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Biomedical subjects

P Gresele

Publications and source records attributed to P Gresele.

At least 91 records · Page 5Linked to original sources
PubMed1985

Thromboxane A2 and prostacyclin do not modulate the systemic hemodynamic response to cold in humans.

The immersion of a limb in a mixture of water and ice induces in normal humans an initial vasoconstriction mediated mainly by catecholamine release. In some studies the cold pressor test was associated with an increase in vasoconstrictor thromboxane A2 and in vasodilating prostacyclin. Dazoxiben hydrochloride, a thromboxane synthase inhibitor, has been reported to suppress cold-induced vasoconstriction. We compared in a double-blind, crossover, placebo-controlled study the effects of indomethacin (a cyclooxygenase inhibitor), dazoxiben hydrochloride, and BM13.177 (a novel thromboxane receptor antagonist) on the changes in cutaneous vascular resistance and arterial blood pressure induced by cold in 12 healthy volunteers. Cold challenge produced an increase in blood pressure and an initial decrease in finger blood flow, reflecting an increase in cutaneous vascular resistance. Neither effective suppression of thromboxane A2 generation or of the effects of thromboxane A2 on platelets by the three active treatments nor increase in prostacyclin generation after ingestion of dazoxiben hydrochloride modified the hemodynamic response to cold. In conclusion, thromboxane A2 and prostacyclin do not play a significant role in the modulation of the systemic hemodynamic response to cold. In addition, thromboxane receptor antagonism in normal humans does not influence basal blood pressure.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

BM 13.177 selectively inhibits endoperoxide analogue induced vascular contractions.

Experiments were performed to evaluate the effects of BM 13.177 on vascular smooth muscle. Rabbit femoral arteries were mounted for isometric tension recording and made to contract with the endoperoxide analogues U44064 and U46619, prostaglandin F2 alpha and E2, norepinephrine, serotonin, histamine and ATP in the absence and in the presence of BM 13.177. This compound (7 X 10(-5)M) inhibited contractions to the endoperoxide analogues and did not affect or slightly potentiated contractions induced with the other agonists except for those evoked with prostaglandin F2 alpha, which tended to be slightly inhibited. In 2 out of 5 unstimulated preparations tested, BM 13.177 at 7 X 10(-6) and 7 X 10(-5)M caused small contractions. It is suggested that BM 13.177 is a selective thromboxane A2 receptor antagonist in vascular smooth muscle.

Animals↗
PubMed1984

Serum albumin enhances the impairment of platelet aggregation with thromboxane synthase inhibition by increasing the formation of prostaglandin D2.

Dazoxiben, a thromboxane synthase inhibitor, inhibits arachidonic acid induced aggregation in platelet-rich plasma from some donors only ("responders"). We have studied the effect of dazoxiben in vitro on platelet aggregation and prostaglandin (PG) metabolism and the influence of the incubation period and of exogenously added serum albumin (SA). SA, which increases the production of anti-aggregatory PGD2 from cyclic endoperoxides, induced "non-responder" human platelets to respond. With rabbit platelets, however, that are insensitive to PGD2, exogenous SA failed to potentiate dazoxiben-induced inhibition. The ratio between PGD2 and TXB2 + PGE2 formed was crucial in determining the response of human platelets to dazoxiben: whenever this ratio was high, platelet aggregation was inhibited. SQ 22536, an adenylate cyclase inhibitor, and NO164, a PGD2 antagonist, reversed the inhibition by dazoxiben in human platelet-rich plasma, stressing the importance of a PGD2 mediated rise of cyclic AMP for the effectiveness of a thromboxane synthase inhibitor.

Adenine↗
PubMed1984

BM 13.177, a selective blocker of platelet and vessel wall thromboxane receptors, is active in man.

BM 13.177, a sulphonamide derivative, prevented platelet aggregation by thromboxane A2 in vitro and selectively inhibited contraction of isolated rabbit femoral arteries induced by two stable endoperoxide analogues. In a double-blind placebo-controlled study, oral BM 13.177 inhibited platelet aggregation induced by arachidonic acid, low dose collagen, and the two stable endoperoxide analogues, and slightly prolonged the bleeding time. Generation of thromboxane or of other prostaglandins was not affected. No side-effects were seen. BM 13.177 appears selectively and safely to block platelet and vessel wall thromboxane receptors and should be useful in elucidating the role of thromboxane A2 in disease.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1983

Dipyridamole inhibits platelet aggregation in whole blood.

Dipyridamole possesses antithrombotic properties in the animal and in man but it does not inhibit platelet aggregation in plasma. We evaluated the effect of dipyridamole ex vivo and in vitro on platelet aggregation induced by collagen and adenosine-5'-diphosphate (ADP) in human whole blood with an impedance aggregometer. Two hundred mg dipyridamole induced a significant inhibition of both ADP- and collagen-induced aggregation in human blood samples taken 2 hr after oral drug intake. Administration of the drug for four days, 400 mg/day, further increased the antiplatelet effect. A significant negative correlation was found between collagen-induced platelet aggregation in whole blood and dipyridamole levels in plasma (p less than 0.001). A statistically significant inhibition of both collagen (p less than 0.0025) and ADP-induced (p less than 0.005) platelet aggregation was also obtained by incubating whole blood in vitro for 2 min at 37 degrees C with dipyridamole (3.9 microM). No such effects were seen in platelet-rich plasma, even after enrichment with leukocytes. Low-dose adenosine enhanced in vitro inhibition in whole blood. Our results demonstrate that dipyridamole impedes platelet aggregation in whole blood by an interaction with red blood cells, probably involving adenosine.

Adenosine↗
PubMed1983

Cholinephosphotransferase activity in human platelets.

Disrupted human platelets possess a cholinephosphotransferase activity (EC 2.7.8.2) whose properties have been studied in this work. The labeling of choline glycerophospholipid (CGP) from radioactive cytidine-5'-diphosphate choline (CDP-choline) in vitro shows a maximum at pH 8.0 (using Hepes [4-(2-hydroxyethyl)-piperazine-1-ethane-2-sulfonic acid] as a buffer) and is stimulated by Mn2+, Mg2+ and diacylglycerol. The enzymic activity is inhibited by Ca2+. The dependence of human platelet cholinephosphotransferase upon CDP-choline concentration does not follow the Michaelis-Menten equation. CMP strongly inhibits the reaction. The functional implications of this newly discovered platelet activity are briefly considered.

Blood Platelets↗
PubMed1983

Thrombolytic therapy for thromboembolism of vertebrobasilar artery.

Thrombolytic therapy was carried out on four patients with brain stem stroke due to thromboembolism of the vertebrobasilar system. Diagnosis was confirmed by angiography. Clinical and instrumental findings indicated a very poor prognosis. Two of these patients were treated with urokinase and the other two with streptokinase for periods ranging from 16 to 44 hours. The interval between onset of symptoms and start of therapy was less than 10 hours for three of these patients. All made a gradual and almost complete recovery after only a few hours of treatment, and only one presented minimal residual neurological disability. The condition of the fourth patient, who started therapy four days after the first episode, remained unchanged until he died 16 hours later. Our observations suggest that thrombolytic therapy may be useful in treating recent acute life-threatening brain stem stroke.

Adult↗
PubMed1982

Ultraviolet spectra of membrane-rich human platelet particulates. Normal data and specular abnormalities in hypo- and hyperbetalipoproteinemia.

The analysis of UV spectra of human platelet particulates showed the existence of an evident protein component ordered in alpha-helical conformation in normal subjects. This ordered component was enhanced in type IIa hyperbetalipoproteinemia and, on the contrary, very low in a case of heterozygous familial hypobetalipoproteinemia. In the latter condition almost all proteins were indeed disordered as random coils. These data thus suggest that cholesterol significantly contributes to the control of molecular arrangement of platelet membrane proteins.

Blood Platelets↗