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Biomedical subjects

M M Galteau

Publications and source records attributed to M M Galteau.

At least 19 recordsLinked to original sources
PubMed1992

Enzyme induction by drugs and toxins.

Enzyme induction by drugs mostly concerns those enzymes involved in drug metabolism: cytochromes P-450, UDP-glucuronosyltransferases, glutathione S-transferases, gamma-glutamyltransferases and epoxide hydrolases. A large variety of molecular forms exists, but not all of them are inducible (e.g. the inducible cytochromes P-450 in man are members of family IA, IIA, IIC, IIE, IIIA). Induction is most common in the liver, but also occurs in other organs (lung, placenta, lymphocytes). Over the past 20 years a relatively small number of drugs and environmental chemicals have been identified as enzyme inducers, perhaps fewer than early studies suggested. Information on inducing properties must be obtained as early as possible during the development of a new drug and made available to clinicians and clinical chemists when the drug is marketed. The main consequences of enzyme induction are changes in pharmacokinetics of the drug itself or of an associated drug. Much progress has been made in methods to identify these inducers.

Animals↗
PubMed1991

Urinary glucuronide excretion of fenofibric and clofibric acid glucuronides in man. Is it polymorphic?

The possible polymorphism of the glucuronidation reaction in man has been investigated using two hypolipidaemic compounds, fenofibrate and clofibrate, as the test probes. The formation of fenofibryl and clofibryl glucuronides was identified by their susceptibility to hydrolyses by beta-glucuronidase. The urinary excretion of the glucuronides was measured in 72 healthy volunteers after a single dose of fenofibrate, and in 104 subjects given a single dose of clofibric acid. Fenofibrate was excreted at a lower rate than clofibrate, since 13.94% and 26.55% of the doses of fenofibrate and clofibrate respectively, were recovered in urine in 8 h. Correlation analysis indicated that sex and body mass index significantly influenced the formation of fenofibryl glucuronide, whereas age and oral contraceptives affected the excretion of clofibryl acid glucuronide. The 8-hour urinary excretion patterns of clofibryl glucuronide and of clofibric acid presented a Gaussian distribution, whereas those of fenofibryl glucuronide and fenofibric acid showed 2 populations. When the metabolic ratio free fenofibric acid/glucuronide was considered, 84.7% of subjects presented the ratio 0.147, and 15.3% had the 3-fold higher ratio of 0.421. The study has shown, in the human population studied, that the glucuronidation of fenofibric acid but not that of clofibric acid may present a polymorphism.

Adult↗
PubMed1991

Highly sensitive immuno-assays for the determination of cotinine in serum and saliva. Comparison between RIA and an avidin-biotin ELISA.

Two immuno-assay methods (RIA and ELISA) have been developed for the accurate and sensitive measurement of cotinine in human body fluids (serum, saliva). RIA uses [3H]cotinine as antigen and charcoal/dextran for separating cotinine-bound antibodies from the free derivative. Another technique (ELISA) was developed to avoid the use of radio-labelled compounds and to determine cotinine in large populations, including passive or non-smokers who usually present very low concentrations. The two techniques were analytically validated. The detection limit was similar (0.1 micrograms/l) and the precision was better than 10% for both techniques. Non-smoker values ranged from 0.1 to 17 micrograms/l by ELISA and 0.1 to 27.5 micrograms/l by RIA, whereas smoker values ranged from 50 to 1000 micrograms/l (ELISA) and from 70 to 800 micrograms/l (RIA). The comparative analysis of cotinine in 96 human sera revealed a good correlation between the two methods (r = 0.97) and a reliable discrimination between the populations of non-smokers and smokers. As usual, the ELISA is more rapid (4 h 30 min) than the RIA (longer than 48 h). ELISA is proposed for use in the epidemiological investigation of the human tobacco risk.

Avidin↗
PubMed1991

Relation between debrisoquine oxidation phenotype and morphological, biological, and pathological variables in a large population.

Factors affecting biological variations in debrisoquine-oxidation polymorphism were investigated in a population of 3065 unrelated supposedly healthy Caucasian subjects, ages 35 to 50 years. This population, including 1526 men and 1539 women, was used to determine whether the debrisoquine-oxidation phenotype can be related with environmental factors such as alcohol intake, smoking habits or medication; with morphological variables; or with 22 blood constituents and some pathological states. A single dose of 10 mg of debrisoquine sulfate was administered to determine the oxidation phenotype. A metabolic ratio (debrisoquine/4-hydroxydebrisoquine) of 10.0 defined a poor metabolizer [frequency of 8.2% (SD 1.0%)] in this sample. Dose recoveries of debrisoquine excretion (mean and SD) were 8.9% (11.9%) and 45.1% (32.2%) in extensive and poor metabolizers, respectively. The mean (SD) amount of debrisoquine administered that was excreted in urine as 4-hydroxydebrisoquine was 17.4% (17.3%) in extensive metabolizers and 0.5% (0.9%) in poor metabolizers. The main factors differing significantly between poor and extensive metabolizers were mean cell volume, mean corpuscular hemoglobin concentration, albumin, and ponderal index. No other blood constituents (e.g., cholesterol, glucose) differed between poor and extensive metabolizers. The lack of correlation with most of the variables tested is of interest in clinical trials, because our findings indicate that no subgroups will be required, making selection of subjects easier.

Administration, Oral↗
PubMed1990

Development of an ELISA to study the polymorphism of dextromethorphan oxidation in a French population.

Simple, sensitive and selective enzyme immunoassays (ELISA) for monitoring urinary dextromethorphan and its major metabolite, dextrorphan, were developed. Dextromethorphan and dextrorphan hemisuccinates were linked to bovine serum albumin and specific antisera against each immunogen were raised in rabbits. The sensitivity of the ELISA was high (limit of detection 740 and 600 pg.ml-1 for dextromethorphan and dextrorphan, respectively). Intra- and interassay variation was less than 10%, and cross-reactivity between the two compounds was less than 1%. The ELISA was employed to phenotype 216 French subjects. The frequency of poor metabolizers was 5.1%.

Chromatography, High Pressure Liquid↗
PubMed1990

Frequency and effects of the apolipoprotein A-IV polymorphism.

Plasma from 158 presumed healthy nuclear families has been analyzed by high-resolution, two-dimensional electrophoresis to study the frequency and effects of the genetic polymorphism in human apolipoprotein A-IV. Two common alleles, apo A-IV 1 and apo A-IV 2 were detected with relative frequencies of 0.943 and 0.057, respectively. Autosomal codominant transmission of these two alleles coded for by a single structural locus was demonstrated. Furthermore, we studied the effects of this apo A-IV variability on total plasma cholesterol, triglyceride, glucose levels and gamma-glutamyltransferase activity. Statistically significant differences among apo A-IV genotypes for the average glucose level were detected. The average effect of the apo A-IV 1 allele was to lower plasma glucose levels by 0.013 mmol/l, whereas the average effect of the apo A-IV 2 allele was to raise glucose levels by 0.213 mmol/l.

Adult↗
PubMed1989

Two-dimensional electrophoresis of plasma proteins and high density lipoproteins during inflammation.

Plasma protein and lipoprotein fractions of five patients were analyzed on day 1, 5, and 15 after severe head injury by combining three types of two-dimensional electrophoresis (2-DE) to obtain information on lipoprotein and apolipoprotein composition. On analysis under nondenaturing conditions in both dimensions on day 5, the samples show modifications of isoelectric point (pI) and molecular weight (Mr) properties of the high density lipoprotein (HDL) fraction in addition to an increase in inflammatory proteins and a return to a normal pattern on day 15. In the second type of 2-DE the samples were analyzed employing isoelectric focusing without denaturant in the first dimension, followed by sodium dodecyl sulfate (SDS) in the second dimension in order to study the protein composition of lipoprotein fractions. On day 5, a decrease of the apolipoproteins apo A-I, apo A-II, and apo C were noted, with simultaneous appearance of an unidentified protein with Mr 12,000 and pI 6.0. In the third type of 2-DE, employing urea and Nonidet P-40 in the first and SDS in the second dimension, the plasma polypeptide composition was studied. The presence of an unidentified polypeptide could be confirmed on day 5, tending to disappear thereafter. This Mr 12,000 component consists of two major spots at pI 5.7 and 6.0 and four minor ones between pI 6.0 and 8.0. These properties suggest that this protein corresponds to serum amyloid A apolipoprotein.

Apolipoprotein A-I↗
PubMed1978

Drug interference in clinical chemistry: studies on ascorbic acid.

The expert group "Drug Interference in Clinical Chemistry" of the Bureau of Reference, Directorate General for Research, Science and Education of the Commission of the European Communities, consisting of one participant of each member of the European Communities, presents this first report on the final results of its activities. Within the framework of a first stage basic program, the paper describes interferences of therapeutic and elevated doses of ascorbic acid on commonly used clinical chemical methods. This is the result of a bipartite study that was jointly planned, carried out and evaluated. Local and personal influences have been eliminated, as have variations due to methodology, measurement equipment and reagents, in order to be able to present distinct causal effects of ascorbic acid. No definite influence of ascorbic acid on analytical values for urea, cholesterol, calcium, protein, bilirubin, aspartate aminotransferase and alkaline phosphatase could be detected. At therapeutic concentrations, ascorbic acid distinctly interferes with the analysis of glucose, uric acid, creatinine and inorganic phosphate. The extent and direction of interferences vary, depending on the type of reaction, kit and apparatus. In some cases the influence of ascorbic acid results in severe disturbance of the analytical methods leading to useless values.

Ascorbic Acid↗
PubMed1978

Effect of anticonvulsant drugs on alkaline phosphatase and gamma-glutamyltransferase activity in human leukocytes.

The authors compared the alkaline phosphatase and gamma-glutamyl-transferase activities in leukocytes from presumably healthy subjects and from epileptic patients treated with anticonvulsants, matched for age and sex. Intraleukocyte alkaline phosphatase activity was higher in women than in men and was greatly reduced by the anticonvulsant drugs. Intraleukocyte gammaglutamyltransferase activity did not vary with sex and was unaffected by the anticonvulsant drugs contrary to findings for the activity of this enzyme in plasma and liver.

Alkaline Phosphatase↗
PubMed1978

[Comparative effects of antiepileptics on the alkaline phosphatase and gamma glutamyltransferase activities in plasma and leukocytes].

Alkaline phosphatase and gamma glutamyltransferase activities have been compared in plasma and leukocytes from presumably healthy subjects and from epileptic patients under treatment with different antiepileptic drugs. Plasma enzyme activities are always increased by antiepileptic treatment, leukocytic enzyme activities are increased only for some patients. No relation has been observed between the variations in any of the two enzyme activities and plasma level of anticonvulsant drugs.

Alkaline Phosphatase↗
PubMed1977

[Biological tests as indirect indicators of the activity of drug metabolizing enzymes. Use of glucaric acid and gamma-glutamyltransferase].

Laboratory tests are increasingly important in the surveillance of drug treatments. People in charge of clinical laboratory science must now become aware of a new development, the use of as indicators of the activity of drug-metabolizing enzymes, especially of the induction of such enzymes. Ideally, the activity of such enzymes should be measured in the tissues. In man, however, easier indirect methods of application are now most often used : measurement of antipyrine half-life, urinary and plasma drug metabolites, protein and specific enzyme levels in palsma, changes in endogenous substrates and endogenous metabolites, and enzymes in circulating blood cells. Of all these, two examinations are now widely performed, those for urinary glucaric acid and gamma-glutamyltrasferase. The value and limitations of these two tests are discussed.

Adult↗
PubMed1977

[Human plasma lactic dehydrogenase activity: individual variations and reference intervals].

Out of a population of 8 7600 people of all origins, we drew up frequent values for the activity of total lactate dehydrogenase. From these values, we defined a reference interval on a selected population. Variations between individuals were determined in relation to the following factors: age (8 to 70 years), sex, height, weight, socio-prefessional categories, any excess weight, exercise and drugs. There exist definite variations in relation to age, especially in children. On the other hand, this enzyme shows little variation in relation to the morphology of the individual adult. Socio-professional groups have more influence on the activity of total lactate dehydrogenase.

Adolescent↗
PubMed1976

Continuous in vivo measurement of creatine kinase variations in man during an exercise.

In order to obtain information concerning the CPK turnover during exercise, we have elaborated a technique to measure its activity continuously in vivo. A colorimetric method has been adapted to total blood. CPK was measured continuously in 5 physically fit athletes exercised on an ergometric bicycle for 30 min. There was practically no increase in enzymatic activity. The starting level was very high, corresponding perhaps to a "permanent state of enzyme release"; the exercise was not hard enough because of the fitness of the athletes or the maximal increase did not occur immediately after the exercise.

Autoanalysis↗