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)

Fifty-two patients on regular haemodialysis at our institution were evaluated for the presence of HCV infection. Evaluation included detailed history, clinical examination, and monthly screening for anti-HCV antibody, liver enzymes (ALT, AST), serum iron and ferritin. Also, three-monthly screening for other viral markers, HBV (HBsAg, HBsAb, HBcAb), CMV (IgG and IgM), EBV, and HIV. Anti-HCV antibody was found in 21 patients (40.4%). There was a significant (P less than 0.05) relationship between presence of anti-HCV antibody and proportion of patients who received blood transfusion. During a 12-month follow-up, four (11.4%) patients seroconverted to be Anti-HCV positive while one case (4.8%) seroconverted to be anti-HCV negative. The frequency of elevation of liver enzymes was significantly higher in Anti-HCV positive cases (14/18) than in negative cases (11/28, P = 0.01). Evaluation of liver biopsies of 13 patients showed chronic persistent hepatitis in six and chronic active hepatitis in seven cases. We concluded that hepatitis C is a common problem among chronic haemodialysis patients at our institution; HCV infection is documented in 70% of all clinically diagnosed NANB hepatitis. Presence of anti-HCV antibodies cannot differentiate between active and past infection and cases with early HCV infection can be missed when relying on the mere detection of anti-HCV antibodies.
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PMID:Hepatitis C virus infection in chronic haemodialysis patients, a clinicopathologic study. 128 48

A 76-year-old male was admitted to our hospital because of general fatigue in June 1987. He had received total gastrectomy against gastric carcinoma two years previously. The examinations revealed the elevation of GOT, GPT and gamma-GTP, and increased CT number of the liver. Specimen of the liver biopsy showed deposition of iron and slight fibrosis. He was diagnosed as idiopathic hemochromatosis. He was given deferoxamine, and his elevated GOT, GPT and gamma-GTP were normalized. Idiopathic hemochromatosis is frequently associated with various malignancies including hepatic carcinoma. However, only a few cases of idiopathic hemochromatosis associated with gastric carcinoma have been reported.
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PMID:[A case of idiopathic hemochromatosis associated with gastric cancer]. 142 60

The effect of iron-overload on both hepatic lipid peroxidation and chemiluminescence was studied in early stages after iron-dextran injection. Total hepatic iron content was markedly elevated over control values 2-6 h after iron dose. A 4-fold increase in light emission was detected after 4-6 h after iron injection. Plasma GOT, GPT and LDH activities were not affected by the treatment suggesting that cell permeability was not affected by necrosis. Increases in the generation of thiobarbituric acid reactive substances (TBARS) and chemiluminescence in liver homogenates, were determined as a function of time after iron administration, in the presence of NADPH as cofactor. Under the same experimental conditions, microsomal cytochrome P-450 content was decreased by 40%, 2 h after iron treatment. To evaluate liver antioxidant defenses, catalase, superoxide dismutase and glutathione peroxidase activities were determined. Glutathione peroxidase activity in the homogenate was not affected by the treatment. Catalase and superoxide dismutase activities declined by 25 and 36%, respectively, compared with control values 4 h after the iron dose. Our data suggest that lipid peroxidation occurs after mild iron overload even though the liver remains functional.
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PMID:Hepatic chemiluminescence and lipid peroxidation in mild iron overload. 147 93

Exposure of cultured primary hepatocytes from Ah-responsive male C57BL/10ScSn mice to a polychlorinated biphenyl (PCB) mixture (Aroclor 1254) at 0.1-20 micrograms/mL for up to 96 hr induced cytochrome P4501AI-mediated activity (ethoxyresorufin O-deethylase, EROD) up to 50-fold. In contrast, pentoxyresorufin O-dealkylase (PROD), which in some circumstances is a measure of phenobarbitone-induced cytochrome P450 isoenzymes, was induced only 5-fold. There were similar findings on EROD activities with the pure compounds 3,3',4,4',5,5'-hexachlorobiphenyl, 3,3',4,4',5,5'-hexabromobiphenyl and 3,3',4,4'-tetrachlorobiphenyl(TCB) and also beta-naphthoflavone but not with 2,2',4,4'-TCB or phenobarbitone. The higher concentrations of Aroclor 1254 were also associated with cytotoxicity as estimated by release of alanine aminotransferase (ALT) into the medium. Unlike in C57BL/10ScSn hepatocytes induction of EROD and cytotoxicity was minimal in hepatocytes from the Ah-non-responsive strain DBA/2. Although in vivo the hepatic toxicity and carcinogenicity of polyhalogenated aromatics are markedly potentiated by iron, no enhancement of the cytotoxicity of Aroclor 1254 towards C57BL/10ScSn hepatocytes by iron was observed in vitro. However, iron caused decreased EROD activities and possibly cytochrome P4501AI (as judged by Western blotting) as in vivo. Even in the presence of iron and the haem precursor 5-aminolaevulinic acid (5-ALA) there was no development of uroporphyria in this system although this occurs with Aroclor in vivo and is enhanced by iron. Accumulation of uroporphyrin did occur after extended culture of C57BL/10ScSn hepatocytes on matrigel for 8 days in the presence of 5-ALA and Aroclor 1254 but again no potentiation by iron was observed. Thus, although culture of Ah-responsive and -non-responsive hepatocytes mimics some aspects of the mechanisms of in vivo toxicity of PCBs, there is some unknown associated influence of iron metabolism which cannot, as yet, be produced in vitro but which is of importance in vivo.
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PMID:Induction of cytochrome P450 activities by polychlorinated biphenyls in isolated mouse hepatocytes. Influence of Ah-phenotype and iron. 151 Jun 96

FEP and other hematological parameters were measured in 157 healthy rural residents (98 females and 59 males). The mean FEP in females was higher than in males (p less than 0.05); mean +/- SD = 62.98 +/- 19.36 and 54.57 +/- 21.20 micrograms/dl.pcv, respectively, although both of the means were within normal limits. There was no significant sex difference in erythrocyte ALA-D activity. Whole blood lead (Pb-B) level in females showed a tendency to be lower than in males, but there was no significant sex difference in erythrocyte lead level. The mean value of hematocrit (Ht), hemoglobin (Hb) and iron in serum (Fe-S) were lower in females than in males (p less than 0.01). Serum GOT and GPT level tended to be lower in females than in males (0.05 less than p less than 0.1). There was hardly any significant relationship between Pb-B and each parameter of lead exposure, because the subjects in this study were only rural residents with no occupational lead exposure and with their Pb-B levels being extremely low. As for the parameters of anemia, Fe-S was positively correlated with Ht and Hb level and negatively correlated with FEP level. By sex, Fe-S was correlated with Ht and FEP level only in females. As for the possible reasons why FEP level in females in higher than in male, women tended to have iron-deficiency induced by blood loss due to menstruation, pregnancy, and difference in dietary pattern from males.
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PMID:[Sex difference in free erythrocyte protoporphyrin (FEP) level. I. Sex difference in FEP level in healthy rural residents]. 151 90

In patients with thalassemia intermedia in whom hyperabsorption of iron may result in serious organ dysfunction, an orally effective iron-chelating drug would have major therapeutic advantages, especially for the many patients with thalassemia intermedia in the Third World. We report reduction in tissue iron stores and normalization of serum ferritin concentration after 9-month therapy with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in a 29-year-old man with thalassemia intermedia and clinically significant iron overload (SF 2,174 micrograms/L, transferrin saturation 100%; elevated AST and ALT, abnormal cardiac radionuclide angiogram) who was enrolled in the study with L1 75 mg/kg/day after he refused deferoxamine therapy. L1-Induced 24-hour urinary iron excretion during the first 6 months of therapy was (mean +/- SD, range) 53 +/- 30 (11 to 109) mg (0.77 mg/kg), declining during the last 3 months of L1 to 24 +/- 14 (13-40) mg (0.36 mg/kg), as serum ferritin decreased steadily to normal range (present value, 251 micrograms/L). Dramatic improvement in signal intensity of the liver and mild improvement in that of the heart was shown by comparison of T1-weighted spin echo magnetic resonance imaging with images obtained immediately before L1 administration was observed after 9 months of L1 therapy. Hepatic iron concentration decreased from 14.6 mg/g dry weight of liver before L1 therapy to 1.9 mg/g liver after 9 months of therapy. This constitutes the first report of normalization of serum ferritin concentration in parallel with demonstrated reduction in tissue iron stores as a result of treatment with L1. Use of L1 as a therapeutic option in patients with thalassemia intermedia and iron overload appears warranted.
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PMID:Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia. 158 21

The precise role of lipid peroxidation in the pathogenesis of alcoholic liver disease is still being debated. To explore the issue, this study was undertaken to investigate the status of lipid peroxidation, antioxidants and prooxidants at two discrete stages of experimental alcoholic liver disease. Male Wistar rats were intragastrically fed a high-fat diet plus ethanol for 5 or 16 wk (the duration that resulted in initiation of centrilobular liver necrosis or liver fibrosis, respectively). Lipid peroxidation was assessed in isolated microsomes and mitochondria with three parameters: malondialdehyde equivalents as determined by thiobarbituric acid assay, conjugated diene formation and 4-hydroxynonenal as a 2,4-dinitrophenylhydrazone derivative. To assess antioxidant systems, hepatic concentrations of glutathione, methionine and alpha-tocopherol were determined. The concentration of nonheme iron, a known prooxidant, was also measured. At wk 5, centrilobular liver necrosis was already evident in the ethanol-fed animals, with two- or threefold increases in plasma AST and ALT levels. At this stage, neither malondialdehyde equivalents nor conjugated diene values were elevated, and the 4-hydroxynonemal level was below 0.2 nmol/mg protein. Hepatic concentrations of methionine and alpha-tocopherol in these animals were increased two- and threefold, respectively, whereas the reduced glutathione level remained unchanged. When alcoholic liver disease had progressed to perivenular or bridging fibrosis at wk 16, all three parameters of lipid peroxidation showed consistent increases that were accompanied by significant reductions in the hepatic glutathione and methionine levels. Interestingly, the control animals pair-fed with the high-fat diet also had significantly elevated 4-hydroxynonenal levels at wk 16 compared to the wk 5 level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased 4-hydroxynonenal levels in experimental alcoholic liver disease: association of lipid peroxidation with liver fibrogenesis. 163 54

In experiments with Wistar rats there was discovered statistically significant circadian rhythm of serum iron concentration reaching its maximum in the evening, minimum--early in the morning, and having an amplitude of at least 20% of the mesor. The reciprocal interrelations between circadian cycles of iron content in blood and liver were also found. The synchronization of blood iron level with lipid peroxidation products in membranous liver structures, as well as serum alanine aminotransferase activity, and their inversion with respect to the circadian rhythms of liver RES absorption ability and liver iron content are considered to be a proof of liver participation in regulation of iron exchange temporal organization in rats.
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PMID:[Role of the liver in the regulation of circadian rhythm of blood iron in rats]. 179 72

A study was carried out on 65 male workers heavily exposed to lead in the ceramic tile manufacturing industry in order to assess the effects of alcohol on the biological indicators of lead (PbB, ALA-D, ALA-U, ZPP). All subjects selected for the study had PbB levels greater than or equal to 60 micrograms/dl, normal levels of serum iron and no haemoglobin disorders. The subjects were divided into three groups according to alcohol intake checked by anamnestic investigation, mean corpuscular volume (MCV) values and liver function parameters, as follows: Group A--27 subjects, controls, with daily alcohol intake less than 80 ml, MCV less than or equal to 95 mu 3, normal GGT, AST and ALT levels; Group B--20 subjects, heavy drinkers, with daily alcohol intake greater than or equal to 80 ml, MCV greater than 95 mu 3, occasionally high GGT, but normal AST and ALT values; Group C--18 subjects, heavy drinkers, with daily alcohol intake greater than or equal to 80 ml, MCV greater than 95 mu 3, abnormal GGT, AST and ALT levels. The length of lead exposure did not significantly differ in the three groups. The well-known effects of ethanol intake on PbB, ALA-D and ALA-U values were confirmed, with the following mean values in the three groups: Group A: PbB = 66.0 (micrograms/dl), ALA-D = 10.3 (mU/ml r.c.), ALA-U = 8.4 (mg/l); Group B: PbB = 68.3 (micrograms/dl), ALA-D = 6.7 (mU/ml r.c.), ALA-U = 9.1 (mg/l); Group C: PbB = 71.5 (micrograms/dl), ALA-D = 4.6 (mU/ml r.c.), ALA-U = 12.7 (mg/l).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Influence of alcohol on the behavior of dose and effect indicators in workers exposed to inorganic lead: unexpected behavior of ZPP]. 180 15

The erythrocyte alanine aminotransferase (E-ALAT) activity with and without in vitro stimulation by pyridoxal phosphate of 60 healthy adolescents was measured before and after 6 weeks of supplementation with different water-soluble vitamins. The subjects who were divided into six groups received placebo (lactose tablets), pyridoxine, pyridoxine + ascorbic acid, pyridoxine + iron, pyridoxine + riboflavin and multivitamin supplements, respectively. Presupplementation E-ALAT activity increased significantly (p less than 0.05) for all supplemented subjects after 6 weeks. Deficient subjects (E-ALAT) index less than 1.16) however failed to respond to a combination of pyridoxine + ascorbic acid or multivitamins. It is suggested that pyridoxine in multivitamin preparations must exceed 1 mg to produce any useful improvement in vitamin B6 status of adolescents on suboptimal vitamin B6 intakes.
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PMID:Effect of supplementation with water-soluble vitamins on erythrocyte alanine aminotransferase activity of healthy adolescents. 187 96


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