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)

The beneficial effects of ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis led to therapeutic trials with this bile acid for the treatment of PSC. In two prospective placebo-controlled trials, UDCA led to a significant improvement of AP, GGT, ALT, AST, and, in one study, also of serum bilirubin. In both studies liver histology improved significantly, mainly due to a decrease of cellular infiltrates in portal triads. Pruritus and fatigue improved in approximately one-third of the patients, but, compared to placebo, this effect was not significant. In a follow-up study after on average 3.1 years of UDCA treatment, 7/43 of the patients with stages I-IV disease developed a stenosis of the common bile duct which was effectively treated by endoscopic dilatations. Of 57 patients with PSC included since 1987 in the study, 14 dropped out and of these in 10 information on the outcome is available. In patients treated by UDCA and, whenever necessary, by endoscopic dilatations, the frequency of transplantations was significantly reduced in comparison to patients who dropped out of the study. Bile duct carcinoma developed in 5% of our patients. The data indicate that treatment of patients with PSC with UDCA and by endoscopic dilatations of common duct stenoses is promising. In patients with endstage disease, the only effective therapy is liver transplantation. Therefore, the early diagnosis of the disease seems very important.
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PMID:Ursodeoxycholic acid therapy in treatment of primary sclerosing cholangitis. 782 79

The rodent liver carcinogen and hepatic peroxisome proliferator methylclofenapate (MCP) has been evaluated for genetic toxicity in a range of in vitro and rodent genotoxicity assays. It gave a negative response in each of the following assays: mutagenicity to S. typhimurium and E. coli (+/- S9 mix, plate and pre-incubation assays), clastogenicity to cultured human lymphocytes and CHO cells (+/- S9 mix), a mouse bone marrow micronucleus assay (24h and 48h sampling), a rat liver assay for UDS in vivo (12h sampling), assays for lac I (Big Blue) and lac Z (Muta Mouse) mutations in the liver of transgenic mice, and an assay of the ability of MCP to modify the mutagenicity to the liver of dimethylnitrosamine in both transgenic mutation assays. The micronucleus and UDS assays were conducted using a single administration of MCP at its maximum tolerated dose, while the transgenic assays were conducted using nine daily administrations of MCP at its cancer bioassay dose level. These nine daily administrations were shown to double the weight of the liver of non-transgenic, Big Blue and Muta Mice, as well as leading to a dramatic proliferation of peroxisomes (electron microscopy) in the livers of each strain. These changed parameters had returned to control levels when the mutation analyses were conducted (10 days after the final dose of MCP). Despite the liver enlargement observed following MCP administration, no evidence of mitotic activity was observed in treated livers, although an increased number of cells were undergoing replicative DNA synthesis during the final 3 days of the 9 days of administration (BUdR assessment of S-phase). Liver biochemistry parameters (ALT, AST, AP, CK, GGT and albumin) were unaffected by the chronic (9 day) administration of MCP indicating an absence of hepatic toxicity. These combined observations favour a non-genotoxic mechanism of action for the hepatic carcinogenicity of MCP. The clastogenicity in vitro of the perixisome proliferator Wyeth 14,643 has been confirmed in CHO cells, but it is noted that this chemical is more soluble than is MCP. In particular, at the highest dose level at which MCP could be tested, Wy 14,643 was also non-clastogenic.
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PMID:Evaluation of the genetic toxicity of the peroxisome proliferator and carcinogen methyl clofenapate, including assays using Muta Mouse and Big Blue transgenic mice. 785 96

Rickettsia spp. infections produce hepatic damage with transaminases elevation and biological signs of cholostasis. Classical biochemical tests of hepatic function were analyzed and compared in 8 patients with Q Fever (QF) and 7 with Boutonneuse Mediterranean Fever (BMF). Liver enlargement was detected in 75% of the QF group of patients as compared with the 57% of the BMF group. Transaminases were raised in 75% of the patients of the QF group and in 85, 7% of the BMF patients. Only one patient in the QF group showed manifest clinical jaundice. Statistically significant differences were found between the values of AST, ALT, alkaline phosphatase and GGT, which were higher in the QF group. Liver involvement is more important in patients with QF than in FBM. There is a large percentage of clinically silent involvement in both diseases. Liver function tests should be carried out in infections by Rickettsia spp.
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PMID:[Liver involvement in Q fever and Mediterranean boutonneuse fever. Comparative study]. 787 63

This study reports on measurement of the ethanol-induced hepatotoxicity in vitro on using the human hepatocyte cell line HepG2. Cells were incubated in the presence of increasing ethanol concentrations (10-80 mM). Cytotoxicity was quantitated spectrophotometrically both by the metabolism of the tetrazolium dye MTT and by the release into the medium of LDH and other marker enzymes of ethanol damage (AST, GGT and GHD). No cytotoxicity was observed up to 40 mM ethanol whereas a dose-dependent increment was found at higher concentrations (60-80 mM ethanol). At 80 mM ethanol, cell viability after 24 hours was reduced to 68% and 60% as assessed by MTT and LDH release respectively (p < 0.0001 vs. controls). Exposure for additional 24 hours did not increase cytotoxicity. Transmission electron microscopy revealed the presence of fat droplets (steatosis) and mitochondrial damage. The method reported appears to be an useful and reproducible technique for the in vitro assessment of the ethanol-induced cytotoxicity in a human liver cell line.
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PMID:In vitro assessment of the ethanol-induced hepatotoxicity on HepG2 cell line. 790 31

The object of the study was to discover the changes in the plasma activities of hepatic enzymes in patients on anticonvulsant drugs. The plasma activities of aspartate transaminase (AST), alkaline phosphatase (ALP), alanine transaminase (ALT) and glutamyltransferase (GGT) were studied in 123 unselected patients on anticonvulsants. The results were compared with 123 control patients not on anticonvulsants matched for age and sex. Patients with known liver disease were excluded. The plasma activities of AST and ALP were similar in the two groups. ALT and GGT were raised in patients on anticonvulsants. No patient developed clinical evidence of liver disease. It was concluded that raised ALT and GGT are not in themselves indications to alter anticonvulsant therapy. Changes in AST and ALP would be more specific markers of liver dysfunction in patients on anticonvulsants.
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PMID:Plasma activities of hepatic enzymes in patients on anticonvulsant therapy. 790 70

The use of cadaveric organ donors with positive serologic tests for hepatitis C (HCV) has caused considerable debate. We have reviewed the clinical course of 43 EIA1 HCV-negative recipients who received kidney transplants from EIA1 HCV-positive donors (Study). We have attempted to define the rate of HCV-RNA transmission and to determine the frequency of HCV disease transmission as determined by abnormalities in liver function tests. Viral transmission was assessed using serologic assays for HCV antibody formation (EIA1, EIA2, and Matrix--an automated multiple antigen immunoblot assay) and with PCR testing for the presence of HCV-RNA on recipient sera. Liver function was followed longitudinally in the Study patients and compared with a group of 103 kidney recipients of organs from EIA1 HCV-negative donors (Control). Of the Study patients, 56% became PCR-positive for HCV-RNA, suggesting the transmission of HCV-RNA from the HCV-positive donor. Interpretation of serologic tests for HCV was complex. Currently available first (EIA1) and second (EIA2) generation serologic assays were always negative. The multiple antigen immunoblots assay (Matrix) had a high positive predictive value (93%) for the presence of HCV-RNA transmission, but one-third of Matrix-negative Study patients were PCR-positive (sensitivity = 66%). Currently, only 38% of recipients have HCV-RNA, suggesting that the virus may have been cleared by one-third of Study recipients who had circulating virus. Traditional tests of liver function (ALT, AST, AP, and GGT) were of limited use in predicting HCV-RNA transmission. Average AST, AP, and GGT were similar in the two groups. Average ALT was increased (93 I/U and 47 I/U) in Study and Control patients, respectively, but this difference was not significant. Episodes of abnormal liver function (ALT 60-99 IU for > or = 14 days) occurred in 22% of Study and 10% of Control patients (P = NS) and lasted longer in Study compared with Control patients (301 vs. 138 days; P < 0.02). Hepatitis (ALT > or = 100 IU for > 14 days) occurred with an equal frequency (6.5%) in both groups. The presence of HCV-RNA did not predict episodes of abnormal liver function. Fulminant hepatitis or rapidly progressive cirrhosis did not occur in the recipients of organs from HCV-positive donors. These data demonstrate a high efficiency of transfer of HCV-RNA by kidney transplantation from an HCV-positive donor to an HCV-negative recipient. A majority of the patients have asymptomatic HCV infection.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Transmission of hepatitis C by kidney transplantation--the risks. 815 29

This study was carried out to evaluated the role of the fibronectin (FN) in chronic liver diseases. For these reasons FN plasmatic concentration was assayed in patient with different degrees of chronic liver disease. For these reasons FN plasmatic concentration was assayed in patient with different degrees of chronic liver disease; the correlation between FN and the most common parameters of liver function was also evaluated. Moreover we also correlated FN plasma levels with laminin and the N-terminale peptide of type III procollagen, serum levels, that are through to be markers of fibrogenesis. 172 patients were studied: twenty-one patients suffering from chronic persistent hepatitis (CPH), 45 from chronic active hepatitis (CAH) and 106 from liver cirrhosis (LC). Last patients were also divided according the Child-Pugh's classification. Control group was composed of 74 healthy blood donors. Significant reduction of plasmatic levels of FN was found in the LC groups in comparison with control group (p < 0.0001) and also with CPH group (p < 0.01) and with CAH group (p < 0.0001). Lower values of FN were found in the LC group at advanced stage (Child-Pugh's B and C classes). In the group of CAH significant correlations with the parameters of cholestasis (GGT, APh, Tot. Bil. p < 0.005) were found, while in the group of LC significant correlations both with the parameters of synthesis (Alb. and Protr. time p < 0.01) and necrosis (AST/ALT p < 0.001). A negative correlation was also found between FN and spleen volume (p < 0.05). No correlation between FN and the parameters of fibrosis was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Plasma fibronectin in chronic liver diseases]. 821 Jun 24

When examining diseased calves, sporadically pronounced haemoglobinuria with dark red urine can be observed. In serious cases the clinical picture may be manifold but peculiar; in easy cases, however, when there are no distinct clinical symptoms, a larger scale of examinations is needed to aid differential diagnosis. Eight roughage-fed bulls aged two months, weighing 55-71 kg were used in this experiment. Selected biochemical indices of the mineral, enzymatic, hepatic, energetic and urinary profile were determined in the blood serum and urine of the animals. After the administration of cold water at an amount representing 12% of the animal's body weight, ionogram values were determined. In all indices a positive correlation with hydraemia and a decrease in Na, Cl, Ca, Mg and P levels were observed. Correction of the above levels occurred within 24 hours, with the exception of Na and P concentrations that did not reach starting values. As to the enzymatic profile (AST, ALT, GGT), no pronounced disturbances could be observed. The most profound changes were seen in AST activity that increased in the 5th hour of the experiment. A slight tendency towards hypoproteinaemia was observed to continue even in 24 hours. Hypoglobulinaemia reached its starting value in the 24th hour while simultaneously albumin levels slightly increased. The increasing bilirubin levels reached their maximum in the 5th and 6th hour; correction of the former occurred within 24 hours. The urinary profile revealed polyuria, aciduria, aquaeous urine and haemoglobinuria, the latter reaching its peak between hours 1 and 3 following water administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Experimental paroxysmal hemoglobinuria in calves and selected biochemical indicators in the blood and urine]. 823 29

To evaluate the effect of ursodeoxycholic acid (UDCA) treatment according to the severity of primary biliary cirrhosis, a long-term prospective open trial in 54 consecutive PBC patients, 19 with histological stage I-II, 24 stage III, and 11 stage IV was carried out. UDCA was administered at a dosage of 250 mg twice a day. Clinical and biochemical assessment (AST, ALT, alkaline phosphatase, GGT, bilirubin) were done initially and every six months. Serum hyaluronate (HY) and type III procollagen amino propeptide (PIIIP) were also evaluated, as they are considered markers of fibrosis and prognosis. All patients were followed-up for at least two years (24-36 months); results were analyzed at 24 months after treatment. The composite pruritus score failed to show significant changes during UDCA treatment, while intensity score demonstrated a significant reduction from the 6th month. Patients with histological stage I-II disease had a significant decrease of liver enzymes (AST, ALT, alkaline phosphatase, GGT) after six months and maintained the levels up to 24 months. The patients with histological stage III disease showed a significant decrease of AST, ALT, alkaline phosphatase (but not GGT) up to month 18; subsequently AST and ALT serum levels increased, reaching values comparable to baseline by 24 months. In patients with histological stage IV disease no significant change in liver enzymes was observed during the follow-up. HY and PIIIP serum levels failed to show significant changes during UDCA treatment in the three groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis according to severity of disease. 828 73

Orthotopic liver transplantation has become the accepted treatment for end-stage liver disease in children. To evaluate the efficacy of the University of Wisconsin (UW) preservation solution in pediatric liver transplantation, a group of 34 livers preserved with UW solution was compared in a nonrandomized fashion with a historical control group of 34 livers preserved with Euro Collins (EC) solution. Primary graft nonfunction did not occur in either group. Both groups were similar with respect to age, sex, weight, diagnosis, severity of the recipient's condition, donor condition at harvest, donor/recipient blood type match, and immunosuppressive management. The UW group had a significantly higher bilirubin, AST, ALT, and GGT during the first week after transplantation when compared with the EC group but no significant differences were noted after the ninth post-transplant day. No differences were noted when the groups were compared as to surgery time (9.1 v 8.4 hours), blood volumes replaced (1.8 v 2.0), number of ICU days (5.0 v 6.5), total number of infections per graft (1.0 v 0.8), total hospital days (31 v 30), and hospital cost ($134,000 v $126,000). The total preservation time was improved from 7 hours (range, 3.2 to 9.9) in the EC group to 13.9 hours (range, 6.9 to 22.3) in the UW group (P < .001). UW solution allows a significant increase in cold ischemic time in liver transplantation when compared with EC. This increase in preservation time resulted in no detrimental effect when compared with EC and potentially led to milder episodes of rejection in the postoperative period.
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PMID:University of Wisconsin preservation solution compared with Euro Collins preservation solution in pediatric liver transplantation. 834 Aug 64


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