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Biomedical subjects

M Ciavatti

Publications and source records attributed to M Ciavatti.

47 records · Page 3Linked to original sources

Biosynthesis of cholesterol and cholesterol precursors in platelets of female rats treated with oral contraceptives.

Rat platelets were incubated with sodium [U-14C]acetate and labeled lipids were analyzed. The major part of the radioactivity was found in phospholipids and in acylglycerols. When the incubation was performed with platelets of female rats treated with contraceptives, the total incorporation of labeled acetate in lipids was 2-fold higher and 33.6% of the radioactivity was found in lanosterol plus 24-dihydrolanosterol. Moreover, there is labeling of cholesterol. All these compounds were analyzed and identified by gas-liquid chromatography/mass spectrometry. In the incubation with sodium [2-14C]mevalonate the labeling of lanosterol plus 24-dihydrolanosterol and of cholesterol was increased by 30% in platelets of treated rats. The effect of contraceptives on one step of cholesterol biosynthesis is discussed and a possible explanation of the correlation between oral contraceptives and thromboembolic accidents is suggested.

Acetates↗

Oral contraceptives, lanosterol, and platelet hyperactivity in rat.

Lanosterol, a cholesterol precursor that increases considerably in the platelets of rats treated with oral contraceptives, was incubated with either platelet-rich plasma or washed platelet suspension. After 2 minutes there was a remarkable dose-related increase in platelet activity. This platelet hyperactivity was measured by clotting time and platelet aggregation could not be reproduced by cholesterol or ethinylestradiol.

Animals↗

Modification by oral contraceptives in rat of 14C acetate incorporation into platelet lipids.

The in vitro incorporation of acetate 14C in platelets lipids was compared in control female rats (Gr. I) to rats treated for 4 days either by an oral contraceptive ethinyl oestradiol + lynestrenol (Gr. II), or by ethinyl oestradiol alone (Gr. III) or lynestrenol alone (Gr. IV). An increase of 43--45% in the incorporation of acetate could be observed in the two groups (II and III) which received ethinyl oestradiol, while the incorporation in group IV was similar to that of the controls. The lipid fractions of which the synthesis was the most considerably stimulated by the oestrogen treatment, were the neutral lipids as separated from the other lipids by TLC. In groups II and III the incorporation in cholesterol and cholesterol esters was increased by 8 fold and by 10 fold in the free fatty acid fraction. In these two groups, even in the phospholipid fractions PS + PI and PE, the radioactivity was significantly increased. The observed effect of the oral contraceptive studied here on platelet lipid synthesis in female rats, appears to be essentially due to the estrogens, since lynestrenol had only minimal effects in that respect.

Acetates↗

Platelet phospholipid in stroke.

A study of platelet phospholipids in patients with stroke has been undertaken comparatively with patients without predisposition to thrombosis. An increase in the phospholipid/protein ratio in platelets was observed in patients with acute cerebrovascular accident. A significant increase of palmitoleic acid is observed in platelet phospholipids of these patients; it is accompanied by a decrease of linoleic acid. These modifications are reflected in plasma where linoleic acid is greatly diminished but where an important increase of palmitic acid is noted besides palmitoleic acid. A possible relation between higher clotting activity of platelets and those modifications in their phospholipids is discussed.

Aged↗

[Changes in the erythrocyte membrane during blood preservation. Influence of progesterone].

Modifications of the erythrocyte membrane during blood conservation are studied. The functional condition of the membrane was observed by means of the biosynthesis of lecithines; modifications occurring at the level of the composition of the membrane proteins were then looked for. The study has been carried out on fresh blood and on blood stroed for 8 days, 15 days, 29 days and 43 days. Another series of assays has been done on stored blood in the presence of progesterone after the same conservation periods. The metabolic activity of the membrane, in the lecithine biosynthesis is studied by measuring the incorporation of fatty acid in the lysolecithines when the membrane is incubated in the presence of linoleic acid or [14] palmitic acid and coenzyme A, or in the presence of [14C] palmitoyl coenzyme A. Variations have been observed during blood conservation: the incorporation or radioactive fatty acid increases during the first 15 days of conservation, then it decreases to a value nearing the original value after 43 days. When the blood is stored in the presence of progesterone (1,6 mumole/1) a more stable incorporation of the fatty acid is observed; variations during conservation are weaker than without progesterone. Membrane proteins have been studied by electrophoresis on polyacrylamide gel after solubilisation by sodium dodecyl sulfate. The intensity of protein zones after coloring, decreases during conservation especially in proteins with a high molecular weight. A quantitative study has been made by chromatography on Sephadex G200 of dansylated proteins with a fluorimetric dosage. In the presence of progesterone, the decrease of the rate of proteins with a high molecular weight is weaker. Therefore, progesterone is proved to allow a better conservation of erythrocyte membrane proteins. As a conclurion, the results of these works show a positive action of progesterone on the erythrocyte membrane during blood conservation.

Blood Preservation↗

Hormonal contraceptive increases plasma lipid peroxides in female rats. Relationship to platelet aggregation and lipid biosynthesis.

We investigated whether changes in plasma oxidative properties could occur after oral (hormonal) contraceptive (OC) administration in female rats and whether such changes could be responsible for the platelet increase in aggregation and lipid biosynthesis observed with that treatment. Platelets and plasma (platelet-poor) from control and OC (ethinyl estradiol + lynestrenol)-treated rats were prepared separately. Thrombin-induced aggregation of control platelets was markedly enhanced after incubation for 4 (p less than 0.025) to 60 (p less than 0.001) minutes in OC as compared with control plasma. Under the same conditions, platelet lipid biosynthesis was increased also (p less than 0.05 to p less than 0.01), but after 3 hours incubation. The enhanced response of platelets to aggregation induced by OC plasma could be inhibited by adding either glutathione (p less than 0.025), vitamin E (p less than 0.025), catalase (p less than 0.05), or peroxidase + glutathione (p less than 0.005) to plasma or 2,6,di-bis(ter-butyl)p-cresol (p less than 0.05) to platelets before incubation. The peroxidized free fatty acids isolated from OC plasma added to normal platelets induced a 150% (p less than 0.001) increase in the response to thrombin as compared with the fatty acids from control plasma. In addition, the level of malondialdehyde and conjugated dienes was significantly (p less than 0.02 to p less than 0.001) increased in OC compared with control plasma. We conclude that the enhanced formation in plasma of lipid hydroperoxides seems to be the initial event stimulating platelets after OC treatment, at least in rats.

Adenosine Diphosphate↗