release of the colocalized transmitters, dopamine and neurotensin, from rat prefrontal cortex. The effect of CNS stimulant drugs on the in vivo release of the colocalized neurotransmitters dopamine and neurotensin in rat prefrontal cortex was studied using microdialysis. Amphetamine, methylphenidate and nomifensine all increased extracellular fluid (ECF) levels of dopamine; however, their effects of neurotensin varied. Amphetamine increased both ECF dopamine (514 +/- 82% of basal) and neurotensin (350 +/- 49% of basal); however, the neurotensin increase lagged behind the increase in dopamine suggesting a possible trans-synaptic effect. Methylphenidate increased both dopamine and neurotensin (226 +/- 26% and 151 +/- 14% of basal respectively) co-synchronously, suggesting exocytosis of vesicles containing both dopamine and neurotensin. The nomifensine-induced increase in dopamine (202 +/- 23% of basal) was similar to that of methylphenidate, whereas the increase in neurotensin was significantly delayed and of lower magnitude (134 +/- 20% of basal). These data suggest that dopamine and neurotensin in part share a common releaseable pool in the prefrontal cortex. Moreover, dopamine may act presynaptically to increase neurotensin release and the different behavioral profiles of these psychostimulants may in part relate to their different effects on neurotensin release.


Carnitine palmitoyltransferase activity in the rabbit choroid plexus: its possible function in fatty acid metabolism and transport. The purpose of the present study was to measure the activity of carnitine palmitoyltransferase (CPT) in the lateral and fourth ventricular choroid plexus (LVCP, FVCP) as an example of an enzyme committed to mitochondrial long-chain fatty acid oxidation. The CPT activity measured with both assays determines total CPT activity, that is, the activity of both CPT-A (outer form) and CPT-B (inner form). CPT-assay 1 (forward reaction) activity was 893.3 +/- 44.5 mU/g and 803.3 +/- 71.3 mU/g (mean +/- S.E.M.) in LVCP and FVCP, respectively. CPT-assay 2 (backward reaction) activity was 3673.7 +/- 92.4 and 3417.0 +/- 277.1 mU/g in LVCP and FVCP, respectively. These data demonstrate that CPT activity is present in the rabbit choroid plexus, and that the activity is somewhat higher per gram wet weight of tissue than the activity observed in the skeletal muscle (CPT-assay 1 = 514.4 +/- 159, CPT-assay 2 = 2492 +/- 576 mU/g). CPT activity has been exclusively localized to the mitochondria of the liver, heart, kidney and the skeletal muscles. Our present study further demonstrates that the choroid plexus is another organ in which high activity of CPT exists.


Effect of the 5-HT3 receptor antagonist ondansetron on hypothalamic self-stimulation in rats and its interaction with the CCK analogue caerulein. It is unclear whether behavioral depression and suppression of food intake by cholecystokinin (CCK) is contributed to by aversive gastrointestinal effects such as nausea. In the present study we examined the effect of a new antiemetic agent, ondansetron, a specific antagonist of 5-HT3 receptors, on suppression of variable-interval self-stimulation by the CCK analogue caerulein. Responding by rats for brain-stimulation reward is especially sensitive to CCK, and provides a convenient means of investigating this question. Caerulein (30 micrograms/kg, s.c.), injected alone, was followed by a profound (ca. 80%) reduction in the rate of self-stimulation, lasting about 30 min. Ondansetron (1.0-1000 micrograms/kg, s.c.) injected on its own had no effect on self-stimulation rate, and a 100-micrograms/kg dose did not lessen the depressant action of caerulein. The behavioural depressant effects of CCK are thus unlikely to depend on brain mechanisms for nausea and vomiting involving 5-HT3 receptors.


Rhythmic expression of Fos-related proteins within the rat suprachiasmatic nucleus during constant retinal illumination. Within the retinorecipient or ventrolateral subfield of suprachiasmatic nuclei (SCN) in rodents, expression of the protein product of the c-fos proto-oncogene, Fos, is regulated by light. In the present study, the expression of Fos and Fos-related proteins within the SCN was examined immunocytochemically for evidence of rhythmic variation in rats sacrificed at different circadian times during exposure to constant retinal illumination (LL). In all animals, nuclear Fos immunoreactivity was mainly confined to an area of the SCN that was coextensive with neuropeptide Y-immunopositive fibers distinguishing the ventrolateral subfield of the nucleus. Moreover, Fos-immunostaining within the ventrolateral SCN of rats exposed to LL fluctuated over the course of the circadian cycle, such that the density of immunopositive cells within this subfield was 2 times greater during the subjective night than during the subjective day. Since Fos expression within the SCN oscillates in the absence of photoperiodic time cues and since the peak of this oscillation coincides with the circadian times when light modulates the periodicity of the SCN pacemaker, these data provide further evidence that expression of the c-fos gene may be a molecular signal in the circadian timekeeping mechanism in the SCN and its regulation by photic stimuli.


Seizure related elevations of extracellular amino acids in human focal epilepsy. Intracerebral microdialysis combined with electrocorticographic recordings was used in a patient subjected to epilepsy surgery. The patient developed a series of partial seizures during an 8 min period. Marked elevations of aspartate (79-fold), glycine (21-fold), glutamate (16-fold) and serine (8-fold) dialysate concentrations occurred in association with onset of the period with seizures. Recurrent seizures occurred, in spite of normalizing amino acid levels. Other amino acids analyzed (aspargine, threonine, arginine, alanine, taurine, tyrosine, phenylalanine, isoleucine and leucine) showed less pronounced changes (1-5 times the basal levels).


Brainstem influences on biceps reflex activity and muscle tone in the anaesthetized rat. This study analyzes the effect of electrical stimulation of the locus coeruleus (LC) and adjacent brainstem structures on the tonic reflex (TVR), the tonic stretch reflex (TSR) and on muscle tone (MT) in anaesthetized rat. Increases in TVR, TSR and MT of the m. biceps were evoked from regions rostrally and ventrally of LC, the caudal pontine reticular nucleus, the cuneiform nucleus and from the ventral parts of the colliculus inferior. Stimulation of the LC did not influence biceps EMG activity. The results indicate that the observed facilitation of muscle activity is due to stimulation of parts of the mesencephalic locomotor region. It is discussed that the recorded increase in TVR, TSR and MT possibly is due to an excitatory action on alpha motoneurones on one hand and to an enhanced fusimotor drive on the other.


Combined histochemical and biochemical demonstration of nigral vulnerability to lipid peroxidation induced by dopa and iron. Using a newly developed lipid peroxidation-inducing system composed of DOPA and iron, we examined the vulnerability of substantia nigra to peroxidation in comparison with that of caudate-putamen obtained from normal or vitamin E-deficient animals. Histochemical detection of lipid peroxidation revealed that substantia nigra was far more susceptible than caudate putamen to DOPA and iron treatment, which was biochemically supported by measurements of thiobarbituric acid-reactive substances. Vitamin E deficiency accelerated such susceptibility of substantia nigra but had no influence on the histochemical findings observed in caudate-putamen.


Chronic estradiol treatment increases anterior pituitary but not striatal D2 dopamine receptor mRNA levels in rats. The effect of chronic 17 beta-estradiol treatment (10 micrograms, twice each day, for 2 weeks) of ovariectomized rats on D2 dopamine (DA) receptor mRNA levels was investigated in striatum and anterior pituitary gland tissues. We used 32P-labeled probes specific for D2 receptor and beta-actin mRNAs in Northern blot analysis. The ratio of D2 DA receptor mRNA/beta-actin mRNA level was significantly increased in the anterior pituitary of estradiol-treated rats compared to vehicle-treated animals. The D2 DA receptor mRNA/beta-actin mRNA ratio in the striatum was not affected by estradiol treatment. However, the medial portion of the striatum showed a significantly lower ratio compared to the lateral portion of the striatum in both vehicle- and estradiol-treated rats. Thus, the estradiol effect on anterior pituitary D2 receptors may implicate transcriptional regulation, whereas our results do not support this hypothesis for the estradiol action on striatal D2 receptors.


Vanilloid receptor loss in rat sensory ganglia associated with long term desensitization to resiniferatoxin. A dose-dependent loss of vanilloid receptors (specific [3H]resiniferatoxin binding sites) was found in sensory ganglia of rats 24 h after s.c. administration of resiniferatoxin (RTX), an ultrapotent capsaicin analog. This receptor loss displayed an ED50 of 30 micrograms/kg both in dorsal root and trigeminal ganglia; the ED50 was 6-fold higher than the ED50 for loss of the neurogenic inflammatory response and 30-60-fold higher than the ED50 for desensitization in the standard eye-wiping (chemogenic pain) response. The receptor loss appeared later (24 h) than the loss of the physiological responses (6 h) and showed modest recovery (to 20-30% of control levels) over the following 4 weeks. This vanilloid receptor loss may represent a novel, specific mechanism for vanilloid-induced chronic desensitization.


Induction of brain ornithine decarboxylase after systemic or intrastriatal administration of kainic acid. The activity of ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, dramatically increases after different types of brain injuries. The role of this induction is still unclear. We report here data on the temporal pattern of ODC induction caused by the excitotoxin kainic acid. After systemic administration, ODC activity increases severalfold peaking at 8 h in the prefrontal cortex and at 16 h in the olfactory cortex and hippocampus. After intrastriatal injection, the peak of induction is reached at 32 h, while a smaller and more transient increase is also observed in the contralateral, saline-injected striatum. We suggest that ODC induction is initially linked to overactivation of neural circuits and, later on, to the development of widespread neural damage.


Visually controlled spatial stabilisation of the human head: compensation for the eye's limited ability to roll. During movements of the head in pitch (yes-yes) or in yaw (no-no) the visual scene appears stable whereas rolling the head (ear down to shoulder) induces an apparent swinging of the world in the opposite direction. This visual instability is due to the inadequacy, in the roll plane, of the reflex eye movements which are effective in stabilising the eyes in space during pitch and yaw. We investigated whether head is stabilised in roll to protect against visual instability. Human subjects were fixed in a gimbal with their heads free and were exposed to unpredictable oscillatory movement in pitch and, for comparison roll, about axes aligned with the head. With vision, during roll motion, the head was displaced from upright by approximately half the amplitude of the gimbal motion. In comparison, with eyes closed relying on vestibular and proprioceptive cues and during pitch stimuli with or without vision, the magnitude of head displacement from upright was approximately equal to that to the gimbal. The superior head stability in roll, dependent on a visual frame of reference, compensates for poverty of eye movement in this plane.


Microencapsulated nerve growth factor: effects on the forebrain neurons following devascularizing cortical lesions. In this study, we report the effects of nerve growth factor (NGF) delivered into the CNS via a novel delivery system for prolonged, controlled release. The effectiveness of NGF incorporated in the biodegradable microspheres was investigated in the rat model for central cholinergic degeneration. Mature male rats were unilaterally lesioned by disruption of the pia arachnoid vessels and vehicle (alginate microspheres without NGF) and microencapsulated NGF was placed at the site of the lesion. Choline acetyltransferase (ChAT) activity was measured in the nucleus basalis magnocellularis (NBM) and cortex in the (a) non-lesioned control animals; (b) lesioned animals treated with 'empty' microspheres and (c) lesioned animals treated with microspheres containing NGF, 30 days following surgery. Similarly lesioned animals received NGF via permanently installed cannulae in order to compare the novel route of administration with the more conventional one. Immunocytochemical results showed an absence of the cholinergic cell body shrinkage in the NBM otherwise observed in lesioned animals. Furthermore, an increase in intensity of ChAT immunostaining in NGF-treated, lesioned animals was evident. The present results stress the experimental therapeutic possibilities of novel delivery systems for administration of trophic factors in the CNS.


Leukemia inhibitory factor (LIF) mediated increase of choline acetyltransferase activity in mouse spinal cord neurons in culture. The effects of leukemia inhibitory factor (LIF) on choline acetyltransferase (ChAT) enzyme activity in cultured mouse spinal cord neurons were examined. The administration of LIF to cultures at concentrations of 10 U/ml and higher enhanced ChAT activity approximately 3- to 4-fold in cultured spinal cord neurons. Among neurotrophic factors tested, basic fibroblast growth factor (bFGF) and insulin-like growth factor I (IGF-I) stimulated the development of ChAT activity but to a smaller extent than LIF, while interleukin 3 (IL-3), interleukin 6 (IL-6) and nerve growth factor (NGF) showed no apparent effect on ChAT development. Our results indicate that LIF, which has not been known to have any trophic effect on mammalian central nervous system neurons to date, acts as a potent differentiation factor for ChAT in cholinergic neurons of mouse spinal cord in culture.


Involvement of a receptor for neurite outgrowth factor (NOFR) in cerebellar neurogenesis. A receptor for neurite outgrowth factor (82 kDa membrane protein, NOFR) was detected in the developing chick cerebellum by immuno- and ligand blots. In immunohistochemical study, NOFR was maximally expressed in the external granular layer of cerebellum at embryonic day 10-12 and gradually decreased until embryonic day 18. Neurite outgrowth and cell migration induced by NOF from cerebellar explants were completely suppressed by the addition of anti-NOFR IgG. These results suggest that NOFR plays an important role in the cerebellar neurogenesis.


Mesolimbic dopamine release elicited by activation of the accessory olfactory system: a high speed chronoamperometric study. Male rats were anesthetized with chloral hydrate, and extracellular dopamine concentrations in the nucleus accumbens were measured using high speed chronoamperometry. Recordings were obtained during application of air passed through bedding obtained from cages that housed estrus female rats and application of depolarizing concentrations of potassium (K+) to the accessory olfactory system. Application of bedding-impregnated air increased the electrochemical signal obtained from within the nucleus accumbens, and this response was enhanced by treatment with the DA re-uptake blocker, GBR-12909. Application of K+ to the vomeronasal nerve layer of the accessory olfactory bulb and to the accessory olfactory bulb, itself, also elicited increases in the electrochemical signal recorded from the nucleus accumbens. These results indicate that the accessory olfactory system is able to activate the mesolimbic DA system.


Accumulation of alpha B-crystallin in brains of patients with Alexander's disease is not due to an abnormality of the 5'-flanking and coding sequence of the genomic DNA. alpha B-Crystallin is a major protein component of Rosenthal fibers, which massively accumulate in the brains of patients suffering from Alexander's disease. To examine whether or not accumulation of alpha B-crystallin is due to any abnormality of the gene structures, we determined the sequence of the alpha B-crystallin gene in two cases of pathologically confirmed Alexander's disease. Direct sequencing of the promoter and coding regions of the alpha B-crystallin gene in patients revealed them to have a normal sequence. Northern blotting showed a single alpha B-crystallin mRNA species expressed in the Alexander's disease brain.


Neuromuscular compartments in the human biceps brachii muscle. Electrophysiological evidence suggests that the human biceps brachii muscle is organized into functional neuromuscular compartments. The purpose of this study was to determine whether there was an anatomical basis for these compartments. Dissection of the biceps revealed both architectural and nerve branching pattern compartmentalization within the muscle. Although the biceps brachii is grossly subdivided into long and short heads, these heads are further subdivided into roughly parallel architectural compartments. Moreover, these architectural compartments usually receive a private nerve branch, thus supporting the notion that the human biceps brachii has neuromuscular compartments.


Responses of rat substantia nigra pars reticulata units to cortical stimulation. In order to study the function of multiple pathways between the sensorimotor cortex (Cx) and the substantia nigra pars reticulata (SNr), responses of SNr units to stimulation of the Cx were studied in anesthetized rats. Most of the units (229 of 236) exhibited repetitive firing with fairly short, regular intervals. The other 7 units displayed long duration spikes, irregular firing intervals and slow spontaneous firing. Stimulation of the Cx usually resulted in a short latency excitation and occasionally a long latency inhibition in both types of units. When strong stimulation was applied, multiple excitatory and inhibitory responses alternating each other with about a 25 ms interval were observed. SNr units responded with different patterns and latencies to stimulation of different sites of the sensorimotor Cx. The results indicate that signals derived from the sensorimotor Cx reach the SNr via multiple pathways and converge on many SNr neurons.


Periaqueductal gray matter stimulation-produced analgesia in diabetic rats. The effect of diabetes on periaqueductal gray matter (PAG) stimulation-produced analgesia (SPA) was examined in rats. PAG SPA was assessed using the tail-pinch test. PAG stimulation produced marked analgesia in both naive and diabetic rats. Furthermore, the degree of PAG SPA did not differ between naive and diabetic rats. PAG SPA was significantly attenuated by a low dose (0.5 mg/kg, s.c.) of naloxone in naive rats, but not in diabetic rats. However, a high dose (5 mg/kg, s.c.) of naloxone significantly and equally attenuated PAG SPA in both naive and diabetic rats. On the other hand, the analgesic potency of morphine (3 mg/kg, s.c.) was significantly reduced in diabetic rats as compared with naive rats. These results suggest that PAG SPA in diabetic rats may be mediated by different opioid receptor interactions as compared with naive rats.


Structural maturation of synapses in the rat superior cervical ganglion continues beyond four weeks of age. We have examined the morphology of preganglionic synapses in the rat superior cervical ganglion (SCG) at 10 days, 4 weeks and 1 year. Between 10 days and 4 weeks the mean thickness of the postsynaptic density (PSD) increased from 45.9 +/- 0.1 nm to 52.1 +/- 1.7 nm (P = 0.017), the mean length of the PSD (0.41 +/- 0.02 microns) did not change, and the distribution of synapses on the neuronal surface changed with a decrease in the proportion of somatic and an increase in the proportion of dendritic spine synapses. Since both synapse elimination and synapse formation are occurring during this period several mechanisms may contribute to these changes. However, between 4 weeks and 1 year, when there is no net change in the number of synapses, the mean length of the PSD increased to 0.53 +/- 0.02 microns (P = 0.001), there was no change in either the mean thickness of the PSD or the distribution of the synapses but the proportion of concave ('smile') synapses increased. A comparison with previous developmental studies of synapses in cerebral cortex of rat and chicken indicate that both the nature and the rate of synapse maturation can vary between different populations of synapses.


Age-dependent effects of deafferentation of the rat superior cervical ganglion on expression of P65 (synaptotagmin) during postnatal development. Previous studies have shown that deafferentation of the rat superior cervical ganglion (SCG) alters the levels of p65 (synaptotagmin), a synaptic vesicle integral membrane protein, within the ganglion. Neonatal deafferentation blocks normal postnatal increases in p65, while deafferentation in adult animals produces a transient increase in p65 expression. The present study examines the time course of the shift from the neonatal to adult pattern of response to deafferentation. Neonatal and 7 day old rats showed the neonatal response to deafferentation. Ganglia from rats aged 14 days or older at deafferentation exhibited the transient increase in p65 at 7 days after surgery. The shift from the neonatal to adult response occurs during the second postnatal week. The change in response to deafferentation may be associated with refinement of synaptic function in a manner yet to be determined.


N-methyl-D-aspartate responses in rat cerebellar granule cells are modified by chronic depolarisation in culture. Following culture in high (25 mM) K+ conditions cerebellar granule cells only respond with a rise in cytosolic free calcium concentration ([Ca2+]i after removal of external Mg2+. When granule cells are grown in low (5 mM) K+ N-methyl-D-aspartate (NMDA) exerts a neurotrophic effect. We show that at the critical time for this effect NMDA will elicit a rise in [Ca2+]i in 5 mM K+ cultures even in the presence of Mg2+ and that growth in 25 mM K+ induces the rapid appearance of a Mg2+ block of NMDA receptors in granule cells. This suggests firstly, that a rise in [Ca2+]i could be involved in the neurotrophic effect of NMDA and secondly, that the characteristics of the NMDA responses in granule cells are modified as a result of growth under depolarising conditions.


The new growth factor pleiotrophin (HB-GAM) mRNA is selectively present in the meningothelial cells of human meningiomas. The distribution of the messenger RNA coding for the recently cloned growth factor pleiotrophin (HB-GAM) was studied in human benign meningiomas using in situ hybridization histochemistry and oligonucleotide probes. Pleiotrophin mRNA was selectively found in the meningothelial cells whilst not detected in the fibroblastic cells, blood vessels and collagen bundles of the meningiomas.


Push-pull modulation of ganglion cell responses of carp retina by amacrine cells. The responses of a ganglion and an amacrine cell were recorded simultaneously in the carp retina. Sinusoidal current injected into amacrine cells modulated ganglion cell discharges either in phase (excitation) or in opposite phase (inhibition). ON-center ganglion cells received excitatory inputs and OFF-center ganglion cells received inhibitory inputs from ON-center amacrine cells. They received inputs of opposite polarity from OFF-center amacrine cells. Namely, inputs from ON-center and OFF-center amacrine cells augment the responses of ON-center and OFF-center ganglion cells in a push-pull manner.


Possible involvement of interleukin-1 in ischemic brain edema formation. To determine the contribution of interleukin 1 (IL-1) on ischemic brain edema formation, the effect of recombinant human interleukin 1 beta (rhIL-1 beta), or zinc protoporphyrin (ZnPP) as an IL-1 blocker, on brain edema was studied in rats. The animals were subjected to 60 min of ischemia in a middle cerebral artery occlusion model. Immediately after reperfusion, rhIL-1 beta at a dose of 10 ng/2 microliters, or ZnPP at doses of 1 and 10 micrograms/2 microliters were topically applied into lateral cerebroventricle. In rhIL-1 beta-treated rats, ischemic brain edema formation was significantly increased in the dorsal and ventral areas of the caudate putamen 24 h after reperfusion, compared to that of vehicle-treated control rats. Furthermore, in ZnPP-treated rats, brain edema was decreased in both caudate-putamen areas. This suggests that IL-1 plays an important role in pathogenesis for post-ischemic brain edema.


Mapping of the cochlear nucleus subregions in the rat with neuronal Fos protein induced by acoustic stimulation with low tones. To explore the mode of appearance of Fos, a gene product of proto-oncogene c-fos, in the cochlear nucleus, a pure tone was given to rats and Fos was detected by immunohistochemistry. Following low-tone stimuli applied with moderate ranges of sound intensity, neurons with Fos-label occurred band-like in the ventral subregions of the dorsal cochlear nucleus. Organization of low-to-high tones in the ventral-to-dorsal orientation became visible at the caudal level. Several other subnuclei consistently exhibited Fos with no topographic pattern. Neurons interspersed in the adjoining vestibulocochlear nerve were also found to elicit Fos. Low-tone stimuli with very high sound intensity led to a rather widespread distribution of Fos, making the tone-specific distribution less visible.


Regional effects of MK-801 on dopamine and its metabolites studied by in vivo microdialysis. The non-competitive N-methyl-D-aspartate receptor antagonist MK-801 was observed to have regionally specific effects on the extracellular concentration of dopamine and its metabolites. In rat anterior striatum, MK-801 transiently decreased extracellular dopamine, in spite of inducing intense circling behaviour which is generally associated with an increase in this neurotransmitter. In contrast, hippocampal extracellular dopamine was increased in a dose-related manner by MK-801. The possible significance of these data is discussed in relation to some of the known behavioural actions of MK-801.


The transcription factor CREB, but not immediate-early gene encoded proteins, is expressed in activated microglia of lumbar spinal cord following sciatic nerve transection in the rat. Expression of CREB, JUN, FOS and KROX-24 proteins was investigated in glial cells of the lumbar spinal cord. In untreated rats, CREB, c-JUN and JUN D were present in glial cells of the ventral and dorsal horn. Following sciatic nerve transection, the number of CREB immunoreactive glial cells increased in both the ipsilateral ventral and dorsal horns between 24 h and 48 h, reached a maximum after 5 days and returned to control levels after 20 days. Counterstaining with Cresyl violet, a general stain of cells, revealed that the increase of CREB positive glial cells was congruent with the increase of the number of glial cells. Staining with GFAP, a marker for astrocytes, showed an increase in intensity of labelling but no change in number of GFAP labelled cells. This indicates a constitutive expression of CREB in activated microglia. The number of glial cells labelled by c-JUN and JUN D did not change, and glial cells were not labelled by FOS and KROX-24 proteins following sciatic nerve transection. These findings demonstrate that proliferation and differentiation of glial cells in vivo can occur in absence of JUN, FOS and KROX proteins.


Oral naloxone reduces constipation but not antinociception from oral morphine in the rat. Oral administration of naloxone (10 mg/kg) antagonized the slowing of the intestinal transit caused by oral morphine (1, 2.5 and 5 mg/kg) in rats. Oral administration of naloxone (10 mg/kg) did not prevent the antinociceptive effect of orally administered morphine (2.5 mg/kg) in the tail-flick test carried out on rats. It is concluded that oral naloxone locally blocks the constipating effect of morphine, while it fails to reduce the central action of morphine due to extensive metabolization after oral administration.


Selective blockade by yohimbine of descending spinal inhibition from lateral reticular nucleus but not from locus coeruleus in rats. The present study was undertaken to compare the effects of the alpha 2-adrenoceptor antagonist yohimbine on inhibition of C-fiber-evoked responses of dorsal horn neurons produced by electrical stimulation of the lateral reticular nucleus (LRN) and the Locus coeruleus (LC) in the rat. In the majority of neurons, C-fiber-evoked responses were significantly inhibited by 53.84 +/- 5.02% and 57.63 +/- 5.79% of control by LRN and LC stimulation, respectively, whereas in less than half of the neurons, A-fiber-evoked responses were reduced by 20.99 +/- 6.06% and 21.78 +/- 4.48% of control, respectively. After systemic or spinal administration of yohimbine, LC-induced inhibition of C-fiber-evoked responses was not affected. In contrast, LRN-induced inhibition was markedly attenuated by yohimbine. The results suggest that alpha 2-adrenoceptors may be involved in mediation of inhibition of spinal nociception induced by stimulation of LRN but not by LC.


Vasopressin administration via microdialysis into the septum interferes with the acquisition of spatial memory in rats. The role of vasopressin (AVP) in the septohippocampal system in spatial memory was studied in 27 male hooded rats of the Long-Evans strain. The rats were implanted with a septal microdialysis probe and assigned to 3 groups. Two days later, they were trained on 3 consecutive days (12 daily trials) to locate the hidden underwater platform in the Morris water maze (MWM) while the probes were perfused with either artificial cerebrospinal fluid (aCSF) or aCSF containing vasopressin or the V1 antagonist d(CH2)5Tyr(Me)AVP (AAVP). Another group of rats (n = 8) remained untreated. Groups receiving microdialysis of aCSF or AAVP acquired the MWM task at the same rate as untreated animals. On the other hand, place navigation learning was significantly impaired by microdialysis of AVP during all sessions. The results indicate that endogenous AVP (at least that affecting the V1 receptor subtype) is not indispensable for the acquisition of spatial memories in the MWM, whereas excessive presence of synthetic AVP interferes with spatial learning.


Localisation of striatal muscarinic receptors involved in dopamine receptor-mediated behavioural responses. Stereotyped sniffing responses to the direct dopamine agonist, apomorphine, were assessed following intrastriatal injection of the alkylating derivative of oxotremorine, BR 401. Subsequently, the localisation and extent of muscarinic receptor alkylation after injection into various striatal sites were assessed by quantitative autoradiography. The results of these experiments provide evidence that a regional subset of striatal muscarinic receptors is involved in apomorphine-induced stereotyped sniffing. In addition, these receptors are localised in a similar area to that previously shown to contain the dopamine D2 receptors responsible for mediating apomorphine-induced sniffing. Thus, striatal muscarinic receptors involved in dopamine-agonist induced behaviours share a close anatomical association with the dopamine receptors at which the agonist acts.


Azimuthal processing in the posterior auditory thalamus of cats. The responses to free-field acoustic stimuli of 157 units in the auditory thalamus of anesthetized cats were studied in relation to the localization of pure tone stimuli in the azimuthal plane. Units were classified as 'directional' if their firing rates at sound levels in excess of 20 dB above threshold varied by more than 50% as a function of azimuth. Sixty-five % of the units in the nucleus of the brachium of the inferior colliculus and 30% in the ventral division of the medial geniculate body were found to be directional, suggesting different processing channels for sound localization between colliculus and cortex.


Interaction of long chain n-alkyl diamines with the NMDA receptor complex. Long chain 1, omega-diamines with 8, 10, 12, 14 and 16 carbon atoms reduced the binding of [3H]MK 801 to rat hippocampal membranes with IC50 values of 333, 72, 16.5, 4.7 and 4.3 microM, respectively. In the presence of medium-effective concentrations of the diamines, the concentration response curve of the stimulation by the polyamine spermine was shifted to higher spermine concentrations, reaching similar maximal stimulation as in the absence of the diamines. In the case of 1,12-diaminododecane (N-12-N) and 1,14-diaminotetradecane (N-14-N), the extent of this shift was compatible with competitive antagonism of spermine. Inhibition of [3H]MK 801 binding by long chain diamines was sensitive to spermine, inhibition by N-12-N and N-14-N exhibited the highest sensitivities. Of all diamines tested, N-12-N and N-14-N seem to be the most likely candidates for inverse polyamine agonists.


The cone electrode: ultrastructural studies following long-term recording in rat and monkey cortex. The achievement of long-term recording of neural signals from the central nervous system has potential clinical and investigative application. To facilitate long-term recording, a novel cone electrode composed of an insulated gold wire within a hollow glass cone had been developed. Cone electrodes containing sciatic nerve or neurotrophic medium were implanted into cerebral cortex in rats and monkeys. Electrophysiologic recordings had been previously obtained from cone tissue for as long as 15 months following implantation and this tissue contained silver-positive processes. We now extend these observations to characterize the fine structural features of the tissue within these long-term implants. Electron microscopy revealed central myelinated axons, dendrites, synaptic profiles, blood vessels, and glia; peripheral nerve was not found in the cones in which sciatic nerve had been placed. These observations further suggest ingrowth of cortical neurites and elements into the hollow glass tip of the cone and support the feasibility of long-term recording using this electrode.


Quantification of beta A4 protein deposition in the medial temporal lobe: a comparison of Alzheimer's disease and senile dementia of the Lewy body type. The distribution of beta-amyloid protein (beta A4) was examined in the medial temporal lobes from cases of Alzheimer's disease (AD) (n = 13), senile dementia of Lewy body type (SDLT) (n = 12) and age matched controls (n = 9). Using a previously described image analysis technique the extent of beta A4 pathology was determined in ten distinct anatomical sites within the medial temporal lobe. AD and SDLT cases contained very similar amounts of beta A4 in the areas sampled and both contained significantly more beta A4 than the age matched controls, particularly in the dentate and parahippocampal gyri. The similarity of the beta A4 load in the two conditions is in contrast to reported differences in the number of neurofibrillary tangles which can be observed. It is suggested that AD and SDLT represent a spectrum of pathology which centres around the aberrant processing of the beta A4 precursor protein.


Student awareness of research findings.

Student awareness of research findings. One problem faced by all faculty who teach research to undergraduate students is how to make the topic of utilization of research both interesting and practical. The author describes an approach that elicited students' active participation in replicating an earlier study by indicating their awareness of research-validated practices. Involvement of the students in an actual study seems a positive way to introduce the topic of utilization and has been used with success in one program over the past 4 years.


Nursing education and HIV disease: a call for action. The continued increase in reported cases of HIV disease has created a compelling need for nursing educators to provide students with comprehensive information on HIV-related issues. The authors discuss the need for students to care for HIV-positive individuals under faculty supervision to overcome fear and anxiety. Faculty education is proposed as a first step to develop a comprehensive approach to HIV education. A guide for integrating HIV content into the curriculum is provided.


A rural nursing practicum: making it work. Inciting the interest of baccalaureate students in the practice of nursing in a rural setting has been an ongoing challenge for many educators. The authors identify difficulties they encountered when attempting to involve students in a rural nursing practicum and delineate several strategies used to overcome these difficulties.


A model for peak performance.

A model for peak performance. This study identified major factors that contributed to peak performance among eight nursing educators. The peak performers were interviewed 3 times over 8 years. Intense commitment to a mission, continual performance assessment, concentration on satisfaction and rewards, and the ability to set priorities and seek social support were delineated as factors in peak performance. Commitment to a personal mission that aligns with the demands of the university was a peak performer's ultimate personal investment and service to students and the university.


Positive reinforcement in clinical teaching. Contrary to the idea that nursing students are intrinsically motivated, findings in research studies show that students repeatedly report the significance of positive feedback to them. Delivery of positive reinforcement by clinical instructors can be developed so that the reinforcement is more meaningful to students and more effective in promoting or maintaining desired student behaviors.


Classroom shared governance.

Classroom shared governance. As shared governance increases in organizations that employ nurses, it becomes an essential element of professional socialization and preservice education. Framing a course in concepts of shared governance offers students experiential learning in uses of power, accountability, organizational decision making, and peer negotiation. The authors present concepts and examples of classroom shared governance from student and teacher perspectives.


Exercise and lean weight: the influence of body weight. Exercise can produce a modest gain of lean body mass (LBM) and loss of fat in weight-stable individuals, but it is important to realize that if much weight is lost during exercise there is a risk of some erosion of the LBM. Data from both human and animal experiments show that exercise cannot conserve lean weight in the face of significant energy deficit, although moderate obesity affords a modicum of protection in this respect.


Making a challenge out of an NLN visit: any more questions? Any educator, regardless of experience, feels apprehension as the final preparations are made for a National League for Nursing (NLN) review. Recognizing that 70% of our faculty had never experienced the review process, school administrators decided to take a novel approach to prepare faculty for the NLN visit. The authors discuss program development for a faculty workshop that modeled a popular television game show.


Should enteral nutrition be considered as primary therapy in acute Crohn's disease? Clinical trials indicate that elemental enteral diets are equally as effective as corticosteroid treatment for acute Crohn's disease; however, a clear efficacy of polymeric formulas has yet to be demonstrated. Moreover, the mechanism of action of enteral nutrition remains uncertain, and further study is needed to define the precise role of specialized enteral formulas in the long-term management of this disease.


Low-calcium diets enhance phytate-phosphorus availability. This study showed that, in chickens, the negative effects of phytate-phosphorus in a low inorganic phosphorus diet could be completely reversed through the additive effects of reduced dietary calcium and increased cholecalciferol. In the future, perhaps greater reliance on more readily available plant phosphorus sources may be instituted in developing countries, where cheap sources of inorganic phosphorus are difficult to obtain.


Using cooperative learning strategies.

Using cooperative learning strategies. Nurse educators are challenged to develop innovative teaching strategies that help students think critically and interact skillfully with others. The authors present the merits of cooperative learning and describe ways that nurse educators can teach essential content using this educational strategy.


Use of gene therapy to correct elevated LDL levels in LDL-receptor deficient rabbits. Recent studies using gene therapy to correct low-density lipoprotein (LDL)-receptor deficiency in rabbits suggest that practical applications of such techniques may be forthcoming. While complete correction of elevated serum cholesterol levels resulting from LDL-receptor deficiency is not yet possible, significant reductions were possible following gene therapy.


Fish oil consumption influences mortality rates of mice challenged with Salmonella typhimurium. A recent report has shown that dietary fish oil consumption increases mortality in mice challenged with Salmonella typhimurium. The mechanism of this effect is uncertain, however.


Computerized cost analysis for the nursing skills laboratory. Cost control and accountability are requirements in the academic world of the 1990s. The author describes a computerized cost analysis system in the nursing skills laboratory that enables administrators to determine the cost of teaching skills, increases efficiency level of teaching by the faculty, and provides data for budgeting and ordering expendable medical supplies.


Regular or decaf? Coffee consumption and serum lipoproteins. Epidemiologic studies indicate that the relationship between coffee consumption and cardiovascular disease is inconsistent. The potential impact of caffeinated vs. decaffeinated coffee on serum lipids has been investigated with similar inconclusive findings. Understanding the effects that various types of coffee beverages may have on serum lipids could be enhanced by identifying and characterizing the putative lipid-altering factor in coffee.


Trace element-gene interactions.

Trace element-gene interactions. For many of the genes encoding proteins involved in the transport, storage, and function of the trace elements, expression is regulated by the availability of the elements concerned. This control is exercised through a variety of mechanisms, including metal-activated transcription factors, modified usage of stop codons, and use of secondary structure within mRNA to regulate its translation and stability. Two widely represented groups of transcription factors, often classed as zinc-finger proteins, depend on constituent zinc ions for their activity. In addition, the sensitivity of growth and fetal development to the lack of zinc is hypothesized to relate to a requirement for the element during certain critical alterations in gene expression. The evidence for this and possible underlying mechanisms is examined.


Nutrition and aging: potentials and problems for research in developing countries. The demographic explosion of persons over 60 years of age is a reality in developed and developing countries alike. There is evidence that research on aging and nutrition in Third World countries is growing and developing. Specific research programs, and the linking of these programs in timely multicenter efforts, promise both valuable descriptive research for the benefit of national populations and comparative insights that will help us to learn more, collectively, about the intrinsic nature of the aging process itself.