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Biomedical subjects

A Prancan

Publications and source records attributed to A Prancan.

5 recordsLinked to original sources
PubMed1988

Effect of indomethacin and of prostaglandins on extrarenal erythropoietin production in rats.

Indomethacin elevates the plasma erythropoietin titer of hypoxic anephric rats and probably does so by increasing extrarenal erythropoietin production. Because indomethacin is a potent cyclooxygenase inhibitor, we postulated that it alters extrarenal erythropoietin production via its effects on tissue prostaglandin levels. Studies were, therefore, performed to determine the effects of indomethacin on hepatic prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) titers. Indomethacin significantly decreased the PGF2 alpha level but its effects on the PGE2 level were, in most experiments, insignificant. We next studied the effects of infusing PGF2 alpha and PGE2 on the plasma erythropoietin levels of hypoxic rats. PGF2 alpha significantly reduced the plasma erythropoietin titer of anephric rats and neutralized the effect of indomethacin when both substances were administered. PGE2 infusion, on the other hand, did not significantly affect the plasma erythropoietin level of anephric rats. The data support the conclusion that PGF2 alpha is a potent inhibitor of extrarenal erythropoietin production, and that indomethacin enhances the rate of extrarenal erythropoietin production by reducing the PGF2 alpha titer in the liver.

Animals↗
PubMed1982

Relaxation of the guinea-pig trachea induced by platelet-activating factor and by serotonin.

Platelet-activating factor (PAF-acether), a known platelet stimulant and bronchoconstrictor (in vivo), is a potential mediator of inflammation and thrombosis. However, all smooth muscle effects of PAF-acether described to date are indirect, relying upon intravascular platelet activation. Novel actions of PAF-acether and serotonin (5-HT) are presented here; these actions may lead to the development of a practical bioassay for PAF-acether and contribute to the understanding of the mechanism of action for both substances. PAF-acether, when added to a spiral cut guinea-pig trachea suspended in a tissue bath containing Krebs-Henseleit buffer, produced a dose-dependent loss of active tissue tension. The ED50 for this effect of PAF-acether was 75 ng/ml. PAF-acether produced a maximal relaxation which was 68% of that produced by PGE1 and the effect could not be modified by aspirin or propranolol pretreatment. 5-HT, alone, contracted the guinea-pig trachea strip in a dose-dependent manner, but caused relaxation instead when methysergide was present. Aspirin, phenoxybenzamine and propranolol did not alter this loss of active tissue tension. A similar observation was made in vivo using the guinea-pig bronchoconstriction model, in which PAF-acether as well as 5-HT given to methysergide-treated animals caused a decrease in intratracheal pressure. This action of PAF-acether may yield a suitable bioassay method which could facilitate routine measurements of the substance. Furthermore, the similarity in action of PAF-acether and of 5-HT on methysergide-treated animals leads one to speculate about the relationship between the two substances and their mechanism of action in smooth muscle.

Acetylcholine↗
PubMed1982

Generation of thromboxane A2 and aorta-contracting activity from platelets stimulated with modified C-reactive protein.

The classical acute phase reactant, C-reactive protein (CRP), appears in markedly elevated concentration in the sera of individuals undergoing reactions of acute inflammation and tissue degradation. We previously demonstrated that like IgG, appropriately purified CRP could be thermally modified (H-CRP) such that it enhanced platelet activation in plasma and initiated platelet responses in isolated systems. We now report that this direct platelet activation by modified CRP results in the secretion of both platelet dense body and alpha-granule constituents, and is sensitive to non-steroidal anti-inflammatory drugs as well as the adenosine diphosphate (ADP)-removing enzyme system creatine phosphate/creatine phosphokinase. Thin-layer chromatographic (TLC) analysis of prostanoate endproducts following platelet activation with H-CRP revealed the formation of thromboxane B2 (the hydrated endproduct of thromboxane A2), an important endogenous platelet activator and contractor of vascular tissue; bioassay on rabbit aorta strips of supernatants obtained from platelets undergoing challenge with H-CRP supported the TLC analysis. Complexes formed between CRP and one major ligand, the polycation, were found to share certain platelet activating properties with H-CRP, as does latex-aggregated CRP. These data imply a potential agonist role for this acute phase reactant in platelet physiology and suggest that the interaction of modified forms of CRP with the platelet at sites of vascular damage could have pathological significance.

Adenosine Diphosphate↗
PubMed1981

Platelet thromboxane production during endotoxin shock.

Circulating thromboxane (TX) is elevated following endotoxin, and platelets become hyperaggregable. Thromboxane synthesis was therefore studied in platelets during endotoxemia. Rabbit blood and platelets were taken at 0, 60 and 120 min after start of E. coli endotoxin infusion (1.10 microgram/kg min, i.v.). Blood incubation with arachidonic acid (AA, 10(-4) M) generated TXA2, which was measured using a superfused rabbit aorta bioassay. Washed platelets were stimulated with 1-14C AA (0.1 microCi) to generate radiolabeled TXB2, which was isolated by TLC and quantitated by scintillation spectrometry. Control (0 time) platelet count was 488 +/- 10(3)/mm3. In the test group, platelet counts fell to 65% of control at 60 min and to 52% at 120 min, while TXA2 generation was 95% (60 min) and 94% (120 min) of control. In contrast a serial dilution of untreated platelets yielded a progressive decline in thromboxane generation. In endotoxemic platelets, the conversion of 1-14C AA to TXB2 (percent/10(9) platelets) was increased at 120 min (0 min, 34.7; 120 min, 40.0: P less than 0.05). Endotoxemic platelets generated greater amounts of thromboxane than did normal platelets, and this condition may account for platelet hyperaggregability in shock.

Animals↗