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Biomedical subjects

G P Pescarmona

Publications and source records attributed to G P Pescarmona.

6 recordsLinked to original sources

4-Methyl-3-(arylsulfonyl)furoxans: a new class of potent inhibitors of platelet aggregation.

A series of 4-methyl-3-(arylthio)furoxans were synthesized by oxidation of 1-(arylthio)-2-methylglyoxymes with dinitrogen tetroxide. Reduction with trimethyl phosphite of the furoxan derivatives afforded the corresponding furazans, while oxidation with an equimolar amount of 30% hydrogen peroxide in acetic acid or with an excess of 81% hydrogen peroxide in trifluoroacetic acid afforded the corresponding arylsulfinyl and arylsulfonyl analogues, respectively. All the furoxan and furazan derivatives showed activity as inhibitors of platelet aggregation. 4-Methyl-3-(arylsulfonyl)furoxans were the most potent derivatives of the series. 4-Methyl-3-(phenylsulfonyl)furoxan (10a), one of the most active derivatives, inhibits the AA-induced increase of cytosolic free Ca2+ and production of malondialdehyde. A primary action of the compound on cyclooxygenase is excluded, as a stable epoxymethano analogue of prostaglandin H2 does not reverse the inhibitory effect of 10a. This compound produces a significant increase in cGMP which is likely to cause inhibition at an early stage of the platelet activation pathway.

Arachidonic Acid

[Aspects of the decrease of some enzyme activities in erythrocytes of subjects with beta-thalassemia].

G6PD, GSH-Px and 6PGD activity was found to be elevated in beta-thalassemia heterozygous erythrocytes. Estimates of the activities of the three enzymes in red cell fractions of differing mean age separated by centrifugation through a density gradient of Ficoll-Triosil layers, showed that the rate of in vivo decline was normal for G6PD and GSH-Px, and decreased for 6PGD. The increased enzyme activity results from increased rate of synthesis for G6PD and GSH-Px, and from higher in vivo stability for 6PGD.

Erythrocytes

Regulation of NAD and NADP synthesis in human red cell.

NAD is synthesized in red cell from nicotinic acid and PRPP through the formation of nicotinate mononucleotide and desamido-NAD. Synthesis of one mole of NAD requires two moles of ATP. NADP comes from NAD phosphorylation by NAD-kinase (EC.2.7.1.23). NAD and NADP analysis on a population with ATP level ranging from 800 to 2500 nmoles/ml red cells showed a close correlation between ATP and pyridine cofactors. Moreover, NADP level appeared to be dependent of the redox-state of NADP/NADPH couple. Subjects with low NADPH (G-6-PD) deficient red cells, Hb Köln) showed lower NADtot/NADPtot ratio, suggesting a NAD-kinase equilibrium shift toward NADP related to lower levels of the negative effector NADPH, as already described in rat liver.

Adenosine Triphosphate

The role of red cell membrane in the regulation of glycolysis and the 2,3-bisphosphoglycerate-cycle.

Pyruvate and K-ferricyanide stimulation of net ATP and 2,3-bisphosphoglycerate synthesis is very probably due to enhancement of glyceraldehyde 3-phosphate dehydrogenase activity. Significant peculiarities in the K-ferricyanide effect and its depression by non-penetrating-SH inhibitors at low concentrations were noted and suggested that membrane-bound enzymes play a substantial part in the synthesis of ATP and 2,3-bisphosphoglycerate. Experiments with isolated ghosts showed their ATP-and 2,3-bis-phosphogylcerate-building capacity. Pulse-labeling with 32P-Pi and determination of specific radioactive in intracellular inorganic phosphate and ATP-gamma-P demonstrated that the ferricyanide-stimulated compartment utilizes only intracellular inorganic phosphate for ATP (and 2,3-bisphosphoglycerate) synthesis, and does so only when extracellular inorganic phosphate is present.

Adenosine Triphosphate

Sherpas living permanently at high altitutde: a new pattern of adaptation.

Adaptation of Sherpas to high altitude has been studied and compared with that of Caucasians acclimatized to high altitude. Sherpas living permanently at 4000 m above sea level do not have increased hematological parameters (i.e., red cell number, hematocrit, hemoglobin content, and 2,3-diphosphoglycerate/hemoglobin ratio) and have a higher affinity of blood for oxygen as compared with acclimatized Caucasians. Sherpas permanently living at low altitude, on the contrary, have lower affinity of blood for oxygen than do Caucasians living at comparable altitude and are mildly "anemic,". Various other red cell biochemical parameters (possibly related to adaptation to altitude) have also been studied in the same population. We suggest that Sherpas are genetically better adapted to high altitude than are Amerindians living on the Peruvian highlands, possibly as a consequence of a much more prolonged exposure to such an ecological factor of selection as high altitude.

Adaptation, Physiological

Effects of sulphydryl compounds on abnormal red cell pyruvate kinase.

The effect of some sulphydryl compounds on two new variants of red cell pyruvate kinase (ATP: pyruvate phosphotransferase, PK) is reported. In vitro a striking correction has been obtained of both the qualitative and, in one case, the quantitative defect of red cell PK. In vivo, a correction of the qualitative and quantitative abnormalities has been produced in both patients, with clinical improvement of one of them. These findings, together with the unexpected results in respect to the functional properties of PK found in the affected members of the two families studied, suggest that the PK abnormality is not the cause of the haemolytic anaemia, but an epiphenomenon of a primary unknown defect that apparently involves the red cell thiol groups.

Adenosine Triphosphate