Static magnetic field expose enhances neurotransmission in crayfish nervous system.

PURPOSE: To investigate the effects of static magnetic field (SMF) exposure on the synaptic transmission in a tail-flip circuit of crayfish. MATERIALS AND METHODS: An O-shaped permanent magnet (35 mT intensity) was placed under the isolated nerve cord of crayfish to provide static magnetic field exposure. Using electrophysiological methods, the excitatory post synaptic potential (EPSP) before and after field exposure in the lateral giant interneuron were measured and compared. RESULTS: The EPSP produced via electrical and chemical synapses in the lateral giant neuron were enhanced after 30 min of SMF exposure (8.08 mT). Perfusion of field-exposed crayfish bath solution or preloading of Ca(2+) chelator and intracellular Ca(2+) release blocker failed to observe the SMF-induced enhancement on EPSP. CONCLUSIONS: Exposure of SMF increases the efficacy of synaptic-transmission in crayfish tail-flip escape circuit and this SMF-induced potentiation is a Ca(2+) dependent phenomenon.

Hemispheric asymmetries on computed tomographic scans in schizophrenia and mania. A controlled study and a critical review.

A major reason for reassessing hemispheric asymmetries in schizophrenics by computed tomography is the methodologic shortcomings of previously published measurement techniques. We used completely blind measurements, multiple measurements performed by two independent examiners of each region of the brain, and an SE of measurement with a confidence level of P less than .01 to define significant asymmetry. The frequency of reversed occipital asymmetry was significantly higher in the 36 schizophrenic than in the 18 manic right-handed male patients. Furthermore, when all of the previously published techniques were applied to these patients, the frequency of such a reversal was consistently higher in the schizophrenic than in the manic group. Further investigation of hemispheric asymmetries in schizophrenics is warranted.

Morphological cerebral asymmetries in autistic children.

A group of 36 children with infantile autism and various neurological disorders matched closely on age, sex, and handedness underwent computerized tomographic (CT) scanning of the brain. All CT scans were assessed blindly and independently by a neuroradiologist. Two techniques modified from two published CT studies concerning cerebral asymmetries were used for measuring frontal and parieto-occipital asymmetries. The present study found that the CT pattern of cerebral asymmetries in autistic children is the same as observed in the neurological patients. Contradictory results were noted when the distributions of such asymmetries between the present autistic group and normal adults included in two previous studies were compared. One of the striking findings in this study is that the brains of the present autistic patients seem to be more symmetric than those of the normals. This finding, however, is also noted in the present matched controls as well as in the dyslexic children previously studied by other investigators. Further sophisticated studies are needed to explain the difference in the brain morphology between normals and children with a developmental disorder or a neurological disorder.

Morphological evidence for brainstem involvement in infantile autism.

Previous neurophysiological and neuroanatomic studies suggest brainstem dysfunction in infantile autism. Therefore, we investigated the brainstem structure of autistic patients by planimetric analysis of midsagittal magnetic resonance imaging scans. We found the entire brainstem and one component--the pons--to be statistically significantly smaller in the autistic group when compared with medical controls. We also noted no correlation between brainstem size and age in the autistic group--a correlation that was found in the control group. These data present morphological evidence of brainstem involvement in the infantile autism syndrome.

Evidence for accelerated generation of hydroxyl radicals in experimental obstructive jaundice of rats.

We present evidence herein of the accelerated generation of hydroxyl radical (.OH) in the plasma and the liver tissue of common bile duct ligated (CBDL) rats, a model for experimental obstructive jaundice. .OH production in the plasma was monitored in vivo by the identification of dihydroxybenzoates in plasma [2,3-dihydroxybenzoate (2,3-DHB) and 2,5-dihydroxybenzoate (2,5-DHB)] using high performance liquid chromatography (HPLC). The average concentrations of 2,3-DHB and 2,5-DHB produced in the plasma of the controls were 33+/-3 microM and 232+/-34 microM (n = 15), respectively, whereas their respective concentrations increased to 149+/-28 microM and 604+/-88 microM in the CBDL rats (n = 19). Furthermore, we also observed a time-dependent decreasing trend of 2,3-DHB and 2,5-DHB production after surgical removal of the ligation of the experimental animals. In addition, the generation of .OH in the liver tissue was studied by using dimethyl sulfoxide (DMSO) as a molecular probe and measuring the amount of methanesulfinic acid (MSA), the product of the trapping reaction. The net production of MSA in the liver tissue of the control rats was 1.22+/-0.05 O.D. unit/g protein (n = 5), whereas its respective concentration of MSA in the liver tissue of CBDL rats increased to 2.05+/-0.15 O.D. unit/g protein (n = 5). In addition, we showed that CBDL rats receiving a pretreatment of mannitol, an .OH scavenger, resulted in the decreased production of MSA. Electron micrographic study indicated that the most prominent change observed in CBDL rats was the alteration of mitochondria, which were swollen with distorted cristae. Meanwhile, the bile canaliculi were moderately more dilated than that of the controls, and an increased neutrophil peripheral blood count was found in CBDL rats when compared to the controls. Taken together, our data suggest that accelerated generation of .OH in the CBDL rats is obvious and may play a key role in the pathogenesis of liver damage associated with obstructive jaundice.

Functional blocking of integrin-associated protein impairs memory retention and decreases glutamate release from the hippocampus.

We have previously demonstrated that integrin-associated protein is involved in memory consolidation of one-way inhibitory avoidance learning in rats and mice. In the present study, we examined the effects of functional blocking of integrin-associated protein on memory retention, long-term potentiation and glutamate release in mice as well as on cell attachment to extracellular matrix protein in primary cultures. The results indicated that integrin-associated protein monoclonal antibody miap301, when directly injected into the dentate gyrus of the hippocampus at moderate doses, significantly impairs memory retention in mice in the same one-way inhibitory avoidance task and decreases the amplitude of tetanic stimulation-induced long-term potentiation in dentate gyrus neurons. At a dose that effectively impairs both memory retention and long-term potentiation, integrin-associated protein monoclonal antibody also significantly blocks potassium chloride-induced glutamate release from the hippocampus in vivo. Results from western blot confirmed the presence of integrin-associated protein at the synaptic area. Cell adhesion experiments further revealed that integrin-associated protein monoclonal antibody markedly inhibits granular cell attachment to thrombospondin, the extracellular matrix protein known to bind integrin-associated protein, but not to collagen and laminin, the extracellular matrix proteins known to bind integrin. From these results we suggest that integrin-associated protein monoclonal antibody may impair synaptic plasticity and behavioral plasticity in mice through blockade of granular cell attachment to extracellular matrix protein and the subsequent signal transduction, and through inhibition of glutamate release from the hippocampus.

Cerebral asymmetry in subtypes of schizophrenia.

CT scans of 26 nonparanoid and 10 paranoid right-handed male schizophrenics were examined. Multiple measurements were made of each region of the brain and a standard error of measurement with a confidence level of p less than .01 was used to define significant asymmetry. Three aspects of cerebral asymmetry, i.e., local hemispheric width, local hemispheric protrusion, and regional hemispheric size, were examined. Paranoid and nonparanoid patients were similar in their patterns of frontal asymmetries. However, a substantial proportion of nonparanoid schizophrenics had wider, longer, and larger right parieto-occipital lobes compared to paranoid patients.

Forebrain structure in infantile autism.

Researchers implicate central nervous system dysfunction in infantile autism, but postmortem examinations and in vivo brain imaging studies have produced conflicting results concerning the neuronal systems involved. Magnetic resonance imaging--a new modality of in vivo brain imaging--was used to investigate the cerebral and thalamic structure of 105 autistic patients. Compared with the control group, there was an overall difference in the forebrain morphology of the autistic subjects due to subtle but statistically significant differences in the anterior ventricular horns, lateral ventricles, and the right lenticular nucleus. These results, when considered with previous studies of cerebral structure, suggest that there are subtle alterations in the forebrain of autistic patients.

Utility of the head computerized tomography scan in child and adolescent psychiatry.

Despite the widespread use of computerized tomography (CT) in child and adolescent psychiatry, studies have not looked at its overall usefulness in a clinical setting. In this report, the authors examined 122 inpatients who had CT scans of the head. Only 27 patients had an abnormal CT scan. None of the patients had a change made in the diagnosis or treatment as a result of the scan findings. The authors suggest that routine CT scans of the head in child and adolescent inpatients is of limited value. In view of the rising costs of medical investigations, and the risk of irradiation to the developing brain, they suggest the need for clear indications for this procedure in clinical child and adolescent psychiatry.

Changes of lipid peroxide levels in blood and liver tissue of patients with obstructive jaundice.

Plasma lipid peroxide levels, hereafter referred to as PLP levels, were measured in a group of 40 apparently healthy controls and 64 cholelithiasis patients, 40 with and 24 without jaundice. Hepatic lipid peroxide (HLP) levels were also measured in 26 patients, 15 with and 11 without jaundice. There was a significantly higher mean concentration of PLP in the jaundiced patients than in the control or jaundice-free cases. However, the difference in PLP levels between the jaundice-free and the control cases was insignificant. Meanwhile, patients with jaundice had significantly higher HLP levels than those without jaundice. In the jaundiced cases, the increased PLP and HLP levels were clearly related to the serum levels of bilirubin respectively. In addition, the HLP levels were positively correlated with the PLP levels; however, in the non-jaundiced cases, there was little evidence of these two relationships. Patients with or without jaundice had lower plasma vitamin E levels in comparison to the control cases. The correlation of plasma vitamin E and PLP levels was weak in all of the jaundiced. However, when we subdivided the jaundiced into two groups, the correlation was strong in those with plasma vitamin E levels < 8.5 micrograms/ml, while the correlation was weak in those with plasma vitamin E levels > 8.5 micrograms/ml. Consequently, these results suggest that there is an involvement of lipid peroxidation in liver cells damaged by obstructive jaundice in cholelithiasis patients and there exists a negative correlation between low vitamin E and lipid peroxide levels in plasma.

Is Rett syndrome a subtype of pervasive developmental disorders?

The author reviews the issue on whether Rett syndrome (RS) is a subtype of pervasive developmental disorders (PDDs). More than 200 articles of RS have been published in the last 10 years. Internal and external validities of RS have been established by several independent studies. There remains the question whether RS presents clinical features that meet the total criteria for PDDs. The available data seem to support the idea of classifying RS as a subtype of PDDs in the DSM-IV.

Etiological implication of maternal age and birth order in infantile autism.

Birth orders and maternal ages of the 113 autistic patients were compared with those of the general population. An excess of mothers aged 35 or older was observed in the autistic group, though the mean maternal age for the whole group was very similar to those of the general population. A deviation from average in birth order was observed in autistics. Significantly more autistics were products of at-risk pregnancies (defined as either first, fourth, or later born, or born to mothers aged 30 or older) than the base population. The results suggest that at least some environmental factors are involved in the causation of autism. The findings support the idea that a multifactorial mechanism is responsible for some or all of the cases.

A pragmatic approach to increase expressive language skills in young autistic children.

This paper is a description of a pilot communication program for autistic children designed to increase communication skills in the context of establishing reciprocal communication exchanges. The methods involved intensive modeling of verbal responses within joint activity routines and using a reinforcement system based on fulfilling the intent of the child's communication. Five male subjects ranging in age from 36 to 68 months participated in the communication program for 6 weeks during an inpatient stay at the Iowa Autism Program, Child Psychiatry Service. Communication exchanges involving requests for actions and objects, descriptions of actions and objects, comments on existence and nonexistence, and requests for recurrence were targeted. Individual gains for each subject are outlined. Posttreatment results indicated a significant increase in the mean length of response, in the mean receptive language level, and in the mean number of semantic-grammatical rules expressed. Suggestions regarding future research are discussed.

The effects of fenfluramine on communication skills in autistic children.

The effect of fenfluramine on communication skills in six autistic males was examined over a 9-month period. Communication behaviors were analyzed via standardized receptive and expressive measures, spontaneous speech samples gathered in the clinic, and videotaped observations of the numbers of noncommunicative utterances, immediate echolalia, and spontaneous initiations. The results demonstrated that fenfluramine had no significant effects on the communication behaviors of these six autistic males.

Comparisons between autistic and nonautistic children on the Test for Auditory Comprehension of Language.

Expressive language differences between autistic and nonautistic populations have been a topic of research in the past decade, yet little information is available in regard to the receptive language performances based on standardized tests. Questions as to the existence of sex differences in language have also been raised. The study examines the performance of 19 matched pairs of autistic and nonautistic children on the Test for Auditory Comprehension of Language. As well, the data were analyzed according to sex for each group. The results indicated that there were no significant differences between groups or between the sexes in either group. Questions for further research are raised.

Fenfluramine treatment of autism: relationship of treatment response to blood levels of fenfluramine and norfenfluramine.

Nine children meeting DSM-III criteria for infantile autism were treated with fenfluramine hydrochloride or inactive placebo in a double-blind crossover trial that followed the protocol for the fenfluramine multicenter study. Parents of the two children who had had the highest fenfluramine blood levels wished to have their children continue on fenfluramine, although the improvement they saw could not be demonstrated on the various rating instruments employed. The results of the study, while providing minimal support in themselves for the effectiveness of fenfluramine, do raise the possibility that fenfluramine blood levels might be related to treatment response.

Free radical-triggered hepatic injury of experimental obstructive jaundice of rats involves overproduction of proinflammatory cytokines and enhanced activation of nuclear factor kappaB.

Excessive production of hydroxyl radicals in blood and liver has previously been demonstrated by us in rats with obstructive jaundice induced by common bile duct ligation (CBDL). In this study, we demonstrate overproduction of superoxide radicals in circulating blood of CBDL rats by the lucigenin-amplified chemiluminescence technique. To pinpoint the molecular agents that mediate these processes, we measured circulating proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta ( IL-1beta), and interleukin-6 (IL-6) in controls and CBDL rats. Concentrations of these cytokines in blood of CBDL rats were markedly elevated when compared to the controls (TNF-alpha: 36.7 +/- 5.0 vs 13.8 +/- 0.5 pg/mL; IL-6: 2,814 +/- 1,740 vs 0 pg/mL; IL-1beta: 11.9 +/- 2.6 vs 0 pg/mL). The overproduction of free radicals triggered by elevated cytokines in CBDL rats was correlated with the activation of NF-kappaB in hepatic tissue. Using the TdT-mediated dUTP nick-end label staining technique, we showed that hepatic tissue sections from CBDL rats had an increase in the apoptotic index (AI). Based on these findings, we propose that the severe hepatic injury in CBDL rats is mediated by a cycle that involves the activation of NF-kappaB by combined action of proinflammatory cytokines and reactive oxygen species (ROS). NF-KB, in turn, initiates the transcription of cytokine genes (eg, IL-6, IL-8, TNF-alpha), which triggers hepatic injury, at least in part, by a free radical-mediated apoptotic mechanism. Elevated ROS may be as a positive-feedback signal that triggers NF-KB reactivation; the severe hepatic injury of CBDL rats may result from perpetuation of this vicious cycle.

Biochemical events associated with ligation of the common bile duct in Wistar rats.

Oxygen free radicals have been implicated as mediators of tissue injury in a variety of diseases. We investigated the role of oxidative injury and oxygen free radical scavengers in liver cell injury associated with obstructive jaundice in Wistar rats. Bile duct ligation for 4 or 7 days led to a decrease in both vitamin E and A in the plasma and liver of male Wistar rats, indicating the malabsorption of lipid-soluble vitamins. Serum bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase activities were increased in the bile-duct-ligated rats. Furthermore, marked increases in lipid peroxide and oxidized glutathione levels indicated cholestatic liver injury. The antioxidant defense system was impaired, as shown by decreases in reduced glutathione and in the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase. Moreover, these high lipid peroxide levels and low levels of antioxidants correlated with the severity of jaundice. After releasing the bile duct ligation, levels of bilirubin, lipid peroxide and oxidized glutathione declined, while the levels of vitamin E and A, reduced glutathione, and the activities of GSH-Px increased, indicating an improvement in liver function. These findings suggest that lipid peroxidation is associated with the pathogenesis of liver damage in animals with bile duct ligation. Meanwhile, free oxygen radical scavengers are reduced in the bile-duct-ligated rats, thereby increasing the susceptibility of the liver to injury by oxygen-derived free radicals.

Synthesis of Hsp72 induced by exercise in high temperature.

An investigation was undertaken involving the physiological effects of exercise in high temperature and its effect on the induction of heat shock proteins synthesis in peripheral lymphocytes and gastrocnemius. Male Long-Evans rats were employed. Environmental temperature was designed as three conditions: room temperature (26-27 degrees C), middle temperature (30-31 degrees C), and high temperature (36-37 degrees C). Rats were divided into one of three groups and exercised passively in an automatic round treadmill. Body temperature, biochemical changes were determined and the synthesis of heat shock protein 72 were analyzed by SDS-PAGE and immunochemical stain with monoclonal anti-Hsp72 antibody. Those results indicated that the body temperature elevated faster and higher in rats of high-temperature exercise group than those of a house temperature significantly (p < 0.05). Hsp72 could be detected only in lymphocytes from rats exercising in high temperature more than 60 minutes whose body temperatures were elevated above 41 degrees C. The induced Hsp72 appeared in lymphocytes 2 hours after exercise and reached maximally at 16-24 hours and then disappeared gradually. In gastrocnemius, Hsp72 could be detected even before the passive exercise, and its amount changed as in lymphocytes did in all three groups. No difference was found in blood sugar, hematocrit and CK among the three groups of rats. On the basis of above results, we can conclude that Hsp72 is synthesized in the muscle of intact rats, and exercise is a sufficient inducer. For lymphocytes, the presence of Hsp72 can be viewed as a heat stress in exercise.

Effect of vitamin E, topical hypothermia and steroid on ischemic liver in rats.

Major hepatic surgery often requires temporary occlusion of the porta hepatis in order to minimize intraoperative bleeding. Occlusion of porta hepatis induces hepatic ischemia and may cause liver damage. This study was conducted to evaluate the effects of vitamin E, topical hypothermia and administration of steroids on ischemic liver by assessing the hepatic levels of lipid peroxides and examining the ultrastructural change of mitochondria. One hundred and twenty male wistar rats were divided into four groups, each of 30. All rats underwent laparotomy and the liver ischemia experiment was conducted by clamping the porta hepatis for 15 minutes. Group A received no further treatment, group B received vitamin E (30IU/Kg/B.W) supplementation for one week before experiment, group C was topically cooled and group D received preocclusion intravenous methylprednisolone (2mg/Kg/B.W). Hepatic lipid peroxides, expressed as nmol MDA/g wet wt were assessed by spectrofluorometric methods, and were measured immediately before occlusion, 15 min after occlusion, and 15 min after reperfusion. The results showed that the concentration of lipid peroxides increased markedly after occlusion of porta hepatis in group A, which received no treatment in ischemic liver (8.76 +/- 3.19 vs. 10.49 +/- 3.35 MDA nmol/g wet wt, p < 0.05, paired t-test), while the concentrations of hepatic lipid peroxides were not found to increase in groups B, C or D. In the meantime, the ultrastructural study showed marked swelling of mitochondria in ischemic liver of group A rats only. This suggests that vitamin E supplementation, topical hypothermia and administration of steroids will inhibit the propagation of lipid, peroxidation and provide protective effects on liver parenchyma during ischemia.