[Antithrombotic therapy].
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Biomedical subjects
Publications and source records attributed to J L David.
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Cyclooxygenase is the key enzyme in the biosynthesis of prostanoids, biologically active substances involved in several physiological processes and also in pathological conditions such as inflammation. It has been well known for 10 years that this enzyme exists under two forms: a constitutive (COX-1) and an inducible form (COX-2). Both enzymes are sensitive to inhibition by conventional non-steroidal anti-inflammatory drugs (NSAIDs). Observations were made that COX-1 was mainly involved in homeostatic processes, while the COX-2 expression was associated with pathological conditions leading to the development of COX-2 selective inhibitors. Several methods have been reported for the evaluation of the COX-1 and COX-2 inhibitory potency and selectivity of conventional or COX-2 selective NSAIDs. In this study, we evaluated the COXs inhibitory profile of both conventional NSAIDs and COX-2 selective inhibitors using two different in vitro methods: the first test was performed using purified enzymes while the second method consisted of a whole blood assay. The results obtained with reference drugs in these two assays will be discussed and compared in this article.
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The influence of platelet activating factor (PAF) was investigated in vivo on the ultrastructure of bovine platelets, and on the platelet count. The effect of an intravenous administration of ketoprofen (a non-steroidal anti-inflammatory drug) pretreatment followed by PAF infusion was also observed in a group of six healthy male Friesian calves. PAF infusion alone caused a moderate thrombocytopenia, which peaked one minute post challenge and returned to levels not significantly different from control after 30 min. Electron microscopy revealed that after PAF infusion, platelets lost their lentiform shape and became irregular, with many pseudopods. Their microtubules became impossible to distinguish. The numbers of alpha granules and dense bodies were significantly decreased. Glycogen particles became rare or even disappeared. Giant platelets occasionally appeared. The Golgi apparatus was more often visible and the number of mitochondria was significantly increased. Ketoprofen pretreatment lowered PAF-induced thrombocytopenia and decrease in the number of dense bodies. Under these conditions, the Golgi apparatus was rarely visible and giant platelets were not observed. These results showed that the morphological ultrastructure of blood platelets in bovines were modified following PAF infusion and that ketoprofen pretreatment before PAF infusion provided partial protection, limiting the extent of the morphological alterations and maintaining a normal platelet count.