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)

Pieces of liver (in vitro ischemia) and isolated microsomes were subjected to incubation at 4 degrees C and 37 degrees C for various time intervals. The effects on microsomal protein, phospholipids, and cholesterol and on microsomal phosphatases and electron transport enzymes were followed as a functional of time and temperature. NADH-cytochrome c reductase was very labile and was completely inactivated by 1 h, whereas G6Pase lost 50% of its activity after 2 h at 37 degrees C. IDPase and NADPH-cyt. c red. were of intermediate susceptibility whereas cytochromes b5 and P-450 were the most stable enzymes assayed. After 24 h of incubation of isolated microsomes at 37 degrees C there was no significant detachment of membrane components (protein, PLP or cholesterol), indicating that the inactivation of the enzymes was not primarily attributable to their solubilization. Instead, experiments with 14C-leucine and 14C-glycerol prelabeled microsomes demonstrated that the proteins detached from microsomes during incubation originated mainly from the intravesicular space due to repture of the microsomal membranes. The addition of a lysosomal extract during incubation did not alter either the rate of inactivation of the enzymes or the proportion of solubilized membrane components indicating that attack from the outside by proteolytic enzymes is not the mechanism for enzyme inactivation. There was no apparent correlation between the rates of inactivation of enzymes in vitro and their calculated half-lives in vivo or their postulated intramembranous localization. Ultrastructurally, enzyme inactivation was initially associated with alterations of the microsomal membranes, such as vesicle aggregation, membrane rupture, loss of unit membrane structure, and subsequently, thickening of membranes and transformation of the microsomes into nonrecognizable amorphous material.
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PMID:Effect of storage and in vitro ischemia on the ultrasture of microsomal membranes and on microsomal enzymes. 18 24

Myocardial ischemia was produced for 2 hours by coronary ligation in 11 dogs pretreated with methylprednisolone (MP, 30 mg/kg). Myocardial blood flow (MBF) was measured with microspheres (15 micrometer) in each tissue sample used for enzymatic analysis. Homogenates of these tissue samples were separated by ultracentrifugation into lysosome-rich and microsomal fractions and were analyzed for N-acetyl-beta-glusosaminidase (NAGA), beta-glucuronidase (beta-gluc), rotenone-insensitive-NADH-cytochrome c reductase (RINCR), and cytochrome oxidase. The enzymatic data from centrifugal fractions were grouped according to MBF values for statistical analysis of inter-group effects of ischemia. Significant losses (P less than 0.001) of NAGA and beta-gluc were seen in all MP-treated lysosome-rich particulate fractions that were isolated from zones demonstrating MBF values less than 25% of control (L-ischemia). Similar significant losses (P less than 0.001) of RINCR were seen in microsomal fractions from L-ischemia zones. Samples with MBF values greater than 25% but less than 75% of control (M-ischemia) also demonstrated significant decreases of lysosomal and microsomal enzymatic activity in specific fractions. When the data of the above MP-treated group were compared with the untreated control group, no significant intergroup effects of treatment with MP were observed. In addition, enzymatic data (NAGA, RINCR) were normalized prior to performing linear regression analyses; percent loss of particulate enzymatic activity was plotted against percent decrease in MBF. The effects of 2 hours of ischemia on the above biochemical parameters were comparable between untreated and MP-treated groups. Finally, when myocardial samples were grouped according to similar levels of MBF, statistical analysis using the general linear models procedure revealed no beneficial effect of MP treatment on changes in lysosomal hydrolases, microsomal RINCR, or latency of lysosomes.
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PMID:Lack of effect of methylprednisolone on lysosomal and microsomal enzymes after two hours of well-defined canine myocardial ischemia. 21 3

The present study evaluated the effect of glycyrrhizin (GR) on an injury of the liver caused by ischemia-reperfusion in rats. In the liver ischemia-reperfusion model, levels of serum GOT, GPT and LDH activities and lipid peroxides in the liver tissue were significantly increased. On the contrary, total glutathione content in the liver tissue and NADPH cytochrome P-450 reductase activity of liver microsomes were decreased. Pretreatment with GR 20 mg/kg, i.v. 10 min before induction of ischemia resulted in significant decreases in serum GOT, GPT, LDH activities and the lipid peroxide level and a higher tissue glutathione content during the period of reperfusion. Electron microscopic studies revealed various hepatocellular damages with an almost intact sinusoidal endothelium in ischemia-reperfused livers. However, the degree of damage was less severe in the livers from the rats pretreated with 20 mg/kg GR. The results indicate that GR is able to provide partial protection against ischemia-reperfused damage.
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PMID:Attenuation of dysfunction in the ischemia-reperfused liver by glycyrrhizin. 151 71

The empiric administration of 50% dextrose to all patients presenting to the ED with altered mental status is a standard of care predicated on the assumption that glucose administration is harmless to nonhypoglycemic patients. Considerable evidence now disputes this assumption. Glucose administration before complete cerebral ischemia in experimental animals worsens neurologic and histologic outcome. Administration of glucose during severe incomplete ischemia has a similar detrimental effect. The translation of these experimental findings into clinical practice has been slow, perhaps hindered by the frequent use of rodent models and large bolus doses of glucose. However, evidence is now provided by primate and human studies and by experimental designs using clinically relevant doses of glucose. These clinical and experimental findings in conjunction with the wide availability of a rapid bedside screen for hypoglycemia provide the rationale for an alteration in the standard of care. The empiric administration of glucose should be avoided in patients at risk of cerebral ischemia, such as those with acute stroke, impending cardiac arrest, or severe hypotension or receiving CPR. A bedside fingerstick blood glucose estimation should be performed immediately on all patients presenting with altered mental status. The administration of 50% dextrose should be reserved for those patients in whom hypoglycemia is demonstrated; this practice will uphold Hippocrates' most basic principle of clinical medicine, "The physician must...do no harm."
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PMID:50% dextrose: antidote or toxin? 212 May 1

The effects of Bifemelane (BF) on lipid peroxidation, the activities of hepatic drug metabolizing enzymes, and the function of cell membranes were examined in rats. In the liver ischemia-reperfusion model, BF suppressed the elevation of the lipid peroxidation level during the period of reperfusion. BF did not exhibit a radical-trapping action using a stable free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH), which was estimated by electron spin resonance (ESR). BF remarkably inhibited NADPH-dependent lipid peroxidation in vitro. BF had no effect on the contents of cytochrome P-450 and b5 and the activities of NADPH cytochrome P-450 reductase and Cu,Zn-superoxide dismutase (SOD). BF suppressed phorbol myristate acetate (PMA)-induced superoxide formation of polymorphonuclear leukocytes (PMNs), protected hypotonic hemolysis of erythrocyte and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and serum phospholipase A activity. These results suggest that BF has neither radical-trapping activity nor any influence on the drug metabolizing enzymes, but BF has a membrane-stabilizing action and it attributes to the suppressive effect of lipid peroxidation.
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PMID:Suppressive effect of bifemelane on lipid peroxidation in rat liver. 215 22

The empiric administration of 50% dextrose to all patients presenting to the ED with altered mental status is a standard of care predicated on the assumption that glucose administration is harmless to non-hypoglycemic patients. Considerable evidence now disputes this assumption. Glucose administration before complete cerebral ischemia in experimental animals worsens neurologic and histologic outcome. Administration of glucose during severe incomplete ischemia has a similar detrimental effect. The translation of these experimental findings into clinical practice has been slow, perhaps hindered by the frequent use of rodent models and large bolus doses of glucose. However, evidence is now provided by primate and human studies and by experimental designs using clinically relevant doses of glucose. These clinical and experimental findings in conjunction with the wide availability of a rapid bedside screen for hypoglycemia provide the rationale for an alteration in the standard of care. The empiric administration of glucose should be avoided in patients at risk for cerebral ischemia, such as those with acute stroke, impending cardiac arrest, or severe hypotension or receiving CPR. A bedside fingerstick blood glucose estimation should be performed immediately on all patients presenting with altered mental status. The administration of 50% dextrose should be reserved for those patients in whom hypoglycemia is demonstrated; this practice will uphold Hippocrates' most basic principle of clinical medicine, "The physician must ... do no harm."
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PMID:50% dextrose: antidote or toxin? 218 38

Hepatic ischemia induced in vivo by ligation of the left hepatic lobe of rats for up to 2 hr had no effect on cytochrome P-450, cytochrome c reductase, or lobe histology; however, cytochrome b5 increased with ischemia duration. Ethylmorphine demethylation decreased 35% after 2 hr of ischemia. Reperfusion of tissue previously made ischemic for up to 2 hr was associated with appreciable necrosis as well as decreases in cytochrome P-450, cytochrome b5, cytochrome c reductase, and ethylmorphine demethylation. Serum alanine transaminase and aspartate transaminase concentrations were increased by reperfusion of previously ischemic tissue. Reperfusion of the previously ischemic lobe for 18 hr was associated with a greater loss of cytochromes P-450 and b5, cytochrome c reductase, and ethylmorphine demethylation than reperfusion for 1 hr. The total decrease in cytochrome P-450 and b5 content was equal to the decrease in total microsomal heme content, although cytochrome P-450 decreased more than cytochrome b5. Ethoxyresorufin deethylation by hepatic microsomes from 3-methylcholanthrene-treated rats was decreased by ischemia-reperfusion; however, pentoxyresorufin dealkylation by hepatic microsomes from phenobarbital-treated rats was not, suggesting specific cytochrome P-450 isozyme loss. In vitro NADPH-dependent lipid peroxidation in hepatic microsomes from control and phenobarbital- and 3-methylcholanthrene-treated rats resulted in a selective decrease of ethoxyresorufin but not pentoxyresorufin dealkylation, similar to that observed in livers subjected to ischemia-reperfusion in vivo. These data suggest that cytochrome P-450, ethylmorphine demethylation, and ethoxyresorufin deethylation are more susceptible to ischemia-reperfusion injury than cytochrome b5 or pentoxyresorufin dealkylation.
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PMID:Effects of hepatic ischemia-reperfusion injury on the hepatic mixed function oxidase system in rats. 225 Jun 63

Animal and human studies have suggested that higher doses of epinephrine than currently recommended may improve resuscitation rates after prolonged cardiac arrest. Because of our failure to resuscitate four patients with the standard American Heart Association protocol for cardiac arrest, we used a larger dose of epinephrine in an attempt to enhance resuscitative efforts. All patients required CPR and had nonperfusing rhythms for at least 20 minutes. The four patients received from 0.12 to 0.22 mg/kg epinephrine. Within five minutes of high-dose epinephrine, all four patients developed perfusing rhythms with maximum systolic blood pressures ranging from 134 to 220 mm Hg. Cardiac dysrhythmias did not occur after these doses of epinephrine. Only one of four patients had ECG evidence of an acute myocardial infarction. In this patient, the history suggested that the myocardial infarction was a primary event, not the consequence of epinephrine. All four patients sustained severe brain injury leading to their demise. This injury was probably due to prolonged cardiopulmonary arrest and global brain ischemia. Pharmacologic and potential pathophysiologic mechanisms of high-dose epinephrine are reviewed.
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PMID:Four case studies: high-dose epinephrine in cardiac arrest. 231 72

Neurologic impairment remains a serious consequence of cardiac arrest. While current investigations are difficult to compare due to their lack of standardization, our understanding of the pathophysiology of CNS ischemia has been greatly increased. Ion fluxes, especially K and Ca, may contribute to injury by initiating a cascade of events culminating in free fatty acid, prostaglandin, and free radical formation, with their related pathogenetic potential. Treatment measures currently consist of CPR (although disagreement exists as to which form of CPR), standard supportive measures, and attention to intracranial pressure control. There is some experimental evidence to support the use of calcium channel-blockers, phenytoin, prostaglandin inhibitors, and free-radical scavengers or inhibitors; however, no human trials have been performed. Steroids and barbiturates have been investigated in human trials and do not appear to be efficacious in ameliorating CNS injury after cardiac arrest.
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PMID:Cerebral function and preservation during cardiac arrest. 264 72

Effect of smoking habits on limb loss rates and cumulative patency rates of 136 arterial reconstructions performed for lower limb ischemia were analyzed in a five year follow-up retrospective study. Of 121 patients, 103 (85%) smoked before the operation and 43 of the smokers (42%) discontinued smoking postoperatively. Patients who continued to smoke more than 15 cigarettes per day (34 patients) increased the probability of losing their limb approximately five times at two years and three times at five years postoperatively, compared with nonsmokers and smokers of up to 15 cigarettes per day (87 patients) (p = 0.013). Cumulative patency rates of nonsmokers and smokers of up to five cigarettes per day (Group A, 66 patients) were not significantly influenced (p = 0.518) by preoperative symptoms (claudication versus limb salvage). However, for smokers of more than five cigarettes per day (Group B, 55 patients), at five years claudicants had a cumulative patency rate of 62.9% compared to 38.3% for limb salvage patients (p = 0.015). In group A at five years, autologous saphenous vein grafts had a cumulative patency rate of 74.2%, compared to 24% for prosthetic grafts (P = 0.013). In group B the CPR differences between autologous saphenous vein and prosthetic grafts were not significantly different (p = 0.394). Multiple interactions between smoking and variables like age, preoperative symptoms, and graft material demonstrate the complexity of the effects of smoking on cumulative patency rate and the need for sub-grouping and removal of confounding factors. In view of the adverse affects of continued smoking on postrevascularization prognosis, patients should be strongly advised to discontinue smoking.
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PMID:The effect of postoperative smoking on femoropopliteal bypass grafts. 271 28


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