Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both increased gamma-aminobutyric acid (GABA)-ergic and decreased glutamatergic neurotransmission have been suggested relative to the pathophysiology of hepatic encephalopathy. This proposed disturbance in neurotransmitter balance, however, is based mainly on brain tissue analysis. Because the approach of whole tissue analysis is of limited value with regard to in vivo neurotransmission, we have studied the extracellular concentrations in the cerebral cortex of several neuroactive amino acids by application of the in vivo microdialysis technique. During acute hepatic encephalopathy induced in rats by complete liver ischemia, increased extracellular concentrations of the neuroactive amino acids glutamate, taurine, and glycine were observed, whereas extracellular concentrations of aspartate and GABA were unaltered and glutamine decreased. It is therefore suggested that hepatic encephalopathy is associated with glycine potentiated glutamate neurotoxicity rather than with a shortage of the neurotransmitter glutamate. In addition, increased extracellular concentration of taurine might contribute to the disturbed neurotransmitter balance. The observation of decreasing glutamine concentrations, after an initial increase, points to a possible astrocytic dysfunction involved in the pathophysiology of hepatic encephalopathy.
 ...
PMID:Amino acid release from cerebral cortex in experimental acute liver failure, studied by in vivo cerebral cortex microdialysis. 162 30

Two benzodiazepine-receptor partial inverse agonists (Ro 15-4513, Ro 15-3505) and one benzodiazepine-receptor antagonist (flumazenil) were administered to rats with hepatic encephalopathy due to acute liver ischemia. Significant improvement (P less than 0.002) of both the clinical grade of hepatic encephalopathy and the electroencephalographic abnormalities was observed after administration of the benzodiazepine-receptor partial inverse agonists: comatose rats with no spontaneous righting reflex regained consciousness immediately after injection of the drug. Only slight improvement in clinical hepatic encephalopathy grade was seen after administration of 25 mg/kg of flumazenil. The present data strongly support a role of increased gamma-aminobutyric acid-ergic tone in the pathogenesis of acute hepatic encephalopathy and provide a rationale for trials of benzodiazepine-receptor partial inverse agonists to restore consciousness in hepatic encephalopathy in humans in the near future.
 ...
PMID:The effects of benzodiazepine-receptor antagonists and partial inverse agonists on acute hepatic encephalopathy in the rat. 165 Mar 20

At present in vivo NMR spectroscopic studies of brain glutamate and glutamine concentrations relative to encephalopathy have mainly been performed in hepatic encephalopathy (HE). In vivo proton NMR studies were performed in rats with hyperammonemia and acute HE due to acute liver ischemia as well as in rats with hyperammonemia due to either repeated urease i.p. injection or i.p. administration of methionine sulfoximine, a well known inhibitor of glutamine synthetase. In man, in vivo proton NMR is described in patients with chronic liver disease: cirrhosis of different etiology and associated with different degrees of HE. In the experimental models proton NMR spectroscopy of the cerebral cortex revealed an increase in glutamine concentration, a decrease in glutamate concentration and a decrease in phosphocholine compounds. In humans no clear distinction between cerebral cortex glutamate and glutamine concentration could be made by in vivo 1H NMR spectroscopy. However, the combined glutamate/glutamine peak increased in a way compatible with an increased cerebral cortex glutamine concentration during chronic HE. In the cirrhotic patients too a decrease in cerebral cortex phosphocholine compounds was observed, the explanation of which is unclear. Both the experimental work and the clinical observations support the hypothesis that impairment of the glutamate/glutamine cycle between astrocytes and neurons plays a role in the pathogenesis of hepatic encephalopathy.
 ...
PMID:What the clinician can learn from MR glutamine/glutamate assays. 167 85

The effects of hyperammonemia on brain function have been studied in three different experimental models in the rat: acute liver ischemia, urease-treated animals and methionine sulfoximine-treated animals. To quantify the development of encephalopathy, clinical grading and electroencephalographic spectral analysis were used as indicators. In all three experimental models brain ammonia concentrations increased remarkably associated with comparable increases in severity of encephalopathy. Furthermore, in vivo 1H-nuclear magnetic resonance spectroscopy of a localized cerebral cortex region showed a decrease in glutamate concentration in each of the aforementioned experimental models. This decreased cerebral cortex glutamate concentration was confirmed by biochemical analysis of cerebral cortex tissue post mortem. Furthermore, an increase in cerebral cortex glutamine and lactate concentration was observed in urease-treated rats and acute liver ischemia rats. As expected, no increase in cerebral cortex glutamine was observed in methionine sulfoximine-treated rats. These data support the hypothesis that ammonia is of key importance in the pathogenesis of acute hepatic encephalopathy. Decreased availability of cerebral cortex glutamate for neurotransmission might be a contributing factor to the pathogenesis of hyperammonemic encephalopathy. A surprising new finding revealed by 1H-nuclear magnetic resonance spectroscopy was a decrease of cerebral cortex phosphocholine compounds in all three experimental models. The significance of this finding, however, remains speculative.
 ...
PMID:Changes in brain metabolism during hyperammonemia and acute liver failure: results of a comparative 1H-NMR spectroscopy and biochemical investigation. 197 48

Two experimental models of hepatic encephalopathy in the rat have been investigated in order to study the postulated relationship between plasma free fatty acids concentration (C6 - C22:0) and the degree of hepatic encephalopathy. As a model of chronic hepatic encephalopathy, porta caval shunted rats were studied for 15 weeks, whereas rats with acute liver ischemia were used as a model for acute hepatic encephalopathy. In porta caval shunted rats only a minor degree of hepatic encephalopathy developed, whereas plasma ammonia concentration increased significantly (82 +/- 8 to +/- 440 +/- 32 mumol/l). Acute liver ischemia induced severe grades of hepatic encephalopathy associated with high levels of plasma ammonia (+/- 1 200 mumol/l). Since no significant changes in plasma free fatty acids were observed during both chronic and acute hepatic encephalopathy no correlation between plasma free fatty acids and the stage of hepatic encephalopathy was found. Our data do not support an important role of free fatty acids in the pathogenesis of acute or chronic hepatic encephalopathy in the rat.
 ...
PMID:The relationship between plasma free fatty acids and experimentally induced hepatic encephalopathy in the rat. 204 60

The metabolism of methanethiol was studied in rats. Administration of a noncomatogenic dose of methanethiol through inspired air or injection into the upper colon resulted in an elevation of the concentrations of methanethiol mixed disulfides in serum (protein--S--S--CH3 and X--S--S--CH3, X yet unknown) and in urine (X--S--S--CH3). The concentrations of methanethiol mixed disulfides proved to be a relative measure of exposure to methanethiol. The levels of volatile sulfur compounds methanethiol, dimethylsulfide and dimethyldisulfide in the air expired by rats exposed to a noncomatogenic dose of methanethiol through the colon were also elevated. Rats with acute hepatic encephalopathy caused by liver ischemia also showed elevation of methanethiol mixed disulfide levels on challenge of methanethiol through the colon or inspired air, but to a significantly smaller extent than did the corresponding sham-operated rats. This suggests that the liver is at least partly responsible for formation of methanethiol mixed disulfides. No additional toxic effects were observed in the rats with ischemic livers on methanethiol exposition when compared with normal rats, suggesting that the liver does not play an essential role in methanethiol detoxification. Metabolism of methanethiol by blood to sulfate, for example, might be more important. In rats with acute hepatic encephalopathy caused by liver ischemia and in dogs suffering from hepatic encephalopathy resulting from chronic liver disease, large and significant increases in ammonia levels were measured. However, the mean levels of methanethiol mixed disulfides in rats and dogs with hepatic encephalopathy were not different from the mean normal levels in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Methanethiol metabolism and its role in the pathogenesis of hepatic encephalopathy in rats and dogs. 232 60

The paper presents some mechanisms which determine or accompany cellular brain edema: intracellular and extracellular osmolality alteration, neuronal excitation, increased extracellular K+ concentration, anoxia, ischemia and hepatic encephalopathy.
 ...
PMID:Cellular edema in nervous tissue. 266 67

Short- and long-term effects of intraperitoneally transplanted microcarrier attached liver cells (MAL) have been studied in two experimental models of severe liver insufficiency in the rat: subtotal hepatectomy (HX) and acute liver ischemia. Intraperitoneal transplantation of MAL immediately after subtotal hepatectomy resulted in a significantly lower plasma ammonia level, a higher caffeine clearance, a higher urea production and a significantly smaller loss in body weight in comparison to sham transplanted control rats. Since thymidine kinase activity in the regenerating host liver was only significantly stimulated at t = 48 h it is concluded that the observed metabolic effects are mainly due to the metabolic activity of the transplanted MAL, although a small stimulative effect of MAL-TX on host liver regeneration cannot be excluded. In the course of acute liver ischemia, MAL transplantation results in delayed development of acute hepatic encephalopathy (HE), judged by clinical grading, EEG spectral analysis and Visual Evoked Response (VER) parameters. Furthermore, MAL transplantation is associated with less increased levels of plasma ammonia during acute liver ischemia.
 ...
PMID:Metabolic activity of microcarrier attached liver cells after intraperitoneal transplantation during severe liver insufficiency in the rat. 267 Nov 20

The progressive course of hepatic encephalopathy developing in rats after massive hepatic ischemia due to hepatic artery ligation within 48 hr of a portacaval shunt was not altered by the injection of a benzodiazepine antagonist, CGS 8216, in a dose that was sufficient to reverse diazepam-induced coma quickly. The onset of hepatic coma was shortened 20 to 25% by the antagonist, rather than being delayed, as would be expected if hepatic coma were due to a gamma-aminobutyric acid (GABA)-ergic effect. The neural binding of GABA by brains from rats in deep hepatic coma was unaffected by the injection of the benzodiazepine antagonist.
 ...
PMID:A benzodiazepine antagonist does not alter the course of hepatic encephalopathy or neural gamma-aminobutyric acid (GABA) binding. 285 Apr 57

During the development of acute hepatic encephalopathy, induced by acute liver ischemia, changes in brain 31P NMR spectra and EEG spectra were studied over 8:45 h in eight rats. At the end of this period the brain amino acid concentrations were determined. The results were compared with the same measurements in four normal and three portacaval shunted rats. Signs of acute HE, as judged by the EEG left index, started 5 h after the induction of acute liver ischemia. No accompanying significant changes in the cortical relative phosphocreatine and ATP concentration and intracellular pH were observed. The cortical relative Pi concentration had only slightly increased at t = 8 h. The concentrations of almost all measured brain amino acids, especially glutamine had increased at t = 8:45 h. At t = 8 h, rats with very severe HE had a small, but significant decrease of brain ATP concentrations. Their brain amino acid concentrations were more disturbed than in rats with less severe HE. It is concluded that a change in the cortical cerebral energy rich phosphate concentration is not an important pathophysiological mechanism during the development of acute HE. The observed changes in brain amino acids concentrations could be either part of a multifactorial pathogenesis or could be epiphenomena.
 ...
PMID:In vivo 31P NMR spectroscopy of the rat cerebral cortex during acute hepatic encephalopathy. 327 25


1 2 3 4 Next >>