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 purpose of this investigation was to explore the mechanisms and possible stereoselectivity of the interaction between warfarin and chloramphenicol in rats. Chloramphenicol had no apparent effect on the serum protein binding of R-(+)-warfarin or S-(-)-warfarin in vitro or in vivo. Treatment with i.p. chloramphenicol, 50 mg/kg every 4 hr or 30 mg/kg every 6 hr, decreased the plasma clearance of free warfarin by one-half or more, with no apparent stereoselectivity. The volume of distribution was not significantly affected; the half-life of each warfarin enantiomer was appreciably increased by chloramphenicol. Treatment with chloramphenicol had no apparent effect on relative liver size and on serum aspartate aminotransferase activity. Prothrombin complex activity in plasma was not affected by in vitro addition or in vivo administration of chloramphenicol alone. Chloramphenicol treatment did not affect significantly the elimination kinetics of endogenous prothrombin complex activity and the plasma concentration of free R-(+)-warfarin or S-(-)-warfarin required to decrease prothrombin complex activity synthesis rate to one-half of normal. It appears that the pronounced potentiation of the anticoagulant effect of warfarin by chloramphenicol is due only to inhibition of warfarin metabolism and that this effect is not stereoselective.
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PMID:Pharmacokinetic and pharmacodynamic studies of acute interaction between warfarin enantiomers and chloramphenicol in rats. 649 77

Single oral doses of N-nitrosodimethylamine or olive oil were given to nonpregnant and pregnant female Holtzman rats on different days of pregnancy (days 7-18, where day 0 was considered to be the sperm positive day). Serological and histopathological studies were performed on animals killed 2 days after treatment. In comparison with the values obtained in nonpregnant controls, the following parameters in pregnant controls were significantly increased: relative liver weights (days 9-20), liver ascorbic acid concentrations (day 12), blood urea nitrogen (days 16-20), serum triglyceride (days 14-20), serum inorganic phosphorus (days 12-18), and serum glutamic-pyruvic transaminase (days 14-20). The following parameters were decreased in pregnant rats compared with nonpregnant controls: relative organ weights (kidneys, adrenals and thyroids), serum glucose (days 12-20), total serum protein (days 9 and 16-20), and serum alkaline phosphatase (day 20). The serum cholesterol levels in pregnant rats were significantly decreased on days 9-15 of pregnancy and significantly increased on day 20. The numbers of mitotic cells in the livers of pregnant rats were greatly increased compared with nonpregnant rats on all days of pregnancy, while the adrenal cortex contained a significantly higher number of mitotic cells only on days 16 and 18. Compared with control values, NDMA given orally (15 or 20 mg/kg body weight) increased the following in both pregnant and nonpregnant rats: numbers of mitotic cells in the liver and adrenal cortex, relative adrenal weights, serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase. NDMA treatment decreased liver ascorbic acid and total serum protein in both pregnant and nonpregnant rats. In nonpregnant rats NDMA also increased relative liver weights (not significant) and serum alkaline phosphatase levels. NDMA increased serum alpha-hydroxybutyric dehydrogenase in pregnant rats on day 20 and decreased foetal weights (in rats treated on days 13 and 18). NDMA treatment was not lethal to nonpregnant rats or to pregnant rats up to day 16 of pregnancy, but single oral doses of 15 and 20 mg NDMA/kg killed 9.4 and 35.3%, respectively, of rats treated on day 18 of pregnancy. In general, the acute toxic effect of NDMA, as measured by changes in the above parameters, was greater in pregnant than in nonpregnant rats, especially near the end of pregnancy.
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PMID:Comparison of the effects of N-nitrosodimethylamine on pregnant and nonpregnant Holtzman rats. 668 27

Sixteen athletes (11 men, 5 women), averaging 21 years of age, were studied before and after four weeks of daily exhaustive exercise (six days/week) during an endurance training course. In comparing blood chemistries before and after training, concentrations of blood glucose, total serum lipids, serum triglycerides, and serum cholesterol were significantly reduced; serum free fatty acid ( SFFA ) level was significantly increased; and serum protein and serum phospholipid concentrations remained unchanged. It was concluded that exhaustive training produces reduced blood glucose (but not clinically significant hypoglycemia) with increased fat utilization as a result of depletion of carbohydrate storage and that such training reduces the resting levels of serum cholesterol and serum triglycerides. The increased hematocrit, serum Na+, and serum K+ concentrations observed were presumably due to plasma water loss from excessive perspiration. Concentrations of blood urea nitrogen (BUN) and serum glutamic-oxaloacetic transaminase (SGOT) were increased significantly; serum glutamic-pyruvic transaminase (SGPT) and serum creatinine showed no significant changes. None of the athletes showed evidences of water-electrolyte deficiency syndrome, renal dysfunction, or liver cell damage, despite a persistent mild degree of dehydration and catabolic state noted after training.
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PMID:Metabolic effects of exhaustive training of athletes. 674 92

Of 510 adult buffaloes examined, 88 (17.3 per cent) were found to be suffering from Fasciola gigantica infestation. There was a reduction in the haemoglobin, packed cell volume and red blood cell count in the fasciola affected buffaloes and an increase in their white blood cell count. There was no significant change in mean corpuscular volume, mean corpuscular haemoglobin or mean corpuscular haemoglobin concentration in the fasciola affected buffaloes. There was also a decrease in total serum protein and albumin concentrations and in the albumin globulin ratio and significant increase in alpha globulin and gamma globulin concentrations and in the activity of the serum enzymes aspartate aminotransferase, alanine aminotransferase, serum alkaline phosphatase and ornithine carbamoyl transferase.
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PMID:Changes in blood cellular components, serum protein concentrations and serum enzyme activities in buffaloes infested with Fasciola gigantica. 714 34

1. The effects of implanting turkeys with trienbolone acetate (TA) upon fluid balance and blood chemistry were studied. 2. The Na and water contents of skeletal muscles were increased by TA treatment while K was unaltered. 3. The extracellular space expressed as a proportion of starved body weight was unaffected by TA implantation. 4. Plasma or serum concentrations of P, Ca, Mg, Na and K and activities of the enzymes aspartate aminotransferase [EG 2.61.1], creatine kinase [EC 2.7.3.2] and gamma-glutamyl transferase [EC 2.3.2.2] were not changed by TA treatment. 5. Packed cell volume was significantly increased by TA implantation after a delay of some 2 to 3 weeks while plasma protein concentrations were immediately decreased for a period of two weeks before nearly normal concentrations were obtained again. 6. Erythrocyte sedimentation rate was decreased by TA treatment, but serum protein electrophoretic pattern was unchanged.
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PMID:The effects of trienbolone acetate implantation of turkeys upon fluid balance and blood chemistry. 726 Jul 1

Our previous studies showed that polybrominated biphenyl (PBB) induced hepatic microsomal cytochrome P-450 in dairy cattle but did not elevate hepatic cytosolic ornithine decarboxylase or serum isocitrate dehydrogenase. These enzymes would be expected to increase during hepatotoxic injury and regeneration. Thus, PBB appeared to be a hepatotoxin in rats but not in cattle. In order to identify and confirm the response capability of bovine liver to hepatotoxins, we administered thioacetamide, a hepatotoxin known to induce hepatonecrosis, to a dairy calf. A progression of clinical signs of toxicosis was evident until the animal was moribund by 23 hr postdosing. Histolopathologic alterations in the liver included centrilobular necrosis with congestion and subcapsular microhemmorrhage. Marked changes in serum protein profiles were not noted. However, distinct increases in serum Fe and bilirubin occurred with progressing toxicosis, as did sharp declines in glucose and triglycerides. Serum lactic dehydrogenase, alkaline phosphatase, glutamic-oxaloacetic transaminase, isocitrate dehydrogenase and glutamic-pyruvate transaminase were elevated. Elevation of ornithine decarboxylase was dramatic when compared to the level in normal fetal bovine liver. From studies of its kinetic properties, bovine liver ornithine decarboxylase appears to have an apparent Km for ornithine decarboxylase of .45 mM. Liver homogenates from PBB-treated animals did not form inhibitors to ornithine decarboxylase. Compared with the thioacetamide-treated calf, the normal adult bovine, pregnant adult and 6-month fetus had relative activities of .2 .4 and 5.8%, respectively. These studies show that ornithine decarboxylase is low in liver of normal cattle, but is elevated markedly by agents that cause hepatonecrosis.
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PMID:Ornithine decarboxylase, serum isocitrate dehydrogenase and clinical chemistry changes during thioacetamide-induced hepatotoxicity in a calf. 734 23

Captive mallards (Anas platyrhynchos) were fed wheat containing 5.8 ppm deoxynivalenol (DON, vomitoxin) from an outbreak of Fusarium graminearium head-blight that occurred on grain crops in Manitoba, Canada, during 1993. There was no evidence of taste aversion to this grain during a 10-day palatability trial. No significant differences were detected in serum protein, calcium, glucose, creatinine kinase, aspartate aminotransferase or uric acid levels, blood packed cell volume, or body or organ weight, between ducks fed contaminated wheat and those fed uncontaminated wheat during a 14-day feeding trial. No gross or microscopic lesions were detected in birds fed contaminated wheat for 14 days. Based on these results, ducks will consume grain containing moderate levels of DON and short-term exposure to this grain will not result in obvious adverse effects.
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PMID:Consumption of deoxynivalenol-contaminated wheat by mallard ducks under experimental conditions. 862 31

Primary sclerosing cholangitis, a chronic cholestatic liver disease, frequently leads to an impairment of liver function. In nine men and two women, aged 23 to 57 years, we prospectively studied for three to six years the effect of treatment with ursodeoxycholic acid (UDCA) on liver function. 10 mg UDCA/kg bw significantly reduced serum activities of AP, gamma GT, AST and ALT for several years. After three years of treatment, however, serum concentration of bilirubin was higher than before therapy in eight out of eleven patients (1.8 +/- 0.8 versus 0.9 +/- 0.1 mg/dl; p = 0.01). Likewise, serum concentration of bilirubin was higher in eight out of nine patients after four years of treatment (1.3 +/- 0.3 versus 0.9 +/- 0.1 mg/dl; p = 0.03). In most cases, however, the increase was discrete. Parameters of synthetic liver function (coagulation, serum protein concentration, serum activity of cholinesterase) remained constant in the observation time. Quantitative liver function tests (galactose elimination capacity and indocyanine green half-life) also showed little variation in the observation time. We conclude that UDCA treatment significantly improves serum activities of liver enzymes for several years. Nevertheless, serum bilirubin concentration, believed to be of prognostic value in patients with PSC, seems to rise slowly over time. Serial determinations of galactose elimination capacity and indocyanine green halflife are not superior to conventional liver function tests in the timing of liver transplantation in the individual patient.
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PMID:[Primary sclerosing cholangitis: conventional and quantitative liver function tests during long-term therapy with ursodeoxycholic acid]. 865 87

In a prospective study 50 children with new onset epilepsy were investigated. Routine screening for complete blood count, serum protein, albumin, gamma-glutamyltransferase (gamma-GT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and coagulation studies before, 3, 6 and 9 weeks after commencement of antiepileptic therapy with valproate were carried out. Serum B12 and folate levels were also determined in 29 patients. The aim of the study was to evaluate the effect of VPA on these laboratory findings. We found a significant reduction of red blood count and platelet count, whereas MCV showed a significant upward trend. Vitamin B12 levels were elevated after starting VPA therapy. We found no elevations of liver enzymes, but a significant transient reduction of ALT after 3 and 6 weeks and significantly reduced serum protein and albumin after 3, 6 and 9 weeks. Coagulation studies revealed a significant downward trend in serum fibrinogen and upward trend in thrombin time. The other parameters showed no significant changes after onset of VPA treatment. We think that reduced red blood cell and platelet counts, and elevated MCV indicate a direct toxic effect on a hematopoietic precursor or stem cell in patients treated with VPA. Furthermore, reduced protein, albumin and fibrinogen indicate an impaired liver synthetic function in asymptomatic children treated with VPA monotherapy.
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PMID:Hematologic manifestations and impaired liver synthetic function during valproate monotherapy. 873 99

There is a large inter-subject variability in serum creatine kinase (CK) response after eccentric exercise. This study examined and compared the variability of CK activity, other serum protein increases (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, aldolase, myoglobin),changes in muscle damage indicators (maximal isometric force: MIF, relaxed and flexed elbow joint angle: RANG and FANG, circumference: CIR, and muscle soreness level: SOR), and changes in magnetic resonance (MR) images. Ten male subjects (21.7 +/- 1.6 yrs) performed 24 maximal eccentric actions of the elbow flexors, and measurements except MR images were taken immediately before and after, and for 10 days after exercise. MR images were taken 7 days after exercise. A large variability in peak CK response (236 - 25,244 IU.I(-1) was found among subjects. Spearman rank-order correlation coefficients (r) revealed significant correlations of peak CK with peak serum protein levels (r = 0.79-0.95), peak changes in MIF (r = 0.73-0.79), RANG (r = 0.69), and CIR (r = 0.91). The higher the peak CK levels, the more profound the abnormality in the MR images and the larger the changes in MR signal intensity (r = 0.90-0.94). It is concluded that the large variability in CK response after exercise seems to be related to the variability in exercise-induced muscle damage.
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PMID:Variability in serum creatine kinase response after eccentric exercise of the elbow flexors. 883 14


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