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Biomedical subjects

A Meskar

Publications and source records attributed to A Meskar.

9 recordsLinked to original sources

[Alcohol-xenobiotic interactions. Role of cytochrome P450 2E1].

Alcohol and xenobiotics share the same oxidative microsomal pathway, which is mainly located in the endoplasmic reticulum of hepatocytes. This pathway involves enzymes that belong to the super family of cytochrome P450 and allows to explain a lot of pharmacokinetic or toxic interactions between alcohol and xenobiotics. Cytochrome P450 2E1 (CYP2E1) is the key enzyme of the microsomal pathway of ethanol oxidation. It is inducible by chronic ethanol consumption and its activity is increased by three to five fold in liver from alcoholics subjects. This induction involves to a lesser extent cytochromes P450 3A4 and 1A2 and contributes to the metabolic tolerance of alcohol and drugs observed in alcoholics. The metabolic tolerance persits several days after ethanol withdrawal. Furthermore, CYP2E1 has a high capacity to activate numerous xenobiotics into toxic or carcinogenic compounds. Drugs currently used such as paracetamol, anesthetics (enflurane, halothane), industrial solvents (benzene or its derivatives), halogenated solvents (CCl4, trichlorethylene) and nitrosamines which are present in food or tobacco smoke are included. Therefore, heavy consumption of alcohol, which results in CYP2E1 induction, increases individual susceptibility to the toxic or carcinogenic effects of these xenobiotics.

Acetaminophen↗

Impaired fetal erythrocytes' filterability: relationship with cell size, membrane fluidity, and membrane lipid composition.

The lipid composition of erythrocytes (red blood cells [RBCs]) plays a significant role in determining certain membrane biophysical properties. We have found that fetal RBCs showed a dramatically low filterability compared with adult RBCs and questioned whether this could be a consequence of their membrane lipid composition. We therefore studied fetal RBCs at two different gestational ages, neonatal RBCs and adult RBCs. Biophysical parameters were studied using two different techniques, filterability and membrane fluidity. The latter was measured by fluorescence polarization using three different probes. The membrane lipid composition was examined by measuring cholesterol and phospholipids. After extraction of the phospholipids, followed by high performance thin-layer chromatography, the fatty acids in the phospholipid subfractions were analyzed by gas-liquid chromatography. The fetal RBCs' filterability was found to be correlated with both the larger size and the higher hemoglobin content of the cells, but there was no correlation between RBC filterability and fluidity or membrane lipid composition. In adult RBCs, compared with neonatal RBCs, the slight increase of unsaturated fatty acids in phosphatidylcholine and phosphatidylethanolamine should have increased the membrane fluidity. However, in RBCs, no change was observed in the fluidity parameters measured by fluorescence polarization.

Adult↗

[Effect of in vitro carbamylation of erythrocytes on their rheological properties].

In order to assess the role of carbamylation of erythrocyte proteins in the modification of rheological parameters of red blood cells observed in uremic patients, and in vitro carbamylation of erythrocytes and hemoglobin was carried out using sodium cyanate. The carbamylation of hemoglobin was determined by observation of the increase of HbA1 fraction. The deformability of erythrocytes and the viscosity of erythrocyte suspensions and of hemolysate were measured. The results showed an increase in the deformability of red blood cells and a decrease in the viscosity of hemoglobin as the carbamylation increased. This is attributed to a decrease of hemoglobin viscosity and to a modification of the electric charge of the membrane. These results show that the reduced erythrocyte deformability observed in patients with renal failure is not due to erythrocyte protein carbamylation.

Adult↗

Glycated haemoglobin: comparison between methods based upon 5-hydroxymethylfurfural determination (colorimetric or HPLC) and ion exchange chromatography (HbA1).

A comparison of methods, two based upon 5-hydroxymethylfurfural determination (colorimetric using a semi-automated procedure and HPLC) and ion exchange chromatography (HbA1 using BioRad method) was performed. The influence of variables on 5-hydroxymethylfurfural determination is reported. The dialysis step appears to be essential for an accurate determination of 5-hydroxymethylfurfural released from glycated haemoglobin. The adjustment of haemoglobin concentration to an accurately known level is required for the colorimetric method, in order to achieve the same background colour absorbance. For the HPLC method this step is not necessary as 5-hydroxymethylfurfural liberation was proved to be stoichiometric. The Sep Pak C-18 cartridge purification appears to be an improvement for the accurate determination of 5-hydroxymethylfurfural using HPLC. When the three methods were compared the overlap between normals and diabetics was found to be less, using the 5-hydroxymethylfurfural HPLC method, suggesting that this procedure, although more time consuming, seems to be more useful in the management of diabetes mellitus.

Chromatography, High Pressure Liquid↗

Glycosylated haemoglobin: high-performance liquid chromatographic determination of 5-(hydroxymethyl)-2-furfuraldehyde after haemoglobin hydrolysis.

A specific and accurate method for the quantitation of the azomethine linkage present in non-enzymatically glycosylated haemoglobin is described. This protein is hydrolysed for 5 h in 1 M oxalic acid at 100 degrees C to yield 5-(hydroxymethyl)-2-furfur-aldehyde (5-HMF), known as a specific degradation product of hexoses linked to the protein. 5-HMF is then purified through a Sep-Pak C18 cartridge and measured by its absorption at 280 nm after separation on a C18 reversed-phase silica column. Quantitation is made accurate by using 1-methylxanthine as internal standard throughout the whole procedure. The identity and the purity of the 5-HMF chromatographic peak was ascertained by UV spectroscopy, gas chromatography on a glass capillary column and mass spectrometry. The method has been successfully used for 5-HMF determinations in monitoring diabetes mellitus patients. The mean values, expressed as nmol of 5-HMF per mg of haemoglobin were 0.64 +/- 0.13 (S.D.) for 27 controls and 1.32 +/- 0.39 for 78 diabetic patients. Unlike the usually employed thiobarbituric acid assay, the present procedure is truly specific for the 5-HMF determination.

Chromatography, Gas↗

Perinatal assessment of glycaemic control in newborn infants of diabetic mothers.

The glycaemic control of infants and of their mothers was studied at delivery and on day 7 after birth in 11 control and 20 insulin-dependent diabetic women. At delivery, venous blood glucose was lower in infants of diabetic mothers compared with control infants (p less than 0.02). Seven days after birth, no significant difference in blood glucose could be found between control and infants of diabetic mothers. C-peptide levels were higher in infants of diabetic mothers compared with control infants (p less than 0.01). On day 7 after birth, the C-peptide levels remained higher only in infants of Class B, C, D diabetic mothers. Glycosylated haemoglobin was lower in the venous blood of infants than of their mothers (p less than 0.001). Glycosylated haemoglobin was lower in control mothers than in diabetic mothers (p less than 0.05), but it was higher in the venous blood samples from control infants compared with infants of diabetic mothers at delivery (p less than 0.05) and 7 days after (p less than 0.01). At delivery infants' glycaemia and infants' glycosylated haemoglobin correlated (r = 0.44, p less than 0.02). C-Peptide and glycosylated haemoglobin levels in infants at delivery also correlated (r = -0.42, p less than 0.05).

Blood Glucose↗

[Glycosylated proteins and control of the diabetic: use of continuous flow insulin pumps by the subcutaneous route].

Ten insulin-dependent diabetic patients were controlled using a portable insulin pump (Pye Dynamic MS 16). They were studied for approximately 10 weeks. The responses of fasting blood glucose, glycosylated serum proteins and glycosylated hemoglobin were studied. Glycosylated serum proteins and glycosylated hemoglobin were measured a semi-automated colorimetric method. Although the fasting blood glucose decreased by about 45%, its variability underlines its limitation as a metabolic control parameter. Glycosylated hemoglobin decreased by 9% in the first week, and 21% by the tenth week. The glycosylated serum proteins decrease was 39% in the first week and 50% by the third week. Four insulin-dependent pregnant women had a similar but less rapid, decrease in the 3 variables compared to the other 6 cases. In all ten diabetics treatment lowered the 3 variables toward normal levels when compared to 73 insulin dependent diabetic patients using the classic method of daily insulin injections. The kinetic patterns of the 3 variables confirms the usefulness of glycosylated serum proteins which respond to altered levels of control more rapidly (10 days) than glycosylated hemoglobin. This is shown both by the response to improved control in insulin-dependent diabetics and secondly by their changes after insulinoma removal. The physiopathological significance of serum protein glycosylation is at present uncertain.

Adult↗

Effect of acetaldehyde generated from ethanol by ADH-transfected CHO cells on their membrane fatty acid profiles.

Ethanol has been previously shown to reduce the unsaturated fatty acid content of cell membranes. It is not known, however, if the observed deleterious effects are due to ethanol itself or its metabolite, acetaldehyde. The present study was undertaken to assess the effect of acetaldehyde produced from ethanol by alcohol-deyhdrogenase-transfected Chinese hamster ovary Cells on the membrane lipids and the lipid peroxidation measured by free and bound malondialdehyde (MDA). The effects of ethanol alone was assessed in the presence of 4-methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase. After 8 days of incubation, total cellular lipids were extracted, subjected to TLC, and analyzed by gas chromatography. MDA concentration were determined by thiobarbituric acid reaction followed by HPLC detection. The level of acetaldehyde in the culture medium increased with concentration of ethanol from 5 to 20 mM as did the lipid peroxidation. Total cholesterol, phospholipids, and triglycerids all increased with increasing concentration of acetaldehyde. These effects were due to acetaldehyde as they were blocked by 4-MP. Some changes in fatty acid profiles were observed by effect of ethanol itself.

Acetaldehyde↗