Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate the effects of exposure to possible environmental pollutants such as Cd, Pb and Hg on haematological and serum biochemistry values, New Zealand White female rabbits were treated orally with distilled water solutions of CdSO4 x H2O, Pb(NO3)2 and HgCl2 (n = 4/treatment) in concentrations of 2.3, 4.1, and 30 mg/kg dry matter, respectively, for 28 days. The initial concentrations of Cd, Pb, and Hg in serum were significantly increased by the treatment. Exposure to Pb significantly decreased the red blood cell (RBC) count, haemoglobin (Hgb) concentration and the haematocrit (Hct) value. The Zn-protoporphyrin concentration did not change as a result of Pb exposure. Pb and Hg loading significantly increased the aspartate aminotransferase (AST) activity. Alanine aminotransferase (ALT) activity was also increased by both Hg and Cd exposure. Comparing the treated and the control rabbits, all the trace elements studied significantly reduced the activity of enzymes in the pancreatic tissues. The haematological results indicate that hyperchromic macrocytic anaemia developed in rabbits treated with Pb. The increased activities of both AST and ALT indicate pathophysiological changes of the liver parenchyma, which was verified by focal fatty infiltration seen histopathologically. Cd exposure could exert a toxic effect on the kidneys, although the slight tubulonephrosis developed would not possibly affect the renal function. The reduced activities of amylase, trypsin, protease and lipase induced by Cd, Pb and Hg suggest toxicity to the pancreas.
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PMID:Effect of ingested heavy metals (Cd, Pb and Hg) on haematology and serum biochemistry in rabbits. 1451 58

The association between the severity of chronic hepatitis C and the variability of the hepatitis C virus (HCV) genome remains controversial, but to our knowledge few data are available to date regarding T-cell epitope coding regions in transplant patients. In the current study, we identified 21 human leukocyte antigen (HLA)-A2-positive Spanish patients with chronic hepatitis C, 14 immunosuppressed liver transplant recipients, and 7 immunocompetent controls. Alanine aminotransferase, aspartate aminotransferase, viral load, and rate of fibrosis progression were determined. Genetic distances of HCV isolates and variations in epitopes of the HCV nonstructural 3 protein (NS3-1393 LIFCHSKKK and NS3-1406 KLVALGINAV) were compared between patients with slow or fast progression of fibrosis. Isolates from transplant patients with fast progression were found to be more divergent (P =.03), had a higher mean value of synonymous (dS) variations (P =.02), and some were differentiated in a phylogenetic tree, compared with isolates from patients with slow progression. The HLA-A2-restricted NS3-1406 epitope was found to be more variable (20 of 21 isolates differed from the prototype) compared with the A3-restricted NS3-1392 epitope (19% vs. 1.25% variation). A shift in the viral peptide was not detected in a subset of transplant patients, but was evident in two of three nontransplant patients with follow-up. There was no correlation noted between a particular amino acid variation and fibrosis progression (slow or fast) in either transplant or nontransplant patients. The results of the current study suggest that 1) there may be different HCV-1b strains in our geographic area, 2) immunosuppression appears to have little effect in amino acid variation at the HCV NS3-1406 epitope, and 3) variations over time might be more frequent in nonimmunosuppressed patients.
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PMID:Genetic variability of hepatitis C virus NS3 protein in human leukocyte antigen-A2 liver transplant recipients with recurrent hepatitis C. 1476 59

Alanine aminotransferase (ALT) is a widely used index of liver integrity or hepatocellular damage in clinics as well as a key enzyme in intermediatary metabolism. In this study, we have cloned the complementary DNAs of murine homologues of human alanine aminotransferase 1 and 2 (ALT1 and ALT2). The deduced peptides of murine ALT1 (mALT1) and ALT2 (mALT2) share 87% and 93% identity, respectively, with their human counterparts at the amino acid level. Murine ALT genes localize to separate chromosomes, with mALT1 gene (gpt1) on chromosome 15 and mALT2 gene (gpt2) on chromosome 8. The murine gpt1 and gpt2 differ in messenger RNA expression: gpt1 is mainly expressed in liver, bowel, and white adipose tissue and gpt2 is highly expressed in muscle, liver, and white adipose tissue. Expression of recombinant mALT1 and mALT2 proteins in Escherichia coli (E. coli) produced functional enzymes that catalyze alanine transamination. The potential diagnostic value of ALT isoenzymes in liver disease was evaluated in an obese animal model. In fatty livers of obese mice, ALT2 gene expression is induced 2-fold, but ALT1 remains the same. Furthermore, in fatty liver, total hepatic ALT activity is elevated significantly by 30% whereas aspartate aminotransferase (AST) activity remains unchanged. In conclusion, these results indicate that ALT2 may be responsible for the increased ALT activity in hepatic steatosis and provide evidence that an ALT isoenzyme-specific assay may have more diagnostic value than the total ALT activity assay currently in clinical use.
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PMID:Murine alanine aminotransferase: cDNA cloning, functional expression, and differential gene regulation in mouse fatty liver. 1512 58

In the Nordic Reference Interval Project (NORIP), data from 102 Nordic clinical chemical laboratories were obtained. Each laboratory reported analytical data on up to 25 of the most commonly used clinical biochemical properties, including results from each of a minimum of 25 reference individuals. A reference material consisting of a liquid frozen pool of serum with values traceable to reference methods (used as the project "calibrator" for non-enzymes to correct reference values) was measured together with other serum pool controls in each laboratory in the same analytical series as the project samples. The data on the controls were used to evaluate the analytical quality of the routine methods. For reference interval calculations, only such reference values on enzymes were accepted that were obtained by applying the International Federation of Clinical Chemistry (IFCC) compatible methods (37 degrees C), while "calibrator"-corrected reference values were used in the cases of non-enzymes. For each property, gender- and age-specific reference intervals were estimated, based on simple non-parametric calculations and using objective criteria to perform partitioning into subgroups. It is concluded that the same reference intervals are applicable in all five Nordic countries. The following descriptive data for the considered properties are presented in the tables: number of measurement values from each country and measurement system, certified/indicative target values for controls, differences between methods and measurement systems together with coefficients of variation, effects of control correction on the measurement values, differences between subgroups as determined by age, gender, country and material, and comparison of the new reference intervals with those presented in standard textbooks. The 25 components involved in this project were (listed in alphabetical order): Alanine transaminase, albumin, alkaline phosphatase, amylase, amylase pancreatic type, aspartate transaminase, bilirubin, calcium, carbamide, cholesterol, creatine kinase, creatininium, gamma-glutamyltransferase, glucose, HDL-cholesterol, iron, iron-binding capacity, lactate dehydrogenase, magnesium, phosphate, potassium, protein, sodium, triglyceride and urate.
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PMID:Descriptive analytical data and consequences for calculation of common reference intervals in the Nordic Reference Interval Project 2000. 1522

In addition to regulating blood pressure and body fluid homeostasis, the renin-angiotensin system (RAS) is also involved in hepatic fibrogenesis. We aimed to investigate the effect of losartan, an angiotensin II (Ang II) antagonist, on CCl4-induced hepatic fibrosis in rats. Hepatic fibrosis was induced by a subcutaneous injection with 50% CCl4 in Sprague-Dawley rats. The amount of CCl4 administered was 1 mg/kg. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in plasma and hydroxyproline (Hyp) contents in liver tissue were assayed by spectrophotometry. Hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels in culture supernatants of Kupffer cells (KCs) stimulated with Ang II was determined by ELISA. Liver samples collected after 12 weeks of CCl4 treatment were stained with hematoxylin and eosin, then scored. Losartan (2.5, 5, and 10 mg x kg(-1), ig) and captopril (100 mg x kg(-1), ig) significantly decreased liver and spleen indexes, serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. Histopathological scores showed that losartan had an inhibitory effect on the progression of hepatic fibrosis. In in vitro experiments, losartan (1 x 10(-9) - 1 x 10(-5) M) significantly reduced TNF-alpha and TGF-beta1 levels in culture supernatants of KCs, but captopril (1 x 10(-5) M) did not. The results showed that losartan significantly inhibited the progression of hepatic fibrosis induced by CCl4, and the inhibitory effect of losartan on hepatic fibrosis might be associated with its ability to inhibit the production of TNF-alpha and TGF-beta1 by activated KCs.
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PMID:Effect of losartan, an angiotensin II antagonist, on hepatic fibrosis induced by CCl4 in rats. 1557 10

The effects of co-administration of nicotinic acid (NA) and alcohol (Alc) on liver function in male Wistar rats were evaluated. The rats were randomized into five groups: (i) Olive oil (Oil), (ii) Alc+Oil, (iii) NA+Oil, (iv) NA+Alc+Oil, and (v) Controls (fed only normal rat chow). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), total cholesterol and triglycerides (TG) were measured. Liver histopathology was also assessed. The Alc+Oil group had higher TG levels compared with the NA+Alc+Oil group and all other groups, as well. NA+Oil group had higher levels of AP compared with Alc+Oil and Oil groups. The NA+Oil group had higher ALT levels compared with the Oil group. The Oil group had lower ALT levels compared with the control group. The Alc+Oil group had higher AST levels compared with the NA+Alc+Oil group, as well as with all other groups. Liver histopathology was within the normal range. A moderate amount of Alc daily together with NA is safe in rats. The NA and Alc co-administration reduces the TG and AST levels in rats, compared with the administration of Alc alone.
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PMID:The effect of nicotinic acid and alcohol co-administration in Wistar rats. 1583 55

Besides the long-term effectiveness of a given compound, safety is a very important feature to consider when developing new compounds for chemotherapy against tuberculosis. Reports of fatal and severe liver injury associated with rifampicin-pyrazinamide (RIF-PZA) treatment regimens for latent tuberculosis infections prompted this study to evaluate whether a mouse model has any potential as a tool to assess liver injury following extensive exposure to tuberculosis drugs. Mice were administered high doses of existing drug regimens for latent tuberculosis over a relatively short time period. Alanine aminotransferase (ALT), aspartate aminotransferase and bilirubin levels were determined after 2 weeks and 4 weeks of treatment in serum samples collected from uninfected mice as well as mice infected with Mycobacterium tuberculosis. ALT levels increased significantly after a RIF-PZA treatment regimen for 4 weeks in uninfected mice and after 2 weeks in infected mice. Bilirubin serum levels were also significantly elevated in the M. tuberculosis-infected mice after 4 weeks of RIF-PZA treatment. The data obtained indicate that changes in serum enzyme levels in mice after extensive exposure to tuberculosis drugs could be useful as an initial indicator of drug-related hepatotoxicity.
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PMID:Significant increases in the levels of liver enzymes in mice treated with anti-tuberculosis drugs. 1595 8

The effects of clomazone (0.5 and 1.0 mg/L) according to nominal concentrations used in paddy rice fields (0.4-0.7 mg/L) on protein and carbohydrate metabolism and haematological parameters were evaluated in silver catfish (Rhamdia quelen) after 12, 24, 48, 96 and 192 h of exposure with a recovery period of 96 and 192 h. Liver glycogen increased significantly (P<0.05) in all periods and concentrations tested. The maximum glycogen increase reaches 250% after 12h of exposure. Muscle glycogen reduced significantly after 24, 48, 96 and 192 h for both clomazone concentrations (P<0.05). Significantly elevated plasma glucose values (P<0.05) and variation in glucose in the liver and muscle of exposed fish were observed. Muscle lactate levels increased after 12, 24 and 48 h of clomazone exposure (22-67%), but reduced in the liver (P<0.05). Protein levels were enhanced in the liver and white muscle, except at 96 and 192 h of exposure, whereas it increased in the plasma in the period from 48 to 96 h (P<0.05). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were significantly elevated in the plasma (P<0.05). In the liver, ALT increased after 24 h, while AST activity was enhanced only after 12 h of exposure. Hematocrit contents were reduced after 96 and 192 h of exposure. Most of the metabolic disorders observed did not persist after the recovery period, except for the liver AST and ALT activity. Clomazone concentrations used in this study appear safe to fish, Rhamdia quelen, because overall parameters can be recovered after 96 and 192 h in clean water. ALT and AST activity may be an early biomarker of clomazone toxicity.
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PMID:Effects of clomazone herbicide on hematological and some parameters of protein and carbohydrate metabolism of silver catfish Rhamdia quelen. 1609 6

Blood serum clinical biochemical parameters of fasted BUT Big 8 male turkeys were determined at the ages of 3 days, 4, 8, 12, 16 and 20 weeks, for a follow-up of the developmental changes of some serum metabolites, enzymes and ions. The serum protein content (total protein, albumin, globulin) increased with age, indicating also the moulting-associated metabolic changes in the age interval from the 8th to the 12th weeks. Creatinine was shown to have a peak at 3 days of age (role of muscle activity in thermogenesis), while urate concentration sensitively reflected the dietary protein amount. Serum triglycerides peaked at the time of yolk catabolism, while cholesterol was shown to indicate the moulting, as was serum malondialdehyde. Serum sodium content increased throughout the study. Alanine aminotransferase and aspartate aminotransferase activities increased along the ontogeny, while alkaline phosphatase activity decreased in parallel with the growth. Serum creatine kinase activity showed an over one-magnitude increase. General metabolic and enzymatic alterations were characteristic and applicable for the description of the ontogenetic development of a precocial (post-hatch triglyceride peak), large bodied, meat-type (lactate dehydrogenase, continuously increasing creatine kinase) bird species.
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PMID:Developmental dynamics of some blood biochemical parameters in the growing turkey (Meleagris gallopavo). 1636 42

Treatment of acute venous thromboembolism (VTE) and prophylaxis of recurrent events has been investigated in the THRIVE (THRombin Inhibitor in Venous Thrombe Embolism) Treatment and the THRIVE III trial using the oral direct thrombin inhibitor ximelagatran. Alanine aminotransferase (ALAT) increased in 9.6% and 6.4% of patients in the THRIVE Treatment and THRIVE III trials, respectively. The authors analysed the time course of the ALAT and in additionally of aspartate aminotransferase (ASAT) in blood from 52 and 23 patients participating in the THRIVE Treatment and the THRIVE III trials in Germany. Analysis of variance for repeated measures and t test were performed. In the THRIVE Treatment trial, ALAT was significantly higher at week 2 for enoxaparin/warfarin (p => .0039, t test) and at months 3 and 6 for ximelagatran (p = .0453, p = .0014, respectively). ASAT and ASAT/ALAT ratio values did not increase and not differ for both groups. In the THRIVE III trial, ALAT and ASAT did not increase and did not differ compared to the comparator placebo. 2 x 36 mg Ximelagatran, induced higher ALAT values at months 3 and 6 compared to 2 x 24 mg ximelagatran (p = .0105, p = .0063, respectively). ASAT did not differ between the two doses of ximelagatran. The ASAT/ALAT ratios were lower at week 2 for enoxaparin/warfarin (t-test, p = .0032) and at month 3 and 6 for 2 x 36 mg versus warfarin or 2 x 24 mg Ximelagatran (p between .0187 and .0002). The authors conclude that ALAT increases dose dependently during therapy with ximelagatran. The less frequent and lower increase of ASAT values compared to ALAT values indicates a nontoxic effect of ximelagatran on liver cells.
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PMID:Observations of alanine aminotransferase and aspartate aminotransferase in THRIVE studies treated orally with ximelagatran. 1671 32


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