Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 effect of the specific muscle toxicant, 2,3,5,6-tetramethyl p-phenylenediamine (TMPD), on urinary creatine and taurine, markers of testicular and liver dysfunction, respectively, has been investigated in male Sprague-Dawley rats. Damage to the gastrocnemius and soleus muscles was accompanied by a rise in serum creatine kinase (predominantly the muscle-specific isoenzyme, CK-MM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Increases in serum alpha-hydroxybutyrate dehydrogenase (HBDH) and total lactate dehydrogenase (LDH) (mainly isoenzymes, LDH1 and LDH2), occurred but only minor damage to the heart and no rise in CK-MB, (heart muscle isoenzyme) was seen. Damage to stage XIV tubules in the testis was evident histologically after the highest dose. This was accompanied by an increase in LDH-C4 testis-specific isoenzyme and a decrease in serum testosterone. Apart from reduced serum albumin, no other serum parameters indicated liver damage and there was only slight liver steatosis in some animals at the highest dose. Urinary taurine was not significantly raised after any dose of TMPD, but there was a significant increase in urinary creatine after the highest dose. It can be concluded that in the presence of discrete muscle damage, the use of urinary taurine and urinary creatine as markers of liver and testicular dysfunction, respectively, is not confounded. However, a variety of different markers should be used in conjunction to fully delineate the tissue damage due to toxic chemicals.
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PMID:Studies on the muscle toxicant 2,3,5,6-tetramethyl p-phenylenediamine: effects on various biomarkers including urinary creatine and taurine. 771 59

The effect of a regular oral diet supplying 167 kJ/kg per d (40 kcal/kg per d) on nutritional state, liver function and serum lipid profile was assessed in thirty severely malnourished alcoholic cirrhotic inpatients. Their diet was monitored by a trained dietitian and they were vigorously encouraged to eat all meals served. One month after their entry into the study, protein and energy intakes were significantly higher (P < 0.001) in keeping with an improvement of their nutritional status as evaluated by means of height-creatinine index, muscular mid-arm circumference, tricipital skinfold thickness (P < 0.01 for all) and fat mass (P < 0.001). Assessment of liver function tests showed that levels of aspartate aminotransferase (EC 2.6.1.1), gamma-glutamyl transferase (EC 2.3.2.2) and bilirubin decreased (P < 0.05, P < 0.02 and P < 0.05 respectively) while prothrombin time values increased (P < 0.05). Similarly, serum albumin increased modestly while transthyretin did not change. Orosomucoid and C-reactive protein decreased (P < 0.001 and P < 0.01 respectively), indicating an improvement of the inflammatory state. Apolipoprotein A1 and high-density-lipoprotein (HDL)-cholesterol correlated with several tests of liver function and improved significantly during the study period (P < 0.001 and P < 0.02 respectively). Moreover, changes in cholesterol and HDL-cholesterol correlated with those in transthyretin (P < 0.02 and P < 0.05 respectively). The changes in ApoA1 and HDL-cholesterol were greater in patients whose fat mass increased significantly. Our findings show that adequate oral nutrition resulted in a better nutritional status in cirrhotics after 1 month of hospitalization. The serum lipid variables appeared to be more useful indicators of functional liver improvement than the classic liver function tests which rather indicate liver damage.
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PMID:One-month regular oral nutrition in alcoholic cirrhotic patients. Changes of nutritional status, hepatic function and serum lipid pattern. 782 13

The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p < 0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.
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PMID:A double-blind randomized controlled trial of colchicine in patients with hepatitis B virus-related postnecrotic cirrhosis. 789 Sep 5

ZF-L cells were derived from normal adult zebrafish liver, and have been growing in culture for more than 100 generations. The cells were derived in basal nutrient medium supplemented with fetal bovine serum (FBS), trout serum, trout embryo extract, bovine insulin and mouse epidermal growth factor. After 50 generations in culture, optimal growth of the cells was achieved in medium supplemented with FBS (5%) and trout serum (0.5%). ZF-L cells were hypodiploid (modal chromosome number = 46) and exhibited an epithelial morphology. ZF-L cell homogenates exhibited alanine and aspartate aminotransferase, glucose-6-phosphatase and alkaline phosphatase enzyme activities. The cells synthesized and released several proteins into the culture medium, including a 70 kDa protein recognized by anti-bovine serum albumin IgG.
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PMID:Derivation and characterization of a zebrafish liver cell line. 799 34

Etoposide is a schedule-dependent cytotoxic drug with high single agent activity in small-cell lung cancer and lymphoma. Despite its clear dose-dependent myelosuppressive activity, dose-dependent evidence of its anti-tumour activity is harder to demonstrate. A number of reports have correlated haematological toxicity with pharmacokinetic and physiological parameters, which explains some of the variability in dynamic effects that exists between patients. Recent reports have also suggested that anti-tumour response may be related to plasma etoposide concentration. In our own studies we have investigated factors that influence the pharmacodynamic effects of etoposide, principally with regard to haematological toxicity, and these studies have highlighted a number of patient groups who are at risk. Impaired renal function causes a reduction in clearance of etoposide, resulting in increased systemic exposure and more profound myelotoxicity. A 30% dose reduction in this group is recommended to normalise the area under the plasma concentration-time curve (AUC). Patients with low serum albumin concentrations (< 35 g/l) also showed significantly worse haematological toxicity, but with no apparent change in total drug pharmacokinetics. There was, however, an increase in the free drug fraction in this group due to decreased protein binding, such that the free drug AUC was similar to that found in patients with renal dysfunction. This would also indicate that a dose reduction of around 30%-40% is required in this patient group. Patients with normal albumin levels but liver enzyme values (aspartate transaminase or gamma-glutamyl transpeptidase) more than 3 times the upper limit of normal also had a less marked but significant increase in neutropenia. In patients with normal organ function, age was the only significant factor in predicting the degree of leukopenia/neutropenia, and increasing age was also associated with decreasing drug clearance and an increase in drug AUC. A small dose reduction and/or careful monitoring is required in this patient group. Further studies are required to elucidate further the relationship between the pharmacokinetics of etoposide and its pharmacodynamics, particularly with regard to anti-tumor activity, and to determine the role of individualised therapy, based on a pharmacokinetic parameter, in reducing the dynamic variability and optimising the use of this drug.
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PMID:Etoposide dosage and pharmacodynamics. 807 31

Methotrexate (MTX) has become an important drug in the treatment of rheumatoid arthritis (RA). The American College of Rheumatology convened a committee to assess the risks of development of clinically significant liver disease (CSLD) during MTX treatment, to evaluate the risk and role of surveillance liver biopsies, and to provide recommendations about monitoring patients for liver toxicity. The committee recommends obtaining liver blood tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, albumin, bilirubin), hepatitis B and C serologic studies, and other standard tests including complete blood cell count and serum creatinine tests prior to starting treatment with MTX. A pretreatment liver biopsy should be considered only for patients with a history of prior excessive alcohol consumption, persistently abnormal baseline AST values, or chronic hepatitis B or C infection. At intervals of every 4-8 weeks the AST, ALT, and albumin levels should be monitored. Routine surveillance liver biopsies are not recommended for RA patients receiving traditional doses of MTX. However, a biopsy should be performed if a patient develops persistent abnormalities on liver blood tests. These are defined as elevations (above the upper limit of laboratory normal) in the AST in 5 of 9 determinations within a given 12-month interval (6 of 12 if tests are performed monthly) or a decrease in serum albumin below the normal range. The recommendations for monitoring and selection of patients for liver biopsy identify patients at potential risk for CSLD, and thus significantly reduce the number or patients who would be exposed to this procedure. Close monitoring is essential to reduce the risk of unrecognized serious liver disease. These recommendations should be revised as necessary to reflect new and compelling information.
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PMID:Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. American College of Rheumatology. 798 33

We measured plasma endothelin-1 (ET-1) concentrations in 20 healthy controls and 63 patients with liver diseases including 9 cases of acute hepatitis (AH), 14 cases of chronic hepatitis (CH), 24 cases of liver cirrhosis (LC), 11 cases of hepatocellular carcinoma with LC (HCC), 3 of primary biliary cirrhosis and 2 of idiopathic portal hypertension. ET-1 levels in AH (5.07 +/- 2.54 pg/ml, mean +/- SD), LC (3.71 +/- 1.17) and HCC (3.08 +/- 0.93) were significantly higher than those in healthy controls (2.18 +/- 0.37). ET-1 levels in AH, LC and HCC were also significantly higher than those in CH (2.05 +/- 0.61). ET-1 levels showed negative correlations with serum albumin levels and Ch-Ease activities, and positive correlations with serum bilirubin levels, AST and ALT activities. However, there was no correlation between plasma ET-1 concentrations and concentrations of serum thrombomodulin which is known to be a marker of injured vascular endothelial cells. In cirrhotic patients, ET-1 levels were significantly influenced by the presence of ascites. The results of the present study suggest that plasma ET-1 concentrations may be a useful clinical indicator for use in the follow-up of patients with chronic liver diseases, e.g., progression from CH to LC, and change in grade of portal hypertension and decompensation in LC.
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PMID:Plasma endothelin-1 concentrations are elevated in acute hepatitis and liver cirrhosis but not in chronic hepatitis. 822 17

Clinical and biochemical parameters associated with the removal of the peritoneal catheter and death following continuous ambulatory peritoneal dialysis (CAPD) peritonitis were analyzed in 120 episodes of peritonitis. Episodes resulting in catheter removal (n = 24, 20%) and those ending in patient death (n = 12, 10%) were respectively compared with episodes in which peritoneal catheters were saved and from which the patients survived. Variables associated with catheter removal included advanced age, long duration of peritonitis, coexisting exit-site/tunnel infection, infection caused by pseudomonas or fungi, elevated aspartate aminotransferase (AST) and malnutrition at presentation with peritonitis (serum albumin 29.5 +/- 7.6 g/L vs 33.8 +/- 4.8 g/L in episodes in which the catheters were saved, p = 0.014), and worsening malnutrition during peritonitis. Variables associated with death from peritonitis included diabetes mellitus, persistence of the infection, removal of the peritoneal catheter, infection with pseudomonas, malnutrition prior to the infection (serum albumin 29.5 +/- 3.2 g/L vs 34.7 +/- 4.2 g/L in survivors, p < 0.001), presentation with elevated AST and worsening malnutrition, and the development of pronounced malnutrition during infection (serum albumin 18.1 +/- 4.1 g/L vs 28.9 +/- 5.8 g/L in survivors, p < 0.001). Deaths were caused primarily by cardiovascular events. Both removal of the peritoneal catheter and death as consequences of CAPD peritonitis are associated with malnutrition and pseudomonas infection. In addition, death is more frequent in diabetic patients.
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PMID:Peritoneal catheter loss and death in continuous ambulatory peritoneal dialysis peritonitis: correlation with clinical and biochemical parameters. 839 4

To evaluate the clinical applications of serum thymidine kinase (TK) activity, we compared the results obtained with this parameter with those of other liver function tests in 27 patients with acute viral hepatitis and 16 normal controls. In those in the acute stage, the serum TK activity increased significantly to 55.5 +/- 66.5 U/L. There was no significant correlation between serum TK activity and findings for serum albumin, bilirubin, alkaline phosphatase or r-glutamyl transpeptidase. However, it did correlate significantly well with the serum activity of aspartate aminotransferase (AST) (r = 0.621, P < 0.01), alanine aminotransferase (ALT) (r = 0.551, P < 0.01), and lactate dehydrogenase (LDH) (r = 0.620, P < 0.01). Serum TK activity reached higher than 70 U/L in 8 of 11 patients with hepatitis A; however, no patients with the other types of hepatitis reached such a high level. During the recovery stage, the serum TK activity decreased significantly to 5.9 +/- 1.7 U/L (P < 0.01), and did not correlate with AST, ALT, LDH or other conventional liver function parameters. The data suggest that an elevation of serum TK in patients with acute viral hepatitis results from hepatocellular damage. A marked elevation of serum TK activity may thus provide a marker for acute hepatitis A infection.
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PMID:Elevated serum thymidine kinase activity in patients with acute viral hepatitis. 844 Apr 24

A controlled trial on nutrition supplementation in ambulatory patients with decompensated alcoholic liver disease was carried out during 1 year. Fifty-one patients were studied; 26 were assigned to an experimental group receiving a daily supplement of 1000 kcal and 34 g of proteins given as a casein-based enteral nutrition product and 25 to a control group receiving one placebo capsule. Patients were examined in a special clinic once a month or more if required. Sixty-eight percent of patients admitted to alcohol ingestion or had alcohol in urine samples on at least one occasion. Dietary recalls showed a significantly higher protein and caloric intake in case patients subjects (p < .0001). Nine patients died during the study, three case patients and six control patients (p = NS). The frequency of hospitalizations was significantly less in the experimental group. This difference was attributed to a reduction in severe infections. Mid-arm circumference, serum albumin concentration, and hand grip strength improved earlier in case patients, although both groups had a significant improvement in these parameters. Bilirubin and aspartate aminotransferase decreased and prothrombin time increased significantly in both groups during the study period, without differences between groups. It is concluded that nutrition support decreases nutrition-associated complications in patients with alcoholic liver disease.
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PMID:Controlled trial on nutrition supplementation in outpatients with symptomatic alcoholic cirrhosis. 845 12


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