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Biomedical subjects

G V Born

Publications and source records attributed to G V Born.

At least 163 records · Page 9Linked to original sources
PubMed1971

Comparison of the effects of drugs on the aggregation of hamster platelets in vivo and in vitro.

1. A method is described for measuring the inhibitory effectiveness of drugs on the aggregation by ADP of hamster platelets in vivo.2. The method was used to compare the effects of several drugs, viz. adenosine, imipramine, desmethylimipramine and aspirin, on platelet aggregation in vivo with their in vitro effects measured photometrically.3. The concentrations of adenosine and imipramine present in the cheek pouch after 10 min infusions were measured using radioactively labelled drugs.4. The results show that adenosine (0.4 muM) inhibited platelet aggregation in vivo by 43%, whereas several times this concentration was required to produce the same inhibition in vitro.5. Imipramine and desmethylimipramine (0.4 muM) did not inhibit platelet aggregation in vivo; in vitro, however, desmethylimipramine caused up to 34% inhibition at concentrations as low at 0.25 muM.6. Aspirin (estimated 0.2 mM) inhibited platelet aggregation in vivo by 37% whereas similar inhibition in vitro required about 1 mM aspirin. Sodium salicylate was several times less potent than aspirin in vivo.

Adenosine↗
PubMed1970

Uptake, metabolism and release of (3H)-adrenaline by human platelets.

1. Measurements were made of the uptake, metabolism and release of [(3)H]-adrenaline by human platelets in citrated plasma or in an artificial medium.2. Radioactive adrenaline was not taken up at 0-2 degrees C. At 37 degrees C there was a slow uptake which continued for at least 5 hours.3. About half of the radioactivity in the platelets was intact adrenaline. The other half was an acidic metabolite from which adrenaline was released by acid hydrolysis.4. The immediate uptake of adrenaline was proportional to its concentration in the plasma up to at least 1 x 10(-5)M. Uptake measured after 1 h also increased linearly with concentration up to about 1 x 10(-4)M but less with higher concentrations. The highest concentration ratio was about 12.5. The concentration of metabolite in the platelets increased with the concentration of added adrenaline only up to about 2 x 10(-4)M.6. The immediate uptake of adrenaline was partially inhibited by phentolamine and dihydroergotamine. Measurement of uptake both immediately and after 1 h showed that the inhibition produced was not increased beyond about 50% by these drugs or by (+/-)-propranolol, chlorpromazine or amitriptyline up to 1 x 10(-4)M.7. Formation of the metabolite was inhibited by pyrogallol, 8-hydroxyquinoline, or tropolone. This inhibition was associated with a corresponding increase in the adrenaline accumulated intact. Formation of the metabolite was not inhibited by monoamine oxidase inhibitors.8. Reserpine caused a small decrease in the uptake of adrenaline radioactivity in 1 h and a great increase in the proportion recovered as metabolite.9. Thrombin caused the release from platelets of intact adrenaline but not of the metabolite.10. Platelets of albino patients with spontaneous haemorrhages accumulated adrenaline radioactivity at the normal rate but this radioactivity was wholly accounted for by metabolite and not released by thrombin.11. After taking up adrenaline, platelets resuspended in artificial medium at 37 degrees C slowly released both adrenaline and its metabolite. At the same time, the intracellular adrenaline was slowly metabolized.12. The Result suggest that human platelets take up adrenaline by two processes, one of which is inhibited by both alpha- and beta-adrenoceptor blocking agents ad well as by phenothiazines; and that in the platelets adrenaline is partly stored in organelles from which, like 5-hydroxytryptamine, it can be specifically released.

Albinism↗
PubMed1970

Observations on the change in shape of blood platelets brought about by adenosine diphosphate.

1. An optical method used for measuring platelet aggregation was adapted for measurements of the change in shape of platelets that rapidly follows the addition of the aggregating agent adenosine diphosphate (ADP).2. Measurements were made using dilute suspension of platelets with sufficient EDTA to prevent their aggregation.3. Measurements of the velocity and magnitude of the optical effects of the shape change were highly reproducible.4. Volumetric measurements showed that the shape change is not associated with an increase in mean platelet volume.5. The velocity of the shape change had a temperature coefficient of about 4.5.6. The velocity and magnitude of the shape change were not affected by pH between 5.8 and 9.2.7. The dependence of the velocity of the shape change on the ADP concentration was in accordance with Michaelis-Menton kinetics. The K(m) was about 7.2 x 10(-7)M.8. The velocity of the shape change was inhibited competitively by ATP, adenosine and 2-chloroadenosine but not by AMP. When the inhibitors were added after the maximum of the shape change they caused a concentration-dependent diminution in the record of the change.9. The results suggest that the shape change is initiated by reaction of the agonist ADP with specific receptor sites on the platelet membrane which leads to energy-requiring changes in the structures responsible for maintaining the disk shape of normal platelets.

Adenine Nucleotides↗
PubMed1969

The relation between the 5-hydroxytryptamine content and aggregation of rabbit platelets.

1. Blood platelets containing different amounts of 5-hydroxytryptamine (5-HT) were produced in vivo by the injection of 5-hydroxytryptamine or of reserpine into normal rabbits and of 5-hydroxytryptamine into reserpinized rabbits. Before and after these injections the aggregation of platelets was measured in vitro.2. Platelets of untreated rabbits were aggregated by adenosine diphosphate (ADP) and by 5-hydroxytryptamine; (-)-adrenaline alone did not produce aggregation but markedly increased aggregation by 5-hydroxytryptamine.3. Platelets saturated with 5-hydroxytryptamine in vivo were no longer aggregated in vitro by 5-hydroxytryptamine or by 5-hydroxytryptamine plus adrenaline, but their aggregation by ADP was unchanged.4. Platelets from reserpinized rabbits lost about 99% of their 5-hydroxytryptamine; the aggregation of these platelets did not differ significantly from that of platelets from control rabbits.5. Platelets from reserpinized rabbits injected with 5-hydroxytryptamine were aggregated neither by the amine alone nor by 5-hydroxytryptamine plus adrenaline, although these platelets contained much less 5-hydroxytryptamine than saturated platelets and only about one tenth as much as platelets from untreated rabbits.6. The findings support the hypothesis that the inhibitory effect of 5-hydroxytryptamine administered in vivo on platelet aggregation in vitro is due to the association of the amine with the platelet membrane.

Adenine Nucleotides↗