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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used in vitro translation and antibodies against phosphoserine and the eukaryotic initiation factors elF-4E, elF-4G, and elF-2 alpha to examine the effects of global brain ischemia and reperfusion on translation initiation and its regulation in a rat model of 10 min of cardiac arrest followed by resuscitation and 90 min of reperfusion. Translation reactions were performed on postmitochondrial supernatants from brain homogenates with and without aurintricarboxylic acid to separate incorporation due to run-off from incorporation due to peptide synthesis initiated in vitro. The rate of leucine incorporation due to in vitro-initiated protein synthesis in normal forebrain homogenates was approximately 0.4 fmol of leucine/min/microgram of protein and was unaffected by 10 min of cardiac arrest, but 90 min of reperfusion reduced this rate 83%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blots of these homogenates showed that neither 10 min of global brain ischemia nor 90 min of reperfusion induced significant alterations in the quantity or serine phosphorylation of elF-4E. However, we observed in all 90-min-reperfused samples elF-4G fragments that also bound elF-4E. The amount of elF-2 alpha was not altered by ischemia or reperfusion, and immunoblotting after isoelectric focusing did not detect serine-phosphorylated elF-2 alpha in normal samples or in those obtained after ischemia without reperfusion. However, serine-phosphorylated elF-2 alpha was uniformly present after 90 min of reperfusion and represented 24 +/- 3% of the elF-2 alpha in these samples. The serine phosphorylation of elF-2 alpha and partial fragmentation of elF-4G observed after 90 min of reperfusion offer an explanation for the inhibition of protein synthesis.
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PMID:Global brain ischemia and reperfusion: modifications in eukaryotic initiation factors associated with inhibition of translation initiation. 886 7

The effect of propentofylline on regional [3H]-leucine incorporation into brain proteins was investigated during early reperfusion following permanent occlusion of vertebral arteries and reversible occlusion of the common carotid arteries of awake rats. In rats subjected to 5 min ischemia/50 min reperfusion the total brain radioactivity and TCA-precipitable radioactivity were reduced in the cerebellum, medulla oblongata, hypothalamus, cortex, striatum and hippocampus and the fractional protein radioactivity was decreased in the cortex, striatum and hippocampus. Propentofylline pretreatment at a dose of 25 mg/kg p.o. daily for 14 days completely reversed the reduction in total radioactivity and partially reversed the reduction in TCA-precipitable radioactivity in all brain regions studied and decreased the reduction in fractional protein radioactivity in the hippocampus. The results suggest that the protective effect of propentofylline on transient ischemia-induced brain damage may be related to improvement of [3H]-leucine incorporation into brain proteins.
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PMID:Effect of propentofylline on [3H]-leucine incorporation into protein of postischemic rat brain. 890 Feb 17

The normal vascular wall contains resident leukocytes, notably tissue macrophages (histiocytes) and mast cells, that confer a rapid, eicosanoid-dependent vasoconstrictor response to agonists typical of leukocytes, such as the complement-derived anaphylatoxin C5a or the formylated peptide f-Met-Leu-Phe (isolated organ methodology). The eicosanoid-dependent vasomotor response is even more intense in pathologies that involve leukocyte infiltration of the blood vessel wall, such as atherosclerosis and serum sickness in the rabbit. The leukocyte compartment of the blood vessel is the likely source of vasoactive mediators (eicosanoids, radicals, cytokines) of physiopathological importance, with possible application in cardiac ischemia, lupus nephritis, vasculitides, and graft rejection. This line of investigation may be compared to the discovery and characterization of endothelium-dependent vasomotor responses. However, the problem is experimentally more demanding: histological correlations, experiments based on leukocyte depletion, reconstitution, and enrichment are useful approaches to document this form of circulatory control.
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PMID:Evidence for vascular tone regulation by resident or infiltrating leukocytes. 893 61

The role of endothelin ETA and ETB receptors as well as of nitric oxide (NO) and prostanoids in the effects of endothelin-1 on the coronary circulation was studied in anesthetized goats. Where blood flow in the left circumflex coronary artery (coronary blood flow) (electromagnetically measured), systemic arterial pressure, left ventricle pressure and d P/dt, and heart rate were recorded. Endothelin-1 (0.01-0.3 nmol), intracoronarily injected, produced marked, dose-dependent reductions in basal coronary blood flow, ranging from 5% for 0.01 nmol to 75% for 0.3 nmol; 0.1 and 0.3 nmol endothelin-1 also reduced systolic ventricle pressure and dP/dt. The effects of endothelin-1 on coronary blood flow were diminished during intracoronary infusion of BQ-123 (cyclo-(D-Asp-Pro-D-Val-Leu-D-Trp). specific antagonist for endothelin ETA receptors. 2-16 nmol/min) in a dose-dependent way, but not during the infusion of BQ-788 (N-[N-[N-[(2.6-dimethyl-1-piperidinyl)carbonyl]-4-methyl-1-leucyl]-1- (methoxycarbonyl)-D-tryptophyl]-D-norleucine monosodium, specific antagonist for endothelin ETB receptors. 2-4 nmol/min). IRL 1620 (Suc-[Glu9, Ala11.15]endothelin-1-(8-21), specific agonist for endothelin ETB receptors. 0.01-0.3 nmol), intracoronarily injected. slightly reduced basal coronary blood flow only when 0.1 and 0.3 nmol were applied (maximal reduction about 25%); 0.3 nmol IRL 1620 also reduced systolic ventricle pressure and dP/dt. The effects of IRL 1620 were not modified by BQ-123 or BQ-788. NG-nitro-1-arginine methyl ester (L-NAME, inhibitor of NO synthesis, 47 mg/kg by i.v. route) reduced resting coronary blood flow by 10% and increased mean systemic arterial pressure and systolic ventricle pressure by 22 and 20%. respectively, without changing systolic ventricle dP/dt and heart rate. With L-NAME, the reductions of coronary blood flow by endothelin-1 were potentiated (P < 0.05), and those by IRL 1620 were not changed (P > 0.05). Meclofenamate (cyclooxygenase inhibitor, 4-6 mg/kg by i.v. route) modified neither the basal values of hemodynamic variables nor the coronary effects of endothelin-1 and IRL 1620. Therefore, endothelin-1 produces marked coronary vasoconstriction, which may be mediated by endothelin ETA receptors, with no participation of endothelin ETB receptors. NO, but not prostanoids, may produce a basal coronary vasodilator tone and may inhibit endothelin-1-induced coronary vasoconstriction. Also, it is suggested that the coronary vasoconstriction by endothelin-1 may impair cardiac performance due to heart ischemia.
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PMID:Coronary vasoconstriction by endothelin-1 in anesthetized goats: role of endothelin receptors, nitric oxide and prostanoids. 896 Aug 82

Myocardial ischemic arrest, using a cold crystalloid cardioplegic solution, decreases intracellular concentrations of glutamate (from 6.2 +/- 0.5 to 4.5 +/- 0.45 micromol/g wet weight, n = 19, P < 0.05) and ATP (from 3.0 +/- 0.4 to 1.9 +/- 0.3 micromol/g wet weight, n = 9, P < 0.05) but not aspartate. After 20 min of normothermic reperfusion, the fall in glutamate and ATP was maintained (4.5 +/- 0.52 and 2.0 +/- 0.2 micromol/g wet weight, respectively), and there was a fall in aspartate (from 1.32 +/- 0.12 to 0.9 +/- 0.1 micromol/g wet weight). Myocardial arrest with cold blood cardioplegic solution did not cause a significant fall in tissue ATP, glutamate, or aspartate. However, after reperfusion all three fell significantly. With the exception of a fall in tissue valine during ischemia with cold crystalloid cardioplegic solution and a rise in alanine during ischemia with cold blood cardioplegic solution, there were no significant changes in tissue alanine, valine, leucine, or isoleucine during ischemia or after reperfusion using crystalloid or blood cardioplegic solutions. This work documents the changes in the intracellular concentrations of important metabolites in the hearts of patients undergoing coronary artery surgery using different myocardial protection techniques.
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PMID:Changes in myocardial concentration of glutamate and aspartate during coronary artery surgery. 908 76

Cathepsin A-like enzyme released from human platelets by thrombin hydrolyzed at the highest rate Cbz-Phe-Ala, Cbz-Phe-Met and Cbz-Phe-Leu, did not require activators and was inhibited by DFP, DCI and mercurial compounds (mersalyl acid, PCMS, PCMB and HgCl2). The optimum activity of secreted enzyme was at pH 5.0-6.0. Cbz-Glu-Tyr was also hydrolyzed at lower pH with optimum at pH 3.5. These enzymatic properties are the same as those of cathepsin A solubilized from whole platelets and purified from other mammalian cells and tissues. High specific activity of secreted cathepsin A, and a broad pH range of activity may have a significance in extracellular proteolysis in local sites of ischemia. Large portion of cathepsin A-like activity was not secretable by high concentration of thrombin and was sedimented with platelet aggregates. No activity of lysosomal carboxypeptidases B and prolylcarboxypeptidase was detectable in supernatants and pellets of thrombin-stimulated platelets.
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PMID:Cathepsin A-like activity in thrombin-activated human platelets. Substrate specificity, pH dependence, and inhibitory profile. 921 30

Proteases as well as alterations in intracellular calcium have important roles in hepatic preservation-reperfusion injury, and increased calpain activity recently has been demonstrated in liver allografts. Experiments were designed to evaluate (i) hepatic cytosolic calpain activity during different periods of cold ischemia (CI), rewarming, or reperfusion, and (ii) effects of inhibition of calpain on liver graft function using the isolated perfused rat liver and arterialized orthotopic liver transplantation models. Calpain activity was assayed using the fluorogenic substrate Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl coumarin (AMC) and expressed as mean +/- SD pmol AMC released/min per mg of cytosolic protein. Calpain activity rose significantly after 24 hr of CI in University of Wisconsin solution and further increased with longer preservation. Activity also increased within 30 min of rewarming, peaking at 120 min. Increased durations of CI preceding rewarming resulted in significantly higher activity (P < 0.01). Calpain activity increased rapidly upon reperfusion and was significantly enhanced by previous CI (P < 0.01). Calpain inhibition with Cbz-Val-Phe methyl ester significantly decreased aspartate aminotransferase released in the isolated perfused rat liver perfusate (P < 0.05). Duration of survival after orthotopic liver transplantation using livers cold-preserved for 40 hr was also significantly increased (P < 0.05) with calpain inhibitor. In conclusion, calpain proteases are activated during each phase of transplantation and are likely to play an important role in the mechanisms of preservation-reperfusion injury.
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PMID:Calpain is a mediator of preservation-reperfusion injury in rat liver transplantation. 925 86

The involvement of glutamate in the development of cerebral metabolic disturbances in mature fetuses after transient ischemia was studied using a hippocampal slice model. We investigated the effects of exogenously applied glutamate or glutamate antagonists on the recovery of energy metabolism and protein synthesis rate (PSR) in hippocampal slices of mature guinea pigs after in vitro ischemia. The slices were incubated in a thermostatically controlled flow-through chamber and gassed with carbogen (95% O2/5% CO2). In vitro ischemia was induced by transferring the slices to an aglycemic, artificial cerebrospinal fluid (aCSF) equilibrated with 95% N2/5% CO2. In a first set of experiments slices were exposed to 10 mM glutamate during a 20-40 min period of in vitro ischemia. In a second set slices were incubated in aCSF containing MK-801 (100 microM) or kynurenic acid (0.5 mM) 30 min before, during and 2 h after in vitro ischemia. After a 12 h recovery phase, the concentrations of adenylates in the slices were measured by HPLC after extraction with perchloric acid. PSR was calculated from the rate of incorporation of [14C]leucine into tissue proteins. Neither glutamate nor glutamate antagonists had any effect on the postischemic recovery of energy metabolism and PSR when applied during in vitro ischemia. It is therefore concluded that glutamate does not play a major role in the development of metabolic disturbances in hippocampal slices from mature guinea pig fetuses subjected to transient in vitro ischemia.
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PMID:No effect of glutamate on metabolic disturbances in hippocampal slices of mature fetal guinea pigs after transient in vitro ischemia. 926 79

Analysis of post-infarct ventricular remodeling consistently shows the accumulation of collagen in failing heart. The goal of this study was to gain insights into the underlying mechanisms of this event. We determined the effect of hypoxia, caused as the result of ischemia, on biological responses including cell viability, basal and growth factor-stimulated proliferative capacity and collagen type I production in cardiac fibroblasts obtained from adult human heart. The cell viability, as examined by light microscopy and analysis of DNA, did not change by hypoxia (2% oxygen). Basal level of protein synthesis, as determined by measuring the incorporation of 3H-leucine, decreased (30%, P<0.05) under hypoxia. Transforming growth factor-beta (TGF-beta1)- and thyroid hormone (T3)-induced increases in protein synthesis did not change under hypoxia. In contrast, basic fibroblast growth factor (bFGF)-stimulated protein synthesis enhanced significantly under hypoxia. Angiotensin II (Ang II)-treatment, which did not induce significant changes in protein synthesis under ambient conditions, led to moderate but significant increase under hypoxia. Basal level of DNA synthesis, as determined by measuring the incorporation of 3H-thymidine into DNA, decreased (32%, P<0.05) under hypoxia. The TGF-beta1-induced inhibition of DNA synthesis which was observed under ambient conditions was reversed [61% (P<0.005) increase under hypoxia]. Under ambient conditions, T3, Ang II and bFGF stimulated DNA synthesis and their effects were enhanced under hypoxia. Northern analysis showed a 46% (P<0.05) increase in the level of pro alpha1(l) collagen mRNA under hypoxia. The TGF-beta1-induced increase in the level of pro alpha1(l) collagen mRNA, under ambient conditions, was not observed under hypoxia. On the other hand, the T3-induced decrease in pro alpha1(l) collagen mRNA was reversed under hypoxia. Ang II- and bFGF-treatment of human cardiac fibroblasts did not cause detectable changes in the level of pro alpha1(l) collagen mRNA under ambient conditions or hypoxia. At the protein level, the amount of immunoreactive collagen type I, as determined by immunoslot blot analysis, was increased (33%, P<0.05) under hypoxia. Treatment of human cardiac fibroblasts with TGF-beta1 and T3 under ambient conditions led to diminished level of collagen type I. Under hypoxia, however, effect of both factors was reversed. The level of immunoreactive collagen type I in Ang II- and bFGF-treated cells, which was comparable to that in untreated cells under ambient conditions, remained unchanged under hypoxia. Together, these results provide evidence that hypoxia regulates growth, proliferative capacity and collagen type I production in human cardiac fibroblasts, and that although hypoxia alone may not be a stimulus for human cardiac fibroblast proliferation, it enhances growth factor-induced DNA synthesis in those cells. Furthermore, hypoxia by increasing the basal levels of collagen type I and by reversing the TGF-beta1- and T3-induced inhibition of collagen type I gene expression in human cardiac fibroblasts can enhance overall collagen type I production. Combinatorial effects of hypoxia on proliferation and collagen type I production in cardiac fibroblasts contribute to the post-infarct remodeling of the collagen matrix in failing human heart.
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PMID:Hypoxia regulates basal and induced DNA synthesis and collagen type I production in human cardiac fibroblasts: effects of transforming growth factor-beta1, thyroid hormone, angiotensin II and basic fibroblast growth factor. 928 54

The activities of calpain and its endogenous inhibitor, calpastatin, were measured in the soluble fraction of perfused rat heart after ischemia for 5-20 min and reperfusion for up to 30 min. The method for m-calpain measurement was modified: washing of the DEAE-cellulose column with 0.18 M NaCl instead of 0.15 M NaCl increased the m-calpain activity 12.5-fold. Ischemia for 20 min followed by reperfusion for 30 min did not affect the m-calpain activity but decreased the calpastatin activity. m-Calpain was enriched in the nucleus-myofibril fraction but was not further translocated on ischemia-reperfusion. Mu-calpain was below the limit of detection on immunoblotting or casein zymography, but its mRNA was substantially expressed, as detected on Northern blotting. Casein zymography also revealed a novel Ca2+-dependent protease without the typical characteristics of mu- or m-calpain. The immunoblotting of myocardial fractions showed that calpastatin was proteolyzed on ischemia-reperfusion. The calpastatin proteolysis was suppressed by a calpain inhibitor, Ac-Leu-Leu-norleucinal. Calpastatin may sequester calpain from its substrates in the normal myocardium, but may be proteolyzed by calpain in the presence of an unidentified activator in the early phase of calpain activation during ischemia-reperfusion, resulting in the proteolysis of calpastatin and then other calpain substrates.
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PMID:Downregulation of calpastatin in rat heart after brief ischemia and reperfusion. 939 77


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