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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An improved understanding of medical problems of alcoholic patients can be gained from commonly encountered laboratory test results. Liver function tests--such as measures of alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase--may provide evidence of altered hepatic activity of different types, such as obstruction and hepatocellular injury. Other test results may indicate impaired hepatic function, such as measurements of albumin, bilirubin, prothrombin time, and blood urea nitrogen. Alterations are also common in electrolytes, blood glucose, magnesium, phosphate, uric acid, and acid-base balance. Disturbances in hematologic function are not infrequent in alcoholic patients, including anemias from many causes, altered granulocyte responses, and thrombocytopenia.
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PMID:Clinical significance in alcoholic patients of commonly encountered laboratory test results. 159 68

Most laboratories in Pakistan use expensive imported clinical chemistry reagent kits resulting in high cost/test to the patients. To reduce these costs, reagents were prepared from basic chemicals, substrates and enzymes imported from Sigma Chemical Company U.K. This reduced the cost/test by up to 500% in some reagents. The quality of these reagents was tested by Wellcome External, Q.C. Locally prepared reagents were comparable to or better than commercial reagents systems in terms of accuracy and precision. This paper describes the preparations according to I.F.C.C., costs and quality control of some of the reagents i.e., glucose, calcium, bilirubin, albumin, total protein, urea, ALT, AST and LDH and their comparisons with equivalent commercial kits.
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PMID:Economy and quality assessment of home made clinical chemistry reagents. 159 26

Previous studies have shown that dichloroacetate and trichloroacetate increase the toxicity of CHCl3. The present experiments were designed to determine if monochloroacetate (MCA) similarly affects CHCl3 toxicity. There were occasional differences, but overall kidney function indices (urine volume, osmolality and electrolyte concentration, glucosuria, retention of urea nitrogen in plasma) were not affected differently at either 24 or 48 hr after CHCl3 in saline and MCA pretreated Sprague-Dawley rats of either sex. Males pretreated with MCA had 45-fold greater plasma alanine aminotransferase (ALT) compared to the saline pretreated group similarly dosed with CHCl3. ALT was increased threefold in female rats, a modest change that suggests hepatic damage, and BUN was nonsignificantly increased. Therefore hepatic and renal functions were assessed in females. MCA pretreatment did not alter the effects of CHCl3 on hepatic excretory function or glomerular or tubular function. Bile production and glomerular filtration were both decreased in the MCA group treated with peanut oil, suggesting that MCA impairs both liver and kidney function in female rats. MCA pretreatment increases CHCl3 hepatoxicity markedly in male rats and only slightly in female rats. This difference is likely due to the different effects, in males and females, of MCA on the cytochrome P450 isoforms that activate CHCl3. The effects of MCA on renal function in females would decrease CHCl3 delivery to kidney cells, suggesting that MCA may alter the distribution of CHCl3.
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PMID:Sex differences in monochloroacetate pretreatment effects on chloroform toxicity in rats. 160 Dec 11

The mercapturate S-(2-bromo-2-chloro-1,1-difluoroethyl)-N-acetyl-L-cysteine, which is apparently derived from the halothane degradation product 2-bromo-2-chloro-1,1-difluoroethene, is excreted in urine. S-(2-Bromo-2-chloro-1,1-difluoroethyl)glutathione (BCDFG) and S-(2-bromo-2-chloro-1,1-difluoroethyl)-L-cysteine (BCDFC) are putative intermediates in the metabolism of 2-bromo-2-chloro- 1,1-difluoroethene and are analogs of nephrotoxic and cytotoxic S-haloalkyl glutathione and cysteine conjugates. The objective of the research was to study the nephrotoxicity and cytotoxicity of 2-bromo-2-chloro-1,1-difluoroethene-derived S-conjugates. BCDFG and BCDFC were nephrotoxic in Fischer 344 rats and caused diuresis, increases in urine glucose and protein concentrations, in blood urea nitrogen concentrations, in kidney/body weight percentages and in serum glutamate-pyruvate transaminase activities. Both S-conjugates also produced severe morphological changes in the kidneys, especially in the proximal tubules. Morphological changes indicative of hepatotoxicity were seen in some animals given BCDFG and BCDFC. Both BCDFG and BCDFC were cytotoxic to LLC-PK1 cells, as shown by lactate dehydrogenase release into the medium. The cytotoxicity of BCDFG was blocked by the gamma-glutamyltransferase inhibitor acivicin, and the cytotoxicity of both BCDFG and BCDFC was blocked by the cysteine conjugate beta-lyase inhibitor aminooxyacetic acid. Also, S-(2-bromo-2-chloro-1,1-difluoroethyl)-DL-alpha-methylcysteine, which can not be metabolized by beta-lyase, was not toxic to LLC-PK1 cells. These in vivo and in vitro data provide evidence that BCDFG and BCDFC are nephrotoxic and that their toxicity is dependent on renal bioactivation by cysteine conjugate beta-lyase.
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PMID:Nephrotoxicity of the glutathione and cysteine conjugates of 2-bromo-2-chloro-1,1-difluoroethene. 160 87

Egyptian scorpion venom was collected by electrical stimulation of the telson. Rats were injected with the lyophilized venom in 3 different doses (100, 200 and 400 micrograms/kg). Blood samples were drawn by heart puncture before and 4 h after venom administration. Serum was separated and collected for determination of glucose, blood urea nitrogen (BUN), creatinine, uric acid (UA), total proteins, cholesterol, sodium, potassium, calcium, inorganic phosphorus, alkaline phosphatase, aspartate aminotransferase (AST, GOT), alanine aminotransferase (ALT, GPT), lactate dehydrogenase and creatine phosphokinase (CPK). Serum glucose, creatinine, GOT, GPT and LDH were increased significantly in all treatments. At the same time serum BUN and CPK were elevated significantly with a dose-response relationship. On the other hand, serum total proteins, uric acid, cholesterol, calcium and potassium were significantly decreased 4 h after administration of the 3 doses. These changes in clinical chemistry parameters are most probably related to the toxic effect of the venom on the target organs.
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PMID:Effect of scorpion Leiurus quinquestriatus (H&E) venom on the clinical chemistry parameters of the rat. 160 45

Serum samples from 254 wild-caught Aotus nancymai were analyzed to determine the reference intervals for serum chemistry parameters in this species. Findings show values of total bilirubin, creatinine, alkaline phosphatase, alanine aminotransferase, urea nitrogen, serum albumin, and gamma glutamic transpeptidase having a non-normal distribution. Based on nonparametric tests, significant differences between male and female values were observed for cholesterol, serum calcium, and gamma glutamic transpeptidase. Males were significantly heavier than females. The reference intervals presented were estimated by the nonparametric percentile method.
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PMID:Serum chemistry of the wild caught karyotype I night monkey (Aotus nancymai). 165 42

Administration of either 2,5-dichloro-3-(glutathion-S-yl)-1, 4-benzoquinone (DC-[GSyl]BQ) or 2,5,6-trichloro-3-(glutathion-S-yl)-1,4-benzoquinone (TC-[GSyl]BQ) to male Sprague-Dawley rats caused dose-dependent (50-200 mumol/kg; iv) renal proximal tubular necrosis, as evidenced by elevations in blood urea nitrogen (BUN), and in the urinary excretion of lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and glucose. Renal proximal tubular necrosis was also confirmed by histological examination of kidney slices prepared from DC-(GSyl)BQ- and TC-(GSyl)BQ-treated animals. Administration of the corresponding hydroquinone conjugates (DC-[GSyl]HQ and TC-[GSyl]HQ), prepared by reducing the quinones with a threefold molar excess of ascorbic acid, resulted in a substantial increase in nephrotoxicity. Moreover, in contrast to other glutathione (GSH)-conjugated hydroquinones, the nephrotoxicity of both DC-(GSyl)HQ and TC-(GSyl)HQ was potentiated when rats were pretreated with AT-125, an irreversible inhibitor of gamma-GT. Neither the quinone-GSH nor the hydroquinone-GSH conjugates caused any effect on liver histology or serum glutamate-pyruvate transaminase levels. The results suggest that coadministration of ascorbic acid with DC-(GSyl)BQ or TC-(GSyl)BQ decreases their interactions with extrarenal nucleophiles, including plasma proteins, and thus increases the concentration of the conjugates delivered to the kidney, and hence toxicity. Furthermore the ability of AT-125 to potentiate the nephrotoxicity of DC-(GSyl)HQ and TC-(GSyl)HQ suggests that metabolism of these conjugates by gamma-GT constitutes a detoxication reaction.
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PMID:Inhibition of gamma-glutamyl transpeptidase potentiates the nephrotoxicity of glutathione-conjugated chlorohydroquinones. 167 58

Periportal (pp) or perivenous (pv) liver parenchymal cells from female adult Uje: WIST rats were isolated after retro- or antegrade digitonin infusion followed by collagenase perfusion in the opposite direction. The morphological results revealed a distinct acinar-related destruction of the pv- or pp-zone by digitonin. The remaining cells of the respective other zone showed a good structural maintenance. After subsequent conventional collagenase perfusion the yield, viability and structural integrity of the isolated hepatocytes were high. The zonal cell separation was indicated by significant differences in the pp marker glucose-6-phosphatase and the pv marker glutamine synthetase found in the isolated pp or pv cell populations. Under our experimental conditions including the use of female rats, the alanine aminotransferase and glutamate dehydrogenase as well as ethylmorphine N-demethylase and ethoxycoumarin O-deethylase activities were evenly distributed in both preparations. Under stimulating conditions the capacity for urea synthesis was similar in both pv and pp cells.
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PMID:Biochemical and morphological studies on perivenous and periportal liver parenchymal cells from female rats isolated by digitonin-collagenase method. 168 Jul 46

1. The hematology and blood chemistry of 10 captive adult Ara rubrogenys is described. 2. They showed 3,650,000 erythrocytes/mm3, a hematocrit of 49.9% and a blood hemoglobin content of 15.2 g/100 ml. 3. Leukocyte number was 10,000 cells/mm3, the differential counts being 42.2% heterophils, 0.8% eosinophils, 2.4% basophils, 49.9% lymphocytes and 4.5% monocytes. 4. The number of thrombocytes was 21,800 cells/mm3. 5. Plasma composition was (mg/100 ml): glucose 295; triglycerides 102; cholesterol 166; urea 5.8; uric acid 5; creatinine 0.3; bilirubin was not detected and total protein concentration was 3.2 g/100 ml. Enzymatic activities were (units/1): GOT 188; GPT 10 and alkaline phosphatase 315.
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PMID:Hematology and blood chemistry of macaws, Ara rubrogenys. 168 90

Diversion of portal blood in congenital portosystemic shunts (CPSS) results in liver atrophy and passage of toxins into the systemic circulation causing hepatic encephalopathy. In some dogs, there is indirect evidence for hepatic insufficiency, but histologic findings are equivocal. This study determined whether hepatocyte integrity in PSS is comprised at a subcellular level using analytical subcellular fractionation of liver biopsies. Six dogs with CPSS had hypoproteinemia (6/6), increased serum alkaline phosphatase (6/6) and alanine aminotransferase (4/6) activity, hypocholesterolemia (6/6), and decreased blood urea (2/6). Liver biopsy specimens had increased activities (mU/mg protein) of alkaline phosphatase (17.9 +/- 10.1; controls 5.1 +/- 5.3: P less than 0.01), but not of other plasma membrane enzymes. There were increased activities of endoplasmic reticular (neutral alpha-glucosidase: 1.67 +/- 0.7; controls 0.86 +/- 0.2: P less than 0.01) and lysosomal enzymes (N-acetyl-beta-glucosaminidase: 12.6 +/- 2.3; controls 6.24 +/- 2.7: P less than 0.01; alpha-mannosidase: 0.85 +/- 0.5; controls 0.39 +/- 0.3: P less than 0.05). Subcellular fractionation on reorientating sucrose density gradients showed a high-density peak of alkaline phosphatase suggestive of a specific increase in the biliary canalicular component of enzyme activity. Neutral alpha-glucosidase was shifted to denser fractions, indicative of an increase in the proportion of rough-to-smooth endoplasmic reticulum and consistent with enhanced synthesis of membranous enzymes. There was also evidence for increased fragility of intracellular organelles, particularly lysosomes. In contrast, histology showed either no abnormalities or minor degenerative changes compatible with hepatic underperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic organelle pathology in dogs with congenital portosystemic shunts. 161 98


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