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Biomedical subjects

G Siest

Publications and source records attributed to G Siest.

At least 19 recordsLinked to original sources
PubMed1979

Effects of membrane perturbants on UDP-glucuronosyltransferase activity in rat-liver microsomes. Circular dichroism studies.

Rat-liver microsomes were treated with two non-ionic detergents, Triton X-100 and Lubrol WX, with phospholipase A2, or with aqueous acetone solution. The activity of the membrane-bound UDP-glucoronosyltransferase (UDPGT, EC 2.4.1.17) was measured after the treatment with these perturbants. At the same time, modifications of the secondary structure of the microsomal proteins were followed and studied by circular dichroism (CD) spectroscopy. The detergents greatly activated UDPGT, maximally at a 1 mM concentration of either detergent. The maximally activating Triton X-100 treatment did not greatly change the ellipticity of the microsomes at 222 nm ((theta)222), whereas that with Lubrol WX affected the secondary structure of the membrane proteins more strongly. UDPGT activation also occurred in phospholipase A2-treated microsomes. Maximal activation was obtained after 1--5 min of incubation and was stable throughout the experiment. Phospholipase A2 at the ratio of microsomal protein to phospholipase 250 : 1 (w/w) slightly increased (theta)222 after 10 min of incubation and did not change it further even after 30 min of incubation. Treatment of liver microsomes with a 10 : 90 (v/v) aqueous acetone solution removed 90% of the total membrane phospholipids, particularly phosphatidylcholine and phosphatidylethanolamine. The UDPGT activity was decreased in lipid-depleted microsomes, and the enzyme was not reactivated when phosphatidylcholine-lysophosphatidylcholine liposomes were added at a low temperature. An even greater decrease was obtained when the lipid binding was carried out at 37 degree C. Lipid-depleted microsomes had a high (theta)222 associated with a red-shift of 2 nm, indicating partial aggregation of membrane proteins and an increase in the alpha-helical content of the protein after acetone extraction. However, this particular protein structure was partially reversible, since a binding of phospholipids to lipid-depleted microsomes gave a (theta)222 close to that found in control microsomes. The UDPGT activity was not dependent on the secondary structure of the membrane proteins.

Acetone↗
PubMed1979

The effect of dietary sulfur-containing amino acids on the activity of drug-metabolizing enzymes in rat-liver microsomes.

Male Wistar rats were fed either a balanced diet whose protein source was a mixture of amino acids (diet 1), or a similar diet which differed only in having 48% less the quantity of the sulfur-containing amino acids methionine and cystine (diet 2). The diets were given either continuously for 1 month or for 15 days after a protein-free diet. Both diets 1 and 2 permitted good growth of rats and relatively stable microsomal protein content. Protein depletion decreased the total proteins, total phospholipids, and cytochrome P-450 content, and it strongly increased UDP-glucuronosyltransferase activity in rat-liver microsomes. Repletion with diet 1 restored those values, to the level found in control rats. However, diet 2, given continuously induced an increase in UDP-glucuronosyltransferase activity and in the cytochrome P-450 concentration. Since high UDP-glucuronosyltransferase activity was related to lessened amounts of sulfur-containing amino acids in the diet, we discuss the possible effect of methionine and cystine on the regulation of glucuronoconjugation in relation to sulfoconjugation.

Amino Acids↗
PubMed1979

Factors affecting the concentration of triacylglycerols (triglycerides in plasma: reference values for adults.

We studied factors influencing concentrations of triglycerides in the blood of a presumably healthy population of about 9000 persons. Using multi-dimensional analysis, we show, in addition to various related to sex and age, the relation between triglycerides and uric acid, overweight, arterial blood pressure, use of oral contraceptives (in women), consumption of alcohol and tobacco, and lack of physical exercise. These factors were classified as a function of their discriminative power by the statistical method of segmentation. We thus chose the following factors as criteria for exclusion from a reference population for the values of triglycerides in blood: in men 20 to 39 years old, overweight more than 90%; in men 40 to 59 years old, overweight of more than 115%, consumption of more than half a liter of wine per day or of more than 11 cigarettes, use of medicines, and a blood uric acid exceeding 420 mumol/L; in women 20 to 39 years old, contraceptives and overweight; in women 40 to 59 years old, overweight or more than 130% and the intake of medicines. At the 97.5th percentile of the reference population as compared with a non-selected population, the values were 80% less for men 20 to 39 years old, 95% less for men 40 to 59 years old, and only 26 to 30% less for women 20 to 59 years old.

Adult↗
PubMed1979

Relations between reported alcohol consumption and certain biological variables in an "unselected" population.

We looked for variables that could serve as indexes of alcohol consumption. We tested iron, gamma-glutamyltransferase, mean erythrocyte volume, mean erythrocyte hemoglobin concentration, urea, uric acid, and alanine aminotransferase, among others, in an unselected population of men, and by principal components analysis we singled out the correlation between the two enzymes and the two hematologic values. On the other hand, calculation of the coefficients of correlation between the total amount of alcohol consumed and the 10 variables studied, together with multiple regression analysis, showed that the three variables that correlated most significantly with alcohol consumption were gamma-glutamyltransferase, mean erythrocyte volume, and the use of tobacco. Critical evaluation of the results leads us to conclude that still more discriminative biological indices msut be sought and that the use of psychosocial data is also desirable.

Adult↗
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

[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

[Influence of oral contraceptive agents on the concentration of amino acids in leukocytes of supposedly healthy women (author's transl)].

The concentration of amino acids has been measured in leukocytes of women taking oral contraceptive agents and also in controls. These assays were made by means of ion exchange chromatography. The amino acid pool in leukocytes was found to be smaller in those patients taking the "pill". Each amino acid concentration decreased except for taurine and glutamine. Taurine represented 64.1 percent of the pool in treated women and only 23.5 percent in controls. Glutamine represented 9.5 percent of the pool in patients and 3.7 percent in controls.

Adult↗
PubMed1977

Influence of glucose and inhibitors of glycolysis on release of total proteins and enzymes from human leukocytes.

We studied the influence of substrates and glycolysis inhibitors on the release of proteins and enzymes from human leukocytes. We show the relationship between metabolic level and percentage of enzyme release. Leukocyte kept alive in a nutrient-free bicarbonate medium liberate enzymes even though their metabolic state is satisfactory. The addition of glucose to themedium significantly decreases this phenomenon without affecting the energy level. Addition of glycolysis inhibitors increases it, reduces the energy level, and interferes with other metabolic pathways. The results are discussed and compared to those obtained by other authors using various cell models.

Adult↗
PubMed1977

Protein and enzyme release from human leukocytes: influence of phenothiazine derivatives.

We studied the influence of chlorpromazine on the release of enzymes (beta-glucuronidase, EC 3.2.1.31; lactate dehydrogenase, EC 1.1.1.27; pyruvate kinase, 2.7.1.40) and proteins using human granulocytes isolated and maintained at 37 degrees C. Chlorpromazine had a biphasic effect on enzyme release and the inhibition of the glycolytic pathway could be demonstrated only at high concentrations of chlorpromazine, after one hour's incubation. The NAD+/NADH ratio was significantly perturbed at all the concentrations. This effect is time dependent. The action of 4 other phenothiazine derivatives made it possible to establish a relationship between their physico-chemical properties and protein release. The results are compared with those from other studies using other biological materials.

Antipsychotic Agents↗
PubMed1977

Gamma-glutamyltransferase activity in plasma: statistical distributions, individual variations, and reference intervals.

Measurement of gamma-glutamyltransferase activity in plasma provides a useful index to liver function. Using as our study population those persons coming to the Center for Preventive Medicine, we described and measured the significance and importance of physiological and environmental variations. We established a classification for the variation factors. The three most important factors affecting this activity were drug intake, alcohol consumption, and excessive weight, followed by sex and age. We suggest a preliminary group of reference intervals for healthy subjects to be used in interpreting a laboratory test.

Adolescent↗
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↗