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)

The levels of amino acids in 6 regions of the brain (cortex, hippocampus, striatum, diencephalon, stem and cerebellum) were determined during an ischemic insult of 30 min and after recovery periods of up to 10 h. The results were analyzed in two groups: putative neurotransmitters (GABA, aspartate, glutamate, taurine, glycine and alanine) and non-neurotransmitters. In the neurotransmitter group, it was found that at the end of 30 min ischemia the levels of aspartate and glutamate slightly decreased whereas those of GABA and alanine rose substantially. The amounts of glycine and taurine remained unchanged. In 30 min after the ischemic insult, there were much larger decreases in aspartate and glutamate and increases in GABA and alanine with no change in glycine and taurine. At 2 h recovery the levels of the neurotransmitter amino acids had almost returned to control values and were fully recovered by 10 h after ischemia. It is postulated that glutamate and aspartate are released during ischemia into the extracellular space and subsequently 'washed-out' into the blood during the reperfusion. Release of GABA, if it occurs, is however, compensated by increase in its synthesis and decrease in its degradation under anaerobic conditions, both of which contribute to the rise in its steady-state level. In the non-transmitter category, increases were seen in amino acids present normally in very small concentrations; tyrosine, lysine, leucine and 3 hydrophobic amino acids: valine, methionine and phenylalanine, which were most pronounced at 2 h after ischemia. It is suggested that the rise in the levels of these molecules is the consequence of stimulation of protein breakdown caused by activation of intracellular proteases by calcium and H+ during the ischemic episode. Regional variations in the patterns of changes were small although in the ischemic models used the brainstem seemed to be least affected.
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PMID:Neurotransmitter amino acids in the CNS. I. Regional changes in amino acid levels in rat brain during ischemia and reperfusion. 614 83

Metabolic, mechanical, thermal, and chemical injury induced ornithine decarboxylase (ODC) activity in rat brain. A two- to sixfold increase in ODC activity was measured at 5-9 h after different modes of injury to the brain. During the early phase of recovery from transient ischemia, when average protein synthesis was less than 50% of control, ODC activity was increased nearly fivefold. The rise in activity could be blocked by anisomycin, or reduced by intracerebral injections of actinomycin D. Drilling burr holes into the skull, injection of the vehicle for actinomycin D, hyperthermia, and freezing lesions all caused increased ODC activity. Neurotoxic chemicals (ammonia, methionine sulfoximine, acrylamide, carbon tetrachloride, and anisomycin) also increased brain ODC activity, whereas other chemicals (mannitol and valine) did not. Treatments known to stimulate the synthesis of heat shock proteins (carotid occlusion, hyperthermia, Cd2+, canavanine, and ethanol) induced ODC activity in the liver, whereas only hyperthermia and ethanol caused significant increases in spleen ODC activity. All increases in ODC activity were blocked by difluoromethylornithine, an irreversible inhibitor of ODC. The cellular response to noxious or stressful stimuli includes the synthesis of a small number of proteins of unknown functions; ODC may be one of these "heat shock" or "trauma" proteins.
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PMID:Induction of brain ornithine decarboxylase during recovery from metabolic, mechanical, thermal, or chemical injury. 642 97

Adult male rats were force-fed either a single dose of 200 mg of DL-methionine or an amino acid mixture with the pattern of casein. The animals were anesthetized with pentobarbital at 0, 1.5, 3 and 4 hours after intubation, and samples of liver were removed by a freeze-clamping technique at 0, 15 and 30 seconds of ischemia. Hepatic ATP, ADP, AMP, Pi, glucose-6-phosphate, glucose and certain nitrogenous compounds as well as plasma glucose were determined. After methionine was given by intubation, hepatic methionine and glutathione increased severalfold within 1.5 hours; cystathionine showed a transient rise at this time but returned to normal at 3 and 4 hours, when taurine was progressively increasing. Several nonessential amino acids decreased, suggesting that they may be utilized for energy. Methionine force-feeding did not modify the concentration of hepatic adenine nucleotides and probably did not change their turnover, as estimated from changes during ischemia. The level and production of Pi during ischemia was increased however. After force-feeding the amino acid mixture, hepatic methionine, cystathionine and taurine were unaffected, and glutathione increased only at hours 3 and 4; glycine and threonine were elevated by 1.5 hours. Hepatic adenine nucleotides, inorganic phosphate and glucose were not significantly affected by the feeding of amino acids by intubation.
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PMID:Effects of excess methionine ingestion on hepatic phosphate, adenine nucleotides and free amino acids in the rat. 707 15

Skeletal muscle regeneration has been induced by injection of the myotoxic drug bupivacaine (Marcaine) into the rat tibialis anterior muscle. Doses of 1.5 and 1.0% wt/vol produce significant levels of muscle regeneration, but these doses also produce large regions of ischemic muscle. Doses of 0.75 and 0.5% bupivacaine are also effective in inducing regeneration and produce little or no ischemia. Regenerating muscle is significantly more active in the incorporation of 35S-methionine into protein than is control muscle, and the activity increase is directly proportional to the bupivacaine dose injected. Polyribosomes were isolated in greater yield from bupivacaine-treated muscles, as compared with control muscles, 5 days postinjection, and were also more active in cell-free protein synthesis than control polysomes. Again, the yield and activity of the muscle polysomes was directly proportional to the bupivacaine concentration used for injection. Polyacrylamide gel electrophoresis of polysomal cell-free reaction mixtures demonstrated the synthesis of a number of myofibrillar proteins.
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PMID:Protein synthesis in bupivacaine (marcaine)-treated, regenerating skeletal muscle. 709 95

To clarify the physiopathologic mechanism leading to a marked increase in aromatic amino acids (AAA) in acute hepatic failure (AHF), we compared two experimental models of AHF. Ten pigs were submitted to one-stage hepatic devascularization (group A); in eight other pigs total hepatectomy was performed (group B). The animals were maintained under constant glucose infusion. The mean survival time in group A was 23 +/- 2 hours; after hepatectomy it was 30 +/- 4 hours. Hepatic coma progressively deepened from 8 +/- 3 hours in Group A animals and was delayed until 17 +/- 5 hours in the anhepatic pigs. AAA, methionine, and tryptophan immediately increased markedly in pigs with liver ischemia. In group B animals, AAA showed a slight increase only 18 hours after hepatectomy, whereas there were no significant differences in methionine and tryptophan. The different amino acid patterns in the two groups of animals demonstrate that hepatocyte necrosis is a major source of plasma amino acids after liver devascularization. The slight increase in AAA after total hepatectomy suggests that a release mechanism from muscular mass is involved in the later stages of the experiment. The onset of coma is related to the increase in AAA rather than to alterations in blood ammonia that did not differ in either group of animals.
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PMID:Plasma amino acid patterns in experimental acute hepatic failure: comparison between hepatectomy and liver devascularization in pigs. 726 30

The role of ATP-sensitive potassium channels (KATP) in the mechanism of ischemic preconditioning (PC) is controversial, partly because descriptions of inhibition of PC by KATP blockers in the literature are inconsistent. We sought a reason for the discrepant findings regarding the effects of glibenclamide (Glib), a specific blocker of KATP, in preventing the reduction of infarct size (IS) induced by PC. The effect of Glib pretreatment (0.3 mg/kg i.v.) on PC was examined in three conditions: (a) when PC was performed with 3- and 5-min ischemia (i.e., potency of PC differs), (b) when rabbits were pretreated with prazosin and metoprolol (0.15 mg/kg i.v. each) to reduce myocardial O2 consumption, and (c) when xylazine was added to pentobarbital anesthesia. In rabbits under pentobarbital anesthesia, the left coronary artery was occluded for 30 min and then reperfused. The area at risk (AAR) and IS were determined 72 h after reperfusion in the first series of experiments and 3 h after reperfusion in the second and third series. IS as a percentage of AAR (%IS/AR) were 31.7 +/- 2.8 and 19.6 +/- 2.5% (SEM) after PC with 3- and 5-min ischemia, respectively, values significantly smaller than %IS/AR in the untreated control group (49.2 +/- 3.3%). The limitation of IS observed with 3- or 5-min PC was not prevented by Glib. Glib also failed to block %IS/AR reduction by PC, even when rate-pressure product (RPP) was reduced to approximately 65% by prazosin/metoprolol (Praz/Met) pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glibenclamide, a blocker of ATP-sensitive potassium channels, abolishes infarct size limitation by preconditioning in rabbits anesthetized with xylazine/pentobarbital but not with pentobarbital alone. 759 19

Intestinal ischemia-reperfusion (I/R) provokes polymorphonuclear neutrophil (PMN)-mediated lung injury via a process characterized by circulating PMN priming, pulmonary PMN sequestration, and increased microvascular leak in the lung. We found in rats subjected to intestinal I/R (ischemia 45 min and reperfusion 6 h) that 1) intestinal phospholipase A2 (PLA2) was activated during ischemia, 2) circulating PMN priming (assessed by superoxide production with N-formyl-Met-Leu-Phe) occurred after 1 h reperfusion, and 3) exaggerated 125I-labeled albumin lung leak occurred after 2 h reperfusion, compared with sham-treated animals (P < 0.05). Treatment with a PLA2 inhibitor, quinacrine, within 15 min of reperfusion reversed the exaggerated gut PLA2 activity and abrogated subsequent PMN priming and lung leak (P < 0.05). However, when quinacrine was administered after 2 h of reperfusion, circulating PMN priming and lung leak continued to evolve despite suppression of intestinal PLA2 activity. We conclude that intestinal PLA2 activation may be a prerequisite for the sequelae of circulating PMN priming and pulmonary microvascular leak observed after intestinal I/R.
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PMID:Gut phospholipase A2 mediates neutrophil priming and lung injury after mesenteric ischemia-reperfusion. 790 Aug

The prevention of oxidant-induced damage following reperfusion was experimentally evaluated. Two pharmacological regimens containing different combinations of antioxidant factors and membrane-stabilizing compounds, such as alpha-tocopherol (vitamin E), methionine, dexamethasone, mannitol and cysteine, were administered. The reduced/oxidized glutathione (GSH/GSSG) ratio in muscle was used to evaluate oxidative stress. Ischaemia was induced by occluding the aorta and the inferior vena cava with an irrigation-occlusion catheter. After 4 h of ischaemia, five sheep were reperfused without any treatment (control group) and five treated with an endoaortic bolus administered at declamping (treatment 1). In five other sheep, treatment started during ischaemia (treatment 2). Ischaemia and, in particular, reperfusion significantly reduced the muscle GSH content, compared with the basal value in the control group; thus the GSH/GSSG ratio decreased significantly in the control group from 10.5(2.2) (mean(s.e.) basal value) to 0.687(0.3) at reperfusion (P < 0.009). Both treatments 1 and 2 significantly prevented a reduction in GSH content induced by reperfusion following ischaemia; the GSH/GSSG ratio (10.5(2.2) basal value) increased to 19.67(4.6) with reperfusion in the treatment group 1, mainly because of a lower decrease of GSH and a lower level of GSSG while it did not change in treatment group 2 (10.7(5.0)). Levels of creatine phosphokinase did not change in the treated groups, although they increased significantly in the control group (P < 0.006). Although oxidative stress is not the only cause of damage in revascularization, this study confirms the protective ability of treatment with free radical scavengers and membrane-stabilizing compounds.
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PMID:Prevention of reperfusion syndrome in acute muscular ischaemia with free radical scavengers and membrane-protecting compounds: an experimental study. 807 54

It was recently reported that in rats exposure to heat shock leads to appearance of a myocardial heat shock protein (HSP 70) and to an increase in myocardial catalase activity. This correlated with an improvement in post-ischemic function either in Langendorff-perfused hearts after low-flow ischemia or in working hearts after short-term, no-flow ischemia. We investigated the effect of the same hyperthermic treatment on functional recovery from no-flow ischemia of various durations in isolated working rat hearts performing at high or low external workloads. Rats were heated to core temperature of 42 degrees C for 15 min. No significant protein oxidation (% oxidized methionine) was observed 2.5 hr after treatment. A protein with migration characteristics similar to HSP 70 was observed in hearts of heat shocked rats 24 hr after this treatment while their myocardial catalase activity was not increased. Hearts of similarly treated rats were excised 24 hr after hyperthermia and perfused in a working mode with Krebs-Henseleit buffer (1.25 mM Ca2+, 11 mM glucose). At 15 cm H2O preload and 100 cm H2O afterload after 30 min no-flow ischemia, control hearts recovered to 36.9%, 2%, 47.6%, and 21.5% of the preischemic values of heart rate-peak systolic pressure product (RPP), aortic output, coronary flow, and cardiac output, respectively. After only 25 min of ischemia the respective recovered values were 61.6%, 11.5%, 58.7%, and 33.5%. Throughout the recovery period these hemodynamic values were consistently higher in hearts of heat shocked animals than in those of control hearts but the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of catalase in myocardial protection against ischemia in heat shocked rats. 817 41

The role of polymorphonuclear neutrophils (PMN) in the injury of the heart following ischemia and reperfusion is still controversial. The aim of this study was to investigate whether small numbers of PMN may cause myocardial dysfunction in an isolated system, how the resulting loss of function can be characterized and whether the formation of hypochlorous acid (HOCl) can be responsible for the PMN-mediated effect. Isolated working guinea pig hearts were subjected to a 90% reduction of coronary flow for 30 min, with or without intracoronary infusion of homologous PMN (approximately 1-2 x 10(5) cells/min, i.e. about 5-10% of normal blood count). This ischemia was followed by a 15 min reflow period in a non-working ("Langendorff") mode before work was resumed. In hearts perfused only with buffer, post-hypoxic heart function recovered to 75-80% of the initial value. Inclusion of unstimulated PMN did not further attenuate cardiac function. However, cardiac output was decreased to 42% of the initial value, provided thrombin (0.3 U/ml) and H2O2 (10(-5) M) were also present, and the retained PMN (about 10% of those infused) were additionally stimulated during reflow by application of FMLP (10(-6) M for 1 min). In these instances, coronary flow at any time of the experiment and release of lactate or purines during ischemia and reflow did not differ significantly between hearts perfused with or without PMN. There was no substantial release of myoglobin in controls and in PMN-treated hearts. Inotropic stimulation of the hearts with noradrenaline or exogenous Ca2+ caused a sustained increase in contractile force. However, the response was significantly reduced in PMN-perfused hearts in comparison to control hearts. The myocardial contents of high-energy phosphates with and without inotropic stimulation proved to be identical irrespective of whether experiments had been performed in the absence or presence of PMN. A similar loss of myocardial function as mediated by PMN could be produced by infusing chemically generated hypochlorous acid (HOCl, 5 x 10(-7) M for 10 min). Strikingly, that portion of the infused HOCl which actually reacted with cardiac tissue was comparable to the amount shown to be generated by stimulating 10(6) PMN retained in the coronary system (about 7 nmoles). Supplementing the perfusate with the scavengers L-methionine (10(-4) M) or uric acid (5 x 10(-4) M) prevented the attenuation of heart function provoked by PMN. The results indicate that small numbers of PMN, sufficiently activated, can depress cardiac function after 30 min of ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Postischemic dysfunction of the heart induced by small numbers of neutrophils via formation of hypochlorous acid. 824 Feb 25


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