Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Thrombomodulin is an endothelial cell membrane protein that is released into the blood in soluble forms (soluble thrombomodulin [sTM]) in response to endothelial cell damage. We evaluated intraoperative sTM as a marker of reperfusion injury in 29 liver transplant recipients using an ELISA. Preoperative sTM levels were significantly elevated, as compared with healthy control subjects (75 +/- 61 ng/ml vs. 17 +/- 10 ng/ml; P < 0.001) and remain unchanged at the end of the anhepatic phase (58 +/- 40 ng/ml). There is an increase to 194 +/- 182 ng/ml 3 min after reperfusion (P < 0.001). Post-reperfusion sTM levels correlate significantly with the early liver enzyme release (aspartate transaminase) (P < 0.001). Patients with pronounced reperfusion injury (postreperfusion arterial sTM > 138 ng/ml, n = 16) present significantly higher maximum aspartate transaminase levels within the first 24 postoperative hr, as compared with patients with less reperfusion injury (arterial sTM < 138 ng/ml, n = 12) (P = 0.001). Released sTM is derived from the graft, since patients with pronounced reperfusion injury present significantly higher sTM levels in the hepatic vein 3 min after reperfusion compared with the portal vein (P < 0.001) and artery (P = 0.025), respectively. In patients with higher reperfusion injury, we found significantly more adherent intrasinusoidal granulocytes in the liver biopsy taken 1 hr after reperfusion (P = 0.006), indicating an interrelation of endothelial damage and the important phenomenon of "leukocyte sticking" in reperfusion injury. Thus the postreperfusion increase of sTM as a marker of reperfusion injury correlates with the early liver enzyme release and the accumulation of intrasinusoidal granulocytes.
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PMID:Soluble thrombomodulin--a marker of reperfusion injury after orthotopic liver transplantation. 767 94

We measured plasma endothelin-1 (ET-1) concentrations in 20 healthy controls and 63 patients with liver diseases including 9 cases of acute hepatitis (AH), 14 cases of chronic hepatitis (CH), 24 cases of liver cirrhosis (LC), 11 cases of hepatocellular carcinoma with LC (HCC), 3 of primary biliary cirrhosis and 2 of idiopathic portal hypertension. ET-1 levels in AH (5.07 +/- 2.54 pg/ml, mean +/- SD), LC (3.71 +/- 1.17) and HCC (3.08 +/- 0.93) were significantly higher than those in healthy controls (2.18 +/- 0.37). ET-1 levels in AH, LC and HCC were also significantly higher than those in CH (2.05 +/- 0.61). ET-1 levels showed negative correlations with serum albumin levels and Ch-Ease activities, and positive correlations with serum bilirubin levels, AST and ALT activities. However, there was no correlation between plasma ET-1 concentrations and concentrations of serum thrombomodulin which is known to be a marker of injured vascular endothelial cells. In cirrhotic patients, ET-1 levels were significantly influenced by the presence of ascites. The results of the present study suggest that plasma ET-1 concentrations may be a useful clinical indicator for use in the follow-up of patients with chronic liver diseases, e.g., progression from CH to LC, and change in grade of portal hypertension and decompensation in LC.
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PMID:Plasma endothelin-1 concentrations are elevated in acute hepatitis and liver cirrhosis but not in chronic hepatitis. 822 17

Endothelial damage within the sinusoids of the liver probably plays a key role in primary liver dysfunction following transplantation. The aim of this work was to study the serum levels of two potential markers of endothelial damage, creatine kinase-BB and soluble thrombomodulin, during human graft revascularization. Thirteen human liver grafts were preserved in UW solution (mean time: 13.8 h). Creatine kinase-BB and transaminase activities and soluble thrombomodulin levels were measured: 1) in effluent and 2) in serum samples sequentially collected before revascularization, then during the first 120 min of revascularization and first post-operative week. No correlation was observed between serum values (peak) and effluent values. In serum, pre-operative creatine kinase-BB activities were correlated with soluble thrombomodulin levels (p = 0.01). Both increased significantly during the first minutes of the revascularization, then decreased markedly. In contrast, AST activity was maximal at day 1. This detectable and early release of creatine kinase-BB and soluble thrombomodulin in blood is in keeping with the early occurence of endothelial damage. Together with previous data, these findings suggest that serum determination of these two markers may be a useful tool in the assessment of endothelial injury in liver transplantation.
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PMID:Serum levels of endothelial injury markers creatine kinase-BB and soluble thrombomodulin during human liver transplantation. 887 93

In 50 human livers harvested for transplantation, injury was assessed by determination of liver enzymes (lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase, and creatine kinase) and of thrombomodulin in the effluent perfusate after cold ischemia. The results were compared with the morphology and the clinical course after transplantation. Whereas the release of the markers of endothelial cell injury correlated neither with the history of the graft nor with the postoperative course, the release of hepatocellular enzymes into the perfusate did indicate the severity of liver injury, even when biopsy showed normal liver tissue. Seven of 12 livers with high activities of hepatocellular enzymes in the effluent (activity of more than twice the median) showed delayed onset of function or primary nonfunction. In the other 38 livers with enzyme activities below this borderline, no delayed functioning or primary nonfunction was observed. Thus, determination of liver enzyme activities in the effluent makes it possible to identify those livers in which initial nonfunction is very unlikely, a potential that is especially valuable in livers shown by anamnesis or morphology to be of borderline quality.
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PMID:Determination of hepatocellular enzymes in effluent of human liver grafts for preoperative evaluation of transplant quality. 893 67

Thrombomodulin is a surface protein on vascular endothelial cells that serves as a binding site for thrombin and plays an important role as an anticoagulant factor. We correlated plasma thrombomodulin levels with early graft function after liver transplant in 58 recipients. Blood samples were collected at the following time points: before surgery, just before reperfusion, 30, 60, 120 min after reperfusion, and post-operative day 1. The first and last 20 cc of caval effluent were also collected. Plasma thrombomodulin levels were measured by a sandwich enzyme-binding assay in the blood samples; tissue expression was determined by immunohistochemistry. Poor early graft function was defined as peak aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2500 U/l during the first 3 post-operative days and prothrombin time >16 s on post-operative day 2. Thrombomodulin levels in the first 20 cc of caval effluent ranged from 1.33 to 91 FU/ml and showed a significant positive correlation with ischemic time, intra-operative blood transfusion requirement, and early graft function. In grafts with high effluent thrombomodulin (>20 FU/ml, n=12), the incidence of poor early graft function and primary nonfunction was 66.7% and 25.0%, respectively; in grafts with low effluent thrombomodulin (<20 FU/ml, n=46), graft function was not impaired. By immunohistochemistry, thrombomodulin was detected in large vessels of every donor liver. Sinusoidal cells, however, showed positive staining only in livers with poor early graft function. Effluent thrombomodulin levels reflect the extent of preservation injury and might be a useful marker for predicting graft function after liver transplantation.
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PMID:Effluent levels of thrombomodulin predict early graft function in clinical liver transplantation. 938 13

Cold preservation/reperfusion leads to sinusoidal endothelial cell (SEC) activation and damage in nearly every liver transplantation; the extent of these changes influences early graft function. Upon reperfusion, activated SEC show increased expression of adhesion molecules, including von Willebrand factor (vWF) which is released into the circulation. This study was designed to evaluate the levels of vWF measured in the caval effluent and correlate these findings with known markers of SEC damage and early graft function. Data were obtained from 35 patients undergoing orthotopic liver transplantation (LTx). Two samples were taken from each patient for measurement of vWF: a) from the portal vein immediately prior to reperfusion; and b) from the first 50 ml of the caval effluent. Commercial assays were used to measure vWF, as well as hyaluronic acid (HA), thrombomodulin (TM), IL-1 beta, IL-6, IL-8 and TNF-alpha. Patients were divided into two groups based on early graft function. Poor early graft function (PEGF) was defined as a peak aspartate transaminase (AST) or alanine transaminase (ALT) level > 2500 U/L during the first three postoperative days (POD) and a prothrombin time (PT) > 16 s on POD 2 (n = 8). The remaining 27 patients had good early graft function (GEGF). In patients with GEGF, vWF levels dropped significantly between the two time points. This change was not observed in those with PEGF. A positive linear correlation was observed in the PEGF group between vWF and HA and IL-6. The different pattern of change in vWF between the two groups, as well as the positive correlation between HA, IL-6 and vWF in PEGF, suggest that vWF may be a useful marker of early graft function.
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PMID:Correlation between von Willebrand factor levels and early graft function in clinical liver transplantation. 1008 31

This study was performed to determine whether human urinary soluble thrombomodulin plays a role in liver ischemia-reperfusion injury. Liver ischemia was induced in two groups of dogs. Group 1 was exposed to 60 min ischemia, and group 2 was exposed to 60 min ischemia after preischemic administration of human urinary soluble thrombomodulin. In group 1, the thrombin-antithrombin complex and hyaluronic acid were significantly elevated after ischemia, compared with the preischemic values. While liver issue blood flow and the plasmin-alpha(2)-plasmin inhibitor complex significantly decreased, AST, ALT and m-AST dramatically increased after reperfusion. In group 2, the increase in the thrombin-antithrombin complex and hyaluronic acid was significantly suppressed, and AST, ALT and liver tissue blood flow significantly improved, compared with group 1. Histologically, in group 2, the hepatic tissue structure, including endothelial cells, was relatively intact. These findings suggest that administration of thrombomodulin inhibits endothelial cell injury and coagulopathy and offers protection from liver ischemia-reperfusion injury.
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PMID:Protective effect of human urinary thrombomodulin on ischemia- reperfusion injury in the canine liver. 1081 Feb 13

Protein C is the zymogen of an anticoagulant serine protease and is converted to its active form (activated protein C: APC) by thrombin in the presence of thrombomodulin. APC plays an important role in regulating coagulation and fibrinolysis by inactivating not only blood coagulation factors Va and VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). The aim of the present study was to examine the effect of a human APC product (designated as CTC-111), compared with that of heparin, on the disseminated intravascular coagulation (DIC) induced by lipopolysaccharide (LPS) in rats. LPS (1 mg/kg/h) infusion was performed through a femoral vein for 4 h. One-fifth amount of the total dosage of CTC-111 or heparin was injected into the other femoral vein, followed by a 4-h infusion of the remainder. Both CTC-111 (10,000-100,000 U/kg) and heparin (400-800 IU/kg) inhibited the decrease in platelet count and fibrinogen level equally. The prolonged activated partial thromboplastin time and prothrombin time observed in DIC rats were further elongated in both CTC-111- and heparin-treated rats. But, this prolongation was less in CTC-111-treated rats than in the heparin-treated ones. Heparin inhibited the increase in fibrin and fibrinogen degradation products more prominently than CTC-111. On the other hand, CTC-111 strongly inhibited the increase in PAI-1 activity but heparin did not. These results suggest that CTC-111 may enhance fibrinolysis through its direct inhibitory effect on PAI-1. The parameters for liver or renal damage, i.e., plasma glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), creatinine (Cre) and blood urea nitrogen (BUN), were significantly increased by LPS infusion. Both CTC-111 (100,000 U/kg) and heparin (800 IU/kg) decreased the increase in GOT and GPT levels significantly, whereas neither affected the increase in Cre or BUN. From these results, the activation of the blood coagulation system might partially contribute to the progression of liver damage caused by LPS, and might be less involved in the progression of renal damage in this model. In conclusion, CTC-111 showed both anticoagulant and profibrinolytic activity in the LPS-induced DIC model without excessive prolongation of coagulation time. From these results, CTC-111 is expected to be a useful remedy for DIC without the risk of bleeding.
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PMID:Effect of activated human protein C on disseminated intravascular coagulation induced by lipopolysaccharide in rats. 1105 Jun 97

Exhaled carbon monoxide concentration (ExCO-C) has been reported to increase in oxidative tissue injuries such as systemic inflammation, and is thought to reflect increased heme breakdown in the affected organ. As a transplanted liver undergoes ischemia-reperfusion, we hypothesized that ExCO-C might also increase following liver transplantation and might serve as a measure of the severity of the graft tissue injury. We prospectively studied 67 living donor liver transplantation (LDLT) patients in a consecutive fashion. During anesthesia, ExCO-C was determined at 6 time points, ranging from anesthesia induction, to admission to the intensive care unit. We also measured two markers of endothelial cellular injury, i.e., serum soluble thrombomodulin (sTM) and intercellular adhesion molecule (ICAM)-1. At 5 min after reperfusion of the grafted liver, ExCO-C markedly increased from 5.69+/-2.34 ppm at baseline, to 9.79+/-4.72 ppm (p<0.0001). There was an excellent correlation among an increase in CO concentration, arterial carboxyhemoglobin levels at the time of reperfusion (r(2)=0.19, p=0.0003), and postoperative total bilirubin levels (day 1, 2, and 3; r(2)=0.102, 0.109 and 0.100; p=0.008, 0.007 and 0.010, respectively). Serum sTM and ICAM-1 levels were also significantly increased after reperfusion (sTM: 3.3+/-0.8 to 5.1+/-1.7 FU/ml, p=0.0001; ICAM-1: 271.9+/-86.3 to 515.0+/-157.8 FU/ml, p=0.0001). ExCO-C had a positive relationship with sTM (r(2)=0.16, p=0.035) and ICAM-1 (r(2)=0.12, p=0.08). There was however, no correlation of ExCO-C with serum AST/ALT levels or clinical outcomes. This study demonstrated that ExCO-C significantly increased after reperfusion during LDLT. The increased ExCO-C may likely reflect increased heme breakdown and endothelial cell injury in the grafted liver.
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PMID:Increased exhaled carbon monoxide concentration during living donor liver transplantation. 1809 19

Apelin, a newly discovered adipocytokine produced by white adipose tissue, is also expressed in kidney and heart. It has been reported that apelin is related to echocardiographic features in hemodialyzed patients. Cardiovascular disease is a major contributor to the mortality and morbidity among patients with chronic renal failure as well as kidney allograft recipients. The aim of this study was to assess the association between apelin and coronary artery disease (CAD) among kidney allograft recipients. We investigated plasma apelin levels in 100 clinically stable, kidney allograft recipients with versus without CAD. We also assessed markers of endothelial cell injury-von Villebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), and CD146; markers of inflammation-high-sensitivity-reactive protein (hsCRP); other hemostatic parameters-tissue plasminogen activator (tPA) and its inhibitor (PAI-1); as well as other adipocytokines-adiponectin and resistin-using commercially available kits. Markers of endothelial dysfunction and inflammation were significantly elevated among patients with CAD levels, as well as with CAD or diabetes, compared with those without CAD. Apelin was significantly lower among patients with CAD, but higher in diabetic patients. Apelin content was similar in hypertensive versus normotensive kidney allograft recipients. We observed significant correlations between apelin and ICAM, resistin, adiponectin, calcium, phosphate, alanine and aspartate aminotransferase levels, with CAD or diabetes. Upon multiple regression analysis as well as CAD, adiponectin, and ICAM were predictors of apelin. Apelin was significantly reduced in kidney allograft recipients with CAD; its level was predicted by the presence of CAD, endothelial damage, or inflammation. Apelin and other adipocytokines may be associated with inflammation and its clinical consequences.
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PMID:Apelin, a novel adipocytokine, in relation to endothelial function and inflammation in kidney allograft recipients. 1910 Apr 14


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