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)

In a chronic toxicity study in the rat, bidisomide administered as a dietary admixture produced a dose-related lowering of reticulocytes and leucocytes. Plasma alanine aminotransferase activity was increased at 300 mg/kg and decreased at 900 mg/kg. The potential mechanisms of these effects were investigated by comparing the responses in groups of male Sprague-Dawley rats receiving a control diet, or 300 or 1200 mg/kg/day bidisomide. Subsets of these groups were co-treated subcutaneously with folinic acid or with a vitamin B1, B6, B12 complex. Subsets of control and 300 mg/kg groups were maintained on a 20-25% feed restriction regimen for 3 months, to mimic the depression in body weight gain observed in animals receiving 1200 mg/kg. Body weight gains were significantly reduced at 1200 mg/kg and in all feed-restricted animals. Plasma and liver alanine aminotransferase (ALT) and plasma aspartate aminotransferase (AST) levels were also reduced at this dose level. At 300 mg/kg, plasma transaminases, glutamate dehydrogenase (GLDH) and sorbitol dehydrogenase (SDH) activities were increased. These changes were prevented in animals receiving folinic acid supplementation. Plasma glucose, triglycerides, and unsaturated and total iron binding capacities were decreased, while plasma iron levels tended to increase, mainly at the high dose. Vitamin supplementation prevented a decrease in reticulocyte counts at 300 mg/kg. Bidisomide increased urinary formimino-glutamic acid (FIGLU) excretion but did not affect methylmalonic acid (MMA) or taurine excretion. The effect on FIGLU at 1200 mg/kg was prevented by folinic acid co-treatment. Absolute liver weight was lowered at both dose levels and in feed-restricted animals. However, the relative liver weights were unaffected. Thymidine kinase and thymidylate synthase activity of the bone marrow cells were not altered by the bidisomide treatment. Except for the increase in plasma transaminase, GLDH and SDH levels at 300 mg/kg, changes in clinical chemistry parameters are considered to result mainly from nutritional restrictions. Changes in hematologic parameters appear to be related to the combination of decreased feed consumption (leukocytes) and decreased availability or utilization of folates (reticulocytes). This alteration, however, did not affect DNA synthesis in bone marrow. The prevention by folinic acid, but not by feed restriction, of the elevation of liver enzymes at 300 mg/kg is an intriguing, yet unexplained finding. There was no evidence that bidisomide affected B6 and B12 availability.
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PMID:Effect of folate supplementation on clinical chemistry and hematologic changes related to bidisomide administration in the rat. 858 20

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

Selected haematological, blood chemical and serological variables were investigated in healthy Thoroughbreds (n = 45) in training. Haemoglobin concentration, haematocrit, red, white and differential cell counts as well as serum concentrations of total and ionized calcium, sodium, potassium, chloride, urea, creatinine, total protein, albumin, inorganic phosphorus, total bilirubin, iron, glucose, magnesium, alkaline phosphatase, gamma-glutamyltransferase, lactate dehydrogenase, aspartate transaminase, alanine transaminase and creatine kinase were found to be within ranges previously reported for horses. No statistically significant difference was found between the haematocrit (Ht) of horses n = 44; mean = 0.44; SD = 0.02) of different performance or between those of different age groups. A significant difference was found between the Ht of males (mean = 0.43; SD = 0.02) and females (mean = 0.45; SD = 0.02) and between quiet (mean = 0.44; SD = 0.02) and excitable (mean = 0.46; SD = 0.02) horses. No significant difference in red cell potassium concentration was found between horses of different performance. Cortisol, insulin, parathormone (C-terminal), aldosterone and folate concentrations respectively varied between 89-204 (mean = 144.4; SD = 25.47) nmol l-1, 4.2-23 (mean = 10; SD = 4.30) m U l-1, 65.2-91.4 (mean = 79.46; SD = 9.34) pmol l-1, less than 138 to 379 pmol l-1 and 9.4-21.5 (mean 14.5; SD = 2.87) nmol l-1. Vit B12 concentrations exceeded 1400 pmol l-1. Blood lead concentrations in all animals were below 15 ug l-1. Fifteen (33.3%) of the horses were carriers of babesiosis. Laboratory findings concerning these horses did not differ from those of the other horses.
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PMID:Selected laboratory parameters of thoroughbreds. 902 43

- Vitamin B12 serum levels and markers for alcohol consumption were determined in 80 male alcohol-dependent patients. Spearman correlation coefficients (r(S)) were calculated. Significant positive correlations between vitamin B12 and hepatic enzyme values were found (gamma-glutamyltransferase: r(S) = 0.58; alanine aminotransferase: r(S) = 0.43; aspartate aminotransferase: r(S) = 0.47; glutamate dehydrogenase: r(S) = 0.43; all P: < 0.001). Therefore, for a proper interpretation of vitamin B12 levels, it may be clinically relevant to take markers of hepatocellular damage into account.
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PMID:Vitamin B12 and hepatic enzyme serum levels correlate in male alcohol-dependent patients. 1113 12

This study aims to determine serum folate and plasma homocysteine levels in healthy pregnant women following a live birth and compare them with healthy non-pregnant women. Fifty healthy gravid multiparous women are included in the study and 25 normal non-pregnant female subjects act as controls (group I). The pregnant women are divided into two groups according to interpregnancy interval: group II (six months or less); group III (18-24 months). Venous blood samples are analysed for red blood cell folate and homocysteine, vitamin B12, serum folate and albumin, and serum aminotransferases (ALT and AST). There was a significant decrease in red cell folate and serum folate in group II compared to the control group (P<0.001). Serum vitamin B12 showed no significant difference. Plasma homocysteine and serum albumin showed significant decreases in both groups II and III compared to the control group. (P<0.001) There was significant positive correlation between homocysteine and serum albumin in the three studied groups. (r=0.42, P<0.001; r=0.45, P<0.001; r=0.51, P<0.001, respectively). There was significant negative correlation between red cell folate and homocysteine in the three studied groups. (r=-0.48, P<0.001; r=-0.53, P<0.001; r=-0.49, P<0.001, respectively). Two cases in group II showed signs of intrauterine growth retardation. The results suggest that pregnant females with short interpregnancy intervals are more likely to develop folate deficiency. Educational strategies are required to increase folate awareness among women to promote the benefits of folic acid supplementation. Mandatory folate fortification of foods should be defined and monitored.
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PMID:Folate and homocysteine levels in pregnancy. 1525 Jun 71

Alzheimer's disease (AD) and dementia with vascular component (DVC) are the most prevalent forms of dementia. Both clinical entities share many similarities, but they differ in major phenotypic and genotypic profiles as revealed by structural and functional genomics studies. Comparative phenotypic studies have identified significant differences in 25% of more than 100 parametric variables, including anthropometry, cardiovascular function, aortic atherosclerosis, brain atrophy, blood pressure, blood biochemistry, hematology, thyroid function, folate and vitamin B12 levels, brain hemodynamics and lymphocyte markers. The phenotypic profile of patients with DVC differs from that of AD patients in the following: anthropometric values (weight, height); cardiovascular function (ECG, heart rate); blood pressure; lipid metabolism (HDL-CHO, TGs); uric acid metabolism; peripheral calcium homeostasis; liver function (GOT, GPT, GGT); alkaline phosphatase; lactate dehydrogenase; red and white blood cells; regional brain atrophy (left temporal region, inter-hippocampal distance); and left anterior blood flow velocity. Functional genomics studies incorporating APOE-related changes in biological markers extended the difference between AD and DVC up to 57%. Brain perfusion studies show a severe brain hypoperfusion in dementia associated with enlarged age-dependent arterial perfusion times. Structural genomics studies with AD-related genes, including APP, MAPT, APOE, PS1, PS2, A2M, ACE, AGT, cFOS and PRNP genes, demonstrate different genetic profiles in AD and DVC, with an absolute genetic variation rate ranging from 30% to 80%, depending upon genes and genetic clusters. Single gene analysis identifies relative genetic variations ranging from 0% to 5%. The relative polymorphic variation in genetic clusters integrated by two, three or four genes associated with AD ranges from 1% to 3%. The main phenotypic differences between AD and DVC are genotype-dependent, especially in AD, probably indicating that different genomic factors are determinant for the expression of dementia symptoms which might be accelerated or induced by environmental and/or cerebrovascular factors.
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PMID:Phenotypic profiles and functional genomics in Alzheimer's disease and in dementia with a vascular component. 1526 64

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

The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of pemetrexed with folate and vitamin B12 supplementation (FA/VB(12)) in Japanese patients with solid tumours and to investigate the safety, efficacy, and pharmacokinetics of pemetrexed. Eligible patients had incurable solid tumours by standard treatments, a performance status 0-2, and adequate organ function. Pemetrexed from 300 to 1,200 mg m(-2) was administered as a 10-min infusion on day 1 of a 21-day cycle with FA/VB(12). Totally, 31 patients were treated. Dose-limiting toxicities were alanine aminotransferase (ALT) elevation at 700 mg m(-2), and infection and skin rash at 1,200 mg m(-2). The MTD/RD were determined to be 1,200/1,000 mg m(-2), respectively. The most common grade 3/4 toxicities were neutropenia (grade (G) 3:29, G4:3%), leucopenia (G3:13, G4:3%), lympopenia (G3:13%) and ALT elevation (G3:13%). Pemetrexed pharmacokinetics in Japanese were not overtly different from those in western patients. Partial response was achieved for 5/23 evaluable patients (four with non-small cell lung cancer (NSCLC) and one with thymoma). The MTD/RD of pemetrexed were determined to be 1,200/1,000 mg m(-2), respectively, that is, a higher RD than without FA/VB(12) (500 mg m(-2)). Pemetrexed with FA/VB(12) showed a tolerable toxicity profile and potent antitumour activity against NSCLC in this study.
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PMID:A phase I study of pemetrexed (LY231514) supplemented with folate and vitamin B12 in Japanese patients with solid tumours. 1694 Sep 81

Dietary cobalamin (Cbl; vitamin B12) deficiency resulted in severe growth retardation in rats, and body weight in the Cbl-deficient rats at 20 wk of age was significantly lower compared with the age-matched Cbl-sufficient control rats. In contrast, liver weight, when normalized to body weight, was greater in the Cbl-deficient rats than in the controls (p<0.05). The expression level of proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, in the liver was significantly enhanced in the deficient rats, suggesting that cell proliferation is abnormally activated in the liver under Cbl-deficient conditions. In addition, plasma alanine aminotransferase (ALT) activity, a marker for hepatic injury, was also significantly elevated in the deficient rats. When L-carnitine, which is used clinically for the treatment of Cbl-deficient patients with methylmalonic aciduria, was administered to the Cbl-deficient rats by intraperitoneal injection twice per day for 2 wk (each 0.5 mmol), the amount of methylmalonic acid excreted into the urine was significantly reduced, and the plasma ALT activity was lowered to a normal level. However, the PCNA expression in the liver was barely influenced by the treatment with carnitine. In contrast, when the deficient rats were fed an L-methionine-supplemented diet (4 g of L-methionine per kg of the diet) for 2 wk, the increased expression of PCNA was normalized.
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PMID:Abnormal increase in the expression level of proliferating cell nuclear antigen (PCNA) in the liver and hepatic injury in rats with dietary cobalamin deficiency. 1696 60

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of alcohol abuse worldwide. Non-alcoholic steatohepatitis (NASH) is the most progressive form of NAFLD. The aim of this study was to investigate the role of apolipoprotein E (APOE) polymorphisms in the development of NASH. We analysed 57 NASH patients and 245 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a case-control study. The diagnosis of the patients was based on liver biopsy. The serum levels of glucose, lipids, vitamin B12, folic acid, homocysteine, insulin, total biluribin, total protein, albumin, ferritin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined in all of the subjects. Body mass index (BMI), waist circumference (WC), AST, ALT, fasting blood sugar (FBS), total cholesterol, triglyceride (TG), low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, insulin and ferritin levels were significantly higher in the 57 patients with NASH compared with the 245 healthy controls. The APOE epsilon3 allele was overrepresented in the whole group of NASH patients (epsilon3=97.37% in NASH versus 82.45% in controls). The APOE polymorphism was statistically significantly associated with NASH (chi(2)=15.741; p=0.008). The APOE3/3 genotype (odds ratio [OR]=7.941; p=0.000) was strongly associated with increased risk for NASH in all NASH patients. Consequently, the APOE3/3 genotype may play a role in the aetiopathogenesis of NASH.
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PMID:Association of apolipoprotein E polymorphisms in patients with non-alcoholic steatohepatitis. 1846 45


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