Synthesis of new pyrazoline-nucleoside analogue derivatives.

In this work, a synthesis of pyrazoline nucleosides analogues is presented, using the stereospecific sodium salt glycosylation procedure. In the first step, chalcones were prepared using Claisen­Schmidt reaction by reacting benzaldehyde with enolizable ketones in ethanolic NaOH solutions. Next, these chalcones were immediately reacted with hydrazine hydrochloride in the presence of dry methanol to obtain the corresponding 2-pyrazolines. Finally, the coupling of the pyrazolines with 1-chloro-arabinofuranose leads to different ß-nucleosides as the major product (13­17) in good yields. The structures of these derivatives were characterized by infrared and 1HNMR spectroscopy and mass spectrometry.

[Production of Th1/Th2 cytokines and nitric oxide in Behçet's uveitis and idiopathic uveitis]. / Production des cytokines Th1/Th2 et du monoxyde d'azote au cours de l'uvéite "Behçet" et de l'uvéite "idiopathique".

INTRODUCTION: The aim of this study was to investigate the role of Th1 (IFN-gamma and IL-12), Th2 (IL-10) cytokines and nitric oxide (NO) in the immunopathologic mechanisms of uveitis related to Behçet's disease and isolated idiopathic uveitis. PATIENTS AND METHOD: This study was conducted on 24 patients with Behçet's syndrome who had active uveitis, ten of whom showed isolated uveitis classified as idiopathic uveitis, and 13 healthy controls. The levels of IFN-gamma, IL-12 and IL-10 in sera and supernatants of PBMC cultures stimulated by PHA were estimated using immunoenzymatic dosage (ELISA sandwich according to the methods recommended by Immunotech France). The production of NO was measured in vivo and in vitro for the same patients using the modified Griess method. RESULTS: The induction of IFN-gamma and IL-12 was higher in the two groups of patients than in the controls (P<0.001). Significant IL-10 levels were recorded in 56.5% of patients with Behçet's disease presenting uveitis versus 30% of patients with idiopathic uveitis. NO production was more pronounced in idiopathic uveitis than in Behçet's syndrome (P<0.02). CONCLUSION: The predominance of the Th1 profile was associated with high production of NO in idiopathic uveitis. A Th1/Th2 profile with a moderated increase in NO production was observed in Behçet's disease. Our data have a clinical impact. The observation of combined Th1/Th2 cytokines and NO elevation in both in vivo an in vitro experiments could have a predictive value in characterizing uveitis associated with Behçet's disease.

[Effect of nitrites and nitrates on bovine retina in vitro]. / Effet des nitrites et des nitrates sur les rétines de boeuf in vitro.

BACKGROUND/AIM: Uveitis is an endocular inflammation that forms one of the most serious manifestations of Behçet disease. Nitric oxide (NO) is a molecule that expresses important immunoinflammatory properties and is produced by NO synthases (NOS). In previous studies, we showed an elevated production of endogenous NO during Behçet's and idiopathic uveitis. These results led us to investigate the effect of nitrites (NO2-) and nitrates (NO3-) (physiologically stable metabolites of NO) on fragments of bovine retina in order to determine the role of nitric oxide (NO) in the genesis of retinal lesions during uveitis. MATERIAL AND METHODS: Retinas were removed from freshly enucleated bovine eyes and cultured in DMEM, 10% CFS in presence of nitrites (NaNO2) or nitrates (NaNO3) at different concentrations. The cultures were processed at 37 degrees C, 5% CO2 in a humidified chamber. Cultured retinas were observed by inverse microscopy and then fixed in formaldehyde. Histological studies were conducted after H & E staining. RESULTS: Cultured retina showed alterations when exposed to concentrations of nitrites and nitrates higher than 200 microM and 250 microM, respectively. These alterations were dose-dependent and affected the cellular and tissular structures. Morphological and histological studies suggested that the toxic effect is apoptotic and/or necrotic for both effectors. CONCLUSION: Our investigations showed that nitrites and nitrates, two physiologically stable metabolites of NO, have a deleterious effect on cultured retina. NO, produced in inflammatory processes during uveitis may be implicated in the genesis of the retinal lesions observed during the exacerbation phase of the disease.