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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uptake of various amino acids was studied in slices from brain regions of rats four weeks after portocaval anastomosis. No differences of the inulin compartment were observed between control and experimental animals. After 60-minutes incubation, uptake showed an overall pattern of diminution. This was more evident for some amino acids: valine, methionine, and lysine exhibited a lowering of about 30%, which was fairly uniform in the four tested regions; others showed a regional decrease-- alanine in pons-medulla, phenylalanine in cerebellum, histidine and GABA in mesodiencephalon. This decrease did not seen to be related to transport classes. The restricted entry of amino acids into brain cells in portocaval encephalopathy is somewhat difficult to explain; a decreased rate of protein synthesis may be of some importance, but other factors, such as a "carrier" impairment, effects on release and on amino acid metabolism, may also be involved.
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PMID:Cerebral amino acid levels and uptake in rats after portocaval anastomosis: I. Regional studies in vitro. 46 64

The regional distribution of binding sites on the GABAA receptor and their kinetic parameters were measured by quantitative autoradiography in brains from normal rats and rats with a portacaval shunt, a model of portal systemic encephalopathy in which GABA neurotransmission may be altered. The ligands used were [3H]flunitrazepam (a benzodiazepine-site agonist), [3H]-Ro15-1788 (a benzodiazepine-site antagonist), [3H]muscimol (a GABA-site agonist), and [35S]t-butylbicyclophosphorothionate (35S-TBPS, a convulsant that binds to a site near the chloride channel). Some brains were analyzed by computerized image analysis and three-dimensional reconstruction. The regional distribution of binding of the benzodiazepines was very similar, but the patterns obtained with [3H]muscimol and [35S]TBPS were different in many areas, suggesting a heterogeneous distribution of several subtypes of the GABAA receptor. The kinetic parameters were determined in brain regions for [3H]flunitrazepam, [3H]Ro15-1788, and [3H]muscimol. For each ligand, the Kd showed a significant heterogeneity among brain regions (at least threefold), contrary to conclusions drawn from earlier studies. In portacaval shunted rats, binding of all four ligands was essentially unchanged from that in control rats, indicating that, if there was an abnormality in GABA neurotransmission during portal systemic shunting, it was not reflected by altered binding to the main sites on the GABAA receptor.
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PMID:Regional distribution and kinetics of three sites on the GABAA receptor: lack of effect of portacaval shunting. 131 40

To evaluate the risk of hepatic encephalopathy and arterial hypotension in cirrhotic patients after acute administration of acamprosate, a GABA mimetic drug used in the weaned alcoholic, a randomized double-blind trial was conducted in 24 cirrhotic patients with low or moderate hepatic insufficiency (Pugh grade A or B). Twelve patients received 666 mg (2 tablets) of acamprosate and 12 received placebo. The 2 groups were similar before treatment, except for a male predominance in the acamprosate group. Tested parameters were the P100 latency of visual evoked potentials using a checkerboard pattern reversal as stimulus, the number connection test and the arterial blood pressure in upright and recumbent positions. The two first parameters were studied before and 2 hours after treatment. Blood pressure was recorded every half hour during 6 hours. No significant effect on the development of subclinical hepatic encephalopathy was noted. Nevertheless, even if some authors disagree with the GABA hypothesis of hepatic encephalopathy, it is possible that the dose was too low to induce subclinical hepatic encephalopathy. A study with more prolonged treatment could be necessary to be sure of the drug's safety in these patients. On the other hand, a transient decrease of diastolic arterial blood pressure was observed without significant systolic blood pressure modification. These results suggest that a moderate dose of acamprosate does not induce subclinical encephalopathy, but transient diastolic hypotension.
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PMID:[Effect of acute administration of acamprosate on the risk of encephalopathy and on arterial pressure in patients with alcoholic cirrhosis]. 142 25

In Alzheimer's dementia (AD) the Primum Movens is Amyloid (AM) production on precapillaries: Dyshoric Angiopathy, and capillaries: Senile Plaques (SP) producing Blood-Brain-Barrier (BBB) disturbances, entry in the brain of toxic metals which displace the zinc. Cerebral AM alone may be asymptomatic. Clinical symptoms (Amnesia, Instrumental Disorders) appear when AM induces Neighbouring neuritic alterations: Paired Hellical Filaments (PHF) and Distant neuronal body lesions: Neurofibrillary Tangles (NFT). The AM is coded by a locus on the chromosome 21 and a duplication of this locus should be the etiology of cerebral AM in AD. In AD cerebral zinc decreases particularly in the hippocampus. The zinc-enzyme Superoxyde-Dismutase (SOD) is coded by a locus also on the chromosome 21 near AM and the plasma level of SOD is high in AD. Zinc deposits observed in capillary AM-SP, result probably from the excess of plasmatic SOD. Other metals: Iron, aluminium are also observed in the AM-SP and their excess in the brain may be related to the decrease of zinc by metal to metal displacement. The decrease of functional zinc in the brain may interfere in the pathogenesis of PHF-NFT by metalotoxicity, neighbouring and distant to AM. Without AM, NFT are produced also by metalotoxicity and therefore brain zinc displacement. a) by lead: Encephalopathia saturnica b) by many metals: Guam Encephalopathy c) by aluminium d) by BBB disturbances leading probably to an abnormal entry of metals in the brain (Dementia Pugilistica, viral encephalitides). NFT may be produced by the deficiency of the following zinc enzymes: 1. Those of DNA metabolism, indicating abnormal DNA and therefore abnormal protein synthesis: PHF-NFT. 2. Those of neuronal detoxication: SOD, Carbonic Anhydrase, Lactate Dehydrogenase leading to neuronal toxicity particularly in the hippocampus normally rich in SOD. 3. Of Glutamate (GLU) Dehydrogenase (GDH) resulting in an excitotoxic increase of GLU. 4. Those of the metabolism of neurotransmitters (NT): neuropeptides, Histamine, GABA, Acetylcholine. Therapeutic proposition: a zinc complex crossing the BBB should be useful a) to prevent that the AM produces PHF-NFT by Neighbouring and Distant metalotoxicity and DNA changes; b) to regularise zinc-enzymes of neuronal detoxification and of neurotransmitters metabolisms. Preliminary trials by zinc Aspartate give yet promising results.
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PMID:[Alzheimer's dementia and zinc]. 170 60

Using an indwelling cisterna magna catheter technique, serial CSF samples were analyzed for amino acid content in rats at various stages of portal-systemic encephalopathy resulting from ammonium acetate administration following portacaval anastomosis. Anastomosis alone resulted in increased CSF concentrations of glutamine, tyrosine, phenylalanine, glutamate and alanine. GABA levels, on the other hand were not significantly changed. Onset of severe neurological symptoms following ammonium acetate administration resulted in selectively increased CSF alanine. Other amino acids were not further increased at severe stages of encephalopathy. Increased CSF alanine probably results from increased glutamine transamination in the brains of portacaval shunted rats.
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PMID:Cerebrospinal fluid amino acids in relation to neurological status in experimental portal-systemic encephalopathy. 174 65

The binding characteristics of gamma-aminobutyric acid-A (GABA-A) receptors and the kinetic characteristics of the target enzyme of GABA synthesis in nerve terminals, glutamic acid decarboxylase (GAD), were studied in a dog model of portal-systemic encephalopathy obtained by porta-caval shunt performed in dimethylnitrosamine pretreated animals. Furthermore the properties of dopamine receptors and the levels of catecholamines of encephalopathic dogs were investigated. The mild stage of encephalopathy was characterized by an up-regulation of the inhibitory GABA-A receptors probably related to a decrese of GABA in nerve terminals since GAD was decreased and by a slight decrease of catecholamines and by an increased synthesis of octopamine associated with a decreased affinity of dopamine receptors. In the severe stage there was a selection of high affinity GABA-A receptors with an increased number of benzodiazepine recognition sites which were supersensitive to GABA stimulation, a decreased number of Dopamine D-2 receptors and a marked reduction of catecholamines. These data seem to suggest that the neurological disturbances of experimental portal-systemic encephalopathy might be the result of an imbalance between inhibitory and excitatory systems leading to a prevalence of the first one.
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PMID:Alterations of GABA-A and dopamine D-2 brain receptors in dogs with portal-systemic encephalopathy. 184 16

Venous blood was collected from 21 patients with liver cirrhosis and portocaval anastomosis for routine laboratory tests and determination of GABA levels by radioreceptor assay. The patients additionally underwent psychometric tests for determining the degree of hepatic encephalopathy. No differences were seen in psychometric tests and laboratory parameters between patients and normals. However, GABA serum levels showed a 10-fold increase and the difference was highly significant. The fact that these patients did not show any signs of hepatic encephalopathy is probably due to an intact blood-brain barrier that prevents the uncontrolled influx of GABA. Therefore, not even high GABA serum levels are associated with symptoms of encephalopathy.
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PMID:[The blood level of gamma-aminobutyric acid in patients with liver cirrhosis and portacaval anastomosis]. 188 23

The functional activity of the gamma-aminobutyric acid (GABAA) receptor-chloride ionophore complex was studied in rats with hepatic encephalopathy (HE) secondary to thioacetamide-induced fulminant hepatic failure (FHF). Muscimol stimulation and benzodiazepine potentiation of GABA receptor-mediated 36Cl- uptake into cerebral cortical synaptoneurosomes was compared in HE and control rats. [3H]Flumazenil binding assays were conducted to determine whether the levels of endogenous benzodiazepine-like ligands in extracts of cortex were increased with stages of encephalopathy in this animal model of HE. In both control and HE rats maximal uptake of 36Cl- via the GABAA receptor complex occurred at muscimol concentrations of 30 microM. Potentiation of muscimol-stimulated 36Cl- uptake into synaptoneurosomes by diazepam (5 microM) was equivalent in both groups. Aqueous extracts of proteolytically digested homogenates of cerebral cortices prepared from control and HE rats were effective in stimulating 36Cl- uptake into synaptoneurosomes. Alkaline organic extracts of proteolytically digested homogenates of cerebral cortices from HE rats were more effective than corresponding extracts from controls at inhibiting the binding of [3H]flumazenil. Inhibition of [3H] fumazenil binding by organic extracts derived from the cerebral cortices of HE rats did not increase with progression of encephalopathy. The results show that muscimol-stimulated 36Cl- uptake into synaptoneurosomes and, consequently, GABAA receptor-mediated chloride channel function are not significantly altered in the model of HE studied and are consistent with the hypothesis that HE results in an increased availability of one or more endogenous ligands which can augment GABA receptor-gated chloride conductance.
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PMID:Gamma-aminobutyric acid (GABAA) receptor-function in a rat model of hepatic encephalopathy. 196 8

Evidence compatible with increased GABAergic tone contributing to the manifestations of hepatic encephalopathy (HE) in animal models of fulminant hepatic failure (FHF) includes: (i) increased resistance to drugs which induce seizures by reducing GABAergic tone; (ii) abnormalities of visual evoked responses (VERs) which resemble those induced by drugs which augment GABAergic tone; (iii) increased sensitivity of CNS neurons to a GABA agonist; and (iv) ameliorations of the encephalopathy induced by a GABA receptor antagonist. Evidence compatible with a benzodiazepine (BZ) receptor ligand with agonist properties contributing to increased GABAergic tone in animal models of FHF includes: (i) abnormalities of VERs which resemble those in BZ agonist-induced coma; (ii) increased sensitivity of CNS neurons to a BZ receptor agonist; (iii) excitation of CNS neurons induced by BZ receptor antagonists; (iv) reversal of the increased sensitivity of CNS neurons to a GABA agonist by a BZ receptor antagonist; (v) presence of a ligand(s) in brain which displaces a radiolabeled ligand from BZ receptors; and (vi) increased affinity of this ligand(s) for BZ receptors in the presence of GABA ("positive GABA shift").
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PMID:Hepatic encephalopathy, GABA-ergic neurotransmission and benzodiazepine receptor ligands. 196 4

A 13-year-old boy was the victim of a strangulation attempt. His behavior was normal by the 6th day after the assault. However, from the 7th day, he developed choreoathetosis, dystonia and marked pseudobulbar palsy. CT and T2-weighted MRI at this time revealed a low density and high signal intensity in the region of the bilateral putamen and caudate respectively for the first time. Thereafter, these symptoms and changes in CTs and MRIs subsided gradually over two months. Sequential analysis of CSF for GABA and dopamine during illness revealed reciprocal changes each other with normal recovery. Because of delayed onset of neurological changes, and findings of CSF with reversible symptoms the delayed encephalopathy after strangulation is probably related to biochemical alteration secondary to anoxia in vulnerable basal ganglia.
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PMID:[Delayed postanoxic encephalopathy after strangulation--the serial neuroradiological and neurochemical studies]. 210 26


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