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)

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

HELLP syndrome is a serious, life-threatening form of pre-eclampsia with a typical laboratory triad. The incidence of the disease is reported as being 0.17-0.85% of all live births. There has been, to date, neither reliable early recognition nor effective prevention of HELLP syndrome. As a result of endothelial dysfunction, activation of intravascular coagulation occurs with fibrin deposition in the capillaries and consecutive microcirculation disorders. The disease manifests itself on average between 32-34 weeks' gestation. HELLP syndrome will occur postpartum in up to 30% of the cases. The clinical cardinal symptom of the disease is right upper quadrant pain or epigastric pain accompanied with nausea, vomiting and malaise. In 20% of the cases with HELLP syndrome there is no hypertension and 5-15% of the pregnant patients present a low level of proteinuria or none at all. The early recognition of hemolysis is most sensitively managed by the determination of the serum haptoglobin. The increase of the aspartate transaminase (AST) and the alanine transaminase (ALT) often precedes a decrease in platelets. The course of HELLP syndrome is incalculable. It is universally agreed that a pregnancy from 32-34 weeks should be immediately delivered. Before 32-34 weeks, expectant management is generally possible in a perinatal center. The frequency for a repeated hypertensive disease in pregnancy ranges from 27% to 48%.
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PMID:HELLP syndrome. 1103 96

Investigations in Prince William Sound (Alaska, USA) following the Exxon Valdez oil spill (EVOS) revealed that river otters (Lontra canadensis) on oiled shores had lower body mass and elevated values of biomarkers, than did otters living on nonoiled shores. In addition, otters from oiled areas selected different habitats, had larger home ranges, and less diverse diets than animals living in nonoiled areas. These differences between river otters from oiled shores and those from nonoiled areas strongly suggested that oil contamination had an effect on physiological and behavioral responses of otters. In this study, we explored the effects of crude oil contamination on river otters experimentally. We hypothesized that exposure to oil would result in elevated values of biomarkers, indicating induced physiological stress. Fifteen wild-caught male river otters were exposed to two levels of weathered crude oil (i.e., control, 5 ppm/day/kg body mass, and 50 ppm/day/kg body mass) under controlled conditions in captivity at the Alaska Sealife Center in Seward (Alaska, USA). Responses of captive river otters to oil ingestion provided mixed results in relation to our hypotheses. Although hemoglobin (Hb, and associated red blood cells) and white blood cells, and possibly interleukin-6 immunoreactive responded in the expected manner, other parameters did not. Aspartate aminotransferase, alanine aminotransferase, and haptoglobin (Hp), did not increase in response to oiling or decreased during rehabilitation. Conversely, principle-component analysis identified values of alkaline phosphatase as responding to oil ingestion in river otters. Our results suggested that opposing processes were concurring in the oiled otters. Elevated production of Hp in response to tissue damage by hydrocarbons likely occurred at the same time with increased removal of Hp-Hb complex from the serum, producing an undetermined pattern in the secretion of Hp. Thus, the use of individual biomarkers as indicators of exposure to pollutants may lead to erroneous conclusions because interactions in vivo can be complicated and act in opposite directions. Additionally, the biomarkers used in investigating effects of oiling on live animals usually are related to the heme molecule. Because of the opposing processes that may occur within an animal, data from a suite of heme-related biomarkers may produce results that are difficult to interpret. Therefore, we advocate the exploration and development of other biomarkers that will be independent from the heme cycle and provide additional information to the effect of oiling on live mammals.
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PMID:Biomarker responses in river otters experimentally exposed to oil contamination. 1150 23

BACKGROUND: Biochemical markers for liver fibrosis (FibroTest) and necroinflammatory features (ActiTest) are an alternative to liver biopsy in patients with chronic hepatitis C. Our aim was to assess the inter-laboratory variability of these tests, and their 6 components (gamma-glutamyl transpeptidase, alanine aminotransferase, alpha2-macroglobulin, haptoglobin, apolipoprotein A1, and total bilirubin) and to identify factors associated with this variability. RESULTS: Serum of 24 patients with chronic hepatitis C or severe alcoholic liver disease were prospectively recorded and analyzed in one reference center and in 8 additional laboratories. When gamma-glutamyl transpeptidase and alanine aminotransferase were expressed in international units, there was no significant difference between laboratories in the results of FibroTest or ActiTest; kappa statistics were greater than 0.50 with only 0.8% of cases (3/384) with a discordance of more than one stage. The main factor significantly associated with variability was the expression of gamma-glutamyl transpeptidase and alanine aminotransferase, as multiples of upper limit of reference values. The use of standardized method with pyridoxal phosphate reduced the variability of alanine aminotransferase expression, and standardized original Szasz method reduced the variability of gamma-glutamyl transpeptidase expression. CONCLUSIONS: The variability of FibroTest and ActiTest was acceptable without clinical consequences for the prediction of the stage of liver fibrosis and grade of activity. Standardized methods and assay calibration should be used and expression of alanine aminotransferase and gamma-glutamyl transpeptidase in multiples of the upper limit of reference values should not be employed.
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PMID:A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease. 1253 83

C-reactive protein (CRP), haptoglobin (Hp) and fibrinogen (Fbgn) are acute phase reactants (APRs), the blood levels of which increase during acute inflammation. However, although the levels of these APRs are used to monitor inflammation in man, their usefulness and sensitivity as markers of inflammation in rodents are less clear. We therefore wished to evaluate, in a comparative fashion, a prototype immunoassay for serum CRP, a commercial assay for serum Hp, and an automated assay for Fbgn, using a model of acute inflammation in the rat. Additionally, pro-inflammatory cytokines and serum protein fractions were also measured. The model of inflammation used was the intraperitoneal injection of Freund's complete adjuvant (FCA). In a concluding experiment, findings with Hp in the FCA rat model were validated in a toxicologically relevant study involving the induction of acute hepatic inflammation using the model hepatotoxicant carbon tetrachloride (CCl(4)). Female Wistar Han rats were treated with a single injection of FCA in a dose-response study (1.25-10.0 ml/kg, sampling at 36 h) and two time-course studies (over 40 h and 21 days). In a final experiment, rats were dosed with CCl(4) at 0.8 ml/kg and sampled over a 17-day period. In FCA and CCl(4) experiments, serum/plasma was prepared and tissues taken at autopsy for histological assessment (CCl(4) study only). In the dose-response study, serum CRP, Hp and plasma Fbgn were increased at all FCA dose levels at 36 h post-dosing. Serum alpha(2) and beta(1) globulin fractions were also increased, while albumin levels were decreased. In the 40-h time-course study, CRP levels peaked at 25-40 h post-dosing, to approximately 120% of control (as 100%). Hp levels increased to a maximum at 25 and 40 h post-dosing with values greater than 400% of control, and alpha(2) and beta(1) globulin fractions peaked at 30 and 40 h post-dosing to 221 and 187% of control, respectively. Increased serum interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) levels peaked at 20 h (11-fold) and 25 h (19-fold), respectively. In a 21-day time-course study, no increased CRP levels were measured despite elevated levels of Hp, which peaked at 36 h (approximately 7-fold above control), and remained elevated up to 21 days. IL-6 and IL-1beta levels peaked at 12 h (19-fold) and 24 h (28-fold), respectively. Liver histopathology of animals treated with CCl(4) showed centrilobular hepatocellular degeneration and necrosis (most significant at 36 h) with an inflammatory response (most significant at 48 h). Resolution of the lesion was complete by 4 days post-dosing. Serum alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase levels peaked at 36 h post-dosing. Hp levels increased maximally at 48 h (426% of control). We conclude that serum CRP is a poor marker of acute inflammation in the rat in comparison with serum Hp and plasma Fbgn. Between Hp and Fbgn, serum Hp is shown to be the most sensitive and useful marker of acute inflammation.
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PMID:Markers of experimental acute inflammation in the Wistar Han rat with particular reference to haptoglobin and C-reactive protein. 1266 91

Combinations of tests comprising alpha2-macroglobulin, haptoglobin, apolipoprotein Al, gamma-glutamyltransferase, total bilirubin (Fibrotest) and alanine aminotransferase (Actitest) are being developed as alternatives to liver biopsy in patients with chronic hepatitis C. The aim of this study was to assess in the same laboratory the impact of parameter assay variations on Fibrotest and Actitest results and intra-patient reproducibility of the two tests. The stability of the samples for each test was studied after storage at -80 degrees C and -20 degrees C. Within-run, between-run and total imprecision for each parameter assay, and for Fibrotest and Actitest results, were determined. Transferability of assay results between different analyzers was studied. Intra-patient reproducibility was assessed in 55 hospitalized patients. Fibrotest and Actitest reference ranges were determined in 300 blood donors (reference group). The stability of the parameters was affected by serum storage at -20 degrees C only. The impact of parameter analytical variability on Fibrotest and Actitest results was less than 10% and intra-patient reproducibility was acceptable (p > 0.05). The transferability between different analyzers of results of assays performed under the same standardized and calibration conditions was excellent. Fibrotest and Actitest reference ranges in blood donors were (mean+/-SE) 0.075+/-0.004 and 0.068+/-0.004, respectively. The low intra-laboratory and intra-patient variability in Fibrotest and Actitest results confirm Fibrotest and Actitest reliability.
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PMID:Intra-laboratory analytical variability of biochemical markers of fibrosis (Fibrotest) and activity (Actitest) and reference ranges in healthy blood donors. 1508 May 67

BACKGROUND: Biochemical marker combinations, including alpha2-macroglobulin, haptoglobin, apolipoprotein A1, gamma-glutamyl transpeptidase, and total bilirubin (all part of FibroTest) plus alanine aminotransferase (all part of ActiTest), are being developed as alternatives to liver biopsy in patients with chronic hepatitis C and other various chronic liver diseases. Considering this premise, the primary aim of this study was to assess the impact of meal intake on FibroTest and ActiTest results. Such studies are very important for patients, as many clinical errors have been related to the absence of baseline evidence. RESULTS: Intra-individual variation was assessed for the 6 above components and for FibroTest and ActiTest, by measuring time dependent variations before and one hour after a standard meal in 64 subjects. These consisted of 29 healthy volunteers and 35 patients with chronic liver diseases. Meal intake had no significant impact on any of the six components, or on FibroTest or ActiTest, as assessed by repeated measure variance analyses (ANOVA all p > 0.90); the Spearman correlation coefficient ranged from 0.87 (total bilirubin) to 0.995 (gamma-glutamyl transpeptidase). The coefficients of variation (CV) between fasting and postprandial measurements fluctuated for the six components from 0.09 (apolipoprotein A1) to 0.14 (alpha2-macroglobulin), and from 0.09 for FibroTest to 0.13 for ActiTest. In contrast, meal intake had a significant impact on triglycerides (ANOVA p = 0.01, CV = 0.65) and glucose (ANOVA p = 0.04, CV = 0.31). As for the prediction of liver injury, the concordance between fasting and postprandial predicted histological stages and grades was almost perfect, both for FibroTest (kappa = 0.91, p < 0.001) and ActiTest (kappa = 0.80, p < 0.001). CONCLUSIONS: The intra-individual variation of biochemical markers was low, and it was shown that measurements of FibroTest, ActiTest and their components are not significantly modified by meal intake. This fact makes the screening of patients at risk of chronic liver diseases more convenient.
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PMID:Intra-individual fasting versus postprandial variation of biochemical markers of liver fibrosis (FibroTest) and activity (ActiTest). 1521 66

INCREASE IN ALANINE AMINOTRANSFERASE (ALAT): Used for many Years in the diagnosis and follow-up of chronic hepatic diseases related to HCV, the determination of ALAT presents various limits: variation from one patient to the other and in the same patient over time, absence of specificity and inconstant increase. HISTOLOGICAL ASSESSMENT OF THE INVOLVEMENT OF THE LIVER: The hepatic needle-biopsy remains the best means of assessing precisely the hepatic impact. Several scores of hepatic involvement exist, the most frequently used is the Metavir score that takes into account not only the necrotic-inflammatory activity but also the fibrosis. OTHER THAN THE HEPATIC NEEDLE-BIOPSY: There are complications with the hepatic needle-biopsy and non-invasive markers of fibrosis and hepatic necrotic-inflammatory activity have been looked for. Two scores have hence been developed from the measurement in the blood of 4 proteins (apolipoprotein A1, alpha2 macroglobulin, haptoglobin and bilirubin) and 2 enzymes (alanine aminotransferase and gamma-glutamyl transpeptidase) which provide an acurate assessment of the fibrosis (Fibrotest) and the necrotic-inflammatory activity (Actitest).
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PMID:[The prognostic tools of hepatitis C virus infections]. 1523 11

The IFCC Committee on Plasma Proteins has been investigating regional differences for commonly assayed plasma proteins to determine whether universal reference intervals can be applied. As a part of this study, we launched an Asian project analyzing the concentrations of 13 serum proteins whose values are standardized to CRM470, and five newer analytes: retinol-binding protein (RBP), cystatin C (CysC), light-chain-kappa (L-kappa), and light-chain-lambda (L-lambda). In Tokyo, Seoul, Kuala Lumpur, Hong Kong, Taipei and Shanghai, serum samples were collected from 146 to 415 apparently healthy individuals with nearly equal gender ratios. All assays were performed in Tokyo on a Behring Nephelometer II (BN II). Seven chemical analytes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (gammaGT), creatinine, total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)) were also measured. These results were used for excluding individuals with possible latent clinical disorders. Positive acute phase reactants were consistently lower, and negative ones were higher, in Tokyo than those in other cities. The most conspicuous difference was observed in C-reactive protein (CRP). There were no regional differences in transferrin, albumin, or CysC. Creatinine was much lower in Tokyo despite comparable CysC levels. ALT and gammaGT were higher in Shanghai, Taipei and Seoul; gammaGT and TG were higher in Shanghai; and HDL-C was higher in Tokyo. Gender-related differences in reference intervals were observed for immunoglobulin (Ig)M, haptoglobin, RBP, transferrin, alpha2-macroglobulin (A2M), transthyretin, alpha1-acid glycoprotein, CysC, and C4 in all cities. Slight age-related differences were observed, irrespective of the region, in IgA and ceruloplasmin (increase) and A2M (decrease). Environmental factors and lifestyle seem to have a great influence on many commonly measured analytes.
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PMID:Diagnostic and epidemiological implications of regional differences in serum concentrations of proteins observed in six Asian cities. 1532 16

Proliferol is an investigational new drug containing lidocaine hydrochloride 0.25%, dextrose 12.5%, glycerin 12.5%, and phenol 1.0% in aqueous solution. Despite extensive human experience with similar drugs administered by intraligamentous injection for chronic musculoskeletal disorders, little is known concerning preclinical toxicity. The purpose of this study was to assess the acute toxicity of intramuscular Proliferol in 96 (48 male, 48 female) Charles River strain rats, which were randomly assigned to low- (1x), medium- (5x), or high- (10x) dose Proliferol (derived from a human dose of 20 ml on a volume per bodyweight basis), or high-dose saline placebo. Observations included clinical observations, biochemistry, hematology, urinalysis, and full histopathology after 24 h or 14 days. There were no signs of ill health or reaction to treatment, and gait and body temperature were within normal limits. Biochemistry findings at 24 h included elevated aspartate aminotransferase, alanine aminotransferase, and haptoglobin; at 14 days all values were within normal ranges. Urinalysis findings at 24 h included increased urobilinogen and blood in all dose groups compared with placebo. Urine concentrations of phenol and lidocaine were greatest at 2 h and absent at 24 h. Histopathology findings included localized acute inflammatory soft tissue changes at the injection sites at 24 h and skeletal muscle regeneration at 14 days, which were consistent with the anticipated mechanism of action of Proliferol. There was no evidence of systemic toxicity from intramuscular injection of Proliferol in rats at up to 10x the human dose.
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PMID:Acute toxicity evaluation of proliferol: a dose-escalating, placebo-controlled study in rats. 1796 32


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