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)

In order to assess the liver protective activity and the antioxidant properties of a new silybin complex (IdB1016), we carried out a short-term pilot study on 20 patients with chronic active hepatitis (CAH), randomly assigned to 240 mg of silybin b.i.d. (10 patients, 4 m/6 f, mean age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood samples were collected before and after 7 days of treatment for liver function tests (LFTs), malonaldehyde (MDA) as an index of lipid peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in protecting cells against free radical-mediated lipid peroxidation. In the treated group, there was a statistically significant reduction of mean (+/- SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0 (+/- 13.3) to 65.9 (+/- 7.5) u/l, (p < 0.01), of alanine aminotransferase (ALT) from 115.9 (+/- 12.9) to 82.5 (+/- 10.6) u/l (p < 0.01), of gamma-glutamyltranspeptidase (gamma-GT) from 51.4 (+/- 9.3) to 41.3 (+/- 4.2) u/l (p < 0.02) and of total bilirubin (TB) from 0.76 (+/- 0.08) to 0.53 (+/- 0.04) mg/dl (p < 0.05). Alkaline phosphatase (AP) fell slightly from 143.4 (+/- 6.4) to 137.5 (+/- 7.8) u/l. There were no significant changes in MDA, Cu or Zn serum concentrations. These results show that IdB1016 may improve LFTs related to hepatocellular necrosis and/or increases membrane permeability in patients affected by CAH.
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PMID:A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis. 822 95

Glurenorm, a IInd generation sulfanylurea preparation, was used for a year as a sugar-reducing drug in 20 patients with non-insulin-dependent diabetes mellitus and concomitant diseases of the liver (cirrhosis, chronic hepatitis, n = 5) and biliferous duct (cholelithiasis, a state following cholecystectomy, chronic cholecystitis, n = 15). A year follow-up has not shown deterioration of liver function as indicated by results of liver tests (AST, ALT, acid phosphatase, gamma-glutamyltranspeptidase, bilirubin, cholesterol, triglycerides). The hypoglycemic effect of the drug proved to be inferior to that of sulfanylurea derivatives, but the absence of side effects permit higher doses of glurenorm (up to 4-6 tablets daily) as against other oral sugar-reducing drugs.
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PMID:[Glurenorm in the treatment of patients with non-insulin-dependent diabetes mellitus with diseases of the liver and bile ducts]. 841 21

The catalytic activities of some mitochondrial and cytoplasmic enzymes were measured in plasma from 19 patients after orthotopic liver transplantation, in order to detect and monitor the evolution of hepatocellular damage and to predict liver rejection. The enzymatic activities determined were: mitochondrial isoenzyme of aspartate aminotransferase, glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltranspeptidase and alkaline phosphatase. The results of all enzymatic activities were normalized by expressing them as multiples of the upper limit of the relevant reference range and then the necrosis index (NI) has been calculated. The proposed NI consists of percent ratio of the normalized mitochondrial enzymatic activities over the sum of cytoplasmic and mitochondrial normalized activities. We observed that NI values higher than 30% correctly identified all but two acute rejection events which were documented by liver biopsies showing a diagnostic sensitivity of 90%, specificity of 78% and a predictive value of 90%.
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PMID:Enzymatic determinations in acute rejection after liver transplantation: preliminary report on necrosis index. 847 83

We measured serum levels of carbohydrate deficient transferrin (CDT) in 420 subjects: 100 healthy blood donors, 82 healthy employees, 70 abstaining patients with different chronic nonalcoholic liver disease, 16 abstaining patients with alcoholic fatty liver, 50 abstaining patients with alcoholic liver cirrhosis, 25 abusing patients with alcoholic fatty liver, 41 abusing patients with alcoholic liver cirrhosis, and 36 patients with alcohol dependence syndrome with a daily ethanol consumption of 173 +/- 120 g the last 4 weeks before blood was drawn. In controls the serum level of CDT was significantly higher in females compared with males (17.7 +/- 5.1 and 13.7 +/- 3.8 units/liter, respectively), and the upper normal limit was defined as 27 and 20 units/liter. Sixty-two of 102 (60.8%) abusing patients with alcoholic liver disease had increased levels of CDT compared with 1 of 66 abstaining (1.5%) patients with alcoholic liver disease, and 10 of 70 (14.3%) abstaining patients with nonalcoholic liver disease among them 3 with primary biliary cirrhosis and 2 with chronic autoimmune hepatitis. No correlation was found between serum CDT and gamma-glutamyltranspeptidase (GGT), AST, ALT, and mean red cell volume (MCV). The sensitivity and specificity for serum CDT was 61 and 92%, respectively, compared with 85 and 18% for GGT and 70 and 66% for MCV. No advantage was gained by using the CDT/transferrin ratio. Our study confirms that CDT is a specific marker for chronic alcohol abuse, except in few patients with other chronic liver diseases. Serum CDT seems to be a better indicator of abstention than GGT; AST and MCV in patients with alcoholic liver disease. However, in our hands CDT is not so sensitive for alcohol abuse in patients with liver disease as reported earlier in unselected alcoholics.
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PMID:Serum carbohydrate-deficient transferrin as a marker of alcohol consumption in patients with chronic liver diseases. 848 62

Nonresponse to tricyclic antidepressant (TCA) treatment is observed in about one-third of depressed patients. The cause(s) for nonresponse - apart from disease-specific effects - might be the failure to build up sufficiently high serum TCA levels due to noncompliance, substance abuse, rapid metabolism, or low dose. We carried out a retrospective analysis relating antidepressant serum levels to patient data obtained in the naturalistic setting of the Psychiatric Hospital of the Bonn University during the introductory phase of drug-monitoring. Case reports of 110 depressed inpatients who were treated with amitriptyline or doxepin were analyzed with respect to the following: medication and comedication, daily dose, type and duration of treatment, serum TCA concentrations (analyzed by the fluorescence polarization immunoassay), age, sex, body weight, abuse of nicotine or alcohol intake, serum transaminases (ALT, alanine aminotransferase, and AST, aspartate amino transferase), gamma-glutamyltranspeptidase (gamma-GT) and creatinine, compliance, and response. The salient findings were: 1. Serum TCA concentrations increased linearly with the daily amitriptyline dose but not with that of doxepin. 2. Interindividually, there was an eight to ten-fold difference in serum TCA concentrations at steady-state with 150 mg/day of either drug; longitudinally, we observed intraindividually a coefficient of variation of 8% and 12% for amitriptyline and doxepin respectively. 3. With amitriptyline (150 mg/day), the correlation between age and serum TCA concentrations was low (r = 0.33, p < 0.055) and no correlation was found after the administration of doxepin (150 mg/day), nor was there any correlation between age and dose-adjusted serum TCA concentrations after the administration of either drug. 4. Nonresponders had significantly lower serum levels than responders. These results suggest that patients should not qualify as nonresponders unless it can be demonstrated (and it is clinically applicable) that the steady-state serum TCA levels are stable within the upper limit of the recommended therapeutic range and serum level.
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PMID:Low serum levels of tricyclic antidepressants in amitriptyline- and doxepin-treated inpatients with depressive syndromes are associated with nonresponse. 873 13

We administered ursodeoxycholic acid (UDCA) orally, at a daily dose of 600 mg, for 4 months to 36 patients with chronic viral hepatitis C. Another 36 patients with chronic viral hepatitis C, treated with placebo for 4 months, served as controls. None of the patients were alcoholics and none suffering from autoimmune hepatitis. Of the 36 patients in the UDCA-treated group, 13 had high levels of serum gamma-glutamyltranspeptidase (GGT), i.e., exceeding 150 U/l (normal < 50 U/l). Histological examination of liver biopsy specimens obtained from 10 patients in this group before treatment suggested that damage of the interlobular bile ducts was prominent in patients with higher levels of serum GGT. After 1 month of UDCA treatment, significant decreases in the levels of serum GGT, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were observed (P < 0.05 for GGT and AST), and the decreases continued for the 4-month treatment period. The reduction of GGT levels was the most prominent change in the liver function indices; the percent change in the GGT level was -25.2 +/- 4.4 (mean percent change +/- SE) at 1 month and -38.0 +/- 5.0 at 4 months. A significant correlation was observed between the serum delta GGT level (GGT value before treatment minus value after 3 months of treatment) and the total score for morphological injury of the bile ducts (P < 0.05). These results suggested that UDCA has the potential to reverse hepatocellular damage in patients with chronic viral hepatitis C, in whom high GGT levels may be due, in part, to a damaged interlobular bile duct. UDCA may be useful for the treatment of chronic viral hepatitis C, especially in patients exhibiting a high level of GGT.
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PMID:Efficacy of ursodeoxycholic acid therapy in chronic viral hepatitis C with high serum gamma-glutamyltranspeptidase levels. 880 32

The technique of normothermic total hepatic vascular occlusion (THVO) is achieved by concomitant clamping of the inferior vena cava above and below the liver in addition to portal inflow occlusion. In this study we investigated the use of THVO for 45 min in a rabbit model with acute cholestasis of 10 days' duration. In rabbits with normal preoperative liver functions (control group), serum total bilirubin, glutamic-pyruvic transaminase (SGPT), glutamic-oxaloacetic transaminase (SGOT), alkaline phosphate, and gamma-glutamyltranspeptidase levels returned to normal ranges within a week after THVO. In the group with persistent cholestasis THVO was performed 10 days after ligation of the extrahepatic bile duct. Total bilirubin and canalicular enzymes remained high while the SGOT and SGPT peaked and almost returned to the preoperative levels at 7 days following THVO in this group. A third group of animals also underwent THVO 10 days after ligation of their extrahepatic bile ducts with relief of the obstruction with a Teflon stent immediately after THVO. This group also showed the trend of normalization of liver canalicular and parenchymal enzymes and bilirubin by the end of 7 days. This study demonstrated the feasibility of THVO in rabbits with acute extrahepatic cholestasis whether the extrahepatic biliary obstruction persisted or not.
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PMID:The safety of total hepatic vascular occlusion in rabbits with acute extrahepatic cholestasis. 883 67

To evaluate the clinical significance of HLA class II matching in living-related liver transplantation, the genotypes of HLA class II including DPB1 were determined by the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method and their matching was compared to the postoperative course. Conventional serotypes included 15.6% and 13.6% errors in DR and DQ, respectively. Among 42 consecutive cases that were followed up over 1 year after transplant, rejection occurred in seven cases. There was no correlation between the matching for each locus and the frequency of rejection episodes. In this study, rejection-free cases were investigated in terms of the potency of immunosuppressive therapy and graft function during 1 year after operation. The doses of tacrolimus in unmatched cases tended to be larger than those in matched cases for every locus except for DQA1. Its trough levels in matched cases were lower than those in unmatched cases, especially at 9-12 months after operation for DRB1 (p < 0.05). The termination of steroid administration tended to be postponed in unmatched cases for every locus. Serum levels of asparatan transaminase, alanine transaminase gamma-glutamyltranspeptidase (gamma-GTP) and total bilirubin were generally lower in matched cases than in unmatched ones for DRB1, DQB1 and DPB1, while in DQA1 the tendency was the opposite, especially total bilirubin and gamma-GTP, which were p < 0.02 and p < 0.05, respectively, at 6 months after operation. Investigation of subclinical immune responses other than rejection episodes showed that DRB1, DQB1 and DPB1 matching had a beneficial effect on graft function, while DQA1 matching seemed to have a varied effect.
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PMID:Evaluating the significance of HLA class II genotype matching in living-related liver transplantation. 884 91

Pretreatment of fasted rats with aminooxyacetic acid (AOAA, 0.25 mmol kg-1, i.p.), methimazole (MTZ, 0.35 mmol kg-1, i.p.) and acivicin (AT-125, 56 mumol kg-1, i.p.) 30 min prior to a 4-h inhalation exposure to 180-200 ppm or 150-180 ppm vinylidene chloride (VDC) was used to study the role of cysteine beta-lyase, cysteine conjugate S-oxidase and gamma-glutamyltranspeptidase (gamma-GT) in VDC-induced liver and kidney toxicity. Pretreatment with AOAA reduced by 65-95% those increases in serum alanine aminotransferase (ALAT), glutamate dehydrogenase (GLDH) and sorbitol dehydrogenase (SDH) caused by exposure to 180-200 ppm VDC. This pretreatment also prevented VDC-induced increases in aspartate aminotransferase (ASAT) and N-acetyl-beta-d-glucosaminidase (NAG) activities and in the concentration of beta 2-microglobulin (beta 2-m) in 24-h urine samples. There was only a slight potentiation of VDC-induced liver and renal toxicities by MTZ given before exposure to 180-200 ppm VDC, but potentiation became significant (40-80%) when MTZ was administered before a slightly lower level of exposure (150-180 ppm). Pretreatment with AT-125 did not significantly change the liver and renal effects of exposure to 180-200 ppm VDC. These results suggest that the formation of a cysteine conjugate may be involved in the renal and liver toxicity of VDC in fasted rats.
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PMID:Role of cysteine conjugation in vinylidene chloride-induced nephrotoxicity and hepatotoxicity in fasted rats. 893 83

We studied the prevalence of hepatitis C virus (HCV) infection in 350 renal transplant (RT) patients with a functioning graft. The determination of HCV infection was based upon second-generation ELISA tests (ELISA-2, Abbott) confirmed by second-generation RIBA tests (RIBA-2, Chiron), including the proteins C22-3, C100-3, C33-C and 5-11. Three hundred and sixteen of these RT patients were on ciclosporin A (CsA) therapy with or without steroids (CS) and azathioprine (AZA); 34 received conventional immunosuppression. Eighty-seven RT patients were found to be HCV-positive (2.5%) when assessed by ELISA-2 tests; RIBA-2 was positive in 61 cases and 'indeterminate' in 26. Most of the HCV-positive patients had antibodies against C22-3 (94%), whereas antibodies against nonstructural antigens (C100-3, C33-C) were observed in 18 and 70% of cases, respectively. More than 88% of the HCV-positive patients were already HCV-positive before renal transplantation. Risk factors of developing HCV infection included: (i) the time on dialysis; (ii) the number of blood transufsions before transplantation, and (iii) the number of previous graft(s). There were significantly more HCV-positive patients among those on conventional immunosuppressive therapy (16 of 39) than among those on CsA (71 of 311; p < 0.02). Of those who where HCV-positive before transplantation, and for whom liver enzyme (LE) results were available (n = 68), 40 had either a normal or a transient increase in alanine aminotransferase (ALT) levels at that time, whereas 28 had a chronic increase in serum ALT +/- gamma-glutamyltranspeptidase levels. After transplantation, there was biochemical evidence of chronic liver disease in 33 patients (48.5%). Interestingly, 41 and 64% of those with respectively normal and increased LEs before transplantation presented with a biochemical chronic liver disease after RT. Surprisingly, 36% of those with a pretransplantation increase in ALT had normalized aminotransferase after transplantation. The daily doses of AZA, CS (i.e. prednisolone) were not statistically different between HCV-positive RT patients on conventional therapy (group A) and those on CsA (group B). Moreover, within each group, the daily doses of AZA, CS or CsA were not statistically different between those with a chronic increase in LEs and those with normal LEs. The percentage of HCV-positive RT patients with chronic abnormal LEs was not different between groups A and B. Surprisingly, the patients who were treated at least once for acute rejection with methylprednisolone pulses had a significantly lower incidence of chronic increases in LEs. Nine patients seroconverted for HCV after transplantation: 6 experienced a chronic increase in LEs. Finally, 7 of 87 patients were coinfected by HBV, all of them had a chronic increase in LEs. These results emphasize the fact that ALT alone cannot be used as a surrogate marker for chronic HCV infection in transplantation patients, thus a liver biopsy is required before and a few years after RT to assess liver damage in this population.
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PMID:Prevalence of antibodies to hepatitis C virus and correlation with liver disease in renal transplant patients. 905 53


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