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 hormonal and biochemical effects of danazol (600 mg a day) and high-dose medroxyprogesterone acetate (MPA; 100 mg a day) were studied in a placebo-controlled, 6-month trial. Serum gonadotrophins and prolactin levels did not change during danazol and MPA treatments, whereas oestradiol and progesterone levels decreased significantly in relation to placebo without any difference between danazol and MPA. Both drugs significantly suppressed the sex hormone-binding globulin level (SHBG), and consequently, the free-androgen index (serum total testosterone nmol/l per SHBG nmol/l x 100) as compared with placebo, the effect of danazol being significantly stronger than that of MPA. Danazol, but not MPA, significantly increased serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and haemoglobin levels, and also thrombocyte counts, whereas MPA, but not danazol, increased the serum concentration of albumin in relation to placebo. Serum total bilirubin, conjugated bilirubin, gamma-glutamyl transferase, creatinine, alkaline phosphatase, sodium and potassium levels and leucocyte counts remained unchanged during both treatments. Danazol and high-dose MPA did not differ from each other in their ovarian and anterior pituitary effects, while the increase in androgenic activity induced by danazol was greater than that achieved with MPA. Danazol also had more biochemical effects than MPA. It interfered with the functions of the liver and the production of thrombocytes and haemoglobin, whereas MPA affected only albumin synthesis/release.
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PMID:Placebo-controlled comparison of hormonal and biochemical effects of danazol and high-dose medroxyprogesterone acetate. 214 9

Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, and alkaline phosphatase activities in the blood serum of women taking the oral contraceptive preparation Microgynon through extended periods were raised; the activity of cholinesterase was simultaneously reduced. In rats liver homogenates ethynylestradiol, one of the active components of Microgynon, acted as an inducer of gamma-glutamyltransferase and alkaline phosphatase while leaving aspartate aminotransferase and alanine aminotransferase unaffected, but reduced the level of cholinesterase. Norgestrel, the other active component of the preparation, suppressed the biosynthesis of gamma-glutamyltransferase and alkaline phosphatase while leaving aspartate aminotransferase, alanine aminotransferase and cholinesterase levels unaffected. A mixture of ethynylestradiol plus norgestrel in the mass proportion occurring in Microgynon produced the same effects upon gamma-glutamyltransferase and alkaline phosphatase as ethynylestradiol alone. Estradiol, the parent hormone of ethynylestradiol, lacked the inducing capability of the latter while ethynylpropargyl chloride induced gamma-glutamyltransferase and alkaline phosphatase so it was concluded the inducing effect of ethynylestradiol must be ascribed to the ethynyl radical. Progesterone, the parent of norgestrel, shared the latter's suppressive activity for gamma-glutamyltransferase and alkaline phosphatase biosynthesis, and behaved like its derivative towards the other enzymes.
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PMID:Changes of activities of some transferases, alkaline phosphatase and cholinesterase in the blood of women using oral contraceptives and in vitro influence of these agents on tissular enzyme levels in rat liver. 260 59

Total proteins (albumin, globulins and their fractions); carbohydrate (intravenous glucose tolerance); lipid (serum cholesterol, triglycerides, and phospholipids); and liver functioning (alkaline phosphatase, lactic dehydrogenase, and aspartate aminotransferase activities in serum, bromsulfathalein retention, and serum bilirubin); were assayed in 12 Thai women who were not lactating. The tests were performed before, and 3 weeks, 3,6,9, and 12 months after the advent of treatment with medroxyprogesterone acetate (DMPA), which was injected intramuscularly in 150-mg doses every 90 days. Triglyceride concentration was unchanged overall; however, mean fasting triglyceride concentration on Day 20 decreased significantly when compared with Day -33 pretreatment control (P .025). A significant increase ( P .01) in mean fasting cholesterol was demonstrated on Day 20; this, however, was thought to be caused by the high dietary lipid intake during hospitalization rather than an effect of the DMPA. In general, serum protein and lipid levels, and liver function and glucose tolerance, remained unchanged over 1 year. There was, however, a significant and persistent increase in insulin level in all subjects after initiation of hormone treatment during the first 30 minutes of intravenous glucose load. The study concludes that DMPA does not interfere with glucose tolerance, lipid and protein metabolism, or liver function during its administration.
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PMID:Effects of medroxyprogesterone acetate on serum lipids, protein, glucose tolerance and liver function in Thai women. 644 43

Several biochemical events accompany and mediate the development of chronic liver disease and its evolution into cancer. Low plasma zinc and high copper levels have been observed in various liver diseases, such as liver cirrhosis and viral hepatitis, while increased oestradiol levels have been documented in chronic liver damage and hepatocellular carcinoma. We administered CCL4 intragastrically to 10 female Sprague Dawley rats for 30 weeks. All animals developed cirrhosis and four also developed hepatocellular carcinoma. Plasma levels of zinc, copper and oestradiol were significantly higher in the latter group than in animals with simple cirrhosis. Progesterone, AST and bilirubin showed a trend toward significant differences whereas testosterone and ALP levels were unchanged. These findings add to the evidence that sex hormones and trace elements are involved in the process of the development of chronic liver damage and carcinogenesis.
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PMID:Sex hormones and trace elements in rat CCL4-induced cirrhosis and hepatocellular carcinoma. 835 89

Plasma L-arginine is usually deficient immediately after hepatic reperfusion in orthotopic liver transplantation, which may also contribute to the occurrence of either hepatic ischemia-reperfusion injury or pulmonary hypertension. In this study, exogenous L-arginine was thus experimentally used to reverse the deficient status of the L-arginine/NO pathway. An in vivo model of 1 hr hepatic ischemia and reperfusion was thus tested in both rats (Experiment A) and pigs (Experiment B). In Experiment A, 10 mg/kg of L-arginine (group 1, n = 7), D-arginine (group 2, n = 7), or saline (group 3, n = 7) was administered through the portal vein. The hepatic tissue blood flow, at 20 min after reperfusion, improved in group 1 (70.7 +/- 7.0% of the preclamp levels) compared to groups 2 and 3. The serum glutamate oxaloacetate transaminase levels at 24 hr after reperfusion were also lower in group 1 (320 +/- 22.2 IU/L) than in either group 2 or group 3. The intrahepatic NO levels showed a temporal burst (> 15,000 pA current) after reperfusion only in group 1. In Experiment B, 10 mg/kg of L-arginine (group 4, n = 5), D-arginine (group 5, n = 5), or 10 ml of saline (group 6, n = 5) was administered through the portal vein. In group 4, the MPAP (mean pulmonary arterial pressure)/MAP (mean arterial pressure) was lower than that observed in groups 5 and 6. In conclusion, exogenous L-arginine administered from the portal vein was thus found to be effective in mitigating both portal hypertension and reperfusion injury by producing an increased amount of NO immediately after reperfusion.
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PMID:Role of exogenous L-arginine in hepatic ischemia-reperfusion injury. 922 19

Combined pills have known adverse effects on liver function. Progesterone based contraceptives are thought to be safer in this regard. The effect of Norplant, a levonorgestrel contraceptive implant, on liver function was evaluated in 149 Bangladeshi women of reproductive age in this study. Liver function tests and ultrasonography of hepato-biliary system were done before and after the implantation. The patients were followed upto two years. There were non-significant transient rise of serum bilirubin and slight enlargement of liver during the first year. There was no significant change in the levels of AST, ALT, alkaline phosphatase, total protein, albumin-globulin ratio and prothrombin time. The results suggest that Norplant has no adverse effect on liver function.
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PMID:Effect of Norplant on liver function. 977 69

The prolonged use of CNI has been associated with nephrotoxicity. MMF is a new immunosuppressive agent. In the present study, the consequences of introducing MMF and reduction of CNI in liver-transplant children were analysed. The present study included eight pediatric liver-transplant patients who had transplantation at least 5 yr previously, had stable graft function and had renal dysfunction as a probable side-effect of CNI therapy. CNI was replaced with MMF in all patients and serum creatinine, uric acid concentration, azotemia and creatinine clearance before and 6 months after study entry were measured. The patients were monitored closely for side-effects of MMF as well as graft function. Six months after study entry serum creatinine, uric acid concentration, azotemia and creatinine clearance improved in all the patients at the last follow-up. The aspartate aminotransferase and alanine aminotransferase concentrations were stable during the study period and did not observe any serum bilirubin increased as well. No side-effects were reported in patients on MMF. Only one patient reported temporary pruritus and nausea. The results indicate that renal dysfunction significantly improved when MMF therapy is started and CNI reduced. Furthermore present data suggest that the risk of acute allograft rejection is very low when the CNI desired reduction is achieved in not too short time and absolutely when the MPA levels are strictly monitored.
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PMID:Mycophenolate mofetil in pediatric liver transplant patients with renal dysfunction: preliminary data. 1487 Aug 93

Depo-medroxy progesterone acetate (DMPA, Depo-Provera) is used in more than 80 countries as a long-acting contraceptive administered as a single intramuscular(i.m) injection of 150 mg/3 months. The present study was set up to investigate the effects of DMPA on 80 average Egyptian women classified into four groups comprising those using the drug for one, two, three and four years, respectively, compared to a control group (N = 20) of married non-hormonally - treated women of similar ages. The drug showed a transient significant elevation of alanine aminotransferase activity (ALT)without an apparent effect on other liver indices, namely total bilirubin (T.Bil) level,aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities. Only the low density/high density lipoproteins cholesterol ratio (LDLC/HDLC) was gradually and non-significantly (ns) increased in comparison to control group, however, neither total cholesterol (TC) nor triglycerides (TG) were affected by the drug. The lipid peroxide product malondialdehyde (MDA) was significantly elevated in an gradual manner with a corresponding decrease in reduced glutathione (GSH), without any change in blood nitric oxide (NO) levels. It can be concluded that DMPA may be considered as a safe contraceptive medication for the studied group of women, but that special care should be exercised for cardiovascular, hepatic and other patients more sensitive to the harmful effects of free radicals. Alternatively, supportive medications are advisable for each exposed case to secure against the possible irreversible adverse effects of the drug by continuous use. In addition, annual re-evaluation is much more advisable despite the proven safety of the drug.
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PMID:Oxidative stress, lipid profile and liver functions in average Egyptian long term depo medroxy progesterone acetate (DMPA) users. 1800 80

Animal testing causes ethical problems and in view of EU regulations (e.g. EU-Guideline (76/768/EEC, February 2003)) or REACH the development of reliable in vitro assays has become even more important. Up to now, we use the modified local lymph node assay (IMDS) for toxicological hazard identification of sensitizing and irritant properties of chemicals in accordance with OECD Guideline 429. In this study, we investigated whether analyses of cell signaling pathways can provide a methodology for the detection of sensitizing compounds in vitro. Murine and human skin explants as well as reconstituted skin models (epidermal model EST-1000 and full-thickness model AST-2000) were exposed to sensitizing (oxazolone and DNFB) or irritant compounds (SDS and TritonX-100). Phosphorylation of MAP-kinases (p38, ERK1/2 and JNK1/2), STAT1 and PLCgamma were determined by cytometric bead array (CBA). In skin explants, all three MAP-kinases were exclusively activated after exposure to sensitizing compounds. For the reconstituted skin models phosphorylations of p38 and JNK1/2 were obtained after stimulation with allergens, whereas treatments with irritant compounds led to ERK1/2 activation. Activation of PLCgamma and STAT1 were never detected. In conclusion, MAP-kinase activation provides a promising in vitro tool for the discrimination between sensitizers and irritants.
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PMID:In vitro differentiation of skin sensitizers by cell signaling pathways. 1802 79

To investigate the effects of the cholinergic anti-inflammatory pathway on hemodynamics, blood biochemistry, the plasma TNF-alpha level, and the nuclear factor-kappaB (NF-kappaB) activation during septic shock, male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP, a model of polymicrobial sepsis) or sham operation. Forty-eight rats were randomly assigned into six equal groups: sham CLP group; CLP group; VGX group was subjected to bilateral cervical vagotomy after CLP; STM group was subjected to bilateral cervical vagotomy after CLP plus the left vagus nerve trunk electrical stimulation; THA group was administered tetrahydroaminoacridine after CLP and bilateral cervical vagotomy; and alpha-BGT group was administered alpha-bungarotoxin before electrical stimulation of the vagus nerve. The right carotid artery was cannulated to monitor MAP. The plasma TNF-alpha level was measured using enzyme-linked immunosorbent assays. The hepatic NF-kappaB activation was determined by Western blotting. Cecal ligation and puncture produced progressive hypotension. Serum aspartate transaminase and alanine transaminase levels significantly increased after CLP challenge. The plasma TNF-alpha level and the hepatic NF-kappaB activation significantly increased after CLP alone or with bilateral cervical vagotomy compared with sham-operated group. Application of constant voltage pulses to the caudal vagus trunk significantly prevented the development of CLP-induced hypotension, alleviated the hepatic damage, and reduced the plasma TNF-alpha production, but electrical stimulation had no effect on the hepatic NF-kappaB activation. Tetrahydroaminoacridine administration after bilateral cervical vagotomy reversed hypotension and attenuated the plasma TNF-alpha response; in addition, it had no effect on the hepatic NF-kappaB activation. alpha-Bungarotoxin pretreatment significantly reversed the inhibitory effect of vagal electrical stimulation, but it had no effect on the hepatic NF-kappaB activation. Our results showed that the cholinergic anti-inflammatory pathway might produce a potential protective effect on polymicrobial sepsis in rats.
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PMID:The protective effect of the cholinergic anti-inflammatory pathway against septic shock in rats. 1839 58


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