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)

In experimental dogs, the effect of APN in alleviating the ischemia-reperfusion injury was prominent. Compared with the sustained ischemia group, superoxide dismutase (SOD) in the ischemic region of myocardial tissue in the ischemia-reperfusion group was significantly decreased and malondialdehyde (MDA) markedly increased: Ca2+ in myocardial cells was increased; and ultrastructural changes of myocardial tissues were severe. In the APN-pretreated ischemia-reperfusion group, on the contrary, all the above parameters showed reversely, i.e., SOD increased, MDA and intracellular Ca2+ decreased, the ultrastructure changes were less distorted.
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PMID:The effect of andrographis paniculata nees (APN) in alleviating the myocardial ischemic reperfusion injury. 787 95

The central nervous system (CNS) contains a large amount of zinc; a substantial fraction of it is located inside synaptic vesicles of glutamatergic terminals in chelatable forms and released in a calcium-dependent manner with intense neuronal activity. Recently, it has been shown that excessive zinc influx can kill neurons in rats subjected to transient forebrain ischemia. On the other hand, severe depletion of zinc has been also reported to induced cell death in certain nonneuronal cells. Since decreases in tissue zinc have been associated with Alzheimer's disease (AD) and senile macular degeneration, we examined whether depletion of intracellular zinc with a zinc chelator can directly induce neuronal death in mouse cortical cultures. Exposure of cortical cultures to a cell-permeant zinc-chelator, N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN, 0.5-3.0 microM) induced gradually developing neuronal degeneration accompanied by various features of apoptosis: cell body shrinkage, nuclear condensation and fragmentation, and internucleosomal DNA breakage. At higher concentrations, TPEN induced additional glial cell death. TPEN-induced cell death was completely blocked by coaddition of zinc. Addition of a protein synthesis inhibitor cycloheximide as well as a caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-fluoromethyl ketone (zVAD-fmk) markedly attenuated TPEN-induced neuronal death. On the other hand, brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), phorbol 12-myristate 13-acetate (PMA), high K+, or an antioxidant, trolox, did not show any protective effect. The present results demonstrated that depletion of intracellular zinc induces protein synthesis-dependent neuronal apoptosis in cortical culture. Combined with the findings that extracellular zinc may promote extracellular beta-amyloid (A beta) aggregation and that total tissue zinc is reduced in AD, present results suggest a possibility that redistribution of zinc from intracellular to extracellular space may synergistically contribute to neuronal apoptosis in AD.
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PMID:Depletion of intracellular zinc induces protein synthesis-dependent neuronal apoptosis in mouse cortical culture. 987 67

Normothermic ischemia and reperfusion (I/R) of the liver remains a major problem after liver surgery and transplantation. Activation of Kupffer cells (KCs) after normothermic I/R is responsible for a massive release of various monokines such as tumor necrosis factor alpha (TNF-alpha) and a decrease in phagocytic activity. Muramyl dipeptide (MDP) is an immunostimulant that increases phagocytic activity of KCs. The aim of this study was to demonstrate that MDP pretreatment might protect the liver against I/R injury by a modification of KC functions. Rats were divided into three groups: group 1, control, Ringer's lactate administration; group 2, MDP (N-acetyl-muramyl-d-alanyl-d-isoglutamine) treatment; group 3, sham-operated control animals. MDP (500 microg/250 g) was injected intravenously 5 min before the induction of 90 min ischemia. Survival rates were compared and serum activities of TNF-alpha, aspartate aminotransferase, and alanine aminotransferase were assessed in the blood collected from the suprahepatic vena cava. Histology of the liver and KC activity were assessed 6 and 9 h after the end of ischemia, respectively. MDP treatment significantly increased 7-day survival (86.6%) compared with nontreated rats (40%, P < 0.001). Serum activities of TNF-alpha and aminotransferases were significantly decreased after MDP treatment, whereas phagocytic capacity of KCs was partially restored. The extent of liver necrosis was decreased after MDP administration. A significant difference was observed for other histological parameters studied, except for steatosis. Our findings have demonstrated that MDP is able to protect the liver from ischemic insult by modulation of KC activity (TNF-alpha release and phagocytic capacity). Control of macrophage activity may offer a new strategy to reduce ischemic injury of the liver.
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PMID:Improvement of normothermic rat liver ischemia/reperfusion by muramyl dipeptide. 987 35

We examined the effects of enalapril and 4'-[(1, 4'-dimethyl-2'-propyl-[2,6'-bi-1H-enzimidazole]-1'-yl)methyl]-[1, 1'-biphenyl]-2-carboxylic acid (BIBR-277), an angiotensin II receptor antagonist, on contractile dysfunction in the stunned myocardium. Dogs were subjected to 20-min ligation of the coronary artery, followed by 60-min reperfusion. Saline, enalapril (1 mg/kg or 3 mg/kg), or BIBR-277 (3 mg/kg) was injected i.v. 10 min before ligation. D-Arginyl-L-arginlyl-L-prolyl-trans-4-hydroxy-L-prolylglycyl -3-(2-thi enyl)-L-alanyl-L-seryl-D-1,2,3, 4-tetrahydro-3-isoquinolinecarbonyl-L-(2alpha, 3beta, 7abeta)-octahydro-1H-indole-2-carbonyl-L-arginine (Hoe-140), a bradykinin B(2) receptor antagonist, at 300 microg/kg was injected i. v. 10 min before drug injection. Contractile function was assessed on the basis of percentage segment shortening (%SS). ATP levels were measured in 60-min reperfused hearts. %SS significantly decreased during ischemia, and recovered during reperfusion, although the %SS was significantly less than the pre-ischemic level. Both enalapril at either dose and BIBR-277 significantly enhanced %SS recovery during reperfusion, an effect which was associated with a tendency toward energy preservation. Hoe-140 completely abolished the effect of enalapril at either dose, while it did not modify that of BIBR-277. Inhibition of angiotensin II formation and bradykinin breakdown may be separately related to the improvement of myocardial stunning.
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PMID:Participation of angiotensin II and bradykinin in contractile function in dog stunned myocardium. 1055 69

The highest activities of leucyl aminopeptidase(LAP, cytosol aminopeptidase, EC 3.4.11.1) in sera have been found in patients with acute hepatitis(Kanno et al., Am J Clin Path, 82: 700-705, 1984). I observed inpatients with very high activities of LAP and alcohol dehydrogenase(AD) in sera. However, only slight elevations of serum pseudo leucine aminopeptidase(PLA), that is, membrane alanyl aminopeptidase(MAA, microsomal aminopeptidase, EC 3.4.11.2) activities for hydrolysis of leucyl-4-nitroanilide were observed in these patients. They were patients in critical care unit with ischemia caused by a cardiopulmonary arrest, multiple trauma, acute myocardial infarction or operation. Therefore, we should measure LAP activities in sera rather than PLA(MAA) activities in these patients.
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PMID:[Comparison between leucyl aminopeptidase and pseudo leucine aminopeptidase activities in sera]. 1106 3

The objective of this study was to investigate the effect of singlet oxygen ((1)O2) scavengers on functional recovery and ascorbyl free radical (AFR) formation in isolated ischemic rat hearts. Hearts were subjected to 40 min. of global ischemia followed by 30 min. of reperfusion. Hemodynamics were measured as heart rate (HR), coronary flow (CF), left ventricular developed pressure (LVDP) and contractility (dP/dt). Electron paramagnetic resonance (EPR) spectroscopy was used to measure AFR release in coronary perfusate during the first two min. of reperfusion as a function of ROS scavengers. Relative to ischemic controls the administration of the (1)O2 scavengers 2,2,6,6-tetramethyl-4-piperidone x HCl (4-oxo-TEMP), carnosine (beta-alanyl-L-histidine) or a combination of the two significantly improved functional recovery as measured by LVDP. While no AFR signal was detected in coronary perfusate collected during preischemic perfusion with and without (1)O2 scavengers, the AFR background signal due to ischemia was significantly increased with the (1)O2 and *O2- scavengers. No such increase was observed with the hydroxyl radical (*OH) scavenger mannitol. Besides the AFR increase with the (1)O2 and *O2- scavengers the functional recovery was only significantly improved with the (1)O2 scavengers. In contrast to previous AFR studies we found with endogenous AFR that an increased AFR formation is not necessarily only reflecting increased oxidative stress but can also report improved functional recovery. Combining the hemodynamic data with increased AFR formation in the presence of several different ROS scavengers gives supportive evidence for (1)O2 also being involved in reperfusion injury.
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PMID:Increased endogenous ascorbyl free radical formation with singlet oxygen scavengers in reperfusion injury: an EPR and functional recovery study in rat hearts. 1115 83

We investigated the effect of L-carnosine (beta-alanyl-L-histidine) on ischemic acute renal failure in rats. Ischemic acute renal failure was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function in untreated acute renal failure rats markedly decreased at 1 day after reperfusion. Pre-ischemic treatment with L-carnosine dose-dependently (1, 10 microg/kg, i.v.) attenuated the ischemia/reperfusion-induced renal dysfunction. Histopathological examination of the kidney of untreated acute renal failure rats revealed severe renal damage, which was significantly suppressed by pre-treatment with L-carnosine, at each dose given. In untreated acute renal failure rats, norepinephrine concentrations in renal venous plasma remarkably increased within 2 min after reperfusion and thereafter rapidly decreased. Pre-ischemic treatment with L-carnosine at a dose of 10 microg/kg significantly depressed the elevated norepinephrine level. On the other hand, although the higher dose of L-carnosine given 5 min after reperfusion tended to ameliorate the renal dysfunction after reperfusion, the improvement was moderate compared with those seen in pre-ischemic treatment. These results indicate that L-carnosine prevents the development of ischemia/reperfusion-induced renal injury, and the effect is accompanied by suppression of the enhanced norepinephrine release in the kidney immediately after reperfusion. Thus, the preventing effect of L-carnosine on ischemic acute renal failure is probably through the suppression of enhanced renal sympathetic nerve activity induced by ischemia/reperfusion.
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PMID:Preventive effect of L-carnosine on ischemia/reperfusion-induced acute renal failure in rats. 1292 72

The effects of dietary supplementation of L-carnosine (beta-alanyl-L-histidine) on ischemia/reperfusion-induced acute renal failure (ARF) in rats were examined. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal functional parameters such as blood urea nitrogen, plasma creatinine, creatinine clearance, urine flow, urinary osmolality and fractional excretion of sodium were measured. Renal function in ARF rats markedly decreased at 1 d after reperfusion. Prior feeding of L-carnosine-containing diet (0.0001 w/w%) for 2 weeks attenuated the ischemia/reperfusion-induced renal dysfunction. Histopathological examination of the kidney of ARF rats revealed severe renal damages, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, which were also significantly suppressed by the dietary supplementation of L-carnosine. These findings strongly suggest that L-carnosine supplementation is useful as a prophylactic treatment in the development of the ischemic ARF.
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PMID:Dietary supplementation of L-carnosine prevents ischemia/reperfusion-induced renal injury in rats. 2488 21

Obesity-related disorders are associated with the development of ischemic heart disease. Adiponectin is a circulating adipose-derived cytokine that is downregulated in obese individuals and after myocardial infarction. Here, we examine the role of adiponectin in myocardial remodeling in response to acute injury. Ischemia-reperfusion in adiponectin-deficient (APN-KO) mice resulted in increased myocardial infarct size, myocardial apoptosis and tumor necrosis factor (TNF)-alpha expression compared with wild-type mice. Administration of adiponectin diminished infarct size, apoptosis and TNF-alpha production in both APN-KO and wild-type mice. In cultured cardiac cells, adiponectin inhibited apoptosis and TNF-alpha production. Dominant negative AMP-activated protein kinase (AMPK) reversed the inhibitory effects of adiponectin on apoptosis but had no effect on the suppressive effect of adiponectin on TNF-alpha production. Adiponectin induced cyclooxygenase (COX)-2-dependent synthesis of prostaglandin E(2) in cardiac cells, and COX-2 inhibition reversed the inhibitory effects of adiponectin on TNF-alpha production and infarct size. These data suggest that adiponectin protects the heart from ischemia-reperfusion injury through both AMPK- and COX-2-dependent mechanisms.
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PMID:Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. 1621 Oct 35

We examined the renoprotective effects of l-carnosine (beta-alanyl-l-histidine) on ischemia/reperfusion (I/R)-induced acute renal failure (ARF) in rats. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. In vehicle (0.9% saline)-treated rats, renal sympathetic nerve activity (RSNA) was significantly augmented during the renal ischemia, and renal function was markedly decreased at 24 h after reperfusion. Intracerebroventricular injection of l-carnosine (1.5 and 5 pmol/rat) to ischemic ARF rats dose-dependently suppressed the augmented RSNA during ischemia and the renal injury at 24 h after reperfusion. N-alpha-Acetyl-l-carnosine [N-acetyl-beta-alanyl-l-histidine; 5 pmol/rat intracerebroventricular (i.c.v.)], which is resistant to enzymatic hydrolysis by carnosinase, did not affect the renal injury, and l-histidine (5 pmol/rat i.c.v.), a metabolite cleaved from l-carnosine by carnosinase, ameliorated the I/R-induced renal injury. Furthermore, a selective histamine H(3) receptor antagonist, thioperamide (30 nmol/rat i.c.v.) eliminated the preventing effects by l-carnosine (15 nmol/rat intravenously) on ischemic ARF. In contrast, a selective H(3) receptor agonist, R-alpha-methylhistamine (5 pmol/rat i.c.v.), prevented the I/R-induced renal injury as well as l-carnosine (5 pmol/rat) did. These results indicate that l-carnosine prevents the development of I/R-induced renal injury, and the effect is accompanied by suppressing the enhanced RSNA during ischemia. In addition, the present findings suggest that the renoprotective effect of l-carnosine on ischemic ARF is induced by its conversion to l-histidine and l-histamine and is mediated through the activation of histamine H(3) receptors in the central nervous system.
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PMID:Renoprotective effects of l-carnosine on ischemia/reperfusion-induced renal injury in rats. 1691 94


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