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Biomedical subjects

P Mandel

Publications and source records attributed to P Mandel.

826 records · Page 46Linked to original sources

Frequencies of glyoxalase I phenotypes as biological markers in chronic alcoholism.

Biological markers for alcoholism would be a valuable tool for early diagnosis. We have studied the phenotype frequencies of genetically determined erythrocyte enzymes in 397 alcoholics, including two populations with liver disease: steatosis (n = 86) and cirrhosis (n = 128) and a population of alcoholics without apparent liver disease (n = 183) compared to a well selected control population (n = 177). Only for Glyoxalase I (GLO) phenotypes (1,2 and 2-1) were significant differences found between the male controls and the male alcoholics. In the total male alcoholic population the frequency of phenotype 1 was significantly increased (23.2% vs. 11%, p less than 0.02), and the frequency of phenotype 2 was significantly decreased (32.3% vs. 46.3 p less than 0.02) compared to the male control population. For normal women the frequency of phenotype 1 and 2 was significantly different from normal men. (1: +177% p less than 0.001, 2: -45% p less than 0.01), but no significant differences were found between alcoholic and normal women. Our results suggest that in male subjects Glyoxalase I phenotype 1 may provide a marker for predisposition to alcoholism.

Alcoholism↗

Blood cell superoxide dismutase and enolase activities as markers of alcoholic and nonalcoholic liver diseases.

Monitoring of chronic alcoholism would be facilitated by using sensitive biochemical markers in blood cells, mainly to detect differences between alcoholic subjects with or without liver injury. We propose two types of markers: the first one is superoxide dismutase (SOD) activity involved in the conversion of superoxide radicals (O2-.) formed during acetaldehyde oxidation by xanthine oxidase after chronic alcohol consumption; the second one is enolase activity with both isoenzyme forms: nonneuronal enolase (NNE) and neuron specific enolase (NSE) which has been shown to be modified in many injuries related to the glycolytic pathways. For SOD activity we found a significant increase in alcoholic patients with liver injury and mainly in cirrhotic patients with ascitis. Both enolase activities were also found to be significantly increased in alcoholic patients with liver injury but NNE activity was also increased in alcoholics without apparent liver disease. Our results suggest that increased activity of SOD and NSE in blood cells may be related to liver injury mainly in alcoholism while increased NNE activity may also be a marker of alcohol abuse without liver injury.

Adult↗

Adenosine diphosphate ribosyltransferase and protein acceptors associated with cytoplasmic free messenger ribonucleoprotein particles.

ADP-ribosyltransferase activity has been characterized in free messenger ribonucleoprotein particles (mRNP) from mouse plasmacytoma cells. This enzymatic activity appears to be associated with the free mRNP and not due to nuclear contamination. The enzyme activity is not stimulated by added DNA or histone H1 and represents 34 per cent of the total cellular ADP-ribosyltransferase activity while the DNA contamination in free mRNP is less than 4 per cent of the total cellular DNA. Moreover, the ADP-ribosyltransferase specific activity per mg of DNA is about 75-fold higher in free mRNP than in the nuclei. During CsCl gradient centrifugation of the cytoplasmic fraction, the ADP-ribosylated material separates out at a buoyant density similar to that of free mRNP. This ADP-ribosyltransferase activity is inhibited by thymidine, nicotinamide and 3-aminobenzamide, while it is highly stimulated by exogenous pancreatic RNase. The in vitro synthesized acid insoluble material is rendered partly soluble by treatment by a proteolytic enzyme or by snake venom phosphodiesterase resulting in phosphoribosyl-AMP formation: the pancreatic RNase does not solubilize this material. Several ADP-ribosylated proteins are detected by lithium dodecylsulfate gel electrophoresis. Such an ADP-ribosyltransferase activity has also been detected in free mRNP from rat liver. It is suggested that this ADP-ribosylation of specific free mRNP proteins may be associated with free mRNP structure and/or with some chemical covalent type of modification rendering mRNA available for translation.

Adenosine Diphosphate Ribose↗

Effects of sodium valproate on diazepam: kinetic profiles in plasma, erythrocytes, and different brain areas in the rat.

The kinetic profiles of diazepam (DZP) were investigated in plasma, erythrocytes, and discrete brain areas in the rat, and the effects of valproic acid (VPA), given as sodium valproate, on kinetic parameters were analyzed. The experiments were performed on two groups of rats treated daily for 15 days, the first receiving only DZP (5 mg/kg/day i.m.), the second treated with DZP (5 mg/kg/day i.m.) and VPA (200 mg/kg/day i.p.). Our results indicate that VPA influences the plasma-protein binding and erythrocyte levels of DZP, as well as its kinetic profile. These data are discussed with regard to the modifications observed in the different brain areas (cerebellum, hippocampus, whole cortex, and pons-medulla) during administration of VPA and DZP. The results presented in this study offer evidence that VPA exerts a peculiar action on the "impregnation" and kinetics of DZP in the CNS, and therefore these findings may be of importance in clinical pharmacology and treatment of epilepsies.

Animals↗

Isolation and characterization of a microvascular fraction from rabbit kidney cortex.

Collagenasic dispersion of rabbit kidney cortex followed by centrifugation on discontinuous sucrose gradient, allowed the simultaneous isolation of a microvascular fraction and of glomerular and tubular fractions. The microvessels were characterized by an overall diameter of 22 micron and the presence of granular and smooth muscle cells. Measurement of cellular renin activity and the muscle specific enzyme creatine kinase showed that these vessels were arteriolar in nature and that they contained the preglomerular arterioles. The glomerular or tubular contamination rates were assessed by means of enzymatic markers. Thus, in the arterioles, potassium fluoride-resistant acid phosphatase was some 10 times lower than in the glomeruli. The specific tubular enzymes gamma-glutamyl-transpeptidase and alkaline phosphatase were about 20 times lower in the arterioles than in the tubular fraction. The possibility of obtaining these fractions may facilitate many types of study on renal hemodynamic and glomerulo-tubular feedback control.

Acid Phosphatase↗

[Comparative study of phosphopeptides in various animal tissues].

We determined the phosphopeptide (PP) level in several tissues and compared the values to the phosphoprotein and phosphatide level. We studied whole organs and subcellular fractions isolated from these organs. The results showed that the PP were preferentially localised in membranes. Among all the organs analyzed, the electrical organ of "Torpedo marmorata" had the highest PP level. The phosphoprotein distribution was different from the PP one; the highest level of phosphorproteins was found in nuclei. There was also an increase in phosphoprotein level comparing whole tissues and membranes isolated from the same tissue. The preferential localisation of PP in membranes is also suggested by the parallelism between PP and phosphatide level, which is also higher in membranes than in whole organs. The peculiar polyanionic structure, as well as the active metabolism and the membranous localisation of PP support the hypothesis that these compounds might be good intermediates in active transport mechanisms.

Anguilla↗

[Pharmacokinetic study of the regional cerebral distribution of diazepam following chronic administration. Correlations with plasma and erythrocyte levels].

The kinetic profile of diazepam (DZP) was studied in plasma, erythrocytes, and eleven discrete brain areas of the rat, after intramuscular subchronic administration (15 days-5 mg/kg). DZP was rapidly distributed in brain areas. Its concentrations and its kinetic parameters were not uniform in the different brain areas we studied. The results showed the highest content of DZP in the hypothalamus, followed by the nucleus caudatus and the colliculi. Our data presented the erythrocyte as a "deep compartment". Comparatively to the results obtained after single administration, this study showed an increase of the apparent elimination half-life. Indeed, one observes a 2 fold increase for the plasma, and a 3.5 fold increase for the cerebral compartment. In the three brain areas studied (nucleus caudatus, hippocampus, and cerebellum) we observed a linear relationship with plasmatic or erythrocytic levels (0.978 less than or equal to r less than or equal to 0.992). It seems important to be considered in clinical pharmacology.

Animals↗