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

The effects of insulin in vitro on perfused liver from streptozotocin-diabetic rats and their untreated littermates during gluconeogenesis from either [3-13C]alanine + ethanol or [2-13C]pyruvate + NH4Cl + ethanol were studied by 13C NMR. A 13C NMR determination of the rate of pyruvate kinase flux under steady-state conditions of active gluconeogenesis was developed; this assay includes a check on the reuse of recycled pyruvate. The preparations studied provided gradations of pyruvate kinase flux within the confines of the assay's requirement of active gluconeogenesis. By this determination, the rate of pyruvate kinase flux was 0.74 +/- 0.04 of the gluconeogenic rate in liver from 24-h-fasted controls; in liver from 12-h-fasted controls, relative pyruvate kinase flux increased to 1.0 +/- 0.2. In diabetic liver, this flux was undetectable by our NMR method. Insulin's hepatic influence in vitro was greatest in the streptozotocin model of type 1 diabetes: upon treatment of diabetic liver with 7 nM insulin in vitro, a partial reversal of many of the differences noted between diabetic and control liver was demonstrated by 13C NMR. A major effect of insulin in vitro upon diabetic liver was the induction of a large increase in the rate of pyruvate kinase flux, bringing relative and absolute fluxes up to the levels measured in 24-h-fasted controls. By way of comparison, the effects of ischemia on diabetic liver were studied by 13C NMR to test whether changes in allosteric effectors under these conditions could also increase pyruvate kinase flux. A large increase in this activity was demonstrated in ischemic diabetic liver.
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PMID:Effects of insulin on perfused liver from streptozotocin-diabetic and untreated rats: 13C NMR assay of pyruvate kinase flux. 303 Apr 12

Free radicals have been implicated in many pathological processes, including ischemia, inflammation, and malignancy. Since a reduction in extrathyroidal outer ring monodeiodination of T4 and rT3 occurs in virtually all systemic illnesses, we have studied the effect of free radicals on iodothyronine (T4 and rT3) 5'-monodeiodinating activity (MA) of liver tissue in vitro. Rat liver microsomes or homogenate were preincubated in Tris buffer for 30 min with a free radical-generating system (FRGS) and then incubated with T4 (2.5 microM) or [125I]rT3 (0.4 nM) and dithiothreitol (DTT; 5-20 mM with T4 and 20-150 mM with [125I]rT3) in the same buffer for 10 or 30 min. T3 generated during incubation was quantified by RIA of ethanol extracts of the incubation mixture. 125I generated from [125I]rT3 was quantified after precipitation of the incubation mixture with trichloroacetic acid or by paper chromatography. Free radicals caused 55% or more reduction in hepatic T4 MA and 44% or more reduction in rT3 MA in various experiments. The inhibition of hepatic rT3 MA after incubation with FRGS persisted despite removal of FRGS and washing of microsomes preincubated with FRGS before studying the MA. However, inclusion of DTT (1-60 mM) during preincubation of tissue with FRGS prevented the FRGS-induced inhibition of rT3 MA. Depletion of the iodothyronine substrate did not occur when FRGS inhibited T4 and rT3 5'-monodeiodination. Free radical scavengers, i.e. superoxide dismutase (600 IU/ml), catalase (300 U/ml), tocopherol (10 mg/ml), thiourea (0.15 M), and tert-butanol (0.15 M), all significantly reduced the inhibition of hepatic rT3 MA caused by FRGS. The FRGS-induced inhibition of hepatic T4 MA was reduced by the same doses of tocopherol, thiourea, and tert-butanol, but not by superoxide dismutase or catalase. Since free radicals may effect tissue damage by lipid peroxidation and since the latter results in generation of malondialdehyde (MDA) as a by-product of the reaction, we studied MDA by its reaction with 2-thiobarbituric acid. Incubation with FRGS caused an approximately 100-fold increase in MDA formation in liver microsomes. Serum MDA was significantly higher in 16 NTI patients than in 8 normal subjects and also higher in turpentine oil-injected rats [an experimental model of nonthyroidal illness (NTI)] than in saline-injected control rats. The data suggest that generation of free radicals may contribute to the reduced extrathyroidal 5'-monodeiodination of T4 and rT3 in NTI.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effect of free radicals on hepatic 5'-monodeiodination of thyroxine and 3,3',5'-triiodothyronine. 310 83

The gastric microcirculation was investigated with the in vivo microscopic analyzing system and reflectance spectrophotometry. The topical administration of either ethanol (greater than or equal to 20%), indomethacin (0.1 mg/kg), leukotriene C4 (0.1 microgram), and platelet activating factor (PAF) (125 micrograms) decreased mucosal blood flow and mucosal blood oxygenation. The subsequent reperfusion of blood and/or addition of hydrocholoride (0.2 N) induced the gastric bleeding and ulceration. Pretreatment with calcium channel blockers (verapamil, flunaridine, and diltiazem) significantly reduced the gastric lesions induced by mucosal ischemia followed by reperfusion. Lipid peroxidation increased only after reperfusion, which was also blocked by pretreatment with calcium channel blockers. Thus, the calcium ion influx and the membrane lipid peroxidation followed by mucosal hypoxia might have a role in the mucosal cell death. The results indicate that the gastric surface mucosal circulation plays an important role in the mucosal protection against high concentrations of ethanol, nonsteroidal anti-inflammatory drugs (NSAIDs), PAF, and leukotriene C4.
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PMID:Microvascular basis of gastric mucosal protection. 318 37

Present concepts of acute ulceration in the gastric mucosa include the hypothesis that mucosal ischemia is an important initiating event. The evidence for this is based upon observations on tissue metabolism and determinations of gastric mucosal blood flow. Using the model of gastric mucosal injury in the rat with ethanol, we have found that mucosal injury could be detected at a time when tissue oxygenation as determined by biochemical, and pharmacological studies of ATP metabolism were not compatible with ischemia. We also found that drugs acting at different subcellular levels were able to both inhibit gastric acid secretion in 4 hour pylorus-ligated rats and gastric mucosal injury after ethanol. Certain drugs, such as histamine and pentagastrin, stimulated acid secretion but inhibited the injury to the mucosa by ethanol indicating that increased cellular activity could occur during the development of mucosal injury.
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PMID:A biochemical and pharmacological approach to the genesis of ulcer disease. I. A model study of ethanol-induced injury to gastric mucosa in rats. 327 71

This study documents the effects of an intoxicating dose of ethanol on the energy metabolism and electrophysiological function of rat brain exposed for 0.5 h to ischemia produced by electrocautery of the vertebral arteries and reversible occlusion of the carotid arteries. One-hour exposure to 5 g kg-1 ethanol led to no significant alterations of the preischemic cerebral contents of glucose, lactate, or energy phosphates. Animals receiving ethanol or isovolumetric amounts of 0.9% saline showed statistically equivalent decreases in glucose, ATP, and phosphocreatine and increases in lactate, ADP, and AMP during 0.5 h of ischemia. Upon recirculation for 0.5-24 h, animals receiving ethanol again showed no significant differences from saline-treated animals in the rate of return of glucose, lactate, and energy metabolites to control levels. Animals receiving ethanol showed a trend for a faster and more complete normalization of the EEG during recirculation. It is concluded that under controlled experimental conditions, intoxicating doses of ethanol have no detrimental effect on the energy metabolism of ischemic and postischemic brain.
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PMID:Influence of ethanol on the energy metabolism of ischemic and postischemic brain. 336 95

A new luminescence procedure based on the creatine kinase reaction was developed for measuring creatine in plasma. The method is highly applicable to small animal work where the amount of blood volume is critical. Only 20 microliter of sample is necessary for creatine analysis. Deproteinizing the plasma sample with ethanol at room temperature is convenient. This extraction method is adaptable to a clinical setting. The ethanol used in the extraction is compatible with the luminescence method but precipitated enzymes in the NADH spectrophotometric method because of the greater sample volume needed for analysis. The creatine concentration is stable in plasma for at least 1 hr in a final anticoagulant concentration of 10 mM EDTA. The correlation between the new luminescence method with the established NADH spectrophotometric method was excellent (r = 0.99). The accuracy of the within-run precision is high, with a mean coefficient of variation, 2-3%. Plasma creatine levels could be an important indicator denoting early cellular damage and of potential prognostic value. Preliminary studies in human muscle ischemia and early shock in rabbits revealed a significant increase in plasma creatine levels. Further investigations are necessary to evaluate its clinical importance.
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PMID:Plasma creatine determination using a luminescence method. 339 6

Protection of the brain and spinal cord against ischemia is a goal of vast clinical importance. One approach to this objective is to reduce the tissue's functional activity in order to preserve energy for the metabolic processes that are essential to viability. Experiments to explore ways of reducing function-related energy demands were performed on isolated rabbit retina, a well-characterized model of organized adult mammalian central nervous system (CNS) tissue. The retina was maintained in a nearly physiological state in a miniature "heart-lung" apparatus. Energy metabolism (oxygen consumption and glycolysis) and electrophysiological function (determined by electroretinogram) of the in vitro retina were monitored, and their responses to a series of agents that may reduce energy requirements were determined. Large reversible reductions in O2 consumption, glycolysis, and electrophysiological function were seen in response to mild hypothermia (-3 degrees to -6 degrees C), phenytoin (Dilantin, 100 to 200 mg/kg), chlordiazepoxide (Librium, 200 microM), lithium (1 to 4 mM), Mg++ (6 to 20 mM), strophanthidin (0.15 to 0.25 microM), CO2 (25% to 30%), 2-amino-5-phosphonovaleric acid (APV, 500 microM), amiloride (1 mM), and dantrolene (1 mM). One retina was exposed simultaneously to a combination of six of these agents, which reduced its oxidative and glycolytic metabolism to less than 50% of the control level. The retina recovered metabolic and electrophysiological function after a 2 1/2-hour exposure period. Other agents tested (diphenhydramine, midazolam, nifedipine, nimodipine, and quercetin) had effects on energy metabolism and electrophysiological function that were poorly reversible. Surprisingly little effect was seen in response to general anesthetic agents (thiopental and Althesin) and other CNS depressants (chlorpromazine, ethanol, lidocaine, paraldehyde, valproic acid, and baclofen). The presumed mechanisms through which these agents reduce cellular energy requirements, as well as their potential roles in the treatment of CNS ischemia, are discussed.
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PMID:Reduction of cellular energy requirements. Screening for agents that may protect against CNS ischemia. 341 90

The acute effect of T-2 toxemia on local blood flow and vascular resistance in hindquarter, mesenteric, and renal vascular beds was continuously measured by the directional pulsed Doppler technique in conscious, male Sprague-Dawley rats. Intravenous injection of T-2 toxin (1 mg/kg) in the conscious rat reduced blood flow and increased vascular resistance in all blood vessels studied but had no significant effect on mean arterial pressure or heart rate. The blood flow in hindquarters gradually decreased to a minimum of -77 +/- 9% (mean +/- SE) 6 hr after the toxin injection. The hindquarter vascular resistance concomitantly increased to a maximum value of +323 +/- 69% above the resistance before toxin administration. Mesenteric and renal blood flow initially increased (slightly) and then gradually decreased. The maximum drop of blood flow, -90 +/- 13% and -76 +/- 13% for the mesenteric and renal vascular beds, respectively, was achieved 4 hr after T-2 toxin injection and the blood flow values remained low for up to 6 hr. Simultaneously with the impairment of blood flow the mesenteric and renal vascular resistance increased to reach the maximal values of +404 +/- 99% and +556 +/- 15%, respectively. In addition, plasma renin activity was markedly elevated (+653 +/- 160%) at the time of reduced renal blood flow. Intravenous injection of the same value of vehicle (10% ethanol in saline) had no significant effect on any of the cardiovascular variables studied. Two of five rats in the T-2 toxin-treated group died within 5 hr after the T-2 toxin injection and only one animal survived 24 hr while all the control animals survived over 24 hr. The results suggest that strong vasoconstriction in skeletal muscle, mesenteric, and renal vascular beds leads to impairment of local blood flow. The ischemia in vital organs together with the earlier reported decrease in cardiac output by T-2 toxin might then be the cause of rapid death in acute T-2 toxemia.
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PMID:Effect of T-2 toxin on regional blood flow and vascular resistance in the conscious rat. 351 54

Reflectance spectrophotometry in assessing gastroduodenal mucosal perfusion was evaluated. Ischemia without congestion, e.g., during hemorrhagic hypotension or celiac artery occlusion, was associated with a reduction in the indexes of mucosal hemoglobin concentration and of oxygen saturation. Ischemia with congestion, e.g., during portal vein occlusion, or in absolute ethanol or suction-induced mucosal lesions, was associated with an increase in the index of mucosal hemoglobin concentration but a reduction in the index of oxygen saturation. An increase in the index of mucosal hemoglobin concentration associated with a normal index of oxygen saturation was found in the postischemic hyperemia after release of celiac artery occlusion and during the sustained increase in corpus mucosal blood flow induced by vagus nerve stimulation. Thus reflectance spectrophotometric measurements reflected ischemia, without or with congestion, and hyperemia. Additionally, although regional differences in reflectance spectrophotometric measurements were demonstrated in the duodenal, antral, and corpus mucosa, such differences bore no consistent relationship to regional differences in blood flow demonstrated in previous studies.
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PMID:Reflectance spectrophotometry for the assessment of gastroduodenal mucosal perfusion. 359 45

An enhanced frequency and morbidity of urinary tract infections (UTI) have been observed in association with alcoholism and liver disease. The causes of these phenomena may relate, in part, to the defects in humoral and cellular immune mechanisms that occur in alcoholism. Urinary catheterization is the most common cause of UTI in hospitalized alcoholics. The severity of the sequelae of UTI in alcoholism is demonstrated by the unusually frequent occurrence of renal papillary necrosis (RPN) in conjunction with pyelonephritis in these patients. Indeed, in over 90% of the reported cases of RPN occurring with alcoholism or liver disease, pyelonephritis has been a contributing factor. The proclivity to medullary ischemia and RPN in this patient group may be, at least in part, a result of interstitial renal edema secondary both to infection and the effect of ethanol per se and to renal arterial vasoconstriction that occurs in cirrhosis. The frequency with which death due to sepsis or renal failure occurs in association with UTI in alcoholics obliges the physician to exercise caution in the prevention and treatment of UTI in these patients.
Recent Dev Alcohol 1986
PMID:Urinary tract infections and renal papillary necrosis in alcoholism. 370 22


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