Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we evaluated the role of proteolytic enzymes belonging to the coagulation, fibrinolytic, and plasma contact systems in the early postoperative phase after orthotopic liver transplantation (OLT). Twenty-nine patients were studied at the time of OLT and during the first 2 postoperative weeks. Blood samples were collected daily after OLT and analyzed for kallikrein-like activity (KK), functional kallikrein inhibition (KKI), plasmin-like activity (PL), and alpha2-antiplasmin (AP). In addition, prekallikrein (PKK), prothrombin (PTH), antithrombin III (AT III), plasminogen (PLG), prothrombin/antithrombin III complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), and plasmin/alpha2-antiplasmin complexes (PAP) were measured. Nineteen patients experienced biopsy-verified acute rejections (AR) and ten patients had uneventful courses and served as controls. Plasma analyses showed that the contact, coagulation, and fibrinolytic systems were activated during OLT. Following OLT, continuous thrombin and plasmin generation was observed, and these effects were more pronounced in the group having an uneventful course than in patients with AR. Factors that could possibly affect plasma proteolytic activity, such as blood product usage during and after OLT and cold ischemia time of the liver graft, did not differ between the groups, nor did the routine liver function tests, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
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PMID:Plasma proteolytic activity in liver transplant rejection. 1036 91

The gene encoding aspartate aminotransferase from the psychrophilic bacterium Pseudoalteromonas haloplanktis TAC 125 was cloned, sequenced and overexpressed in Escherichia coli. The recombinant protein (PhAspAT) was characterized both at the structural and functional level in comparison with the E. coli enzyme (EcAspAT), which is the most closely related (52% sequence identity) bacterial counterpart. PhAspAT is rapidly inactivated at 50 degrees C (half-life = 6.8 min), whereas at this temperature EcAspAT is stable for at least 3 h. The optimal temperature for PhAspAT activity is approximately 64 degrees C, which is some 11 degrees C below that of EcAspAT. The protein thermal stability was investigated by following changes in both tryptophan fluorescence and amide ellipticity; this clearly suggested that a first structural transition occurs at approximately 50 degrees C for PhAspAT. These results agree with the expected thermolability of a psychrophilic enzyme, although the observed stability is much higher than generally found for enzymes isolated from cold-loving organisms. Furthermore, in contrast with the higher efficiency exhibited by several extracellular psychrophilic enzymes, both kcat and kcat/Km of PhAspAT are significantly lower than those of EcAspAT over the whole temperature range. This behaviour possibly suggests that the adaptation of this class of endocellular enzymes to a cold environment may have only made them less stable and not more efficient. The affinity of PhAspAT for both amino-acid and 2-oxo-acid substrates decreases with increasing temperature. However, binding of maleate and 2-methyl-L-aspartate, which both inhibit the initial steps of catalysis, does not change over the temperature range tested. Therefore, the observed temperature effect may occur at any of the steps of the catalytic mechanism after the formation of the external aldimine. A molecular model of PhAspAT was constructed on the basis of sequence homology with other AspATs. Interestingly, it shows no insertion or extension of loops, but some cavities and a decrease in side chain packing can be observed.
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PMID:Aspartate aminotransferase from the Antarctic bacterium Pseudoalteromonas haloplanktis TAC 125. Cloning, expression, properties, and molecular modelling. 1078 2

Previous morphological studies failed to show appreciable injury of biliary epithelial cells (BEC) after cold ischemia of rat liver, although recent evidence indicated that BEC integrity and function were impaired in this model. We tested the hypothesis that analysis of bile for enzymes, such as lactate dehydrogenase (LDH), alanine transaminase (ALT), and aspartate transaminase (AST), can be used for assessing cold ischemic injury of BEC. Furthermore, we examined whether biliary gamma-glutamyltransferase (GGT) reflects warm ischemic injury of BEC and whether normothermic reperfusion aggravates the negative effect of cold ischemia on BEC integrity and function. Rat livers were reperfused after different periods of cold or warm ischemia using a blood-free perfusion model. Compared with controls, perfusate LDH, ALT, and AST levels and parameters of hepatocyte function, including hepatocyte tight junction permeability, were not significantly altered by 18-h cold ischemia. On the other hand, 9-h cold ischemia markedly increased biliary LDH, ALT, and AST levels. However, only LDH release into the bile was strongly dependent on the time of cold storage. Biliary GGT, LDH, and glucose levels decreased during the reperfusion period following 18-h cold ischemia. The results suggest that biliary LDH can be used for assessing injury of BEC in cold-preserved livers and that normothermic reperfusion does not aggravate preservation-induced injury of BEC after cold ischemic storage.
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PMID:Bile analysis as a tool for assessing integrity of biliary epithelial cells after cold ischemia--reperfusion of rat livers. 1103 93

The underlying mechanisms of hyperkalemia occurring immediately after revascularization in orthotopic liver transplantation (OLT) are unknown. We investigated the possible pathophysiological mechanisms of hyperkalemia in relation to the donor and recipient. The study included 64 consecutive patients undergoing OLT. Recipients were divided into two groups: Group 1 consisted of 47 patients with serum K(+) concentration <5.5 mmol/L at 1-min postrevascularization, and Group 2 consisted of 17 patients with serum K(+) exceeding 5.5 mmol/L. Increased serum K(+) concentration, more progressive metabolic acidosis, and decreased mean arterial blood pressure and cardiac index during the anhepatic phase were recognized in Group 2. Multiple regression analysis showed that cardiac index, serum lactate, and serum K(+) concentration during the anhepatic phase were independent and significant factors that could predict serum K(+) concentration 1-min postrevascularization. Hyperkalemia at 1-min postrevascularization did not correlate with the extent of preservation injury of the graft liver (represented by the peak value of aspartate aminotransferase measured within the first 72 h after OLT) or the duration of cold ischemia. We conclude that hyperkalemia occurring immediately after revascularization in OLT is mainly caused by metabolic acidosis as a result of insufficient cardiac output during the anhepatic phase.
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PMID:Pathophysiological mechanisms of postrevascularization hyperkalemia in orthotopic liver transplantation. 1109 78

In situ split-liver transplantation is a new surgical technique where the bipartition of a single liver allows procurement of a right graft (segments I, IV, V-VIII) for an adult recipient (75% of the total liver volume), and a left graft (segments II and III) for a child recipient. The present study was designed to assess the effects of ischemia-reperfusion on right grafts obtained by in situ split-liver transplantation. To this aim, hepatic glutathione and conventional plasmatic markers of allograft function (alanine and aspartate aminotransferase, total bilirubin, prothrombin time, lactate dehydrogenase, gamma-glutamyltranspeptidase, and alkaline phosphatase) were evaluated in four adult recipients. At the time of reperfusion, a marked glutathione decrease was found in the segment VI in three cases, whereas the amount of glutathione in segment IV was related to the duration of cold ischemia in all cases. Upon reperfusion, a marked increase in plasmatic alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase was found. A recovery in prothrombin time was observed from the first day in three cases. An increasing trend in total bilirubin, gamma-glutamyltranspeptidase, and alkaline phosphatase was noted from the second day after transplant. This preliminary study suggests a possible relationship between the duration of cold ischemia, amount of glutathione in segment IV of the right graft, and the trend in plasmatic markers of allograft damage during in situ split-liver transplantation in adult recipients.
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PMID:Effects of ischemia-reperfusion on hepatic glutathione and plasmatic markers of graft function during in situ split-liver transplantation in adult recipients. 1111 71

The development of biliary strictures (BSs) after liver transplantation (LT) continues to affect 10% to 30% of patients, causing substantial morbidity. The cause of BSs is multifactorial, including technical, immune, and, in particular, ischemic factors. The importance of adequate flushing of the peribiliary arterial tree has been stressed. We hypothesized that high-viscosity (HV) preservation solutions in the donor do not completely flush the small donor peribiliary plexus, leading to inadequate preservation of the bile ducts and posttransplant BSs. To test this hypothesis, we retrospectively compared the incidence of BSs in 2 groups of adults undergoing LT using different types of aortic preservation solution in the donor: group 1 (n = 24), low-viscosity (LV) Marshall solution; and group 2 (n = 27), HV University of Wisconsin (UW) solution. All donors in both groups received additional portal flushes with UW. All LTs were performed between November 1995 and August 1998 at 2 centers by the same surgeon, eliminating a technical bias. Terminal duct-to-duct anastomosis was performed in all recipients except 1 patient in group 1, who underwent a bile duct-to-jejunum anastomosis. BSs were first suspected on clinical and biochemical grounds and then confirmed by endoscopic retrograde cholangiopancreatography. Identical medical protocols were used in all patients. One-year patient survival rates in groups 1 and 2 were 92% and 100%, respectively (P =.9). One-year graft survival was identical to patient survival. The incidence of BSs in group 1 was 4.1% (1 of 24 patients), compared to 29.7% in group 2 (8 of 27 patients; P =.02). The BS in group 1 occurred 4 months post-LT and was anastomotic. BSs in group 2 occurred between 1 and 12 months post-LT and were anastomotic, extrahepatic, intrahepatic, or combined intrahepatic and extrahepatic. There were no significant differences in the following factors between groups 1 and 2: donor age, local versus imported liver, split-liver or full-liver transplantation, incidence of multiple vessels in the donor liver, indications for LT, recipient age, T-tube versus no T-tube, post-LT peak aspartate aminotransferase level, and treatment for rejection. There was no hepatic artery thrombosis or primary nonfunction in either group. Interestingly, cold ischemia time (CIT) was longer in group 1, which had the least incidence of BSs (692 +/- 190 v 535 +/- 129 minutes in group 2; P =.001). Follow-up was longer in group 1 (28.9 +/- 8.3 v 15.6 +/- 8 months in group 2; P =.0001). Preservation costs per procurement were 1.9 times greater in the UW group than in the Marshall group. Donor aortic flushing with an HV preservation solution leads to more frequent BSs compared with an LV preservation solution. The impact of preservation solution outweighs the previously described deleterious impact of prolonged CIT. Mixed preservation solution (Marshall solution in the aorta, UW solution in the portal vein) might protect against BS formation while providing optimal liver graft preservation, function, and survival despite a mean CIT longer than 10 hours.
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PMID:Type of donor aortic preservation solution and not cold ischemia time is a major determinant of biliary strictures after liver transplantation. 1144 84

This study examines a method to rapidly rewarm the core using total liquid ventilation with warmed, oxygenated perfluorocarbon. Yucatan miniswine were splenectomized and surgically implanted with telemetry devices to transmit electrocardiographic response, arterial pressure, and core temperature. Hypothermia (core temperature = 25.9 +/- 1.3 degrees C) was induced by placing cold-water circulating blankets over the animals. Control animals (N = 7) were rewarmed using warm (37.8 degrees C), humidified oxygen. Experimental animals (N = 6) were rewarmed with oxygenated perfluorocarbon liquid (37.3 degrees C). The time to rewarm was significantly shorter in experimental animals (1.98 +/- 0.5 vs. 8.61 +/- 1.6 hours, p < 0.0001), with almost no afterdrop in the experimental group. Lactate dehydrogenase and aspartate aminotransferase were significantly increased in the control animals compared with the experimental animals. All animals that survived being chilled to 25 degrees C survived rewarming. This method may provide a means of more rapidly rewarming profoundly hypothermic victims while reducing the risks associated with current methods.
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PMID:Comparison of oxygenated perfluorocarbon and humidified oxygen for rewarming hypothermic miniswine. 1160 34

In liver preservation, the substitution of the anion Cl(-) by lactobionic acid (LB) prevents reperfusion edema and extends the preservation time for human livers. We studied the effect of compounds that are structurally related to lactobionic acid: anionic polycarbohydrates (sulfated anionic polysaccharide, SAP, and pentosan polysulfate, PPS) on liver function and leukocyte-endothelial cell interaction in isolated perfusion and liver transplant models. Rat livers, cold-stored (24 h) in a Cl(-) -containing control solution, became edematous during 1 h of reperfusion. Substitution of Cl(-) by either LB, SAP, or PPS decreased reperfusion edema in a Cl(-) concentration-dependent fashion. Reperfusion edema was abolished completely after preservation in 100 mM SAP solution or PPS solution. Also hepatic lactic dehydrogenase (LDH) and aspartate aminotransferase (ASAT) release was lowest after preservation in those solutions. After preservation in LB or anionic polycarbohydrate solutions, portal venous resistance was significantly higher than after preservation in Cl(-)-containing control solution. Capillary blood flow was 391 +/- 83 pl/s and 398 +/- 174 pl/s after preservation in SAP solution (SAPs) and PPSs, and 803 +/- 117 pl/s and 641 +/- 219 pl/s after preservation in LB or Cl(-)-containing control solution. The number of leukocytes sticking to the vascular wall was lower ( P < 0.05) after preservation in SAPs or PPSs (109 +/- 31 cells/mm(2) and 108 +/- 60 cells/mm(2), respectively), when compared with preservation in Cl(-)-containing control or LB solutions (429 +/- 63 cells/mm(2) and 277 +/- 59 cells/mm(2)). In rat liver preservation, anionic polysaccharides are antiedematous compounds, with a higher potency than LB and additional antiadhesive properties.
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PMID:Anionic polysaccharides. A class of substances with hepatoprotective and antiadhesive properties in rat liver preservation. 1187 8

Emotional stress affects cellular integrity in many tissues including the heart. Much less is known about the effects of social stress. We studied the effect of emotional (immobilization with or without cold exposure) or social (intermale confrontation) stress in mice. Tissue injury was measured by means of the release of enzyme activities to blood plasma: lactate dehydrogenase (LDH), creatine kinase (CK), aspartate transaminase (AST), and alanine transaminase (ALT). Tape-immobilization increased all these activities in the plasma. AST-ALT ratio was also increased in these animals. Electrophoretic analysis of CK isoenzymes showed the appearance of CK-MB. These results indicate that the heart was injured in immobilized mice. Analysis of LDH isoenzymes and measurement of alpha-hydroxybutyrate dehydrogenase (HBDH) activity suggests that other tissues, in addition to the heart, contribute to the increase in plasma LDH activity. Restraint in small cylinders increased plasma LDH, CK, AST, and ALT activities, but to lower levels than in tape immobilization. Because the decrease in liver glycogen and the increase in plasma epidermal growth factor (EGF) were also smaller in restraint than in the tape-immobilization model of emotional stress, we conclude that the former is a less intense stressor than the latter. Cold exposure during the restraint period altered the early responses to stress (it enhanced liver glycogen decrease, but abolished the increase in plasma EGF concentration). Cold exposure during restraint enhanced heart injury, as revealed by the greater increase in CK and AST activities. Intermale confrontation progressively decreased liver glycogen content. Plasma EGF concentration increased (to near 100 nM from a resting value of 0.1 nM) until 60 minutes, and decreased thereafter. Confrontation also affected cellular integrity in some tissues, as indicated by the rise in plasma LDH activity. However, in this type of stress, the heart appeared to be specifically protected because there was no increase in plasma CK activity, and both AST and ALT increased, but the AST-ALT ratio remained constant. Habituation to restraint (1 h/d, 4 days) made mice resistant to restraint-induced tissue injury as indicated by the lack of an increase in plasma LDH, CK, AST, or ALT activities. Similar general protection against homotypic stress-induced injury was observed in mice habituated to intermale confrontation.
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PMID:Acute stress-induced tissue injury in mice: differences between emotional and social stress. 1189 86

The effect of donor nutritional status on hepatic function recovery after cold ischemia is still debated. We demonstrated previously that a 48-h fast diminished the survival rate of liver-transplanted rats and that the deleterious effect of fasting was prevented by infusion of alanine to the recipient at reperfusion. Whether the duration of fasting influenced the protective effect of alanine and whether this effect was metabolic were not known, and the elucidation of these questions is the aim of this study. The effect on hepatic function recovery of fasting periods of 24 h, 48 h and 72 h prior to cold ischemia were studied in a model of isolated, perfused rat liver. After a cold-ischemic time of 24 h in University of Wisconsin (UW) solution at 4 degrees C, livers were reperfused for 3 h. The combined effect of alanine (8 mM) infusion at liver reperfusion was evaluated for each prior fasting period. The addition of pyruvate (8 mM), a metabolic intermediary of alanine, was only tested in the 72-h fasting group. The evaluation criteria were: liver weight after reperfusion, release of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in the perfusate, bile production, vascular resistance and liver histology after reperfusion. The enzyme release at reperfusion was significantly higher when livers were harvested from rats submitted to a 48-h fast (ALT) or a 72-h fast (ALT, AST, LDH), as compared to those from fed rats. Vascular resistance was increased in 72-h fasted livers. An addition of alanine (8 mM) at reperfusion lowered the release of AST, ALT and LDH. This effect was more obvious when the fasting duration was increased. By contrast, the addition of pyruvate at reperfusion did not improve the recovery of livers submitted to a 72-h fasting period before preservation. A long fasting period is deleterious as compared to feeding; however, this effect can be compensated by infusion of alanine at reperfusion. The mechanism involved is not metabolic. In a clinical setting, the infusion of alanine to the recipient at reperfusion may be a convenient way to compensate for donor undernutrition, especially after a long stay in an intensive care unit.
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PMID:Combined effects of fasting and alanine on liver function recovery after cold ischemia. 1193 65


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