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)

Lp(a), an independent risk factor of thrombotic and arteriosclerotic diseases, was determined in subjects undergoing health examinations, and the significance of the determination of Lp(a) in such examinations was investigated by studying its relation wih other risk factors for arteriosclerosis, etc. The subjects were 838 individuals. Lp(a) was determined by latex immunoassay (LIA). The mean Lp(a) value for all of the subjects was 10.9 +/- 7.2 mg/dl. Both gender groups were compared by age, but no significant changes were observed. In a study of Lp(a) in accordance with complications, there was no significant difference between the DM group and the non-DM group. There was also no significant difference between the IHD group and the non-IHD group. In the hyperlipemia group, the value of Lp(a) tender to be higher than in the non-hyperlipemia group. In the abnormal ECG group, the Lp(a) value was significantly higher than in the normal ECG group. When the relation between Lp(a) and other factors was studied, there was positive correlation with TC, beta Lp and LDLC, and a significant negative correlation with TRG. There was significant negative correlation with GOT, GPT and TTT. When the incidence of disease was compared by cut-off value, the incidence of abnormal ECGs was significantly higher at Lp(a) values of 25 mgdl or higher. In this study, Lp(a) showed positive correlations with TC, beta Lp and LDLC, the atherogenic risk of Lp(a) was evident. Because of the significant incidence of abnormal ECGs at the Lp(a) cut-off value of 25 mg/dl or higher, the risk range for Lp(a) should probably be considered as 25 mg/dl or higher.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The significance of determination of Lp(a) in health examinations]. 793 55

Fostriecin is an antitumor antibiotic with marked activity against ovarian, breast, and lung cancer cell lines in the human tumor clonogenic assay. The mechanism of cytotoxicity in vivo is unknown; in vitro it has been shown to inhibit macromolecular synthesis, interact with the reduced folate carrier system, and inhibit topoisomerase II. Phase I testing of fostriecin in a daily for 5 days schedule has begun in cancer patients. A high-pressure liquid chromatographic method to measure fostriecin in plasma samples was developed using sulfaquinoxaline as an internal standard and ultraviolet detection (268 nm). The extraction efficiency is 70% and the sensitivity limit is 100 ng/ml. The pharmacokinetics of fostriecin were determined in six rabbits following intravenous injection of 12 mg/m2. The mean distribution space was 4.44 L/m2 and the mean plasma clearance was 302 ml/min/m2. The elimination half-life was 11.95 +/- 8.55 min. All rabbits exhibited a 10-60-fold increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that resolved within 48 h of drug administration.
Ther Drug Monit 1994 Apr
PMID:Determination of fostriecin pharmacokinetics in plasma using high-pressure liquid chromatography assay. 800 68

We report a case of hepatic injury after treatment with nortriptyline in a therapeutic dose. There were symptoms of hepatitis and increased prothrombin time, serum alanine aminotransferase and alkaline phosphatases. The patient recovered after discontinuation of the drug.
Ther Drug Monit 1996 Feb
PMID:Nortriptyline-induced hepatic failure. 884 11

A randomized concentration-controlled clinical trial (RCCCT) is a trial design in which patients are randomized to predefined blood drug concentrations (low, medium, high). If the concentration ranges are sufficiently separated, this study design can reveal important blood concentration-response relations. Tacrolimus is a potent yet "infant" immunosuppressant for the treatment and prevention of graft rejection and has been shown to exhibit significant clinical activity in some immune-mediated disorders. A tacrolimus artificial intelligence modeling system (AIMS) was used to guide patient dosing to achieve target concentrations specified by the study protocols. In the Multiple Sclerosis study group, we were able to define a concentration range (0.3-0.7 ng/ml) that appeared to show efficacy and minimal tacrolimus toxicity. Patients randomized to the high zone (0.6-1.2 ng/ml) in the Primary Biliary Cirrhosis study group showed significant reduction (approximately 50%) in surrogate efficacy markers [aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT)] compared with patients in the low zone (0.1-0.6 ng/ml). Therefore the RCCCT allowed the detection and delineation of clinically significant concentration-response relations in an ethical and efficient manner.
Ther Drug Monit 1996 Aug
PMID:Computer-guided randomized concentration-controlled trials of tacrolimus in autoimmunity: multiple sclerosis and primary biliary cirrhosis. 885 64

The relationship between ritonavir plasma concentration, efficacy, and tolerance was evaluated in 31 children with advanced HIV infection who were receiving a triple therapy with ritonavir as protease inhibitor. Median CD4+ lymphocyte count and median viral load before the initiation of ritonavir-containing combination therapy were 1320 cells/mL and 5 log10 copies/mL, respectively. Ritonavir was given at a dose ranging from 300 to 450 mg/m2 twice daily. The median follow-up of triple therapy was 19 months. Response was defined as a drop of viremia of more than 1 log. Plasma drug levels were determined twice during the observation period: after at least 4 weeks and after 3 months of combined treatment. Samples were collected before (residual) and 2 hours (T2) after drug intake. Cholesterol, triglycerides, alanine transaminase, aspartate transaminase, and gamma-glutamyl transpeptidase were assessed at the same time. The median values of ritonavir residual and T2 levels were 1.64 mg/L and 5.9 mg/L at observation 1 and 3.35 mg/L and 6.29 mg/L at observation 2, respectively. According to virologic response, median residual concentrations of ritonavir were 3.17, 2.52, and 1.04 mg/L for the complete, the partial, and the no-response groups. The authors observed a wide intersubject variability of ritonavir concentrations with an increase in residual levels between the two observation periods. Residual levels were correlated with virologic response whereas there was no direct association between T2 levels and long-term response. Patients with complete or partial response displayed statistically significantly higher residual concentrations than the no-response group. No correlation could be demonstrated between elevated plasma drug concentrations and abnormal cholesterol or triglycerides values. These results emphasize the importance of a sustained high ritonavir concentration to achieve optimal treatment efficacy. Furthermore, these results prove the clinical benefit of therapeutic drug monitoring and could potentially improve patient evaluation in terms of treatment efficacy, compliance, and viral resistance.
Ther Drug Monit 2000 Aug
PMID:Relationship between efficacy, tolerance, and plasma drug concentration of ritonavir in children with advanced HIV infection. 1094 79

The aim of the study was to determine the level of total cholesterol and LDL-cholesterol in blood samples taken from 102 patients with recurrent major depression (according to DSM-IV). The analysis was performed during the acute period of major depression in 3 subgroups: with and without suicidal ideation (S+, S-), and after suicidal attempts (AS), and during remission of depressive symptoms. Putative correlations between the level of total cholesterol and severity of depressive symptoms and between total serum cholesterol and LDL-cholesterol and suicidal risk were evaluated. The patients did not suffer from any additional disorders, factors such as specific diet or pharmacotherapy, which could influence the levels of lipids, were absent. The subgroups were identified using clinical evaluation, medical records and Hamilton Depression Rating Scale--HAMD-S as well as a subscale of MMPI-DMS. Biochemical analyses were performed twice in all patients, in the acute period, before pharmacotherapy and after effective pharmacotherapy, in remission. The following parameters were evaluated: total serum cholesterol and LDL-cholesterol, T3, T4, TSH, ALT, AST, proteinogram. In all depressed patients with acute depression symptoms, low levels of total cholesterol and LDL-cholesterol were shown. The level of total cholesterol 160 mg/dl or less and the level of LDL-cholesterol 100 mg/dl or less were observed in persons with suicidal behavior only (S+ and AS). Low total cholesterol and LDL-cholesterol levels in persons in the acute period of major depression provided a useful parameter of suicide risk. A significant statistical correlation between the low level of total cholesterol and suicidal ideation was also found (r = 0.82, p < 0.05) as well as between the low level of serum total cholesterol and severity of depression, as evaluated by HAMD-S (r = 0.27, p < 0.05). During the remission of depressive symptoms, total cholesterol level and LDL-cholesterol increased significantly (p < 0.05) but a significant difference (p < 0.05) between subgroups (S-, S+, AS) were still observed. Low total cholesterol and LDL-cholesterol levels in remission in persons with the diagnosis of recurrent major depression may help to estimate the risk of suicidal behavior in the next depressive disorder. Possibly, low level of serum total cholesterol is a stable feature in some persons with recurrent major depression, probably dependent on their predisposition to autoaggression and presence of depressive disorder.
Med Sci Monit
PMID:Levels of serum total cholesterol and LDL-cholesterol in patients with major depression in acute period and remission. 1120 67

The aim of the study was to asses influence of selected epidemiologic and virusologic factors on the course of chronic hepatitis C (CHC). Data obtained from 550 CHC patients was analyzed (F/M: 241/309; age: 14-87, average age: 44.9 +/- 15.6). HbsAg and HIV-positive, as well as patients taking drugs were excluded from the study. Progression of the liver disease was assessed by the maximal ALT activity, presence of clinical or histopathological symptoms of hepatic cirrhosis, and 363 liver biopsy results. Clinical and histological data was analyzed depending on: patients sex, age (= 40, and > 40 years old), portal of infection (history data on transfusion or another source of infection), history of HBV infection (presence or absence of anti-HBc antibodies), and HCV genotype (1b or no-1b group). HCV genotype was determined in 170 patients by the use of commercial InnoLipa kit (Innogenetics). Statistical analysis was based on t-Student test and chi-squared test with or without Yates correction. It was proved that in patients over 40 years old or with history of transfusion inflammatory activity and liver fibrosis activity are significantly higher than in the rest of patients. More advanced age, transfusion and history of HBV infection are risk factors for hepatic cirrhosis development in CHC patients. Neither patient's sex nor HCV genotype were found to have significant influence on the course of CHC.
Med Sci Monit 2001 May
PMID:Factors influencing natural history of chronic hepatitis C. 1221 22

The daily dose of ribavirin is currently determined based on body weight. In the present study, the authors examined factors influencing total plasma clearance (CL(total)) and the toxic level on red blood cells of ribavirin in such body weight-based dosage adjustment in Japanese chronic hepatitis C patients (13 male and 6 female). Patients received ribavirin (600 or 800 mg/d) orally, depending on their body weights, together with interferon alpha-2b (6 million units) intramuscularly. A steady-state trough plasma concentration (C(pss)) was achieved approximately 4 weeks after the initiation of treatment, but the value was scattered among patients in a range from 1100 to 4200 ng/mL. The high C(pss) of ribavirin of approximately 4000 ng/mL decreased hemoglobin concentrations to less than 8.5 g/dL. The individual CL(total), estimated by dividing dose normalized by body weight by C(pss), of ribavirin correlated significantly with the patient's creatinine clearance. In contrast, no relationship was observed with other parameters such as age, body weight, serum creatinine concentration, alanine aminotransferase (ALT) concentration, or aspartate aminotransferase (AST) concentration, though ALT and AST concentrations decreased with ribavirin treatment in most patients. These results indicate that CL(total) of ribavirin is dependent on renal function (creatinine clearance), and hemolysis is induced by high ribavirin concentrations in plasma. Dosage adjustment of ribavirin based on renal function and body weight would provide effective and safer treatment without causing hemolysis.
Ther Drug Monit 2004 Feb
PMID:Dosage adjustment of ribavirin based on renal function in Japanese patients with chronic hepatitis C. 1474 43

There are data suggesting an association between mycophenolic acid (MPA) levels and acute rejection and toxicity in renal transplant recipients treated with mycophenolate mofetil (MMF), and therefore, knowledge of factors determining MPA levels may aid in accurate adjustment of MMF dosage. A total of 4970 samples taken 12 hours postdose were analyzed for MPA by immunoassay at regular intervals from the first week posttransplantation in 117 renal transplant patients immunosuppressed with MMF and tacrolimus in a steroid-sparing regimen (prednisolone for the first 7 days only). MPA levels rose in the first 3 months and stabilized thereafter; dose-normalized MPA levels rose throughout the first 12 months and subsequently stabilized. Multivariate analysis by means of a population-averaged linear regression showed positive associations between MPA level and total daily dose (P < 0.001) but not individual dose or total daily dose corrected for body weight. Positive associations were also seen with serum albumin (P = 0.01), tacrolimus trough level (P = 0.01), and female gender (P = 0.002). The association with tacrolimus levels diminished with time. Negative associations were seen between MPA level and higher estimated creatinine clearance (P < 0.001), and also with increasing alanine transaminase levels (P = 0.002), the use of oral antibiotics (P < 0.001), and infective diarrhea (P < 0.001). The latter findings may be related to changes in enterohepatic recirculation of MPA. Many clinical variables show associations with trough MPA levels. An understanding of these factors may aid therapeutic monitoring of MMF.
Ther Drug Monit 2005 Aug
PMID:Determinants of mycophenolic acid levels after renal transplantation. 1604

The Esmoriz-Paramos lagoon is one important ecosystem located in the Northwest coast of Portugal. This study is concerned with the assessment of pollution of the lagoon contributed by urban, industrial and agricultural activities. The parameters selected for this aim were the occurrence of hepatic histological alterations and plasma blood biochemistry in Liza saliens, the dominant fish in this lagoon. Blood parameters were compared between mullets collected from the lagoon and from the sea and included plasma enzyme activities (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)), glucose (GLU) and total protein (TP). A positive relationship between hepatocyte vacuolization index and hepatosomatic index was found, suggesting that lipid accumulation could have contributed to the increase of liver weight. The hepatic alterations recorded included general diagnostic categories and additionally large areas of heterogeneous parenchyma, composed of hepatocytes with different spectrum of vacuolization. Liver histopathological evaluation revealed a sample prevalence of 34% for heterogeneous parenchyma, 31% for foci of necrosis and 9% for non-neoplastic lesions. No neoplastic lesions were found. Livers with heterogeneous parenchyma showed higher Cu and Zn content than livers without this category of lesion, suggesting that metals accumulated could trigger this hepatic alteration. AST was higher in mullets from the lagoon than in mullets from the sea, but no differences in ALP and ALT were found, suggesting a change in protein metabolism as an adaptive response to metals exposure. The higher glucose and protein contents observed in fish caught in the lagoon are consistent with a stress response and the measurement of plasma AST activity could be a sensitive indicator of lagoon fish stress. In conclusion, Esmoriz-Paramos lagoon biomonitorization, using indicator species will proceed to assess the impact of the restoration program under development by the Portuguese government.
Environ Monit Assess 2008 Oct
PMID:Monitoring pollution in Esmoriz-Paramos lagoon, Portugal: liver histological and biochemical effects in Liza saliens. 1805 33


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