Non-steroidal anti-inflammatory drugs react with two sites on platelet cyclo-oxygenase evidence from ‘in vivo’ drug interaction studies in rats

Non-steroidal anti-inflammatory drugs inhibit platelet cylco-oxygenase activity. This study shows that salicylate, diflunisal, sulphinpyrazone and indomethacine prevent in vivo aspirin inhibitory effect of cyclo-oxygenase activity as measured by the formation of malondialdehyde and thromboxane B₂, two products of platelet arachidonic acid metabolism. Salicylate also prevents the inhibitory effect of indomethacin. All these drugs therefore appear to interact with the same site on platelet cyclo-oxygenase. Since salicylate is inactive by itself on this platelet enzyme and diflunisal and sulphinpyrazone were used at ineffective doses, it is suggested that their interaction with aspirin (or indomethacin) occurs at the level of a supplementary site is necessary but not sufficient for the efficacy of these drugs as cyclo-oxygenase inhibitors. Acetylation by aspirin of the active site appears to be a phenomenon secondary to the binding of salicylate moiety to the supplementary site.     

On the double nature of productivity in inflectional morphology

Inflection is generally considered to be more productive than derivation. To justify such an assumption, the syntactic function of inflectional morphology is contrasted with the mainly lexical function of derivational morphology. In this paper, the whole question will be carefully discussed with the help of recently developed quantitative approaches to productivity. On the basis of data taken from Italian, it will be shown that a quantitative approach to productivity can shed light on this intricate question by revealing the double nature of inflectional morphology, which on the one hand sides with derivational morphology because of its lexically conditioned inflectional classes. On the other, it scores very high productivity rates for the single inflectional categories in accordance with its syntactic function. Furthermore, the productivity rates of the inflectional categories considered are shown to be not uniform: several factors may influence their productivity, as for instance the substitutive usage of periphrases with modals, even in a language like Italian in which the latter are far less grammaticalized than in others. Parts of this paper were presented at the XI International Morphology Meeting held in Vienna, 14th–17th February 2004, and in lectures given at the Universities of Graz, L’Aquila, Marburg, Roma Tre, and Salerno. I wish to express my gratitude to the people who discussed with me the ideas contained in the paper, and in particular to my colleague and friend Davide Ricca, who has been sharing with me the pleasure and the hard work of conducting quantitative investigations on Italian morphology. Many ideas contained in the paper are the result of constant and animated discussions with him. Finally, I am very much indebted to the editor Ingo Plag and two anonymous reviewers for remarkable observations and comments. Needless to say, I carry the full responsability for errors and misunderstandings contained in the paper.     

Prostacyclin and human foetal circulation.

Tissues from human umbilical cord arteries and placental veins generated much greater prostacyclin activity than vessels from normal adults. High prostacyclin generation could contribute to maintaining the low peripheral vascular resistance typical of foetal circulation in which blood pressure is low despite very high cardiac output.