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)

Ten male Holstein-Friesian calves naturally infected by Mycobacterium paratuberculosis were experimentally re-infected orally at an average of 17 days. Monthly measurements were conduced of the following activities, in the period between post infection days 160 and 400: total protein (TPR), albumin (ALB), cholesterol (CHOL), triglycerides (TRIG), Zn and Cu concentrations as well as sorbitol dehydrogenase, lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), gamma-glutamyltransferase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), alkaline phosphatase and fructose-1,6-diphosphate aldolase (ALD). TPR, ALB, TRIG, and CHOL were reduced by day 400, in conjunction with disorders of digestion and absorption. Increased activities of CK, ALD, LDH, alpha-HBDH, AST and ALT primarily indicated damage to skeletal muscle and/or liver. Serum CK and ALD activities as well as TRIG and TPR concentrations may serve as aids to specific diagnosis of paratuberculosis, particularly in the advanced stage of the disease.
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PMID:Experimental paratuberculosis (Johne's disease)--studies on biochemical parameters in cattle. 277 44

Cyclopiazonic acid (CPA) was given daily to groups of guinea pigs at doses of 0.00625, 0.0125, 0.025, 0.05, 0.1, 0.2, 0.4, 0.8, 1.6, and 1.95 mg/day for 30 days. All guinea pigs were sensitized and survivors were skin tested twenty-five days later with Mycobacterium tuberculosis. Mortalities occurred only in the two greatest dose groups. Signs of disease included anorexia, roughened hair coat, diarrhea and incoordination. The major histopathologic changes occurring in these two groups included hepatocellular vacuolar degeneration and necrosis of the gastric mucosa with infiltration of neutrophils in the deep gastric mucosa. CPA did not affect cutaneous hypersensitivity to M. tuberculosis, complement activity, serum glycocholic acid concentrations or weight gains. There were increases in aspartate aminotransferase, alanine aminotransferase, and sorbitol dehydrogenase concentrations in the serum of guinea pigs in the two greater dose groups, but no changes were found in serum concentrations of SAP. There was a slight increase in the serum bilirubin concentrations in the greater dose groups.
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PMID:Effect of cyclopiazonic acid on delayed hypersensitivity to Mycobacterium tuberculosis, complement activity, serum enzymes, and bilirubin in guinea pigs. 309 99

The paper investigates the relationships between hydrophobic parameters and antituberculotic activity of 2-alkylthio-6-benzamidobenzothiazoles, tested on INH-resistant strain of Mycobacterium tuberculosis. In the group of compounds with linear alkyl substituents in position 2, the tuberculostatic effect is increasing with decrease of lipophility of alkyls. Branching of the alkyls strongly increases the activity. The hepatotoxicity of compounds under study was investigated by means of the activity of serum aminotransferases (ALT, AST) in Wistar type rats. The hepatotoxicity of compounds seemed to be smaller than that of the thiobenzamides.
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PMID:[Relation between chemical structure, antitubercular activity and hepatotoxicity of 2-alkylthio-6-benzamidobenzothiazoles]. 312 40

Abnormal liver chemistries, unexplained fevers, or hepatomegaly prompted 36 liver biopsies on 34 patients with the acquired immunodeficiency syndrome. The most common finding was the presence of hepatic granulomas, seen in 13 of the biopsy specimens. Eight of these granulomas were ill-defined, and 5 were more clearly associated with mycobacterial disease. Portal fibrosis and fatty infiltration were common, but a paucity of significant inflammatory activity was seen despite elevated aspartate aminotransferase levels, perhaps related to the underlying immunoincompetent status. Other noteworthy histopathologic findings included 1 patient each with peliosis hepatis and cryptococcal hepatitis. Electron-microscopic evidence of cytoplasmic tubular structures or viral particles were seen within the hepatocytes of 2 patients. It is concluded that a broad spectrum of hepatic histopathology may be seen in the acquired immunodeficiency syndrome, and that liver biopsy may be diagnostically valuable in the clinical investigation of such patients.
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PMID:The spectrum of liver disease in the acquired immunodeficiency syndrome. 372 95

The effects of 2,3-dimercaptopropane sulphonate (DMPS) and N-(2-mercapto-2-methylpropanoyl)-L-cysteine (bucillamine) against the renal damage induced by gold sodium thiomalate (AuTM) in adjuvant-arthritic rats were studied. Arthritic rats induced by adjuvant using Mycobacterium butyricum were injected intraperitoneally with a chelating agent (0.6 mmol/kg) immediately after intramuscular injection of AuTM (0.066 mmol/kg) every other day for 21 days. Treatment with DMPS and bucillamine prevented increases in the urinary excretion of protein, aspartate aminotransferase, and glucose and blood urea nitrogen level after AuTM injection. AuTM prevented the increase in both adjuvant-injected and uninjected hind-feet volumes. The prevention of these inflamed lesions by AuTM was not affected by DMPS and bucillamine. These chelating agents decreased the gold concentration in the kidney and liver after AuTM administration, but did not affect the hepatic and renal concentrations of copper, zinc, iron, and calcium except the renal copper level after AuTM. These findings suggest that DMPS and bucillamine are very useful antidotes for gold toxicity.
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PMID:The utility of chelating agents as antidotes for nephrotoxicity of gold sodium thiomalate in adjuvant-arthritic rats. 771 81

Rifapentine is a rifamycin antibiotic with antimycobacterial activity. Rifapentine is generally more active against Mycobacterium tuberculosis than rifampicin (rifampin), although strains resistant to rifampicin are usually cross-resistant to rifapentine. Sputum culture conversion rates were slightly higher after 6 months of rifapentine- versus rifampicin-based therapy in patients with pulmonary tuberculosis in a Western study; however, relapse rates were higher in rifapentine recipients during follow-up. The excess relapses in the rifapentine group appeared to be related to poor compliance with nonrifamycin antituberculosis drugs during the intensive phase (first 2 months) of therapy. Rifapentine- and rifampicin-containing regimens produced similar sputum culture conversion rates with low rates of relapse in 2 randomised clinical trials in patients with smear-positive tuberculosis in China. In one trial, there was no difference in sputum culture conversion rates in patients treated with rifapentine once weekly or rifampicin twice weekly in combination with isoniazid and ethambutol during the continuation phase of treatment. Hyperuricaemia, which was reported only during the intensive phase, elevated ALT and AST levels and neutropenia were the most common treatment-related adverse events reported in patients receiving rifapentine- or rifampicin-containing regimens for tuberculosis in 1 Western study.
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PMID:Rifapentine. 980 7

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

This time, we compared conventional method Well pack P (the proportion method on Ogawa egg medium) with automated instrument BACTEC MGIT 960 AST system for Mycobacterium tuberculosis drug susceptibility testing. Fifty-three M. tuberculosis stock strains were used. Concordance rates between the two methods were SM: 94.3%; INH: 100%; RFP: 100%; and EB: 90.5%. All 23 drug-susceptible strains corresponded to four drugs. Discrepant results were observed in six of 30 drug-resistant strain. The mean times for results from the MGIT 960 AST system was 8.7 days. On the other hand, with Well pack P, growth of drug resistant strains was slow, and it was still difficult to judge four weeks later. Although the MGIT 960 AST system has problems, such as its high cost of labor and reagents, and the confirmation of contamination, because it is an automatic instrument, there are no discrepancies due to different technician techniques. The MGIT 960 AST system was found to be a rapid and excellent method.
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PMID:[Basic evaluation of BACTEC MGIT 960 Series for drug susceptibility testing of antimicrobial agents against Mycobacterium tuberculosis]. 1596 80

Mycobacterium tuberculosis is a concern in patients with human immunodeficiency virus (HIV) infection. Rifampin (RIF), an agent used against M. tuberculosis, is contraindicated with most HIV protease inhibitors. Atazanavir (ATV) has clinical efficacy comparable to a standard of care regimen in naive patients and, when dosed with low-dose ritonavir (RTV), also in treatment-experienced patients. We evaluated here the safety and pharmacokinetics of ATV, resulting from three regimens of ATV, RTV, and RIF in 71 healthy subjects. The pharmacokinetics for ATV and RTV were assessed after 6 and 10 days of dosing with ATV 400 mg (n = 53) and with ATV-RTV at 300 and 100 mg (ATV/RTV 300/100; n = 52), respectively. Steady-state pharmacokinetics for ATV, RTV, RIF, and desacetyl-rifampin (des-RIF) were measured after 10 days of dosing of ATV/RTV/RIF 300/100/600 (n = 17), ATV/RTV/RIF 300/200/600 (n = 17), or ATV/RTV/RIF 400/200/600 (n = 14). An RIF 600-alone arm was enrolled as a control group (n = 18). With ATV/RTV/RIF 400/200/600, ATV area under the concentration-time curve values were comparable, but the C(min) values were lower relative to ATV 400 alone. ATV exposures were substantially reduced for the other RIF-containing regimens relative to ATV 400 alone and for all regimens relative to ATV/RTV 300/100 alone. RIF and des-RIF exposures were 1.6- to 2.5-fold higher than with RIF 600 alone. The incidence of grade 3/4 alanine aminotransferase/aspartate aminotransferase values was limited to 1 subject each in both the ATV/RTV/RIF 300/200/600 and the ATV/RTV/RIF 400/200/600 treatments. Coadministration of ATV with RIF was safe and generally well tolerated. Since ATV exposures were reduced in all regimens, ATV and RIF should not be coadministered at the dosing regimens studied.
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PMID:Effect of rifampin on steady-state pharmacokinetics of atazanavir with ritonavir in healthy volunteers. 1700 14

We reevaluated the BACTEC MGIT 960 antimicrobial susceptibility testing system (MGIT 960 AST) by using 1,112 isolates of Mycobacterium tuberculosis. When the results of MGIT 960 AST were compared with that of the proportion method using Ogawa medium (Ogawa PM), discrepant results were obtained for 30 strains with isoniazid, all resistant by MGIT 960 AST but susceptible by Ogawa PM. For 93% of the strains that produced discrepant results, the MIC was 0.4 or 0.8 microg/ml, showing resistance by the proportion method using Middlebrook agar plates. Furthermore, it was also established by analyses of the katG and inhA genes that strains resistant only by MGIT 960 AST have a low level of isoniazid (INH) resistance, indicating that MGIT 960 AST is a reliable method. Ninety-six strains were resistant to 0.1 microg/ml INH by MGIT 960 AST. When they were divided into three groups, Low-S (susceptible at 0.2 microg/ml), Low-R (resistant at 0.2 microg/ml), and High-R (resistant at 1.0 microg/ml), by Ogawa PM, 43.3% of the Low-S strains had mutations in the promoter region of inhA and no mutations were detected in katG codon 315, while 61.7% of the High-R strains had katG codon 315 mutations or a gross deletion of katG. These results suggest that mutations in inhA are associated with low-level resistance to INH and katG codon 315 mutations are associated with high-level resistance to INH. In addition, the analyses demonstrated some relationship of mutations in the inhA gene with ethionamide resistance for the Low-S strains, but not for the High-R strains.
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PMID:Biological and molecular characteristics of Mycobacterium tuberculosis clinical isolates with low-level resistance to isoniazid in Japan. 1850 39


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