54 research outputs found
Prevention by the CXCR2 antagonist SCH527123 of the calcification of porcine heart valve cusps implanted subcutaneously in rats
IntroductionCalcification is a main cause of bioprosthetic heart valves failure. It may be promoted by the inflammation developed in the glutaraldehyde (GA)-fixed cusps of the bioprosthesis. We tested the hypothesis that antagonizing the C-X-C chemokines receptor 2 (CXCR2) may prevent the calcification of GA-fixed porcine aortic valves.Materiel and methodsFour-week-old Sprague Dawley males were transplanted with 2 aortic valve cusps isolated from independent pigs and implanted into the dorsal wall. Four groups of 6 rats were compared: rats transplanted with GA-free or GA-fixed cusps and rats transplanted with GA-fixed cusps and treated with 1 mg/kg/day SCH5217123 (a CXCR2 antagonist) intraperitoneally (IP) or subcutaneously (SC) around the xenograft, for 14 days. Then, rats underwent blood count before xenografts have been explanted for histology and biochemistry analyses.ResultsA strong calcification of the xenografts was induced by GA pre-incubation. However, we observed a significant decrease in this effect in rats treated with SCH527123 IP or SC. Implantation of GA-fixed cusps was associated with a significant increase in the white blood cell count, an effect that was significantly prevented by SCH527123. In addition, the expression of the CD3, CD68 and CXCR2 markers was reduced in the GA-fixed cusps explanted from rats treated with SCH527123 as compared to those explanted from non-treated rats.ConclusionThe calcification of GA-fixed porcine aortic valve cusps implanted subcutaneously in rats was significantly prevented by antagonizing CXCR2 with SCH527123. This effect may partly result from an inhibition of the GA-induced infiltration of T-cells and macrophages into the xenograft
Lutte contre la iatrogénie médicamenteuse à l'hôpital (l'application d'une exigence)
AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF
Comment on `metformin-related lactic acidosis with acute kidney injury: results of a French observational multicenter study'
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Intérêts thérapeutiques des médicaments antiangiogéniques disponibles en cancérologie
L’angiogénèse est un processus physiologique finement régulé aboutissant à la formation
de nouveaux vaisseaux sanguins. Son implication dans les processus tumoraux est bien
décrite et en fait un élément déterminant du pronostic des cancers. Le rôle majeur des
Vascular Endothelial Growth Factors (VEGF) et de leurs récepteurs a permis le
développement de molécules au potentiel antitumoral original. Cette revue a pour objectif
de décrire les bases pharmacologiques de l’angiogénèse tumorale et la raison pour laquelle
cette nouvelle classe de médicaments dits « antiangiogéniques », dont trois sont
actuellement disponibles en France, suscite l’espoir de traiter de nombreux cancers.
L’évaluation clinique ici synthétisée montre néanmoins que l’activité pharmacologique
étudiée en laboratoire ne se traduit pas toujours en progrès thérapeutique. En effet,
l’efficacité modeste des antiangiogéniques et leurs nombreux effets indésirables ne sont
pas toujours en leur faveur. Une optimisation de leur emploi serait sans doute nécessaire
Therapeutic Strategy for Metformin-Associated Lactic Acidosis Reply
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Comment on 'metformin-related lactic acidosis with acute kidney injury: results of a French observational multicenter study'
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