Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbon tetrachloride (CCl4) produces hepatic necrosis and Galactosamine (GALN) causes acute hepatocellular injury in dogs. 8 Beagle dogs were treated orally twice with 0.4 ml/kg CCl4 and 12 Beagle dogs with 200 mg/kg GALN i.v. After intoxication, groups of dogs were given antithrombin III (AT III) (Kybernin) from human plasma (25-100 U/kg i.v., days 1-3). Serum enzymes (GOT, GPT) were elevated, alkaline phosphatase values and serum bilirubin were increased in all animals. Dogs developed severe coagulation disorders reflecting intravascular coagulation and depressed levels of factors produced by the liver, such as AT III or fibrinogen. First toxic symptoms were seen after 48 h. Untreated dogs died between 48 and 72 h after GALN. AT III reduced the toxic effects on the coagulation system dose-dependently (minimal effective dose 3 X 50 U/kg). Decrease of fibrinogen and of platelet count were less pronounced, coagulation tests (Quick, TEG) less altered than in untreated dogs. Death rate was reduced. In CCl4 intoxicated animals also serum enzyme levels normalized after AT III. In GALN treated animals serum glucose levels were decreased in control dogs. These experimental results confirmed clinical effects of AT III in acute hepatic intoxications of humans.
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PMID:[Effect of antithrombin III on experimental hepatotoxin poisoning in dogs]. 653 7

We evaluated the usefulness of preoperative portal vein embolization (PVE) in rats for increasing the safety of liver resection. During PVE, portal vein branches that perfused the central and left lobes of the liver were embolized. Liver weight, the elimination of indocyanine green, and the number of Kupffer cells were examined 7 days after PVE and in intact rats. Then we examined rats that had undergone PVE (PVE group), rats in which the embolized part of the liver was resected 7 days after PVE (PVE-Hx group), rats without PVE in which the same lobes of the liver were resected (Hx group), and rats that had undergone a sham operation (sham-operation group) for liver weight, the mitotic index of the hepatocytes, serum alanine aminotransferase activity, total bilirubin, and antithrombin III activity. Some rats in the four groups received an intravenous injection of 0.5 or 2.5 mg/kg endotoxin 48 hr after the operation (the second operation, if done), and the 24-hr survival rate was calculated. Some rats given 0.5 mg/kg endotoxin were killed 6 hr after the injection, and the extent of liver injury was examined biochemically and histologically. Seven days after PVE, the nonembolized part of the liver was about twice the weight of the corresponding lobes in the intact rats, the density of Kupffer cells was doubled, and the hepatic function per unit weight was about the same as that in these controls. Hepatic dysfunction and the endotoxin-induced liver injury were significantly slighter in the PVE and PVE-Hx groups than in the Hx group. Preoperative PVE could make hepatectomy safer.
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PMID:Increased safety by two-stage hepatectomy with preoperative portal vein embolization in rats. 799 47

The polymerase chain reaction (PCR) was used to detect hepatitis C (HCV) viral sequences (HCV-RNA) in clotting factor concentrates that had been stored at 4 degrees C for 1 to 16 years. A total of 43 concentrates were tested, comprising 31 batches of factor VIII, 6 of factor IX, 2 of antithrombin III, 3 of FEIBA, and 1 of factor VII. HCV-RNA was detected in 13 of the 43 batches (30.2%). Concentrates that had not undergone viral inactivation during manufacture were significantly more likely to contain detectable HCV-RNA than concentrates that had been virally inactivated (56.3% v 14.5%, P = .006). HCV sequences were more commonly detected in concentrates made from paid donor plasma than in those made from volunteer donor plasma (44% v 11%, P = .041), and more commonly in virally inactivated concentrates with pre-1989 than with post-1989 expiration dates (50% v 0%, P = .004). Of the four batches of heat-treated products that were HCV-RNA positive, at least three transmitted non-A, non-B hepatitis (NANBH). An association between the presence of HCV-RNA in concentrates and the development of NANBH was demonstrated in nine previously untreated patients on prospective follow-up. HCV-RNA was detected in the concentrates administered to the six patients whose alanine aminotransferase (ALT) abnormalities met the diagnostic criteria for NANBH and who later seroconverted for HCV, but it was not detected in the concentrates administered to the three patients whose ALT abnormalities failed to satisfy the diagnostic criteria and who did not seroconvert. We suggest that the use of this PCR technique to monitor clotting factor concentrates derived from pooled blood may potentially contribute to product safety.
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PMID:Hepatitis C viral RNA in clotting factor concentrates and the development of hepatitis in recipients. 838 99

In Italy, although a national decree (DPCM of 10/2/84) established that quality control programs involving clinical laboratories should be carried out on a regional basis, external quality assessment schemes (EQAS) are actually run only in some regions. Among these is Lombardy, where an EQAS in clinical chemistry concerning 20 analytes was set up in 1986, and where at present EQA programs (for clinical chemistry, haematology and coagulation) compulsory for both private and public laboratories, are under way. This was made possible by both regional laws and the constant care shown by the regional Committee on pathology department system (Comitato Regionale per l'Ordinamento dei Servizi di Patologia, CROSP). The participation in the schemes (including control material supply) is free of charge. The identity of participants is known only to officers in charge of quality control and analytical results are therefore managed anonymously. Consequently EQAS carried out in Lombardy are not exacting or punitive. In the EQAS for clinical chemistry the following analytes are considered: glucose, urea, proteins, albumin, chloride, sodium, potassium, total calcium, inorganic phosphate, iron, urate, creatinine, cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine phosphokinase, gamma glutamyl transferase and alkaline phosphatase. In the EQAS for haematology and coagulation the tests are: a) leukocytes, erythrocytes, haemoglobin, haematocrit, mean cell (erythrocyte) volume, platelets; b) prothrombin time, activated partial thromboplastin time, fibrinogen and antithrombin III. The general organization of the schemes, the statistical procedures adopted for the analysis of data, and some of the results obtained in the three EQA programs are reported in detail in the present article.
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PMID:External quality assessment programs in Lombardy, Italy. 854 65

In a multicenter, double-blind clinical trial in 1,968 inpatients 1 daily subcutaneous administration of LMW heparin plus 2 placebo injections or 3 x 5,000 IU unfractionated (UF) heparin was given for 10 (8-11) days. The primary end point was the incidence of proximal deep-vein thrombosis or pulmonary embolism. Patients were assessed during the study period for development of proximal deep-vein thrombosis by compression sonography at days 1 and 10 and for pulmonary embolism by scintigraphy in symptomatic patients. Aim of the study was to demonstrate the equivalence of both treatment regimens. A total of 1,968 patients were randomized to receive UF or LMW heparin. Of these, 378 patients were excluded during the study period, so that 780 patients on UF and 810 on LMW heparin were included in the efficacy analysis. Four primary end points were observed with UF and 6 with LMW heparin, demonstrating the equivalence of treatments (p = 0.012). Additionally, pulmonary embolism was suspected as the cause of death in 6 patients who died during the study (3 per treatment group). A higher frequency of death (n = 32) was observed in the LMW-heparin group (p = 0.02) particularly documented in a part of the centers. Safety analysis showed a higher frequency of local pruritus, local erythema and subcutaneous hematoma, a higher increase in plasma levels of triglycerides, total cholesterol, alanine aminotransferase and aspartate aminotransferase, and a decrease of antithrombin III in patients receiving UF heparin. A decrease in platelet count (values ranging between 40,000 and 80,000/microliter) was observed in 4 patients with UF and in none with LMW heparin. No severe thrombocytopenia was observed. Subcutaneous LMW heparin is as effective as UF heparin for prophylaxis of thromboembolism in bedridden, hospitalized medical patients.
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PMID:Subcutaneous low-molecular-weight heparin versus standard heparin and the prevention of thromboembolism in medical inpatients. The Heparin Study in Internal Medicine Group. 873 87

The effect of antithrombin III (AT III) supplementation on energy status, microcirculation, cytoprotection, and prostacyclin (PGI2) production during and after a period of warm ischemia of the rat liver was investigated. AT III supplementation (250 units/kg) stimulate prostaglandin I2 (PGI2) production from 1 hour after administration, with maximal production observed at 3 hours. Ischemia was induced by occluding the hepatoduodenal ligament for 30 minutes, and experiments were continued for 60 minutes after reperfusion. The rats received AT III (250 units/kg IC) 30 minutes before induction of liver ischemia (AT III group). In the AT III group, recovery of the beta-ATP/inorganic phosphate ratio measured by 31P nuclear magnetic resonance showed significant improvement (p < 0.01), and the recovery of tissue blood flow markedly improved (p < 0.01) compared to the saline-treated group (control group). Leakages of aspartame aminotransferase, alanine aminotransferase, and lactate dehydrogenase were mitigated in the AT III group (p < 0. 05). Ultrastructural alterations of sinusoidal endothelial cells were markedly reduced in the AT III group. The PGI2 level at the end of reperfusion was significantly elevated (p < 0.01) in the AT III group compared to the control group. The results of this study indicated that pretreatment with AT III significantly improved the energy status and microcirculation, as well as histologic damage, after liver ischemia and reperfusion. One of the fundamental effects of AT III might be mediated through the production of prostacyclin.
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PMID:Protective effects of antithrombin III supplementation on warm ischemia and reperfusion injury in rat liver. 879 66

Gastric mucosal pH reflects splanchnic perfusion. Monitoring gastric mucosal pH might be useful in predicting outcome after liver transplantation. Forty patients were included in the study. Gastric mucosal pH and gastric mucosal pH corrected for systemic pH were compared with regard to initial liver function and morbidity. Eighty percent of the patients had at least one episode with a gastric mucosal pH of <7.32, and 84% of these had a concomitant arterial pH of <7.32. No differences in morbidity were found between patients with a gastric mucosal pH of <7.32 and those with a gastric mucosal pH of >7.32. If gastric mucosal pH was corrected for arterial pH, only 49% of the patients had an episode during transplantation with a corrected gastric mucosal pH of <7.32. Comparing these patients with the group that did not have such an episode, we found that flow in the venovenous bypass system was significantly lower (2.9 v 3.4 L/min; P < .02) in the first group. Also alanine aminotransferase and aspartate aminotransferase levels were higher, antithrombin III levels and lidocaine clearance rates were lower, and prothrombin times were longer in the group with corrected gastric mucosal pH of <7.32. No differences with regard to major morbidity and mortality were noted. Gastric mucosal pH during liver transplantation should be corrected for arterial pH. Patients with a corrected gastric mucosal pH of <7.32 are more likely to develop initial liver function tests disturbances, but morbidity is not different from patients with gastric mucosal pH of >7.32.
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PMID:Gastric mucosal pH is associated with initial graft function but is not a predictor of major morbidity after liver transplantation. 940 62

The aim of this study was to evaluate the tolerance of normothermic liver ischemia with different degrees of hepatic function in cirrhotic rats. Liver cirrhosis was induced by administering carbon tetrachloride (CCl4) in water solution to male Wistar rats. Hepatic function was graded using the plasma levels of antithrombin III, albumin, and bilirubin and the presence of ascites. Rats were distributed in four groups: noncirrhotic (control group), compensated cirrhosis (group A), decompensated cirrhosis (group B), and decompensated cirrhosis with ascites (group C). Groups A, B, and C were significantly different in all four parameters studied (P < .003). Subtotal liver ischemia was performed for periods of 0, 30, 45, 60, and 75 minutes. At the end of the procedure, the nonischemic lobes were resected. Postoperative evolution of alanine aminotransferase, aspartate aminotransferase, and bilirubin levels was also recorded. Survival rates after the same periods of ischemia were statistically different (P < .05): control group, 7 of 7 after 45 minutes (100%), 7 of 7 after 60 minutes (100%), and 4 of 9 after 75 minutes (44%); group A, 7 of 7 after 45 minutes (100%) and 1 of 7 after 60 minutes (14%); group B, 7 of 7 after 0 minutes (100%), 5 of 7 after 30 minutes (71%), and 1 of 7 after 45 minutes (14%); and group C, 0 of 5 after 0 minutes (0%) and 1 of 7 after 30 minutes (14%). No differences were found in the postoperative course of transaminases. However, bilirubin levels found 24 hours and 7 days after ischemia were significantly greater in cirrhotic rats, and this was directly related to the degree of hepatic insufficiency (P < .001). Histological examination of the livers exposed to CCl4 showed features of liver cirrhosis with ductal proliferation. The ischemia time tolerated by cirrhotic rat livers is shorter than the time tolerated by normal rats. Tolerance to hilar vascular occlusion depends on the degree of hepatic insufficiency. Rats with decompensated cirrhosis and ascites do not tolerate any surgical procedure.
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PMID:Vascular occlusion in hepatic resections in cirrhotic rat livers: an experimental study in rats. 940 63

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

A 36-year-old woman underwent emergency caesarean section following the diagnosis of HELLP syndrome. Four years earlier, after having undergone the same procedure for HELLP syndrome, she had experienced hypovolemic shock, renal failure, and disseminated intravascular coagulopathy during the postoperative period. This time, the patient showed bleeding, elevation of liver enzymes (ALT, AST, LDH) and a reduction of antithrombin III activity in the 36th week of pregnancy. Anesthesia was induced by thiamylal 4 mg.kg-1 and suxamethonium 1 mg.kg-1 and after delivery maintained by oxygen-nitrous oxide-isoflurane, and all procedures were performed without any incident. No major complications such as intraperitoneal bleeding, renal failure, or disseminated intravascular coagulopathy occurred during the postoperative period. It is suggested that caesarean section should be carried out as soon as possible after the diagnosis of HELLP syndrome is confirmed.
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PMID:[Caesarean section in a patient with a history of HELLP syndrome]. 1048 22


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