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Présenter les recommandations de pratique clinique (RCP) de la Société française d’otorhinolaryngologie–chirurgie de la face et du cou concernant l’utilisation des AINS dans les infections ORL pédiatriques.

Les causes et le traitement de l’énurésie nocturne primaire isolée (EnPI) sont depuis longtemps controversés. Nous proposons un consensus de recommandations pratiques, appuyé sur une analyse formalisée de la littérature et validé par un large panel d’experts.

From the discovery of competitive hexapeptide inhibitors, potent and selective HCV NS3 protease macrocyclic inhibitors have been identified. Structure−activity relationship studies were performed focusing on optimizing the N-terminal carbamate and the aromatic substituent on the (4R)-hydroxyproline moiety. Inhibitors meeting the potency criteria in the cell-based assay and with improved oral bioavailability in rats were identified. BILN 2061 was selected as the best compound, the first NS3 protease inhibitor reported with antiviral activity in man.

Starting from palinavir (1), our lead HIV protease inhibitor, we have discovered a new series of truncated analogues in which the P3-P2 quinaldic-valine portion of 1 was replaced by 2‘,6‘-dimethylphenoxyacetyl. With EC50's in the 1−2 nM range, some of these compounds are among the most potent inhibitors of HIV replication in vitro, reported to date. One of the most promising members in this series (compound 27, BILA 2185 BS) exhibited a favorable overall pharmacokinetic profile, with 61% apparent oral bioavailability in rat. X-ray crystal structures and molecular modeling were used to rationalize the high potency resulting from incorporation of this structurally simple, achiral ligand into the P3-P2 position of hydroxyethylamine-based HIV protease inhibitors.

A series of HIV protease inhibitors containing a novel (hydroxyethyl)amidosuccinoyl core has been synthesized. These peptidomimetic structures inhibit viral protease activity at low nanomolar concentrations (IC50 < 10 nM for HIV-1 protease). The inhibition constant (Ki) for inhibitor 19 was determined to be 7.5 pM against HIV-1 and 1.2 nM against HIV-2 proteases, respectively. Several compounds (19−24) inhibited HIV-1 replication in cell culture assays with 50% effective concentrations (EC50) = 3.7−35 nM. This series of inhibitors was found to exhibit poor bioavailability (<10%) in the rat, following oral administration. The synthesis and biological properties of these compounds are discussed. In addition, an X-ray structure of one of these inhibitors (23) in complex with HIV-2 protease provides insight into the binding mode of this novel class of HIV protease inhibitors.

The effects of endothelin-1 in the spontaneously beating atrium and the field-stimulated right ventricular strip preparation and the binding of [125I]endothelin-1 to membrane preparations from the atrium, ventricle, lung parenchyma, kidney and brain were compared using the 90-day-old dystrophic hamster strain CHF 147 (a strain displaying marked cardiomyopathologies at this age) and its age/genetically matched normal control, CHF 148. In the atrium, endothelin-1 produced dose-dependent positive inotropic and positive chronotropic effects in both CHF 148 and CHF 147 over the dose range of 10(-8) M to 3 x 10(-7) M. However, although no significant difference between CHF 148 and CHF 147 was observed for the positive chronotropic effects of endothelin-1, it produced a small, but significantly less positive inotropic effect in CHF 147 compared to CHF 148 at endothelin-1 concentrations of 2 x 10(-8) M and 3 x 10(-8) M. Field-stimulated right ventricular strips from CHF 148 contracted with a greater force compared to those from CHF 147. Endothelin-1 produced a dose-dependent decrease in the developed tension of the field-stimulated ventricular strip preparation, the extent of which did not differ between CHF 148 and CHF 147. [125I]Endothelin-1 bound with high affinity and in an apparently irreversible manner to membranes from both CHF 148 and CHF 147 atrium, ventricle, lung parenchyma, kidney and brain. No significant differences were noted between CHF 148 and CHF 147 for [125I]endothelin-1 binding to membranes prepared from the various tissues.(ABSTRACT TRUNCATED AT 250 WORDS)