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

The role of ischaemia in the pathogenesis of acute pancreatitis is unknown. Some experimental studies have shown that ischaemia has little effect on the pancreas, while others have found an association with pancreatic injury. Ischaemia-reperfusion damage has been well documented in other sites such as the intestine, cardiac muscle, and skeletal muscle. However, in the pancreas, injury is usually seen only after complete ischaemia, which is uncommon clinically. Experimental chronic pancreatitis is characterized by low pancreatic blood flow, low interstitial pH, and impaired pancreatic tissue oxygenation, which are all findings consistent with the ischaemia-reperfusion mechanisms. Acute pancreatitis is also associated with a reduction in pancreatic blood flow and evidence of free radical generation, similarly suggesting the possibility of ischaemia-reperfusion injury. Ethanol ingestion, which is commonly associated clinically with both chronic and acute pancreatitis, may itself contribute to an ischaemic-reperfusion injury. We have shown that administration of ethanol to cats decreases pancreatic blood flow and may also directly activate neutrophils. Further investigation is needed to determine whether or not these findings are also associated with an ischaemia-reperfusion injury.
 ...
PMID:Ischaemia-reperfusion mechanisms in acute pancreatitis. 886 66

This study tests the hypothesis that glutamate receptors are altered in the brains of alcoholics as a result of chronic alcohol neurotoxicity. Release of the neurotransmitter glutamate after seizures or brain ischemia may damage postsynaptic neurons by increasing calcium flux through N-methyl-D-aspartate (NMDA) receptor-gated ion channels. Alcohol has two opposite effects on glutamate receptor ion channel complexes, depending upon the duration of exposure. Acute exposure to alcohol inhibits ion flow through these receptor-channel complexes, whereas chronic exposure up-regulates the number of these receptors and thereby increases ion flow. Acute withdrawal from alcohol results in hyperexcitability and seizures in the presence of up-regulated channels, thereby making postsynaptic neurons vulnerable to excitotoxic damage. We selected 13 histologically normal brains from alcoholics and 13 brains from controls from our brain bank that were matched for age, postmortem interval, and storage time. Maximal binding and affinities of glutamate receptor subtypes were determined by quantitative autoradiography in the superior frontal cortex, Brodmann area 8. The most alcohol-sensitive subtype, NMDA receptor-channel complexes, were modestly but consistently increased in alcoholics. This included agonist sites (NMDA-sensitive [3H]glutamate), and antagonist site ([3H]CGP-39653), and a [3H]MK-801 binding site in the channel interior, although the increase of the latter did not reach statistical significance. Age, autopsy delay, time in storage, liver diseases, thiamine deficiency, CNS medications, and various diseases causing acute and chronic hypoxia did not significantly affect receptor density or affinity. In contrast, the other two glutamate channel subtypes, AMPA and kainate receptors, were not significantly different in alcoholics compared with controls. In conclusion, chronic alcoholism moderately increases the density of the NMDA subtype of glutamate receptors in the frontal cortex. This up-regulation may represent a stage of alcohol-induced chronic neurotoxicity.
Alcohol Clin Exp Res 1996 Oct
PMID:Glutamate receptors in the frontal cortex of alcoholics. 890 65

Although alcohol is likely to have direct effects on the subcellular integrity of the pancreas, other factors arising outside the pancreas may modulate or potentiate alcohol-induced damage. Among these factors are the hepatic metabolism of ethanol to acetaldehyde (via isoenzymes of ADH), the hepatic production of free radicals, the release of G.I. hormones, pancreatic ischemia (and reperfusion injury), hyperlipemia, diet and smoking. This article summarises what is known about these extrapancreatic factors. It is suggested that the pathogenesis of alcoholic pancreatitis is multifactorial but that many studies in this field are difficult to interpret because of methodological problems, particularly with regard to inadequate controls.
Alcohol Alcohol Suppl 1994
PMID:An overview of extrapancreatic factors in the pathogenesis of alcoholic pancreatitis. 897 59

Pancreatic hyperstimulation with simultaneous duct obstruction does not cause the typical features of acute pancreatitis, therefore the role of an additional challenge, such as either ethanol intoxication or short-term ischemia, was studied. Alcoholic pancreatitis was induced in 28 rats by acute ethanol intoxication (0.25 LD50) and an obstruction/hyperstimulation mechanism (clip of the biliopancreatic duct for 20 min and intravenous stimulation with 5 U of cholecystokinin and secretin each). Ischemic pancreatitis was performed by obstruction/hyperstimulation and subsequent pancreatic ischemia by clamping the supplying arteries for 40 min. The macro- and microscopic alterations were evaluated and graded by a scoring system. Additionally, the pancreas was removed in 50% of the animals and the pancreatic acini were prepared. From those acini the intracellular enzymes trypsinogen, kallikreinogen, amylase, lipase, glucuronidase, and acidic phosphatases were determined. While obstruction/hyperstimulation, 40 min of ischemia, or ethanol alone did not induce acute pancreatitis, a combination of obstruction/hyperstimulation with either ethanol or ischemia resulted in acute pancreatitis in 68 and 60% of treated rats, respectively. Similarly, both models were characterized by extrapancreatic fat necrosis and acinar necrosis at the periphery of the lobules. Almost all intracellular enzymes were elevated in both pancreatitis models compared to sham-operated controls. Both alcohol and ischemia were insults that sensitize the pancreas to develop acute pancreatitis after obstruction/hyperstimulation. Since the observed morphologic and enzymatic alterations in both models are very similar, alcohol and ischemia might have some common pathways by which they make the pancreas vulnerable to enzymatic attacks.
 ...
PMID:Similar morphological and intracellular biochemical changes in alcoholic acute pancreatitis and ischemic acute pancreatitis in rats. 898 5

Reactive oxygen metabolites (ROM) have been reported to be important in the pathogenesis of ischemia/ reperfusion-, ethanol-, nonsteroidal antiinflammatory drug-, or Helicobacter pylori-induced gastric mucosal injury. Rebamipide, a novel antiulcer agent, has been reported either to prevent various acute experimental gastric mucosal lesions or to accelerate the healing of chronic gastric ulcers. The underlying mechanism by which rebamipide exerts its cytoprotective effect in the damaged stomach is not fully determined. We investigated the role of rebamipide in protecting against ROM-mediated cell damage in gastric mucosal cells and in inducing cytoprotective proteins. Cells were exposed to ROM enzymatically generated by hypoxanthine-xanthine oxidase. Cytotoxicity was quantified by measuring specific 51Cr release from prelabeled cells. ROM caused dose-dependent increase in cytotoxicity and amount of thiobarbituric acid-reactive substances (TBA-RS). ROM-induced cytotoxicity and TBA-RS were dose-dependently decreased by the addition of rebamipide and/or catalase, but not by superoxide dismutase alone. The effects of rebamipide on electric spin resonance signal were investigated. We found that the DMPO spin adduct ESR signal of hydroxyl radicals (DMPO-OH) was significantly attenuated by rebamipide. Western blot analysis showed that induction of heat-shock protein (HSP70) was significantly increased following rebamipide administration in a dose-dependent manner. Based on these results, it is concluded that rebamipide exerted a protective effect on HX-XO-induced gastric mucosal cell cytotoxicity through one or more of the following mechanism(s): (1) inhibition of lipid peroxidation of the cell membrane; (2) hydroxyl radical scavenging activity; and (3) induction of cellular cytoprotective protein such as HSP70.
 ...
PMID:Role of rebamipide on induction of heat-shock proteins and protection against reactive oxygen metabolite-mediated cell damage in cultured gastric mucosal cells. 901 34

Melatonin, a pineal hormone, is known to scavenge oxygen free radicals and to be present in the gut but little is known about its role in the protection of gastric mucosa against the damage accompanied by a marked increase in these radicals. This study was designed to determine the effects of melatonin on the formation of acute gastric lesions induced by ischemia-reperfusion and, for comparison, by a topical irritant such as 100% ethanol. It was found that pretreatment with melatonin at a dose of 5 mg/kg given intragastrically reduced significantly gastric lesions induced by ischemia-reperfusion and this was accompanied by a reduction in free radicals in the blood and by attenuation of the fall in gastric blood flow. In contrast, melatonin failed to affect acute gastric lesions induced by 100% ethanol. We conclude that melatonin is capable of protecting gastric mucosa from the damage caused by ischemia-reperfusion and that this action is mediated, at least in part, by limitation of the generation of free radicals and by attenuation of the fall in gastric blood flow.
 ...
PMID:Melatonin affords protection against gastric lesions induced by ischemia-reperfusion possibly due to its antioxidant and mucosal microcirculatory effects. 908 73

Epidemiologic studies indicate that long-term alcohol consumption decreases the incidence of coronary disease and may improve outcome after myocardial infarction. Attenuation of ischemia-reperfusion injury after myocardial infarction improves survival. This study investigates the possibility that alcohol consumption can improve survival after myocardial infarction by reducing ischemia-reperfusion injury. Hearts were isolated from guinea pigs after drinking ethanol for 3-12 weeks and subjected to global ischemia and reperfusion. Hearts from animals drinking ethanol showed improved functional recovery and decreased myocyte damage when compared with controls. Adenosine A1 receptor blockade abolished the protection provided by ethanol consumption. These findings indicate that long-term alcohol consumption reduces myocardial ischemia-reperfusion injury and that adenosine A1 receptors are required for this protective effect of ethanol. This cardioprotective effect of long-term alcohol consumption mimics preconditioning and may, in part, account for the beneficial effect of moderate drinking on cardiac health.
 ...
PMID:Regular alcohol consumption mimics cardiac preconditioning by protecting against ischemia-reperfusion injury. 909 76

Focal cerebral ischemia was induced in a rat model of middle cerebral artery occlusion. Three groups of adult male Sprague-Dawley rats, given food and water ad libitum, were subjected to 4 hr of middle cerebral artery occlusion. All were given vehicle control and ethanol pretreatments intraperitoneally 1 hr before. Mean ipsilateral brain water content in the control, 2 g/kg ethanol, and 2 g/kg ethanol + insulin-treated groups showed: ischemia core: 81.1%, 82.5%, and 80.9%; intermediate zone: 81.0%, and 80.3%; and outer zone: 80.3%, 81.3%, and 80.1%, respectively. Brain Na+ and K4 content in these groups paralleled the water content. In addition to significantly (p < 0.05) more brain edema, the 2 g/kg ethanol-treated animal group also had significant hyperglycemia. In contrast, the 2 g/kg ethanol + insulin-treated animals were normoglycemic and had ischemic, intermediate, and outer zone Na+, K+, and Cl- levels comparable with the control group (p > 0.05). These results stress the importance of measuring and controlling plasma glucose levels in the in vivo studies of the neurotoxic effects of acute ethanol.
Alcohol Clin Exp Res 1997 Jun
PMID:Acute ethanol effects on focal cerebral ischemia in nonfasted rats. 919 34

We have previously demonstrated that chronic alcohol consumption (8 to 10 weeks with ethanol as 36% of the caloric intake) does not exacerbate the effects of ischemia reperfusion injury on the heart. In those same studies, however, Gram-negative sepsis caused myocardial depression in both control and alcoholic rats, but also protected hearts from further damage due to ischemia-reperfusion. In the present study, we determined if preconditioning, a very short ischemia-reperfusion episode that protects the heart from more prolonged ischemia, would have similar effects on hearts from alcoholic and control rats with or without sepsis. Thus, rats were fed a liquid diet supplemented with ethanol or dextrin for 8 to 10 weeks. Some alcoholic and control rats were made septic with Escherichia coli injected into the subcutaneous space, whereas others received an injection of sterile saline. Isolated, isovolumically beating hearts were studied the following day. Hearts were made ischemic for 5 min, reperfused for 5 min, and then made ischemic for 35 min and reperfused for 25 min. Data from similar groups of hearts receiving only 35 min ischemia, and studied at the same time as the present groups, have been previously reported. The 5-min preconditioning episode was more effective in protecting hearts in the alcohol group than in the control group. Postischemic left ventricular developed pressure and +dP/dtmax were not significantly decreased from the preischemic values in the alcohol group, but were significantly decreased in the control group. The time to recovery of spontaneous contractions was decreased by preconditioning in the alcohol group but not in the control group, and the recovery of coronary flow was enhanced in the alcohol group, but not in the control group by pre-conditioning. Thus a single 5-min ischemic procedure was effective in protecting the heart from prolonged ischemia in the alcohol group, whereas it was not sufficient to elicit protection in the control group. Sepsis depressed preischemic function in both groups, but recovery from ischemia was complete.
Alcohol Clin Exp Res 1997 Aug
PMID:Chronic alcohol consumption causes accelerated myocardial preconditioning to ischemia-reperfusion injury. 926 37

Previous studies have found an association between prior ethanol consumption and aggravated stroke outcome. Gerbils were intermittently given ethanol injections (s.c.) for 21 days at doses of 1 and 4 g/kg. After cessation of injections and appropriate weight gain, subjects underwent bilateral carotid occlusion while amino acid neurotransmitter levels in the hippocampus were monitored. Both the low and high dose ethanol groups demonstrated significantly decreased glutamate release compared with saline-treated controls during ischemia (p < 0.05). These results are consistent with a long-lasting ethanol-induced decrease in synaptic density in the hippocampus. That no intergroup differences on histological or neurobehavioral measures was found may suggest a functional dissociation of glutaminergic involvement in the pathogenesis of aggravated stroke outcome with alcoholism.
 ...
PMID:Attenuated glutamate release during ischemia in ethanol-administered gerbils. 935 77


<< Previous 1 2 3 4 5 6 7 8 9 10