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)

The effect of danazol in a dose of 600 mg a day was studied in 20 women with moderate or severe endometriosis. The clinical effect was found to be excellent and repeat laparoscopy after about 6 months treatment revealed a marked regression in all patients with only small residual foci of endometriosis in two of them. The side effects were few. The metabolic studies revealed a significant increase in serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum potassium, serum albumin and serum creatinine, but a significant decrease in serum gamma glutamyl transpeptidase (GT). Serum sodium showed no alteration. A longitudinal study of basal plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and their responses to 25 microgram gonadotrophic releasing hormone (GnRH) i.v. as well as basal plasma levels of oestradiol, oestrone, progesterone and prolactin was performed. During treatment with danazol (600 mg a day) basal levels of LH, FSH, oestradiol, oestrone and progesterone were low but did not differ from the levels found in the early follicular phase of the menstrual cycle. On the other hand the pituitary response to GnRH was significantly greater for both LH and FSH than observed during the early follicular phase. These conflicting results are discussed. It seems that danazol inhibits the pituitary secretion of biologically active LH and FSH and this action is responsible for the decreased ovarian steroid secretion. Whether the atrophy of the uterine and ectopic endometrium is an effect of the reduced oestradiol levels or is a direct effect of danazol on endometrial oestrogen receptors, or a combination of both modes of action, is not clear.
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PMID:Hormonal, metabolic and clinical effects of danazol in the treatment of endometriosis. 53 48

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

The effect of exogenous luteinizing hormone (hCG), prolactin and prostaglandin F2 alpha, separately or in combination, on the activities of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in rat serum was studied. The changes of enzyme activities varied with the different hormones. Luteinizing hormone hCG and prolactin acted synergistically or antagonistically, depending on the enzyme response. Prostaglandin F2 alpha did not seem to modulate the effect of luteinizing hormone (hCG).
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PMID:Interactions between exogenous luteinizing hormone (hCG), prolactin and prostaglandin F2 alpha on serum enzymes in the rat. 346 21

Selective dopamine D1-receptor antagonists have been shown to exhibit similar effects in animal models for antipsychotic action as the selective D2 antagonists. NNC 01-0687, a benzazepine with selective and high affinity to the D1-receptor, was well tolerated by healthy subjects allocated to double blind, placebo controlled studies. Complaints of moderate restlessness and drowsiness were reported after administration of 25 mg NNC 01-0687, indicating the dose to be the maximum tolerated single dose. The highest multiple dose level of a daily dose of 45 mg NNC 01-0687 administered t.i.d. for 14 days was assessed as safe and well-tolerated with few reports of adverse events. Some alanine aminotransferase (ALT) elevations appeared in both treatment groups (active and placebo) and no evident influence of NNC 01-0687 on the liver function could be derived. No statistically significant or clinically relevant effects were observed in haematological parameters, urinalyses, blood pressure, heart rate, ECG or plasma levels of prolactin, cortisol or growth hormone. The plasma drug concentration curves indicated a fast absorption with tmax at 0.5-1 h and an apparent elimination half-life of 3-4 h. Both AUC and Cmax appeared to be linearly correlated to the dose, indicating linear pharmacokinetics. With similar Cmax and AUC on day 1 and day 10 no accumulation was observed. When administered just after lunch, the Cmax was reduced by 50-60% and the tmax increased to 3 h, but without change of AUC.
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PMID:Tolerability, safety and pharmacokinetics of single dose and multiple dosing of the selective D1 antagonist NNC 01-0687 in healthy subjects. 858 9

ICI 204,636 is a new, potentially atypical antipsychotic. In early phase II trials, the antipsychotic was well tolerated and results suggested efficacy in the treatment of the positive and negative symptoms of schizophrenia. The efficacy and safety of ICI 204,636 were evaluated on a larger scale in a 6-week, multicenter, double-blind trial. Hospitalized patients who met DSM-III-R criteria for chronic or subchronic schizophrenia with acute exacerbation, as well as other criteria, were randomized to ICI 204,636 (75 to 750 mg daily) (N = 54) or placebo (N = 55). Patients were assessed weekly by use of the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and Clinical Global Impression Scale (CGI) for efficacy and the Simpson Scale and Abnormal Involuntary Movement Scale for extrapyramidal side effects (EPS). Significant differences (p < or = 0.05) between treatment groups, which favored ICI 204,636, were identified throughout the trial. Endpoint differences were significant (by analysis of covariance) for BPRS factor IV (activation) and SANS scores and were marginally significant for total BPRS, BPRS factor III (thought disturbance), BPRS positive-symptom cluster, and CGI Severity of Illness item scores (p = 0.07, 0.09, 0.06, and 0.09, respectively). ICI 204,636 was well tolerated, although it was associated with mild transient increases in alanine aminotransferase and a higher incidence of somnolence and anticholinergic effects compared with placebo. In the dose range studied, treatment with ICI 204,636 did not induce EPS as determined by analysis of Simpson Scale total scores and lack of treatment-emergent acute dystonic reactions. Furthermore, ICI 204,636 did not produce sustained levels of prolactin; the mean change from baseline at endpoint (-7.2 micrograms/L) was comparable (p = 0.44) to that for placebo (-8.2 micrograms/L). These findings distinguish ICI 204,636 from standard antipsychotics and confirm preclinical predictions that ICI 204,636 is an atypical antipsychotic.
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PMID:ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia. U.S. SEROQUEL Study Group. 869 Aug 31

We tested the hypothesis that nutritional state affects seawater acclimation by transferring either fed or food-deprived (2 weeks) male tilapia (Oreochromis mossambicus) from fresh water to full-strength sea water. Food-deprivation resulted in a significant increase in plasma concentrations of Na+, Cl-, cortisol, glucose, total amino acid, glutamate, serine and alanine, and in hepatic pyruvate kinase (PK) and lactate dehydrogenase (LDH) activities, whereas the prolactin-188 to prolactin-177 ratio (tPRL188:tPRL177) and plasma prolactin-188 (tPRL188), lactate, arginine and hepatic glycogen content and hepatic alanine aminotransferase (AlaAT) and 3-hydroxyacyl-Coenzyme A dehydrogenase (HOAD) activities were lower than in the fed group. Seawater transfer significantly increased the tPRL188:tPRL177 ratio and plasma concentrations of Na+, Cl-, K+, growth hormone (GH), glucose, aspartate, tyrosine, alanine, methionine, phenylalanine, leucine, isoleucine and valine levels as well as gill Na+/K+-ATPase activity and hepatic PK and LDH activities, whereas plasma tPRL177, tPRL188, glycine and lysine concentrations were significantly lower than in fish retained in fresh water. There was a significant interaction between nutritional state and salinity that affected the tPRL188:tPRL177 ratio and plasma concentrations of Cl-, GH, glucose, aspartate, tyrosine, serine, alanine, glycine, arginine and hepatic PK, LDH, AlaAT, aspartate aminotransferase, glutamate dehydrogenase and HOAD activities. These results, taken together, indicate that food-deprived fish did not regulate their plasma Cl- levels, despite an enhancement of plasma hormonal and metabolic responses in sea water. Our study also suggests the possibility that plasma prolactin and essential amino acids may be playing an important role in the seawater acclimation process in tilapia.
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PMID:Food-deprivation affects seawater acclimation in tilapia: hormonal and metabolic changes 932 Mar 94

Tall fescue (Festuca arundinacea) is a forage grass that is widely used in pastures in the eastern US for cattle, sheep and horses. The endophytic fungus Neotyphodium coenophialum is endemic in tall fescue pastures in the US. The turfgrass industry intentionally infects fescue cultivars with strains of the fungus to impart desirable growth and disease tolerance qualities to the plants. In contrast, ergot and pyrrolizidine alkaloid toxins produced by fungus-infected plants have been incriminated causally in bovine tall fescue toxicosis, a poorly defined syndrome of morbidity that occurs in cattle that consume endophyte-infected tall fescue (E+TF). We compared the serum biochemistry profiles from cattle that grazed E+TF with those from control cattle that grazed on endophyte-free tall fescue (E-TF). Cattle were bled on 7 dates from April 1 to August 30, 1996 and on 5 dates from May 1 to July 30, 1997. Cattle that grazed E+TF retained rough winter haircoats and had lesser weight gains, typical of tall fescue toxicosis, compared to those grazing E-TF. They had decreased activities of alkaline phosphatase and alanine aminotransferase. Compared to controls, they had lower values for serum prolactin and globulin concentrations. The concentration of creatinine and the albumin/globulin ratio were increased in the cattle grazing E+TF. Isozyme determination of alkaline phosphatase indicated that the decrease in serum activity of cattle grazing E+TF was due to decreases in both intestinal and bone isozymes. Serum protein electrophoresis indicated that the decrease in serum globulin concentration was due to decreases in both alpha and gamma globulin fractions of this protein. The data collected in these experiments add to our understanding of the alterations that occur in the serum chemistry profiles when cattle consume E+TF for prolonged periods of time.
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PMID:Alterations in bovine serum biochemistry profiles associated with prolonged consumption of endophyte-infected tall fescue. 1034

The objective of the current study was to delineate changes that occur in serum analytes and blood cellular elements in cattle that graze endophyte-infested (Neotyphodium coenophialum) tall fescue. Tall fescue is grown on more than 35 million acres (14.2 million ha) of pasture in the United States, and three-fourths of the pastures are infected with the endophyte at a 60% or greater level. Tall fescue toxicosis caused by endophyte-produced ergot alkaloids continues to be the most important grass-related disease in the United States, in terms of economic loss to animal producers. However, the agronomic attributes of tall fescue make it an attractive forage species because of its ability to withstand cool temperatures, drought, poor soil conditions, and intensive defoliation from herbivore species, including insects. Tall fescue toxicosis is a complex disease and the need exists to understand the mechanisms of the toxic effects in order to institute effective, prophylactic control measures. Our group previously reported changes that occur in serum biochemical analytes of cattle that graze endophyte-infected tall fescue. An additional year's worth of data have been added, strengthening and corroborating these data. Consistent and significant changes associated with tall fescue toxicosis during the 3-yr study included decreased serum concentrations of cholesterol, globulin (increased albumin/globulin ratio), prolactin, total protein, and copper. The activity of alanine aminotransferase was decreased in serum, whereas an increase in serum concentrations of creatinine and total bilirubin occurred. The present report also documents comparative hemograms of cattle that grazed endophyte-infected or endophyte-free tall fescue over a prolonged period. The mean erythrocyte counts were increased in cattle that grazed endophyte-infected tall fescue, whereas mean corpuscular hemoglobin and mean corpuscular volume were decreased, as were mean eosinophil counts. Thus, repeatable changes have been identified that occur in serum biochemical and blood cellular values of cattle grazing endophyte-infected tall fescue that will aid in understanding the pathogenesis of the disease. In addition, these consistently altered parameters can be used to assess the effectiveness of potential prophylactic treatments.
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PMID:Alterations in hemograms and serum biochemical analytes of steers after prolonged consumption of endophyte-infected tall fescue. 1078 95

An increasing number of women is treated with adjuvant cyclophosphamide, methotrexate and 5-fluorouracil therapy for breast cancer. The effects of the chemotherapy on many laboratory tests are, however, inadequately known. This study investigates the effects of the treatment on various laboratory tests. Fifteen premenopausal women receiving adjuvant cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy and optional radiotherapy were included in the study. Common hormonal, biochemical, hematological, protein and lipid laboratory tests were taken serially during a 10-month follow-up. Twelve women became amenorrheic. Their serum follicle stimulating hormone and luteinising hormone concentrations increased accordingly. Other serum hormones (testosterone, androstenedione, sex hormone-binding globulin, prolactin, dehydroepiandrosterone sulfate, cortisol, parathyroid hormone and thyroid hormones) changed only slightly. Hemoglobin concentration and white blood cell count decreased slightly. Serum alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, angiotensin-converting enzyme, amylase, glucose, potassium, phosphate, urea and triglycerides concentrations increased slightly whereas serum bilirubin, haptoglobin, and immunoglobulin A and M decreased slightly. Serum alpha1-antitrypsin fluctuated around the baseline concentration. Other test results remained at their pretreatment concentrations. With the exception of increases in serum gonadotrophins, the changes observed were slight and the mean concentrations remained within reference limits. Therefore, cyclophosphamide, methotrexate and 5-fluorouracil adjuvant treatment is unlikely to complicate the diagnosis of other diseases.
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PMID:Alterations in laboratory test results during adjuvant breast cancer treatment. 1095 29

Twenty-one participants in a mobilising labour market project offering temporary, alternative employment in Sweden were followed longitudinally for one year, including a six month post-participation follow-up period. Earlier analyses of self-rated psychosocial data have indicated consistent improvements in mental health and quality of life. In the present study, however, a significant rise in serum prolactin, plus decreased dehydro-epiandro-sterone sulphate levels and tendencies towards increased alanine aminotransferase, gamma-glutamyl transferase and diastolic blood pressure, seem to disconfirm the hypothesis that biological markers of psychosocial health would improve in a similar fashion. It is speculated that this apparent inconsistency could be part of a protective adaptation to long-term unemployment similar to the cocooning tendencies in maternal behaviour. Specifically, we argue that this could protect against the stress of being in an uncontrollable and 'helpless' situation by facilitating a re-focusing on more private matters as opposed to 'hopeless' job seeking. While being potentially detrimental for people with fair chances on the labour market, it is possible that such an adaptation may be helpful for more vulnerable groups.
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PMID:Psychophysiological effects of temporary alternative employment. 1133 Jul 75


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