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)

It was shown that when injected into a suspension of sarcoplasmic reticulum (SR) vesicles phosphatidyl ethanol-amine hydroperoxide (HP) slightly activated Ca++-dependent ATPase and increased the permeability of SR membranes for Ca++ during the enzyme function. Linoleic acid HP had no effect on the parameters of the enzymatic Ca++- transporting system (activity of Ca++-dependent ATPase, Ca/ATP ratio, rate of Ca++ efflux) in the SR membranes due to its insufficient incorporation into the SR fragments. It is concluded that among the primary molecular products of lipid peroxidation (free fatty acid HP, phospholipid HP) induced both in vitro (by the Fe++ + ascorbate system) and in vivo (ischemia, E-avitaminosis), only the phospholipid HPs were modifiers of Ca++ transport in the SR membranes.
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PMID:[Disruption of the Ca++ transport enzyme system in sarcoplasmic reticulum membranes upon exposure to phospholipid hydroperoxides and fatty acid hydroperoxides]. 15 51

The hydroxyl radical (OH.) scavenger dimethyl sulfoxide (DMSO) was found to dose-dependently inhibit interleukin 8 (IL-8) production in LPS-stimulated human whole blood. At a concentration of 1% (vol/vol), DMSO blocked IL-8 release by approximately 90% in the presence of 1 microgram/ml LPS at a 24-h time point, but did not affect cell viability or reduce the production of tumor necrosis factor (TNF), interleukin 6, or interleukin-1 beta (IL-1 beta). DMSO was found to directly inhibit IL-8 expression at the level of transcription. Furthermore, this effect was not LPS-specific, in that IL-8 production was reduced by DMSO to a similar extent upon stimulation of blood with phytohemagglutinin, aggregated immune complexes, TNF, or IL-1 beta. Other oxygen radical scavengers that have been shown to inhibit OH.-dependent reactions (dimethyl thiourea, thiourea, mannitol, and ethanol) also inhibited IL-8 production. Conversely, addition of H2O2 caused a dose-dependent stimulation of IL-8 release. These results provide evidence that reactive oxygen metabolites play an important role in the regulation of IL-8 production and suggest that reduction of IL-8 release may contribute to the beneficial effects of antioxidants in experimental models of inflammation and ischemia/reperfusion injury.
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PMID:Oxygen radical scavengers selectively inhibit interleukin 8 production in human whole blood. 133 Nov 81

Effects of treatment with (+/-)-1-(3,4-dimethoxyphenyl)-2-(4- diphenylmethylpiperazinyl)ethanol dihydrochloride (NC-1100), a calcium entry blocker, on ischemic neuronal damage were investigated. Monkeys were subjected to temporary occlusion of eight (bilateral common carotid, internal and external carotid, and vertebral arteries) major arteries. Blood flow was restored after 5, 10, 13, and 15 min occlusion, and NC-1100 (1 mg/kg) was then immediately infused intravenously. Monkeys were killed by perfusion fixation 5 days after occlusion. All brain regions were then histologically investigated for ischemic neuronal changes. Physiological data of NC-1100-treated subjects were not significantly different than those of untreated subjects. Heart rate tended to decrease after ischemia in treated subjects. Occlusion of 8 arteries for 10 to 15 min produced ischemic neuronal damage confined exclusively to the CA1 subfield of the hippocampus. Treatment with NC-1100 markedly reduced ischemic neuronal damage in the CA1 subfield of the hippocampus. It is suggested that postischemic treatment with the calcium entry blocker, NC-1100, might protect the brain from the ischemic damage produced in patients suffering from transient ischemia.
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PMID:Calcium entry blocker ameliorates ischemic neuronal damage in monkey hippocampus. 139 25

Neural injury due to ischemia and related insults is thought to involve the action of excitatory amino acids at N-methyl-D-aspartate receptors, which results in the influx of extracellular Ca2+ and the generation of nitric oxide. Because ethanol inhibits physiologic responses to excitatory amino acids, we examined its effect on toxicity induced by N-methyl-D-aspartate and by the nitric oxide donor sodium nitroprusside in neuron-enriched cultures prepared from rat cerebral cortex. Both N-methyl-D-aspartate and sodium nitroprusside were cytotoxic, as measured by the release of lactate dehydrogenase and by microfluorescent determination of cell viability. Ethanol (3-1,000 mM) protected cultures from N-methyl-D-aspartate but not sodium nitroprusside toxicity, and the ability of a series of n-alkanols to reproduce the effect of ethanol was related to carbon-chain length. Neuroprotection by ethanol was accompanied by a decrease in the N-methyl-D-aspartate-evoked elevation of free intracellular Ca2+ and did not appear to involve gamma-aminobutyric acid- or cyclic GMP-mediated mechanisms. These findings suggest that ethanol inhibits excitotoxicity at an early step in the N-methyl-D-aspartate signaling pathway, probably by reducing Ca2+ influx, and not by interfering with the action of nitric oxide.
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PMID:Ethanol and excitotoxicity in cultured cortical neurons: differential sensitivity of N-methyl-D-aspartate and sodium nitroprusside toxicity. 143

Although significant morbidity and mortality have been associated with the combined use of cocaine and ethanol, the cardiovascular effects of this combination are unknown. In this study, the effect of ethanol on cocaine-induced cardiovascular alterations was examined in two groups (n = 8 each) of dogs, which were randomized to receive either ethanol (1.68 gm/kg intravenously) or saline solution and cocaine (2 mg/kg intravenously). Ethanol had no effect on heart rate, mean arterial pressure, or rate-pressure product; but it increased ventricular end-diastolic pressure (p < 0.05), reduced coronary diameter (p < 0.02), and decreased ejection fraction by 16% +/- 4% (p < 0.005) from baseline. Cocaine produced increases in mean arterial pressure, rate-pressure product, and left ventricular end-diastolic pressure that were similar in both groups. After administration of cocaine, left ventricular ejection fraction decreased 16% +/- 2% (p < 0.001) from the baseline value in controls and 32% +/- 5% (p < 0.0002 vs baseline; p < 0.01 vs controls) in the ethanol group. Coronary diameter decreased (p < 0.05) in both groups after administration of cocaine; however, there was no difference between groups in the response of coronary circulation to cocaine. Cocaine and ethanol depress myocardial function, and their effects are additive. Failure of ethanol to enhance cocaine-induced coronary vasoconstriction suggests that the additive myocardial depressant effect of this combination is not related to ischemia but rather to a direct toxic effect of these drugs. Individuals who combine ethanol and cocaine may be at increased risk of hemodynamic compromise.
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PMID:Additive myocardial depressant effects of cocaine and ethanol. 144 96

The pathogenesis of acute pancreatitis is based on the following principles: 1. Biliary. In biliary pancreatitis there is a causal relationship between the induction of acute pancreatitis and the migration of gallstones. The basic pathomechanism seems to be a combination of an increase in permeability and pressure in the ductal system. 2. Intraacinar. Caerulein-pancreatitis is a well established experimental model which reflects the intracellular/interstitial type of activation. Basolateral secretion of pancreatic enzymes into the interstitial space represents the initial event. Intracellular activation of trypsin by the fusion of zymogen-granules and lysosomes has been advocated as an alternative mechanism. 3. Alcohol. The acute alcohol pancreatitis comprises a combined pathogenesis. Obstruction and reflux as well as the cytotoxic effect of alcohol seem to be the main principles. 4. Disturbance of pancreatic microcirculation. Ischemia of the pancreas seems to play a key role in the transition from pancreatic edema to necrosis. Improvement of capillary perfusion by isovolemic hemodilution with dextran 60 has been shown to be an efficient therapeutic tool.
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PMID:[Etiology and pathogenesis of acute pancreatitis]. 152 49

The operating characteristics of thallium stress testing for detection of significant epicardial coronary artery disease (CAD) in hypertensive subjects with chest pain or electrocardiographic (ECG) ischemia have not been previously defined. This becomes important because of the high prevalence of both hypertensive heart disease and CAD. Ninety-two hypertensives with a history of typical or atypical chest pain or ECG myocardial ischemia underwent coronary arteriography, 2D-guided echocardiography, and thallium-201 stress testing, combined with intravenous dipyridamole if the rate-pressure product was less than 20,000. Patients with myocardial infarction, prior revascularization procedure, valvular heart disease, and chronic ethanol abuse were excluded. The mean age was 54.8 +/- 9.9 years with 55% blacks and 46% women. Eighteen patients (19.6%) had significant (greater than or equal to 50% luminal diameter narrowing) epicardial CAD at catheterization, of whom 17 had positive thallium scans. Overall, there were 17 true positives, 47 true negatives, 27 false positives, and one false negative resulting in 94.4 +/- 5.4% sensitivity (95% confidence limits [95% CL] 71 to 100%), 63.5 +/- 5.6% specificity (95% CL 51 to 74%), 38.6 +/- 7.3% positive predictive value (95% CL 25 to 54%), 97.9 +/- 2.1% negative predictive value (95% CL 88 to 100%), and 69.6 +/- 4.8% overall accuracy (95% CL 59 to 79%). For hypertensive patients with chest pain or ECG myocardial ischemia, the high sensitivity and negative predictive value and low false negative rate support the role of thallium stress testing +/- dipyridamole as an exclusion test for significant CAD.
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PMID:A negative thallium (+/- dipyridamole) stress test excludes significant obstructive epicardial coronary artery disease in hypertensive patients. 153 15

Ethanol was injected intraperitoneally to dd-strain mice (20-25 g) with a dose of 5 g/kg body weight. The animals were sacrificed by the cervical dislocation at 4, 8, 12 and 24 hr after the ethanol injection. The changes of the ultrastructure of liver, heart, lung and kidney were examined by a transmission electron microscope. The results; from 4 hr to 24 hr after ethanol injection, deposition of fat droplets, swelling of mitochondria, enlargement of rough endoplasmic reticulum and loss of glycogen granules were observed in hepatocytes. Also, the edema of hepatocytes and intravascular hemostasis were found. These changes were aggravated with time course. In the heart, intravascular hemostasis, edema of myocardium, remarkable decrease of glycogen, swelling of mitochondria and appearance of I bands of myocardial fibers were observed. The damage to the myocardium by ethanol injection was similar to that associated with ischemia and anoxia. In the lung and the kidney, at early time after ethanol injection intravascular hemostasis and cell edema were observed but no other electron microscopical changes were found during the experiment. At 4 hr and 24hr after ethanol injection the edema of sinusoidal endothelial cell of liver and at 24hr that of endothelial cell of capillaries of heart were observed. These histological results suggest that the cell damages and intravascular hemostasis would be caused mainly by a direct action of ethanol. The damages of the liver and the heart, however, on the time blood ethanol was not detected would be caused by the disturbance of metabolism owing to ethanol oxidation.
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PMID:[Ultrastructural changes of liver, heart, lung and kidney of mice in a large dose of ethanol injection]. 158 89

Upper respiratory and pulmonary complications of cocaine addiction have been increasingly reported in recent years, with most of the patients being intravenous addicts, users of freebase, or smokers of "crack." The toxicity of cocaine is complex and is exerted via multiple central and peripheral pathways. Recurrent snorting of cocaine may result in ischemia, necrosis, and infections of the nasal mucosa, sinuses, and adjacent structures. Pulmonary complications of cocaine toxicity include pulmonary edema, pulmonary hemorrhages, pulmonary barotrauma, foreign body granulomas, cocaine related pulmonary infection, obliterative bronchiolitis, asthma, and persistent gas-exchange abnormalities. Respiratory manifestations are nonspecific and include shortness of breath, cough, wheezing, hemoptysis, and chest pains. Severe respiratory difficulties have been reported in neonates of abusing mothers. In the absence of a cocaine-abuse history, it may be difficult to recognize the etiological role of cocaine, especially in the absence of needle tracks pointing to previous intravenous drug abuse and/or negative toxicology.
Recent Dev Alcohol 1992
PMID:Respiratory complications of cocaine abuse. 158 7

Phospholipase D (PLD) activity was found to be present in the membrane fraction of rat myocardial cells by in vitro assays (36.7 +/- 4.1 nmol/mg protein per h against 1-palmitoyl-2-arachidonoyl- phosphatidylcholine) and demonstrated in intact cells by the specific transphosphatidylation reaction (in the presence of 0.02% ethanol) quantitated using n-[1-14C]butanol (201.16 +/- 7.1 pmol/min per g dry weight in the whole heart). Both methods showed a significant increase in PLD activity (by 62 and 44%, respectively) in hearts subjected to reversible (30 min) global normothermic ischemia followed by reperfusion (30 min). In hearts prelabeled with [1-14C]arachidonic acid, ischemia/reperfusion induced a significant increase in the amount of radiolabel incorporated into phosphatidic acid (PtdOH) (by 49.6%) and diacylglycerol (DG) (by 259%). DG kinase inhibition by 100 microM dioctanoylethylene glycol did not affect the ischemia/reperfusion DG and PtdOH levels while PtdOH phosphohydrolase inhibition with 40 microM propranolol produced a further increase in PtdOH (to 2.36-fold the baseline level) and a reduction in DG (to only 145% over the baseline levels). Put together, all these results suggest an activation of PLD during myocardial ischemia/reperfusion generating intracellular PtdOH, part of which is converted by PtdOH phosphohydrolase to DG. We further investigated the possible pathophysiological significance of the observed PLD activation. Stimulation of PLD with sodium oleate (20 microM) induced a significant improvement of functional recovery of ischemic hearts during reperfusion (as monitored by coronary flow and left intraventricular pressure measurements) and an attenuation of cellular injury as expressed by lactate dehydrogenase and creatine kinase release in the coronary effluent during reperfusion. These results suggest a PLD-mediated signaling in the ischemic heart which may benefit functional recovery during reperfusion.
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PMID:Phospholipase D signaling in ischemic heart. 161 Sep 13


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