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)

1 Poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme activated by strand breaks in DNA, which are caused by reactive oxygen species (ROS). Here we investigate the effects of the PARS inhibitors 3-aminobenzamide (3-AB), nicotinamide and 1,5-dihydroxyisoquinoline (ISO) on the circulatory failure and the organ injury/dysfunction caused by haemorrhage and resuscitation in the anaesthetized rat. 2 Haemorrhage (sufficient to lower mean arterial blood pressure to 50 mmHg for 90 min) and subsequent resuscitation with shed blood resulted (within 4 h after resuscitation) in a delayed fall in blood pressure to 66+/-4 mmHg (control, n=13). This circulatory failure was not affected by administration (5 min prior to resuscitation) of 3-AB (10 mg kg-1 i.v., n=7), nicotinamide (10 mg kg-1 i.v., n=6) or ISO (3 mg kg-1 i.v., n=6). 3 Haemorrhage and resuscitation also resulted in rises in the serum levels of urea and creatinine. This renal dysfunction was attenuated by 3-AB and nicotinamide, but not by nicotinic acid (n=7), an inactive analogue of nicotinamide. Although ISO (n=6) also attenuated the renal dysfunction caused by haemorrhage and resuscitation, its vehicle (10% DMSO, n=4) had the same effect. 4 Haemorrhagic shock resulted in enhanced serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lipase, indicating the development of hepatocellular and pancreatic injury, respectively. Similarly, haemorrhagic shock also resulted in an increase in the serum levels of creatine kinase (CK) indicating the development of neuromuscular injury. This was attenuated by 3-AB and nicotinamide, but not by nicotinic acid. Although ISO also attenuated the liver, pancreatic and neuromuscular injury caused by haemorrhagic shock, its vehicle had the same effect. 5 Thus, activation of PARS contributes to the organ injury and dysfunction caused by haemorrhage and resuscitation in the rat.
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PMID:Effects of inhibitors of the activity of poly (ADP-ribose) synthetase on the organ injury and dysfunction caused by haemorrhagic shock. 1057 50

The Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA) of vitamin B-6 for children were recently estimated by extrapolating from adult values because of limited available information. To determine vitamin B-6 requirements and provide recommendations for intakes, vitamin B-6 intake, nutritional status and anthropometry of 168 healthy children (79 boys and 89 girls) were studied in Tainan, Taiwan. Direct and indirect vitamin B-6 status indicators were measured in plasma, erythrocytes and urine. Anthropometric data of children in this study were similar to those of the first Nutrition and Health Survey in Taiwan (NAHSIT) conducted in 1993-1996. The plasma pyridoxal phosphate (PLP) concentration of each child was >/=30 nmol/L, indicating an adequate vitamin B-6 status. Daily dietary vitamin B-6 intakes of boys and girls were 0.80 +/- 0.16 and 0.74 +/- 0.16 mg/d, respectively. Daily dietary vitamin B-6 intakes of children who had adequate urinary 4-pyridoxic acid (4-PA) (>3.0 micro mol/L), erythrocyte alanine aminotransferase activity coefficient (EALT-AC) (<1.25) and aspartate aminotransferase activity coefficient (EAST-AC) (<1.8) were not different from those of children who had adequate plasma PLP, although the percentages of adequacy for urinary 4-PA, EALT-AC and EAST-AC ranged from 20 to 91%. Vitamin B-6 status indicators were strongly correlated with vitamin B-6 intake. Adequate values of PLP, EALT-AC, EAST-AC and urinary 4-PA were used to determine the EAR according to Dietary Reference Intake (DRI) committee methodology. We determined the vitamin B-6 EAR (RDA) for boys and girls aged 7-12 y to be 0.84 (1.01) and 0.75 (0.89) mg/d, respectively.
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PMID:Determination of vitamin B-6 estimated average requirement and recommended dietary allowance for children aged 7-12 years using vitamin B-6 intake, nutritional status and anthropometry. 1236 6

Because of limited available information, the Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA) of vitamin B-6 for adolescents were recently estimated by extrapolation from adult values. To determine vitamin B-6 requirements and to provide recommendations for intakes, vitamin B-6 intake, nutritional status and anthropometry were studied in 134 healthy adolescents (63 boys and 71 girls) aged 13-15 y in Tainan, Taiwan. Direct and indirect vitamin B-6 indicators were measured in plasma, erythrocytes and urine. The anthropometric data of the adolescents in this study were similar to those of the first Nutrition and Health Survey in Taiwan (NAHSIT), conducted from 1993 to 1996, showing the normal growth and development of this adolescent group. All subjects had plasma pyridoxal-5'-phosphate (PLP) concentrations > or = 20 nmol/L, indicating an adequate vitamin B-6 status. The mean dietary vitamin B-6 intakes of boys and girls were 1.04 +/- 0.24 and 0.83 +/- 0.26 mg/d, respectively. Vitamin B-6 status indicators, including plasma PLP, erythrocyte alanine activity coefficient (EALT-AC), aspartate aminotransferase activity coefficient (EAST-AC) and urinary 4-pyridoxic acid (4-PA), were correlated with vitamin B-6 intake (r = 0.84, -0.84, -0.77 and 0.86, respectively, P < 0.01). Adequate values of plasma PLP (> or = 20 nmol/L), EALT-AC (<1.25), EAST-AC (<1.8) and urinary 4-PA (>3.0 micromol/d) were used to determine the EAR according to the Dietary Reference Intake committee methodology. The present study suggests that vitamin B-6 EAR (RDA) for adolescent boys and girls aged 13-15 y are 1.07 (1.28) and 0.90 (1.08) mg/d, respectively.
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PMID:Assessment of vitamin B-6 estimated average requirement and recommended dietary allowance for adolescents aged 13-15 years using vitamin B-6 intake, nutritional status and anthropometry. 1451 9

Niacin extended-release/lovastatin is a new combination product approved for treatment of primary hypercholesterolemia and mixed dyslipidemia. This open-labeled, multicenter study evaluated the safety of bedtime niacin extended-release/lovastatin when dosed as initial therapy and patient compliance to treatment in various clinical practice settings. A total of 4,499 patients with dyslipidemia requiring drug intervention was enrolled at 1,081 sites. Patients were treated with 1 tablet (500 mg of niacin extended-release/20 mg of lovastatin) once nightly for 4 weeks and then 2 tablets for 8 weeks. Patients also received dietary counseling, educational materials, and reminders to call a toll-free number that provided further education about dyslipidemia and niacin extended-release/lovastatin. Primary end points were study compliance, increases in liver transaminases to >3 times the upper limit of normal, and clinical myopathy. Final study status was available for 4,217 patients (94%). Compliance to niacin extended-release/lovastatin was 77%, with 3,245 patients completing the study. Patients in the southeast and those enrolled by endocrinologists had the lowest compliance and highest adverse event rates. Flushing was the most common adverse event, reported by 18% of patients and leading to discontinuation by 6%. Incidence of increased aspartate aminotransferase and/or alanine aminotransferase >3 times the upper limit of normal was <0.3%. An increase of creatine phosphokinase to >5 times the upper limit of normal occurred in 0.24% of patients, and no cases of drug-induced myopathy were observed. Niacin extended-release/lovastatin 1,000/40 mg, dosed as initial therapy, was associated with good compliance and safety and had very low incidences of increased liver and muscle enzymes.
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PMID:Safety and compliance with once-daily niacin extended-release/lovastatin as initial therapy in the Impact of Medical Subspecialty on Patient Compliance to Treatment (IMPACT) study. 1527 93

Metabolic pathways are controlled primarily by protein degradation rates. Degradation rates, in turn, are controlled by changes in physiologic condition or nutrient supply. Vitamin B(6) is associated with a greater variety of reactions than most other vitamins. Moreover, the vitamin B(6) needs of the elderly tend to be higher than those of young adults. Neutrophils seem to be appropriate cells for assessing protein turnover as affected by macronutrients and micronutrients. Thus, we assumed that vitamin B(6) supplementation, particularly in an elderly population, would change the turnover rates of the neutrophil proteins. Protein synthesis was measured after 30 minutes of (35)S-Met incorporation followed by a 30-minute washout incubation; degradation was measured after an additional 5-hour incubation. Following protein separation, radioactive images of short-lived proteins were electronically separated into bands. Vitamin B(6) supplementation significantly increased the synthesis of most neutrophil protein bands. There was a significant decrease of 25 to 66% in the degradation rates of 235 protein bands. We even detected by statistical evaluation a 20% decrease in the degradation rates of distinct protein bands. Activation coefficients of erythrocyte aspartate aminotransferase (AC-AST) decreased markedly. There was a significant positive correlation between the decrease in AC-AST and protein degradation. The N-end rule proposes that pyridoxal 5'-phosphate decreases degradation rates of short-lived proteins by binding to lysyl residues. A biochemical model of the mechanism of cellular protein turnover, as affected by nutritional intervention, in human neutrophils is demonstrated.
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PMID:Effect of vitamin B6 supplementation on degradation rates of short-lived proteins in human neutrophils. 1553 25

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

From the leaves of Viburnum tinus L. (Adoxaceae) two acylated iridoid glucosides (viburtinoside A and B), a coumarin diglucoside scopoletin 7-O-beta-D-sophoroside and a natural occurred dinicotinic acid ester 2,6-di-C-methyl-nicotinic acid 3,5-diethyl ester were isolated. In addition to these, 10 known compounds were isolated, namely two bidesmosidic saponins, a hexamethoxy-flavone and five flavonol glycosides, as well as suspensolide A and oleanolic acid were isolated for the first time in this genus and species, respectively. The structures were determined mainly by spectroscopic methods (UV, IR, ESI-MS, 1H-, 13C NMR and DEPT). Toxicity of the investigated extract was determined (LD50=500 mg/kg). CCl4-induced hepatotoxicity has been evaluated in terms of the determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipid peroxide and nitric oxide levels in serum and compared using adult male rats weighing 150-180 g. Their highly elevated levels were significantly reduced by treatment with the investigated aqueous methanol extract in dose-dependent manner.
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PMID:Phytochemical constituents and hepatoprotective activity of Viburnum tinus. 1630 55

Pharmacologic lipid-lowering interventions should be monitored periodically to assess efficacy and safety parameters. Statins are usually well-tolerated drugs and major side effects include increased serum liver and muscle enzymes (AST, ALT, CK). Treatment should be stopped or diminished in case of significant increase of AST or ALT (> 3x ULN), or CK (> 10x ULN). Other lipid lowering agents may also produce hepatotoxicity or myositis, especially in association with statins (fibrates and nicotinic acid) or in presence of metabolic abnormalities (thyroid, liver or renal disorders). Nicotinic acid can also increase glucose and uric acid plasma levels. Laboratory tests might be performed prior to hypolipidemic drug treatment and should be repeated every three months during the first year and then at 6-mo intervals. Shorter intervals should be recommended in individual cases.
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PMID:[Special recommendations for lipid-lowering treatment: efficacy and safety]. 1640 Mar 89

The serum concentrations of Unsaturated Vitamin B(12) binding (UBBC) capacity and the three individual transcobalamins were measured in 34 malnourished children aged 9 months-5 y. Levels of serum vitamin B12, aspartate aminotransferase, alanine aminotransferase, albumin and total proteins were also estimated. The serum UBBC, Transcobalamin I (TC I), Transcobalamin III (TC III), vitamin B12 and the enzyme activities were significantly higher in the kwashiorkor children when compared with both the marasmic and control children. There was also a marked reduction of serum Transcobalamin II (TC II), albumin and total proteins in the kwashiorkor children. In contrast with kwashiorkor, there was a slight increase of serum TC II in the marasmic children. Their serum UBBC, TC I, TC III and B12 were also raised but not as high as in kwashiorkor. These results are discussed in the light of the hepatic dysfunction in kwashiorkor affecting the production of TC II in the liver, while the elevated serum B12 in Protein-energy malnutrition (PEM) may be due to both hepatic damage and intensified release of TC I as a result of infection.
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PMID:Clinical significance of serum transcobalamins in protein-energy malnutrition. 1682 16

Vitamin B(12) contains a cobalt complex and accumulates at high levels in the liver. Vitamin B(12) was examined for its hepatoprotective effect on dimethylnitrosamine-induced liver injury in mice. Vitamin B(12) decreased the blood levels of aspartate aminotransferase and alanine aminotransferase, and clearly inhibited the overaccumulation of collagen fibrils. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the liver showed that the gene expression of alpha-smooth muscle actin and heat-shock protein 47, which are markers of fibrosis, were suppressed by vitamin B(12) administration. Our findings indicate that vitamin B(12) could be an effective hepatoprotective agent.
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PMID:Hepatoprotective effect of vitamin B12 on dimethylnitrosamine-induced liver injury. 1823 93


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