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Biomedical subjects

J A May

Publications and source records attributed to J A May.

28 records · Page 2Linked to original sources
PubMed1995

Effects of ticlopidine administered to healthy volunteers on platelet function in whole blood.

Ticlopidine is thought to be a selective inhibitor of ADP-induced platelet function. Here we have investigated the effects of ticlopidine on platelet function in whole blood induced by ADP and by other platelet agonists. Whole blood was used because it was considered that ADP derived from red cells might act synergistically with other platelet agonists to enhance platelet responses, and that ticlopidine might interfere with this process. Measurements were performed using blood from 16 healthy volunteers before ticlopidine administration, after taking ticlopidine 250 mg daily for 10 days, after taking ticlopidine 250 mg twice daily for a further 10 days, and after 14 days off treatment. Ticlopidine proved to be a very effective inhibitor of the platelet aggregation induced by ADP; it was most effective in enhancing the reversibility of the aggregation response. The drug modestly but significantly reduced streptokinase, adrenaline, collagen, sodium arachidonate, PAF and U46619 - induced platelet aggregation. The drug significantly reduced the extent of the release reaction (14C-5HT release) induced by ADP, streptokinase, PAF, ristocetin and sodium arachidonate, and also reduced the extent of the synergistic 14C-5HT release induced by combinations of ADP and PAF, ADP and adrenaline and PAF and adrenaline. The various inhibitory effects of ticlopidine were evident after treatment with 250 mg daily but were more pronounced after 250 mg twice daily. All values had returned to normal after 14 days off treatment. Ticlopidine had no effect on serum thromboxane B2 production nor on several parameters of coagulation and fibrinolysis. We conclude that ticlopidine is an effective inhibitor of ADP-induced platelet aggregation and also the platelet aggregation and 14C-5HT release induced in whole blood by a number of platelet agonists and combinations of agonists. These latter effects are probably mainly via a selective effect on ADP. The inhibitory effects of the drug are dose-related.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Inhibition of platelet aggregation by transdermal glyceryl trinitrate.

OBJECTIVE: To determine the optimum conditions for the demonstration of an antiplatelet effect of nitric oxide and to use these conditions to elucidate the effects of a transdermal glyceryl trinitrate patch on platelet aggregation in normal volunteers. METHODS: An open prospective crossover study. The effects of nitric oxide on platelet aggregation in whole blood and platelet rich plasma as stimulated by adenosine diphosphate and U46619 was assessed in the presence and absence of iloprost and MB22948. Optimum conditions for the demonstration of an antiplatelet effect of nitric oxide were then applied to whole blood from normal volunteers in the presence and absence of a transdermal glyceryl trinitrate patch. SETTING: University hospital. SUBJECTS: Eight normal volunteers. MAIN OUTCOME MEASURES: Platelet aggregation in the presence and absence of transdermal glyceryl trinitrate. RESULTS: The optimum conditions for the demonstration of an antiplatelet effect of nitric oxide in whole blood were collecting blood into a tube containing MB22948 and citrate and stimulating platelet aggregation with adenosine diphosphate in the presence or absence of iloprost. Using this method a significant effect of transdermal glyceryl trinitrate on platelet aggregation was shown (P < 0.03) in the presence and absence of iloprost. CONCLUSIONS: These results are consistent with an inhibitory effect on platelet aggregation of nitric oxide liberated by transdermal glyceryl trinitrate. Optimum test conditions are needed to show this effect. The clinical significance of the antiplatelet effect of transdermal glyceryl trinitrate is unknown.

Adenosine Diphosphate↗
PubMed1984

Identification of a glycosidase activity with apparent specificity for 2-deoxy-D-glucose in glycosidic linkage.

2-Deoxy-D-glucose (dGlc) is a carbohydrate with significant activity as an inhibitor of glucose metabolism and as a precursor in the synthesis of glycosylated macromolecules; several of the enzymes associated with its metabolism remain uncharacterized. In the present report, the partial purification and some of the properties of a mammalian enzyme that appears to be relatively specific for the hydrolysis of dGlc bound in glycosidic linkage is described. The physiological function of this enzymatic activity is unknown. In addition, dGlc has been shown to be taken up by HTC cells in culture and incorporated into macromolecular bound form, both as dGlc and as 2-deoxygalactose which is formed from dGlc.

Animals↗
PubMed1983

Relationship of spontaneous chemical transformation of arylsulfonylhydrazones of 2-pyridinecarboxaldehyde 1-oxide to anticancer activity.

The arylsulfonyl-hydrazones of 2-pyridinecarboxaldehyde 1-oxide represent a relatively new class of antineoplastic agents with the potential for clinical usefulness. The requirement for spontaneous chemical transformation of these agents to exert anticancer activity was evaluated using as the prototype the most potent member of this class synthesized to date, the 3,4-dimethoxybenzene sulfonylhydrazone of 2-pyridinecarboxaldehyde 1-oxide (3,4-DSP. 3,4-DSP was chemically unstable, decomposing with a half-life of 19 min in 0.01 M potassium phosphate buffer (pH 7.4) at 37 degrees. The major chemical decomposition product was identified as 2-pyridylcarbinol 1-oxide by comparison with the authentic compound. This carbinol is hypothesized to be formed via the intramolecular abstraction of hydrogen from the arylsulfonyl-hydrazone, a process that leads to the release of 3,4-dimethoxybenzenesulfinic acid and the formation of 1-oxidopyridin-2-yldiazomethane, which subsequently reacts with water. The diazomethane intermediate is a potent alkylating agent which, if generated in cells, would have the potential to alkylate nucleophilic groups of biologically important macromolecules. The proposed reactive species was trapped using both 4-(4-nitrobenzyl)pyridine (NBP) and morpholine, and the latter product was characterized by mass spectroscopy. The importance of the chemical formation of an alkylating species to cytotoxicity was demonstrated by studies in which solutions of 3,4-DSP were "aged" prior to addition to L1210 leukemia cells in culture and prior to incubation with NBP. The "aging" of 3,4-DSP for 20 min resulted in a 4-fold decrease in cytotoxicity, and aging for 1 to 3 hr led to complete loss of cytotoxicity. Correspondingly, a 20-min aging period decreased alkylation of NBP by 51%, and 3-hr aging resulted in essentially no alkylation of the nucleophile. Further support for the above proposed chemical activation pathway was provided by correlations between in vitro cytotoxicity, in vivo antineoplastic activity, chemical stability, and the degree of alkylation of NBP by a wide variety of arylsulfonyl-hydrazones. The lack of the 1-oxide, envisioned to be required for intramolecular hydrogen abstraction, the steric prevention of the abstraction, or the replacement of the proton of the nitrogrn of the side-chain by a methyl group resulted in a marked increase in chemical stability and a corresponding loss of the ability to alkylate NBP and to inhibit the replication of L1210 leukemia cells in culture.

Alkylating Agents↗
PubMed1979

Synthesis and biological activity of potential antimetabolites of L-fucose.

6-Substituted 6-deoxy-L-galactose (L-fucose) derivatives were synthesized as potential antimetabolites of L-fucose. The cytotoxic effects of these compounds were evaluated on P388 leukemia cells in culture. The L-fucose analogues which showed the most potent growth inhibition were the sulfonyl ester, bromo, and iodo derivatives; since these compounds were all capable of alkylation, it is conceivable that their cytotoxic action is a consequence of this property. In agreement with this interpretation, none of the agents synthesized showed specific inhibition of the incorporation of L-[3H]fucose into glycoprotein.

Animals↗
PubMed1978

Antineoplastic properties of arylsulfonylhdrazones of 3-formylpyridazine 2-oxide and 4-formylpyrimidine 3-oxide.

The antineoplastic activity of several arylsulfonylhydrazones of 4-formylpyrimidine 3-oxide and of 3-formylpyridazine 2-oxide has been investigated. Derivatives of the latter heteroaromatic N-oxide showed excellent antineoplastic potency against the murine neoplasm Sarcoma 180 but were inactive against leukemia L1210. In contrast, derivatives of 4-formylpyrimidine 3-oxide were inactive against both of these transplanted tumors.

Animals↗
PubMed1976

Spinner films for reticulocyte counts.

The widely practiced method for performing a reticulocyte count includes counting 1000 normal erythrocytes while searching for a relatively small population of reticulocytes. A method is presented using a spinner reticulocyte preparation which avoids the need to count the normal erythrocytes, thereby eliminating most of the tedium from the test. The accuracy and reproducibility of this new method, as compared to the currently practiced method, is presented, along with the results of an on-line comparison.

Erythrocyte Count↗