Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
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The main biochemical indices of hepatic functions (the activities of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, alpha-amylase, choline esterase and the concentrations of total bilirubin, cholesterol, and glucose) were studied in the sera of 256 patients with chronic opisthorchiasis. It was found that with diseases manifested in different clinical forms (cholangitis, cholecystitis, cholangiocholecystitis, cholangiohepatitis, cholecystitis in combination with pancreatitis), most study indices are within the normal ranges, but significantly differ from the means in a group of apparently healthy individuals. The findings suggest that such clinical forms of opisthorchiais as cholangiocholecystitis and cholangiohepatitis are characterized by manifestations of cytolysis and cholestasis, as cholecystitis is manifested by cytolysis, as cholecystitis in combination with pancreatitis, by cholestasis, and as cholangitis, by cholestasis and hepatic cell insufficiency. It is possible that further studies will provide evidence for how to correct detected disorders during pathogenetic therapy.
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PMID:[Biochemical characteristics of hepatic functions in different clinical forms of chronic opisthorchiasis]. 1222 56

Quantitative determination of newly reported enzymes activity in the crude skin toxin (CST) of catfish revealed highest activities of hyaluronidase and lipase, lesser activities of phospholipase A2, lactate dehydrogenase (LDH), cholinesterase (CE), alkaline phosphatase (ALP), and aspartate transaminase (AST), and least activities of proteinase and 5-nucleotidase (5'-NT). The CST has a hemolytic activity of 54% and no ichthyotoxicity up to 500 ug/ml. The chosen dose of CST (LD12.5) showed a potential cytotoxic activity against solid Ehrlich carcinoma-bearing mice demonstrated by an increase in the mean survival time (238.8%) and tumor growth inhibition ratio (T/C) of 73%. The CST ameliorated the relative weights of heart and liver after three weeks, while modulating the elevation in the relative spleen weight throughout the treatment periods (three, six, and nine weeks). The levels of serum triglyceride, total cholesterol, and liver total lipids were normalized after three weeks, whereas the serum albumin and hepatic glycogen concentrations, as well as ALT, AST, 5'-NT, and G-6-Pase activities were ameliorated after 6 weeks. Serum levels of glucose, LDH, and creatine kinase (CK) activities were significantly modulated throughout the treatment periods. Histological examinations of the tumor and liver tissues of treated tumor-bearing animals were carried out. Tumor tissues showed many cytolytic and cytopathic changes after treatment, while liver tissues showed moderate dysplastic changes after six weeks of treatment, which became more marked after nine weeks.
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PMID:Biological activities of the crude skin toxin of the Suez Gulf oriental catfish (Plotosus lineatus) and its antitumor effect in vivo (mice). 1250 71

To determine the role of redo hepatic portoenterostomy (HPE) in biliary atresia (BA) patients with insufficient bile excretion after the initial HPE, 25 patients (type I, correctable: 2; type III, uncorrectable: 23) undergoing the initial HPE at 25 to 119 days of age were studied. Four patients achieved disappearance of jaundice (total bilirubin [T.Bil] < 2 mg/dl) postoperatively. A redo HPE was performed at 2 to 8 months of age with sufficient and extensive removal of granulation and scar tissue at the hepatic hilum. Five patients became free of jaundice in 3 to 6 months (group 1), while the remaining 20 did not (group 2). Disappearance of jaundice after the initial HPE had been achieved in 2 of 5 patients (40%) in group 1 and 2 of 20 (10%) in group 2 ( P < 0.05). Age, serum T.Bil, aspartate aminotransferase albumin, prothrombin time, cholinesterase, total cholesterol, and Fischer's ratio at redo HPE showed no significant differences between the two groups. On liver histology obtained at redo HPE, cirrhosis and hepatocyte degeneration were seen in 1 of 5 cases (20%) in group 1 and 12 of 20 (60%) in group 2 ( P < 0.05). Redo HPE may thus be effective in BA patients with insufficient bile drainage who achieved disappearance of jaundice after the initial HPE and have not developed cirrhosis.
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PMID:Indication for redo hepatic portoenterostomy for insufficient bile drainage in biliary atresia: re-evaluation in the era of liver transplantation. 1268 51

1,2,3-Trichloropropane is a colorless liquid used as a paint and varnish remover, solvent, and degreasing agent, and as a crosslinking agent in the synthesis of polysulfides and hexafluoropropylene. 1,2,3-Trichloropropane may be found as an impurity in certain nematocides and soil fumigants and as a contaminant of drinking and ground water. Studies on the toxic and carcinogenic effects of 1,2,3-trichloropropane were initiated because of the close structural relationship of this chemical to other short-chain halogenated compounds that were demonstrated to be carcinogenic in experimental animals, and because of the potential for human exposure. Toxicology and carcinogenicity studies were conducted by administering 1,2,3-trichloropropane (greater than 99% pure) in corn oil by gavage to groups of F344/N rats and B6C3FI mice for 17 weeks and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium strains, mouse lymphoma cells, and Chinese hamster ovary cells. 17-Week Studies: Groups of 20 male and 20 female rats received 1,2,3-trichloropropane in corn oil by gavage at doses of 8, 16, 32, 63, 125, or 250 mg/kg body weight 5 days per week for up to 17 weeks; 30 male and 30 female rats received corn oil alone and served as controls. Animals were evaluated at 8 or 17 weeks. All rats in the 250 mg/kg groups died by week 5. One male and four female rats in the 125 mg/kg groups died during the study. The mean body weight gains and final mean body weights of males receiving 63 mg/kg and of males and females receiving 125 mg/kg were lower than those of the controls. Hematocrit values, hemoglobin concentrations, and erythrocyte counts decreased with dose in males and females. Serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase activities were significantly increased in some female rats receiving 125 mg/kg. Serum pseudocholinesterase activity decreased with dose in females. Increases in kidney and liver weights were related to chemical administration. The principal toxic lesions associated with the administration of 1,2,3-trichloropropane to rats were hepatocellular necrosis, karyomegaly, and biliary hyperplasia of the liver; renal tubule necrosis, regeneration, and karyomegaly of the kidney; and necrosis and inflammation of the nasal olfactory and respiratory epithelium. Groups of 20 male and 20 female mice received 1,2,3-trichloropropane in corn oil by gavage at doses of 8, 16, 32, 63, 125, or 250 mg/kg 5 days per week for up to 17 weeks; 30 male and 30 female mice received corn oil alone and served as controls. Sixteen male and seven female mice in the 250 mg/kg groups died by week 4. The final mean body weights and mean body weight gains of dosed mice were similar to those of the controls, except those of 250 mg/kg males, which were lower than those of controls. The principal toxic lesions associated with the administration of 1,2,3-trichloropropane were hepatocellular necrosis and karyomegaly of the liver; necrosis, regeneration, and hyperplasia of the bronchiolar epithelium in the lung; and acanthosis (hyperplasia) and hyperkeratosis of the forestomach epithelium. 2-Year Studies: Groups of 60 male and 60 female rats received 0, 3, 10, or 30 mg 1,2,3-trichloropropane/kg body weight in corn oil by gavage 5 days per week for up to 104 weeks. Selection of 30 mg/kg as the high dose in these studies was based on the following chemical-related effects in the 17-week studies: deaths and liver and kidney lesions at 125 and 250 mg/kg and reduced final mean body weights and mean body weight gains at 63 mg/kg or greater. Groups of 60 male and 60 female mice received 0, 6, 20, or 60 mg 1,2,3-trichloropropane/kg body weight in corn oil by gavage 5 days per week for up to 104 weeks. Selection of 60 mg/kg as the high dose was based on chemical-related deaths and lesions of the liver, lung, and forestomach at 125 and 250 mg/kg in the 17-week studies. 15-Month Interim Evaluations: Up to 10 rats and 10 mice from each dose group were evaluated at 15 months. Absolute and relative liver and kidned kidney weights of dosed rats were significantly greater than those of the controls. Chemical-related nonneoplastic lesions and neoplasms of the forestomach, oral mucosa, pancreas (males), kidney, mammary gland (females), preputial gland, and clitoral gland were observed in dosed rats. Chemical-related nonneoplastic lesions and neoplasms of the forestomach and liver (females) were observed in dosed mice. Survival and Body Weight in the 2-Year Studies: Survival of male and female rats receiving 10 or 30 mg/kg 1,2,3-trichloropropane was significantly lower than that of controls. Two-year survival rates of male rats were: control, 34/50; 3 mg/kg, 32/50; 10 mg/kg, 14/49; 30 mg/kg, 0/52; and of females were: 31/50, 30/49, 8/52, 0/52. At 30 mg/kg, survival was markedly reduced due to chemical-related neoplasms, and survivors were killed in weeks 67 (females) or 77 (males). Final mean body weights of 30 mg/kg rats were 13&percnt; lower for males and 12&percnt; lower for females than those of controls; mean body weights of 3 and 10 mg/kg rats were similar to controls. Survival rates of mice receiving 6, 20, or 60 mg/kg 1,2,3-trichloropropane were also significantly lower than those of controls. Two-year survival rates of male mice were: 42/52, 18/51, 0/54, 0/56; and of female mice were: 41/50, 13/50, 0/51, 0/55. Because of reduced survival at 20 and 60 mg/kg due to chemical-related neoplasms, survivors were killed in weeks 73 (60 mg/kg females), 79 (60 mg/kg males), or 89 (20 mg/kg males and females). Final mean body weights were 16&percnt; lower for 60 mg/kg males, 18~ lower for 60 mg/kg females, and 13&percnt; lower for 20 mg/kg males than those of controls. Final mean body weights of 6 mg/kg males and females and 20 mg/kg females were similar to controls. Neoplasms and Nonneoplastic Lesions in the 2-Year Studies: Administration of 1,2,3-trichloropropane to rats induced benign and malignant neoplasms of the oral mucosa (pharynx and tongue), forestomach, and preputial and clitoral glands in males and females; benign neoplasms of the exocrine pancreas and kidney in males, and malignant neoplasms of the mammary gland in females. The incidences of squamous cell papillomas and carcinomas of the oral mucosa were significantly increased in 10 and 30 mg/kg rats, while the incidences of squamous cell papillomas or carcinomas (combined) of the forestomach were significantly increased in all dosed groups. The incidence of pancreatic acinar adenoma was significantly increased in dosed males, but not in dosed females. Similarly, the incidence of adenoma of the kidney was significantly increased in 10 and 30 mg/kg male rats only. The incidences of adenoma or carcinoma (combined) of the preputial gland in 30 mg/kg males and of the clitoral gland in 10 and 30 mg/kg females (homologous organs) were significantly increased. The incidence of adenocarcinoma of the mammary gland was significantly increased in the 10 and 30 mg/kg females. The incidences of Zymbal's gland carcinomas were increased in 30 mg/kg males and females. Adenocarcinomas of the intestine occurred in small numbers of dosed rats and may have been chemical related. In mice, the incidence of squamous cell carcinoma of the oral mucosa was significantly increased only in 60 mg/kg females. In contrast, the incidences of squamous cell papilloma and carcinoma of the forestomach were significantly increased in all groups of dosed mice. The incidences of hepatocellular adenoma or carcinoma (combined) were significantly increased in all dosed groups of males and 60 mg/kg females. The incidences of harderian gland adenoma were significantly increased in 20 mg/kg males and in 60 mg/kg males and females. The incidences of uterine adenoma, adenocarcinoma, and stromal polyp were significantly increased in 60 mg/kg females. Genetic Toxicology: 1,2,3-Trichloropropane was mutagenic in vitro in the presence of S9 metabolic activation. At two laboratories, positive responses were obtained for mutagenicity in Salmonella typhimurium strains TA97, TA98, TA100, and TA1535 in the presence of S9; no mutagenic activity was observed in TA1537, with or without S9. 1,2,3-Trichloropropane induced trifluorothymidine resistance in L5178Y mouse lymphoma cells with, but not without, S9. In cultured Chinese hamster ovary cells, sister chromatid exchanges and chromosomal aberrations were induced by 1,2,3-trichloropropane; however, significant increases in the endpoints of both cytogenetic effects occurred only in the presence of S9. Conclusions: Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in male F344/N rats based on increased incidences of squamous cell papillomas and carcinomas of the oral mucosa and forestomach, adenomas of the pancreas and kidney, adenomas or carcinomas of the preputial gland, and carcinomas of the Zymbal's gland. Adenomatous polyps and adenocarcinomas of the intestine may have been related to chemical administration. There was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in female F344/N rats based on increased incidences of squamous cell papillomas and carcinomas of the oral mucosa and forestomach, adenomas or carcinomas of the clitoral gland, adenocarcinomas of the mammary gland, and carcinomas of the Zymbal's gland. Adenocarcinomas of the intestine may have been related to chemical administration. There was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in male B6C3F1 mice based on increased incidences of squamous cell papillomas and carcinomas of the forestomach, hepatocellular adenomas or carcinomas of the liver, and harderian gland adenomas. Squamous cell papillomas of the oral mucosa may have been related to chemical administration. There was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in female B6C3F1, mice based on increased incidences of squamous cell carcinomas of the oral mucosa, squamous cell papillomas and carcinomas of the forestomach, hepatocellular adenomas or carcinomas of the liver, harderian gland adenomas, and uterine adenomas, adenocarcinomas, and stromal polyps. Nonneoplastic lesions associated with exposure to 1,2,3-trichloropropane included increased severity of nephropathy in male rats and increased incidences of basal cell and squamous hyperplasia of the forestomach, acinar hyperplasia of the pancreas, renal tubule hyperplasia, and preputial or clitoral gland hyperplasia in male and female rats. Increased incidences of squamous hyperplasia of the forestomach and eosinophilic foci in the liver in male and female mice were chemical related. Synonyms: Allyl trichloride, glycerol tnchlorohydrin, glyceryl tnchlorohydrin, trichlorohydrin
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PMID:NTP Toxicology and Carcinogenesis of 1,2,3-Trichloropropane (CAS No. 96-18-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1269 52

The aim of this study was to assess the influence of surgical intervention on changes in liver enzymes in patients with antibodies to hepatitis C virus (HCV). Of 623 patients who underwent laparotomy in our department during the 2 years between January 2000 and December 2001, a group of 39 (6.3%) who were positive for the HCV antibody were enrolled in this study. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and cholinesterase (ChE) were the standard liver tests performed. The antibody to HCV was measured in serum using an ELISA kit that can detect antibodies against the combined epitopes. The postoperative elevated values of AST and ALP in the anti-HCV-positive group were significantly higher than those in the anti-HCV-negative group ( p < 0.05). The postoperative decreased values of ChE in the anti-HCV-positive group were significantly greater than those in the anti-HCV-negative group ( p < 0.02). The postoperatively decreased ratios of ChE in the anti-HCV positive group were significantly greater than those in the anti-HCV negative group ( p < 0.0001). Using multivariate logistic regression modeling, testing positive for the antibody to HCV was independently and significantly associated with abnormal levels of ALT and ALP ( p = 0.035 and 0.018, respectively). Monitoring liver enzymes such as ChE, ALT, and ALP might be effective for evaluating liver function after surgery in anti-HCV-positive patients.
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PMID:Changes in liver enzymes after surgery in anti-hepatitis C virus-positive patients. 1517 2

Conflicting views exist at the present regarding the influences of a deep saturation dive on liver function in divers. Therefore, we first reevaluated whether a deep saturation dive (400 msw) induces a hepatic disturbance. As the result, plasma activities of both transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) increased significantly, whereas cholinesterase (Ch-E) activity decreased markedly, being highly suggestive of liver dysfunction. Assuming that the liver dysfunction was attributable to oxidative stress, we next examined the effects of supplementation of antioxidants (600 mg of vitamin C, 150 mg of alpha-tocopherol, and 600 mg of tea catechins per day) on liver function in saturation divers. As was anticipated, the antioxidants taken appeared to prevent a hepatic disturbance, indicating that a deep saturation dive provokes liver dysfunction probably due to oxidative stress. Thus, we recommend that saturation divers should take supplements of antioxidants.
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PMID:Supplementation of antioxidants prevents oxidative stress during a deep saturation dive. 1529 42

The change from measuring enzyme catalytic activity concentrations from 25 degrees C to 37 degrees C in the German Federal Republic has led to the need for new reference ranges for defined patient groups and for healthy individuals. Up to now, these are only present as tentative values and are incomplete, especially for children. This article describes a method for deriving reference ranges from results obtained from measurement at 25 degrees C and 37 degrees C and the use of percentiles to establish values for 37 degrees C. A total of 1,111,378 data from 507,305 patients were used to establish reference ranges for the following 11 enzymes at 37 degrees C using the test kits from Roche Diagnostics measured on the Modular analyser: acid phosphatase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, cholinesterase, creatine kinase, creatine kinase - MB subunit, gamma glutamyl transpeptidase, glutamate dehydrogenase, lactate dehydrogenase and lactate dehydrogenase - isoenzyme 1. The computed reference ranges from the data used gave rise to reference ranges, some of which were in agreement with the data from the producer, some of which, however, showed deviations from the values given by the producer. Ranges for newborns, children and adolescents could be computed with the prerequisite that ranges for 25 degrees C were available and that these had been established and validated. This method of establishing reference ranges for catalytic enzyme activities can be used for all producers, providing the number of data used is sufficient to allow for valid statistical analysis.
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PMID:Establishment of reference intervals for enzyme catalytic activity concentration measurements at 37 degrees C--a practical approach. 1533 May 15

Hematologic, protein electrophoresis, serum biochemistry, and cholinesterase values were determined in 36 free-living black stork nestlings (Ciconia nigra) between 25 and 53 days of age in order to establish normal reference values for this population. The following values were evaluated: white blood cell counts, red blood cell counts, packed cell volume, hemoglobin, heterophils, lymphocytes, monocytes, eosinophils, prealbumin, albumin, alpha-globulin, beta-globulin, gamma-globulin, total protein, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, calcium, phosphorus, iron, cholesterol, glucose, triglycerides, uric acid, urea, creatinine, total solids, bile acids, and butyrylcholinesterase. Sex-dependent differences were observed in hemoglobin, prealbumin, albumin, gamma-globulin, total protein, alkaline phosphatase, and triglycerides. Packed cell volume, butyrylcholinesterase, aspartate aminotransferase, creatine kinase, and creatinine increased with age, whereas albumin, mean cell volume, calcium, phosphorus, cholesterol, and total solids decreased with age. These hematologic and serum biochemistry values can be used as reference ranges in free-living black stork nestlings.
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PMID:Hematologic, protein electrophoresis, biochemistry, and cholinesterase values of free-living black stork nestlings (Ciconia nigra). 1610 73

A complex of biochemical parameters of hepatic functions was analyzed in 170 patients with chronic opisthorchiasis and in 90 apparently healthy dwellers from a region wherein opisthorchiasis is endemic. The activity of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, alpha-amylase, and choline esterase and the serum concentrations of bilirubin, cholesterol, and glucose were studied. A correlation analysis indicated that prolonged Opisthorchis invasion rearranged the system of interactions of the biochemical parameters of the functions of the liver and pancreas. The auxiliary ("local") standards obtained from a study of a group of apparently healthy dwellers from an opisthorchiasis-endemic region may be use to consider the results of individual examinations of patients with chronic opisthorchiasis in order to correct the processes of treatment and rehabilitation.
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PMID:[Analysis of a complex of biochemical parameters of hepatic functions in opisthorchiasis]. 1644 32

Although several cytogenetic biomonitoring studies on workers exposed to pesticides have been reported, there is only limited information on this topic from developing countries where pesticides have been widely used over the years. People in developing countries are at higher risk from exposure, due to poor working conditions and a lack of awareness of the potential hazards during manufacturing and application of the pesticides. The present study has assessed the genotoxic effects of pesticides on workers involved in the pesticide manufacturing industry. Subjects in the exposed group (29) were drawn from workers at a pesticide production plant in district Multan (Pakistan). The control group (unexposed) composed of 35 individuals from the same area but was not involved in pesticide production. Liver enzymes, serum cholinesterase (SChE), micronucleus assay and some haematological parameters were used as biomarkers in this study. A statistically significant (P < 0.001) increase in levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase was detected in exposed workers with respect to the control group. There was a significant (P < 0.001) decrease in the level of SChE in the exposed group. Exposed individuals exhibited cytogenetic damage with increased frequencies (P < 0.001) of binucleated cells with micronuclei and total number of micronuclei in binucleated lymphocytes in comparison with subjects of the control group. A decrease (P < 0.001) in cytokinesis block proliferation index similarly demonstrates a genotoxic effect due to pesticide exposure. The results indicate that the pesticide industry workers have experienced significant genotoxic exposure. This study highlights the risk to workers in the pesticide manufacturing industries of developing countries such as Pakistan and the need for implementation of suitable safety measures to prevent/limit exposure to harmful toxins.
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PMID:Cytogenetic analysis of Pakistani individuals occupationally exposed to pesticides in a pesticide production industry. 1654 Apr 94


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