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

High-resolution proton magnetic resonance (MR) spectroscopy was performed on perchlorate extracts of tumors (24 cases) or peritumoral vermis (five cases) obtained at surgery. Fifteen tumors were typical cerebellar astrocytomas and nine were posterior fossa primitive neuroectodermal tumors/medulloblastomas. Spectra obtained from the five samples of peritumoral vermis revealed a pattern of metabolites similar to that reported for cerebellar tissue, but concentrations of most metabolites were low, perhaps due to dilution from peritumoral edema. The astrocytomas were characterized by high levels of valine, alanine, and choline, an increase in the choline:N-acetylaspartate (NAA) ratio, and a shift from glutamate to glutamine. Elevations in lactate, pyruvate, and glucose were the result of ischemia during sampling. The primitive neuroectodermal tumors/medulloblastomas were distinguished from astrocytomas by a greater increase in the choline:NAA ratio, a smaller decrease in the glutamate:glutamine ratio, and a relative increase in glycine, taurine, and inositol levels. These metabolic patterns may be of value diagnostically as in vivo MR spectroscopy achieves higher resolution.
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PMID:High-resolution 1H-magnetic resonance spectroscopy of pediatric posterior fossa tumors in vitro. 791 30

We have developed a unique rat AGML model produced by ischemia/reperfusion plus 0.2% ammonia (I/R.NH3), either treatment which would not induce mucosal injury when used alone. The effects of troxipide and other gastric mucosal defensive drugs were investigated with this I/R.NH3-induced AGML model and other AGML models in rats. The following results were obtained: 1) Like allopurinol, troxipide at 50-200 mg/kg, p.o. dose-dependently prevented I/R.NH3-induced development of AGML and also the ischemia/reperfusion-induced increase of gastric mucosal thiobarbituric acid (TBA)-reactive substances; 2) Troxipide at 10(-6)-10(-4) M, like allopurinol, inhibited concentration-dependently in vitro xanthine oxidase activity in gastric mucosal homogenates; 3) Troxipide at 50-200 mg/kg, p.o. inhibited AGMLs induced by bleeding plus 0.2% ammonia and by 1.0% ammonia alone; and 4) Troxipide and sofalcone were similar in preventing all AGMLs tested and also the increase of mucosal TBA-reactive substances, but somewhat differed from teprenone, cetraxate hydrochloride, azulene plus L-glutamine and sucralfate. These findings suggest that troxipide may inhibit I/R.NH3-induced AGML development by preventing generation of oxygen free radicals and by protecting against mucosal fragility due to reduced energy metabolism from poor blood flow and also against ammonia-induced disruption of the gastric mucosal barrier. Therefore, troxipide may be highly effective for various AGMLs with multifactor involvement.
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PMID:[Preventive effects of troxipide on a newly developed model of acute gastric mucosal lesion (AGML) induced by ischemia/reperfusion plus ammonia in the rat]. 795 22

Extracellular concentrations of amino acids in halothane-anesthetized rats were measured using a microdialysis fiber inserted transversely through the dorsal spinal cord at the level of the lumbar enlargement in conjunction with HPLC and ultraviolet detection. After a 2-h washout and a 1-h control period, 20 min of reversible spinal cord ischemia was achieved by the inflation of a Fogarty F2 catheter passed through the femoral artery to the descending thoracic aorta. After 2 h of postischemic reperfusion, animals were transcardially perfused with saline followed by 10% formalin or 4% paraformaldehyde. The glutamate concentration in the dialysate was significantly elevated after 10 min of occlusion and returned to near-baseline during the first 30 min of reperfusion. Taurine was elevated significantly 0.5 h postocclusion and continued to increase throughout the 2 h of reperfusion. Glycine concentrations showed a tendency to be slightly above baseline during the reperfusion period. Glutamine concentrations modestly increased following 2 h of reperfusion. No significant changes in aspartate, asparagine, and serine were detected. In control animals no significant changes in any amino acids were detected. To assess the role of complete spinal ischemia on spinal glutamate release, studies were carried out using cardiac arrest. Twenty minutes after induction of cardiac arrest, the glutamate concentration was increased about 350-400%. In a separate group of animals, spinal cord blood flow (SCBF) and its response to decreased CO2 were measured using a laser probe implanted into the epidural space at the level of the L2 vertebral segment. SCBF decreased to 5-6% of the control during aortic occlusion. After reversible ischemia, marked hyperemia was seen for the first 15 min, followed by hypoperfusion at 60 min. Under control-preischemic conditions a decrease in arterial CO2 content caused a decrease in SCBF of about 25%. This autoregulatory response was almost completely absent when assessed 60 min after a 20-min interval of aortic occlusion. Histopathological analysis of spinal cord tissue from these animals demonstrated heavy neuronal argyrophilia affecting small and medium-sized neurons located predominantly in laminae III-V. These changes corresponded to signs of irreversible damage at the ultrastructural level. Occasionally, small areas of focal necrosis, located in the dorsolateral part of the dorsal horn and anterolateral part of the ventral horn, were found. The results are consistent with a role for glutamate in ischemically induced spinal cord damage and suggest that taurine elevation detected during the early reperfusion period may serve as an important indicator of irreversible spinal cord neuronal damage.
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PMID:Transient spinal ischemia in rat: characterization of spinal cord blood flow, extracellular amino acid release, and concurrent histopathological damage. 801 7

This study was undertaken to elucidate the roles of neurons and glial cells in the handling of glutamate and glutamine, a glutamate precursor, during cerebral ischemia. Slices (400-600 microns) from human neocortex obtained during surgery for epilepsy or brain tumors were incubated in artificial cerebrospinal fluid and subjected to 30 min of combined hypoxia and glucose deprivation (an in vitro model of brain ischemia). These slices, and control slices that had not been subjected to "ischemic" conditions, were then fixed and embedded. Ultrathin sections were processed according to a postembedding immunocytochemical method with polyclonal antibodies raised against glutamate or glutamine, followed by colloidal gold-labeled secondary antibodies. The gold particle densities over various tissue profiles were calculated from electron micrographs using a specially designed computer program. Combined hypoxia and glucose deprivation caused a reduced glutamate immunolabeling in neuronal somata, while that of glial processes increased. Following 1 h of recovery, the glutamate labeling of neuronal somata declined further to very low values, compared to control slices. The glutamate labeling of glial cells returned to normal levels following recovery. In axon terminals, no consistent change in the level of glutamate immunolabeling was observed. Immunolabeling of glutamine was low in both nerve terminals and neuronal somata in normal slices and was reduced to nondetectable levels in nerve terminals upon hypoxia and glucose deprivation. This treatment was also associated with a reduced glutamine immunolabeling in glial cells. Reversed glutamate uptake due to perturbations of the transmembrane ion concentrations and membrane potential probably contributes to the loss of neuronal glutamate under "ischemic" conditions. The increased glutamate labeling of glial cells under the same conditions can best be explained by assuming that glial cells resist a reversal of glutamate uptake, and that their ability to convert glutamate into glutamine is compromised due to the energy failure. The persistence of a nerve terminal pool of glutamate is compatible with recent biochemical data indicating that the exocytotic glutamate release is contingent on an adequate energy supply and therefore impeded during ischemia.
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PMID:Redistribution of glutamate and glutamine in slices of human neocortex exposed to combined hypoxia and glucose deprivation in vitro. 809 18

During brain ischemia in vivo the extracellular concentration of the excitotoxic amino acid, glutamate, increases. This increase could be caused either by an enhanced formation rate of glutamate (from glutamine) or by an impaired re-uptake (or both). This re-uptake occurs to a large extent in astrocytes. In the present study we have determined glutamate uptake and the ability of the cells to maintain their glutamate content during exposure to anoxia, substrate deprivation and combined substrate deprivation and anoxia ('simulated ischemia') for a duration of up to 4 h. Isolated anoxia had no significant effect, whereas both substrate deprivation alone and 'simulated ischemia' reduced glutamate uptake and glutamate content by one-half after 2 h. Under hypothermic conditions (incubation at 32 degrees C), which in in vivo experiments exerts some protection against ischemic cell death in neurons, ischemia of intermediate duration (2 h) decreased glutamate uptake and glutamate content to a less extent than at 37 degrees C. Hypothermia did not have a similar effect during exposure to isolated substrate deprivation.
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PMID:Glutamate uptake and glutamate content in primary cultures of mouse astrocytes during anoxia, substrate deprivation and simulated ischemia under normothermic and hypothermic conditions. 810 87

Although considerable evidence supports a role for amino acids in transient global cerebral ischemia and permanent focal cerebral ischemia, effects of transient focal cerebral ischemia on the extracellular concentrations of amino acids have not been reported. Accordingly, our study was undertaken to examine the patterns of changes of extracellular glutamate, aspartate, GABA, taurine, glutamine, alanine, and phosphoethanolamine in the striatum of transient focal cerebral ischemia, as evidence to support their pathogenic roles. Focal ischemia was induced using the middle cerebral artery occlusion model, with no need for craniotomy. Microdialysis was used to sample the brain's extracellular space before, during, and after the ischemic period. One hour of middle cerebral artery occlusion followed by recirculation caused neuronal damage that was common in the frontoparietal cortex and the lateral segment of the caudate nucleus. During 1 h of ischemia, the largest increase occurred for GABA and moderate increases were observed for taurine, glutamate, and aspartate. Alanine, which is a nonneuroactive amino acid, increased little. After recirculation, the levels of glutamate and aspartate reverted to normal baseline values right after reperfusion. Despite these rapid normalizations, neuronal damage occurred. Therefore, uptake of excitatory amino acids can still be restored after 1 h of middle cerebral artery occlusion, and tissue damage occurs even though high extracellular levels of glutamate are not maintained.
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PMID:Changes in the extracellular concentrations of amino acids in the rat striatum during transient focal cerebral ischemia. 811 94

Intestinal ischemia/reperfusion (I/R) causes formation of reactive oxygen intermediates (ROI) which lead to mucosal cell injury. Glutathione (GSH), an ROI scavenger, protects tissues from ROI-mediated cell injury. Since GSH biosynthesis is partially dependent on glutamine (Gln) levels, we tested the hypothesis that intravenous Gln infusion will assist in maintaining mucosal cell GSH levels and decrease membrane lipid peroxidation during intestinal I/R. The external jugular vein of male Sprague-Dawley rats was cannulated and infused with normal saline (NS) at 2 cc/hr. After 3 days, matched pairs of rats received either NS alone or NS+ 3% Gln for an additional 24 hr. Next, mucosal GSH levels were measured after a sham I/R in 6 rats and after either 30 or 60 min of ischemia/60 min of reperfusion in a group of 8 and 12 rats, respectively. Finally, conjugated diene (CD), a byproduct of membrane lipid peroxidation, was measured following 60 min of ischemia/60 min of reperfusion in a separate group of 12 rats. Control rats had the highest GSH levels and there was no difference between NS vs NS + 3% Gln rats (2.50 +/- 0.48 vs 2.50 +/- 0.43, P = NS). With 30 and 60 min of ischemia/60 min of reperfusion, GSH levels were significantly lower in NS-infused rats compared to those in NS + 3% Gln-infused rats (30 min: 1.54 +/- 0.14 vs 1.80 +/- 0.16, P < 0.05; 60 min: 1.27 +/- 0.15 vs 1.52 +/- 0.20, P < 0.04). In addition, CD levels were lower in NS + 3% Gln-infused rats compared to those in NS alone-infused rats (5.58 +/- 0.87 vs 7.94 +/- 0.55, P < 0.04). In conclusion, Gln supplementation partially maintains gut GSH levels during bowel I/R, which in turn lessens I/R-induced cell membrane lipid peroxidation.
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PMID:Glutamine preserves gut glutathione levels during intestinal ischemia/reperfusion. 815 29

In a global model of brain ischemia, accumulation of amino acids was studied in the extracellular space of the auditory cortex and the internal capsule using microdialysis, and in CSF of halothane anesthetized cats. In both brain regions, blood flow determined by hydrogen clearance decreased below 10 ml/100 g/min after extracranial multiple-vessel occlusion, and extracellular potassium activity (Ke) measured in the dialysate increased significantly. A delayed rise in Ke was observed in CSF. In contrast, ischemic amino acid accumulation differed markedly between the two brain regions investigated. In cortex, transmitter amino acids glutamate, aspartate, and gamma-aminobutyric acid (GABA) rose almost immediately after onset of ischemia, and increased 30-, 25-, and 250-fold, respectively, after 2 h of ischemia. The nontransmitter amino acids taurine, alanine, and serine increased 10-, seven-, and fourfold, respectively, whereas glutamine and essential amino acids (valine, phenylalanine, isoleucine, and leucine) increased only 1.5-fold. In the internal capsule, increases in amino acids, if any, were delayed and much smaller than in cortex. The largest alteration was a fivefold elevation of GABA. In CSF, changes in amino acids were small and comparable to those in the internal capsule. Our results demonstrate that ischemia-induced extracellular amino acid accumulation is a well localized phenomenon restricted to gray matter structures that possess release and reuptake systems for these substances. We assume that amino acids diffuse slowly into adjacent while matter structures, and into CSF.
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PMID:Ischemia-induced accumulation of extracellular amino acids in cerebral cortex, white matter, and cerebrospinal fluid. 841 67

The severity of brain injury following interruption of blood flow depends on a number of ischemic and post-ischemic variables. The most important ischemic variables are the duration of ischemia, the amount of residual blood flow, the type and depth of anesthesia, brain glucose content and temperature. Among the post-ischemic factors the no-reflow phenomenon, edema and a variety of biochemical disturbances are of particular importance. Due to the complex interaction of these factors irreversible brain injury usually occurs after less than 10 min cerebrocirculatory arrest in normothermia. However, the safe ischemia time of the brain can be substantially extended when appropriate therapeutic measures are used to alleviate post-ischemic injury. NMR-spectroscopy is particularly suited for the analysis of this process. Recording of 31P, 1H and 19F spectra allow the continuous non-invasive assessment of such basic parameters as brain energy state, tissue pH, the content of lactate and blood flow (using Freon-23 as an inert tracer). In addition, information is obtained about changes in the content of phosphomonoesters and -diesters, glutamate, glutamine, aspartate and N-acetyl aspartate. These measurements can be combined with in vivo electrophysiological and post-mortem biochemical investigations for the further refinement of functional/metabolic monitoring. We have used this approach to study the potentials of post-ischemic resuscitation after one hour complete ischemia of the normothermic cat brain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:NMR-spectroscopic investigation of cerebral reanimation after prolonged ischemia. 842 52

The suitability of two-dimensional (2D) proton spectroscopy for monitoring, in vivo, the changes in levels of brain metabolites induced by cerebral ischemia was investigated in an experimental model of 30-min reversible ischemia induced by four-vessel occlusion in the rat. The resulting data were compared with those obtained by one-dimensional (1D) proton and phosphorus spectroscopy. Phosphorus spectra obtained during ischemia showed significant drops in levels of phosphocreatine (-73%), beta-ATP (-60%), and intracellular pH (to 6.30) and an increase in inorganic phosphate level (905%). 1D and 2D proton spectra showed decreases in the N-acetylaspartate/creatine-phosphocreatine ratio that were not significantly different [-21% (1D) and -32% (2D)]. Similarly, the increases in lactate/creatine-phosphocreatine ratio were not significantly different [2,546% (1D) and 3,020% (2D)]. 2D spectroscopy also indicated a decrease in aspartate (-66%) and an increase in the inositol-choline derivative (+124%) pools during ischemia and an increase in alanine pool (+516%) during reperfusion. The glutamate-glutamine pool and taurine content did not change significantly during ischemia but decreased during reperfusion. The glucose level transiently decreased (-67%) during ischemia and increased immediately after (+261%). The levels of all the metabolites investigated returned to control values within 175 min after ischemia. 2D spectroscopy seems to be a reliable method of monitoring the changes in levels of cerebral compounds known to be involved in ischemia.
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PMID:A one-dimensional (proton and phosphorus) and two-dimensional (proton) in vivo NMR spectroscopic study of reversible global cerebral ischemia. 863 74


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