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

L'Erythropoïétine, agent d'optimisation de la thérapie cellulaire par progéniteurs endothéliaux dans l'AVCischémique et l'ischémie aiguë des membres inférieurs.

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Lutte contre la iatrogénie médicamenteuse à l'hôpital (l'application d'une exigence)

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

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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

Plasma metformin levels at almost 24 hours would help with the delicate decision to start renal replacement therapy: We disagree as lactate that is more widely and early available should be a much better trigger to start renal replacement therapy! Reply

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Therapeutic Strategy for Metformin-Associated Lactic Acidosis Reply

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Plasma Metformin Levels at Almost 24 Hours Would Help With the Delicate Decision to Start Renal Replacement Therapy: We Disagree as Lactate That Is More Widely and Early Available Should Be a Much Better Trigger to Start Renal Replacement Therapy! 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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