In vitro and in vivo evaluation of a dextran-graft-polybutylmethacrylate copolymer coated on CoCr metallic stent

International audienceIntroduction: The major complications of stent implantation are restenosis and late stent thrombosis. PBMA polymers are used for stent coating because of their mechanical properties. We previously synthesized and characterized Dextrangraft-polybutylmethacrylate copolymer (Dex-PBMA) as a potential stent coating. In this study, we evaluated the haemocompatibility and biocompatibility properties of Dex-PBMA in vitro and in vivo.Methods: Here, we investigated: (1) the effectiveness of polymer coating under physiological conditions and its ability to release Tacrolimus®, (2) the capacity of Dex-PBMA to inhibit Staphylococcus aureus adhesion, (3) the thrombin generation and the human platelet adhesion in static and dynamic conditions, (4) thebiocompatibility properties in vitro on human endothelial colony forming cells (ECFC) and on mesenchymal stem cells (MSC) and in vivo in rat models, and (5) we implanted Dex-PBMA and Dex-PBMA TAC coated stents in neointimal hyperplasia restenosis rabbit model. Results: Dex-PBMA coating efficiently prevented bacterial adhesion and release Tacrolimus®. Dex-PBMA exhibit haemocompatibility properties under flow and ECFC and MSC compatibility. In vivo, no pathological foreign body reaction was observed neither after intramuscular nor intravascular aortic implantation. After Dex-PBMA and Dex-PBMATAC coated stents 30 days implantation in a restenosis rabbit model, an endothelial cell coverage was observed and the lumenpatency was preserved.Conclusion: Based on our findings, Dex-PBMA exhibited vascular compatibility and can potentially be used as a coating for metallic coronary stents

Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome

Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven different truncating mutations, one of which was recurrent. The mutant alleles encode GP130 receptors bearing the transmembrane domain but lacking both the recycling motif and all four STAT3-recruiting tyrosine residues. Upon overexpression, the mutant proteins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6, IL-11, LIF, and OSM. Moreover, the patients’ heterozygous leukocytes and fibroblasts respond poorly to IL-6 and IL-11. Consistently, patients with STAT3 and IL6ST mutations display infectious and allergic manifestations of IL-6R deficiency, and some of the skeletal abnormalities of IL-11R deficiency. DN STAT3 and IL6ST mutations thus appear to underlie clinical phenocopies through impairment of the IL-6 and IL-11 response pathways

Test de type-log rank pour l'évolution de la qualité de vie liée à la santé

Longitudinal epidemiological studies on health related quality of life (HrQoL) had a significant development these last years in particular for chronic diseases, where no perspective of definitive cure exists. So, the main goal of such studies is an epidemiological surveillance of health, including HrQoL and survival. Such surveillance is mainly based on comparison of longitudinal evolution of the HrQoL between groups of patients. To that end and when the number of groups is two, we propose a global log-rank statistical test built on the HrQoL rate of degradation.Usually, in longitudinal clinical studies, patients are asked to fill out HrQoL questionnaires on fixed dates, so it's possible to evaluate their HrQoL. The amount of degradation of HrQoL reflects HrQoL evolution in comparison with an initial date (baseline). A threshold x can be chosen to define maximum acceptable degradation of HrQoL. So, patients are considered as degraded at time t if degradation of HrQoL is higher than x. We generalized the partial likelihood score statistic in order to take into account the event of interest degradation of HrQoL for a fixed rate x. We proved that the normalized vector score process converges to a mean zero variate Gaussian process. Then we supposed that the rate of degradation of HrQoL x, is varying. By using empirical process theory we obtained that the normalized vector score process converges in distribution to a Gaussian process. These results entitled to develop a global nonparametric statistical test in order to compare rate of degradation of HrQoL between two groups of patients.Simulations and an application to a Cohort of HIV- infected patients were discussed.Les études épidémiologiques longitudinales sur la qualité de vie (QdV) connaissent un essor depuis quelques années, surtout pour les maladies chroniques où aucun traitement curatif n'existe. L'objectif de ces études est la surveillance de la santé incluant la QdV et la survie. Une telle surveillance repose sur la comparaison de l'évolution longitudinale de QdV entre groupes de patients. Aussi, avons nous élaboré un test global de type log-rank pour l'évolution longitudinale de QdV par rapport à un taux de dégradation de QdV pour deux groupes de patients. Généralement lors de ces études, des questionnaires de QdV sont donnés à remplir aux patients permettant de calculer leur score de QdV. L'évolution de QdV se traduit par le concept de dégradation de QdV. Un taux critique x de dégradation de QdV peut être fixé. Les patients sont considérés comme dégradés si leur score de QdV est supérieur à x. Nous étendons la statistique du score de vraisemblance partielle afin de prendre en compte un taux x de dégradation de QdV préalablement fixé et montrons que le vecteur du processus de score normalisé converge vers un processus gaussien centré. Le taux x de dégradation de QdV est ensuite supposé variable. A l'aide de la théorie des processus empiriques nous prouvons la convergence en distribution de la statistique du score normalisé vers un processus gaussien. Ces travaux ont permis de construire, lorsque le taux x de dégradation de QdV est variable, un test de type log-rank permettant de comparer l'évolution longitudinale de la dégradation de QdV pour deux goupes de patients.Des simulations et une application à une cohorte de patients infectés par le VIH sont présentées

Test de type log-rank pour l évolution de la qualité de vie liée à la santé

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Misspecified regression model for the subdistribution hazard of a competing risk.

We consider a competing risks setting, when evaluating the prognostic influence of an exposure on a specific cause of failure. Two main regression models are used in such analyses, the Cox cause-specific proportional hazards model and the subdistribution proportional hazards model. They are exemplified in a real data example focusing on relapse-free interval in acute leukaemia patients. We examine the properties of the estimator based on the latter model when the true model is the former. An explicit relationship between subdistribution hazards ratio and cause-specific hazards ratio is derived, assuming a flexible parametric distribution for latent failure times. Copyright (c) 2006 John Wiley & Sons, Ltd

Efficient Carbonyl Hydrosilylation Reaction: Toward EVA Copolymer Crosslinking

International audienceIn this article, the hydrosilylation reaction of carbonyl groups of acetate derivatives and SiH groups of hydride-terminated polydimethylsiloxane at high temperature (100-130 degrees C) are described. Triruthenium dodecacarbonyl, Ru(3)(CO)(12), was used as effective catalyst for hydrosilylation reaction. The hydrosilylation reactions with octyl acetate and 4-heptyl acetate were investigated by multinuclear NMR spectroscopy ((1)H, (13)C, and (29)Si). This work provides evidence of the addition reaction of SiH groups onto carbonyl groups. The influence of the nature of the acetate structure on the reaction kinetics was shown and the slight contribution of side reactions at high temperature highlighted. Hydrosilylation reaction was extent to the crosslinking of ethylene-vinyl acetate (EVA) copolymer in the same range of temperature. The formation of EVA chemical network was demonstrated by HR-MAS NMR spectroscopy and by measuring the gel fraction of EVA chains in hot toluene. From Flory theory, the crosslinking density of elastic strand was calculated to be 80 mol m (3) in agreement with the measurements from swelling ratio (VA/SiH molar ratio: 11.8)