Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet-activating factor (PAF), one of the chemical mediators related to inflammation reaction, is also involved in the pathologic state induced by endotoxin or ischemia. PAF antagonist has been reported to block the action of PAF and protect cells from its deleterious effects. The effects of a PAF antagonist, CV-6209, were evaluated in this study by means of a partial liver ischemia model, in which ischemia was induced by clamping only part of the liver without causing intestinal congestion. This model allowed the study of ischemic liver injury without influence from other organs. After 30, 60, and 90 minutes of ischemia, the bile flow, ATP level, and energy charge of the ischemic lobes were compared for the effects with and without CV-6209. After 60 minutes of ischemia, those that had received CV-6209 showed more bile production and higher ATP level and energy charge, with values of 0.25 +/- 0.05 ml/hr, 3.9 +/- 0.9 nmol/mg dry liver weight, and 0.61 +/- 0.02, respectively. In contrast, the values for the control group were 0.05 +/- 0.05 ml/hr, 1.7 +/- 0.8 nmol/mg dry liver weight, and 0.43 +/- 0.08, respectively. Other liver function tests (aspartate aminotransferase and lactate dehydrogenase levels) could also be improved if an appropriate dose of PAF antagonist were administered. The results imply that PAF, as has been suggested in other studies on ischemic injury, plays a role in liver ischemia and that its deleterious effects can be blocked by PAF antagonist. We conclude that the PAF antagonist offers promise in the field of liver surgery, including liver transplantation, as a means of protecting the liver from ischemic injury.
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PMID:Protective effect of platelet-activating factor antagonist on ischemia-induced liver injury in rats. 841 92

Studies were made on the effects in rat lungs of aerobic and anaerobic conditions on the intracellular levels of adenosine triphosphate and its related metabolites, the releases of intracellular enzymes, and the secretion of pulmonary surfactant. After warm ischemia for 120 min, the ATP content of lungs inflated with air was significantly higher (8.0 +/- 1.2 mumol/g dry weight) than those of deflated lungs and lungs inflated with nitrogen (0.8 +/- 0.7 mumol/g dry weight and 2.0 +/- 0.7 mumol/g dry weight, respectively; P < 0.001). The amounts of intracellular enzymes, such as lactate dehydrogenase, cytosolic and mitochondrial aspartate aminotransferase, and protein in the bronchoalveolar lavage fluid (BALF) of air-inflated lungs were significantly less than those in BALFs of deflated and nitrogen-inflated lungs (P < 0.001). The BALF-contents of dipalmitoyl phosphatidylcholine (DPPC), the main component of alveolar surfactant of aerobic and anaerobic ischemic lung were, however, similar. During 120-min warm ischemia after lavage, air-inflated lungs secreted significantly more DPPC into the alveolar space than nitrogen-inflated lungs did (P < 0.001). We conclude that cell membranes in the lungs are damaged under anaerobic conditions, but that inflation of ischemic lungs with air is effective for protecting them from cell injury and for maintaining the intracellular level of ATP and the ability of the cells to secrete pulmonary surfactant.
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PMID:Attenuation of warm ischemic injury of rat lung by inflation with room air--assessment of cellular components and the surfactant in the bronchoalveolar lavage fluid in relation to changes in cellular adenosine triphosphate. 842 61

Cell damage within the sinusoidal lining of human liver grafts during transplantation is an early event that is critical in ischemia-reperfusion injury and probably plays a key role in primary liver dysfunction after transplantation. No simple biochemical marker for sinusoidal injury is currently available. Because creatine kinase activity has been described in heart endothelial cells, we hypothesized that release of this enzyme might serve as an index of sinusoidal injury. To test this hypothesis, we used several in vivo and in vitro experimental models. Occlusion of the rat hepatic pedicle in situ for 60 min (normothermic ischemia) induced a significant increase in serum creatine kinase levels relative to those in laparotomized controls (2,530 +/- 530 vs. 389 +/- 64 IU/L, mean +/- SEM; p < 0.005). In the isolated perfused rat liver, 60-min ischemia induced early (< or = 3 min) creatine kinase and AST release (0.87 +/- 0.14 vs. 0.08 +/- 0.01 IU/min/gm liver, respectively). A similar phenomenon was observed after 24-hr or 48-hr hypothermic conservation in University of Wisconsin solution. Electrophoretic analysis and immunoinhibition studies showed that creatine kinase activity comprised creatine kinase-BB (approximately 50%) and mitochondrial creatine kinase. Trypan blue infusion showed a loss of viability in sinusoidal cells, whereas hepatocytes were relatively spared. Finally, murine sinusoidal cells were isolated, cultured and then lysed by a freeze-thaw cycle and sonication. Creatine kinase activity was found in endothelial cells (creatine kinase-BB), Kupffer cells (creatine kinase-BB) and Ito cells (creatine kinase-MM). Creatine kinase-BB was not found in hepatocytes, but mitochondrial creatine kinase was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Creatine kinase-BB: a marker of liver sinusoidal damage in ischemia-reperfusion. 827 65

Increased morbidity and mortality following transplantation surgery due to the primary nonfunction and dysfunction of the liver poses a great challenge and has increased the crescendo of research work in this field. In this study, we have tried to address the issue concerning the changes in Ca2+ homeostasis and hepatic microcirculation in 90 min of ischemia followed by reperfusion of the liver after FK506 pretreatment. Twenty dogs divided into two groups; group I (0.15 mg/kg/day FK506 for 3 days, im) and group II (control) were used for the measurement of mitochondrial (mit) and total cellular Ca2+ by atomic absorption spectrophotometer and hepatic microcirculation with laser Doppler flowmeter. Serum AST leakage was significantly (P < 0.05) suppressed in group I at 6 hr after reperfusion. The percentage gain in mit Ca2+ in group I was significantly (P < 0.05) inhibited compared to that in group II at 15 min after reperfusion and also when compared with the preischemic value it was significantly (P < 0.05) elevated at 30 min after reperfusion in group II only. FK pretreatment significantly (P < 0.05) inhibited the overload in total cellular Ca2+ at 15 and 30 min after reperfusion. Moreover, hepatic microcirculation was significantly (P < 0.001) better in group I between 2 and 6 hr after reperfusion. In conclusion, the ameliorating property of FK in ischemia-reperfusion may be explained by prevention of the cellular Ca2+ overload during the perireperfusion period.
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PMID:FK506 maintains cellular calcium homeostasis in ischemia-reperfusion injury of the canine liver. 859 5

Superoxide anion radical (O2-) is one factor related to ischemia/reperfusion injury to the liver. The sites of O2- production and injury have yet to be determined. Superoxide dismutase (SOD), a specific scavenger for O2-, has an inhibitory effect on injury caused by O2-. SOD is of low molecular weight; hence, it has a short half-life in the circulating blood. Mannosylated SOD is taken up in sinusoidal endothelial cells of the liver by receptor-mediated endocytosis. In rats with an occluded inflow against 70% of the liver for 30 min followed by reperfusion there were elevations of serum aspartate aminotransferase and alanine aminotransferase, and lipid peroxide concentrations in liver tissue were significantly inhibited by intravenous administration of mannosylated SOD compared to treatment with normal saline. Electron microscopic examination showed that mannosylated SOD protected against damage to the sinusoidal endothelial cells caused by ischemia/reperfusion and that conventional SOD had no such protective effect. Thus, O2- produced by ischemia/reperfusion apparently damages sinusoidal endothelial cells, and damage to hepatic parenchymal cells is secondary. Mannosylated SOD deserves further study for possible use in surgical resection of the liver and for liver transplantations.
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PMID:Mannosylated superoxide dismutase inhibits hepatic reperfusion injury in rats. 859 29

A review of 550 consecutively transplanted liver grafts stored in University of Wisconsin solution (UW) was performed during a 4-year period to ascertain whether graft function was impaired by flushing the aorta with Eurocollins (EC) rather than UW during the harvesting. The outcome of 255 liver grafts flushed with UW in both the aorta and portal vein (group UW/UW) was compared with 295 liver grafts flushed with EC through the aorta and UW through the portal vein (group ECUW). Liver grafts in both groups were flushed with 1 L of UW during the back table procedure and subsequently stored in UW at 4 degrees C before transport. Donor and recipient characteristics, cold and warm ischemia times, and methods of transplantation were similar in both groups, except that the recipient prothrombin time (PT) before liver transplantation (LT) was lower in the UW/UW group. There was no significant difference between the groups with peak transaminases aspartate aminotransferase (AST) and alanine aminotransferase, maximum value of serum bilirubin within 10 days following LT, incidence of primary nonfunction, need for retransplantation, and patient and graft survival at 1 month. Results were improved, however, in the EC/UW group in regard to PT after LT, operative bleeding and proportion of grafts with histologic lesions at the reperfusion biopsy (P<0.001). These better results in the EC/UW group were confirmed when grafts transplanted in urgent situations were excluded from analysis and by multivariate analysis assessing the effects of pretransplant PT and AST values of the recipients combined with the method of liver cooling with each of the aforementioned criteria. In conclusion, the method of using EC for the aortic flush during liver procurement reduces the amount of UW solution by 50% with improved graft function. This method seems justified in that it is less expensive while affording improved graft function.
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PMID:Beneficial effects of Eurocollins as aortic flush for the procurement of human livers. 860 71

The objective of this review is to provide an overview of the use of biochemical markers for the detection of Central Nervous System (CNS) complications after cardiac surgery and extracorporeal circulation (ECC). A computerized literature search in MEDLINE from 1966 onward was the basis for the references. The literature covering the following biochemical markers is reviewed: adenylkinase, creatine phosphokinase isoenzyme BB (CK-BB), lactate, neuron-specific enolase (NSE), S-100 protein, myelin basic protein, lactate dehydrogenase, aspartate aminotransferase, glutathione, vasointestinal neuropeptide, and 7B2-specific neuropeptide. For clinical purposes, it is necessary to have a biochemical marker that can be measured in blood. Lactate, although a primary marker of anaerobic metabolism, and CK-BB values, calculated from the arterio-internal jugular venous difference, appear to correlate with periods of ischemia during ECC. S-100 protein levels have been shown to correlate with duration of ECC, and when combined with NSE values, could be used to identify patients with CNS dysfunction after cardiac surgery. The use of NSE may be limited by its presence in erythrocytes and platelets because the high levels that can result from hemolysis can render it less specific. Although recently introduced, S-100 protein may have the potential to be a valuable marker for CNS dysfunction after ECC.
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PMID:Markers of cerebral ischemia after cardiac surgery. 863 77

The purpose of the study reported here was to explore a new strategy for the aerobic preservation of transplants using stable concentrated fluorocarbon emulsions as an oxygen delivery system. Fluorocarbons (FCs) are synthetic molecules, chemically and biologically inert, with a high oxygen-dissolving capacity. As they do not mix with water, it is necessary to emulsify them for intra-vascular use. Perfluorooctyl bromide (or perflubron) can be emulsifled with egg-yolk phospholipid (EYP), a nontoxic emulsifiant. The recent adjunction of amphiphilic fluorocarbon-hydrocarbon diblock molecules allows the obtaining of stable emulsions. By contrast with hemoglobin, fluorocarbons release oxygen following Henry's linear law rather than Barcroft's sigmoid curve. Release of oxygen by the FCs is only slightly influenced by temperature, which is an advantage for the preservation of organs. We tested a new 90% w/v fluorocarbon stem emulsion (perflubron/EYL/F6H10) diluted to 36% w/v with a hydroelectrolytic solution containing albumin, on four multiple organ blocks (MOBs; heart-lungs, liver, pancreas, kidneys, small intestine) of rats (EMOBs). Five control MOBs were perfused with a 50% v/v mixture of rat-blood and Krebs solution (KBMOBs). The lungs were ventilated with a FiO2 = 100%. In all cases the survival of the MOBs was greater than 210 min, with stable hemodynamics and preserved hydroelectrolytic and acid-base balances. The levels of lactate, amylase, and CK of the EMOBs were inferior (P < 0.05) to those of the KBMOBs between the first and the second hour. The diuresis of the EMOBs was higher (P < 0.05) than that of the KBMOBs (5.65 +/- 1.76 vs 1.21 +/- 0.28 mg/min). The production of bile, and the AST and ALT levels, were not significantly different. The PaO2 of the EMOBs was higher (P < 0.01) than for the KBMOBs. In normothermy, the maintenance of an aerobic metabolism using the FC emulsion caused less damage to the organs. Aerobic preservation of organs using FC emulsions therefore appears to be an attractive alternative to the presently used cold ischemia.
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PMID:Aerobic preservation of organs using a new perflubron/lecithin emulsion stabilized by molecular dowels. 866 Dec 39

We investigated whether anticoagulation would diminish ischemia-reperfusion injury of the liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. Anticoagulant was injected intravenously 10 min before occlusion. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, reaching a peak at 6 hr, then decreasing gradually to control levels by 24 hr. CINC levels in rats pretreated with heparin (50 units/kg), AT-III (250 units/kg), or DEGR-Xa (10 mg/kg) peaked at 3 hr after reperfusion and declined to baseline within 12 hr; peak CINC values were significantly lower than in untreated control rats. Expression of CINC mRNA in liver tissue paralleled the CINC serum levels. Both myeloperoxidase activity and the number of neutrophils in the liver were decreased in the anticoagulant groups. In addition, significant correlations were observed between the maximum values of AST, ALT, and LDH versus the peak CINC levels following ischemia-reperfusion. These results indicate that the release of CINC after ischemia-reperfusion of the liver is mediated by activation of coagulation within the hepatic microcirculation.
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PMID:Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver. 868 28

Between March 1991 and August 1995, 36 livers from donors >/=70 years old were transplanted. In donors, we recorded the following risk factors: alanine aminotransferase > 120 and rising, dopamine dose > 15 microg/kg/min, hypotension (systolic blood pressure <80) >1 hr, stay in the intensive care unit >5 days and body mass index >/=27. In 35 recipients, we recorded pretransplant United Network for Organ Sharing (UNOS) status, cold/warm ischemia time, intraoperative blood loss, and occurrence of poor early graft function or primary nonfunction. Mean recipient age was 55 years (range, 25-75 years). Four recipients were UNOS status 1, 19 were UNOS 2, and 12 were UNOS 3. Two livers were used as second grafts for primary graft nonfunction. Mean donor age was 73 years (range, 70-84 years). Intracranial bleeding was the cause of death in the majority of donors. The 36 donors had 40 risk factors; 10 donors had >1 risk factor. Mean cold and warm ischemia times were 9:08 +/- 2:57 hr and 51 +/- 9 min. Mean total operative time was 7.5 hr. Posttransplant mean peak alanine aminotransferase and aspartate aminotransferase levels were 937.3 +/- 703.1 IU/L and 923.3 +/- 708.5 IU/L, respectively. Mean prothrombin time on postoperative day 2 was 14.9 +/- 1.6 sec. Average total bilirubin on postoperative day 5 was 4.9 mg/dl. Median length of stay in the intensive care unit was 4 days. One recipient had poor early graft function; two recipients had primary nonfunction. Mean follow-up was 503 days (range, 110-1714 days). Three-month actual graft and patient survival rates were 85% and 91%, respectively. One-year actuarial graft and patient survival rates were also 85% and 91%, respectively. We conclude that older livers can be used safely. Advanced donor age should not be a contraindication to liver procurement.
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PMID:Safe use of hepatic allografts from donors older than 70 years. 869 47


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