Etude rétrospective descriptive de l'utilisation de la daptomycine à l'hôpital Bichat-Claude Bernard sur l'année 2010

PARIS-BIUP (751062107) / SudocSudocFranceF

Analyse rétrospective de deux années d'utilisation du voriconazole en ATU (Autorisation Temporaire d'Utilisation) à l'Hôpital Saint Louis

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Analyse rétrospective d'une cohorte de patients atteints d'un lupus suivis dans un service de dermatologie

PARIS-BIUP (751062107) / SudocSudocFranceF

Structure-activity studies of heparan mimetic polyanions for anti-prion therapies.

Polysulfated molecules, as the family of heparan mimetics (HMs) and pentosan polysulfate, are considered among the more promising drugs used in experimental models of prion diseases. Regardless of their therapeutic potential, structure-function studies on these polyanions are still missing. Here, we report the syntheses of a library of HMs of different molecular sizes, containing various sulfation and carboxylation levels, and substituted or not by different hydrophobic cores. The HMs capacities to inhibit the accumulation of PrPres in chronically infected cells (ScGT1-7) and their PrPc binding abilities were examined. Our results showed that an optimal size and sulfation degree are needed for optimum activity, that incorporation of hydrophobic moieties increases compounds efficacy and that the presence of carboxymethyl moieties decreases it. These structural features should be considered on the modelling of polyanionic compounds for optimum anti-prion activities and for advancing in the understanding the mechanisms involved in their biological actions

Continuité documentaire « lycée-université » dans l'académie de Lille : un dispositif expérimental généralisable ?

International audienc

A synthetic glycosaminoglycan mimetic (RGTA) modifies natural glycosaminoglycan species during myogenesis

International audienceCrucial events in myogenesis rely on the highly regulated spatiotemporal distribution of cell surface heparan sulfate proteoglycans to which are associated growth factors, thus creating a specific microenvironment around muscle cells. Most growth factors involved in control of myoblast growth and differentiation are stored in the extracellular matrix through interaction with specific sequences of glycosaminoglycan oligosaccharides, mainly heparan sulfate (HS). Different HS subspecies revealed by specific antibodies, have been shown to provide spatiotemporal regulation during muscle development. We have previously shown that glycosaminoglycan (GAG) mimetics called RGTA (ReGeneraTing Agent), stimulate muscle precursor cell growth and differentiation. These data suggest an important role of GAGs during myogenesis; however, little is yet known about the different species of GAGs synthesized during myogenesis and their metabolic regulation. We therefore quantified GAGs during myogenesis of C2.7 cells and show that the composition of GAG species was modified during myogenic differentiation. In particular, HS levels were increased during this process. In addition, the GAG mimetic RGTA, which stimulated both growth and differentiation of C2.7 cells, increased the total amount of GAG produced by these cells without significantly altering their rate of sulfation. RGTA treatment further enhanced HS levels and changed its sub-species composition. Although mRNA levels of the enzymes involved in HS biosynthesis were almost unchanged during myogenic differentiation, heparanase mRNA levels decreased. RGTA did not markedly alter these levels. Here we show that the effects of RGTA on myoblast growth and differentiation are in part mediated through an alteration of GAG species and provide an important insight into the role of these molecules in normal or pathologic myogenic processes

Molecular Properties and Pharmacokinetic Behavior of Cetirizine, a Zwitterionic H 1 -Receptor Antagonist

International audienc

Performance of Repeated Measures of (1–3)-β-D-Glucan, Mannan Antigen, and Antimannan Antibodies for the Diagnosis of Invasive Candidiasis in ICU Patients: A Preplanned Ancillary Analysis of the EMPIRICUS Randomized Clinical Trial

International audienceBackground. We aimed to assess the prognostic value of repeated measurements of serum (1-3)-β-D-glucan (BDG), mannanantigen (mannan-Ag), and antimannan antibodies (antimannan-Ab) for the occurrence of invasive candidiasis (IC) in a high-risk nonimmunocompromised population. Methods. This was a preplanned ancillary analysis of the EMPIRICUS Randomized Clinical Trial, including nonimmunocompromised critically ill patients with intensive care unit-acquired sepsis, multiple Candida colonization, and multiple organ failure who were exposed to broad-spectrum antibacterial agents. BDG (>80 and >250 pg/mL), mannan-Ag (>125 pg/ mL), and antimannan-Ab (>10 AU) were collected repeatedly. We used cause-specific hazard models. Biomarkers were assessed at baseline in the whole cohort (cohort 1). Baseline covariates and/or repeated measurements and/or increased biomarkers were then studied in the subgroup of patients who were still alive at day 3 and free of IC (cohort 2). Results. Two hundred thirty-four patients were included, and 215 were still alive and free of IC at day 3. IC developed in 27 patients (11.5%), and day 28 mortality was 29.1%. Finally, BDG >80 pg/mL at inclusion was associated with an increased risk of IC (CSHR[IC], 4.67; 95% CI, 1.61-13.5) but not death (CSHR[death], 1.20; 95% CI, 0.71-2.02). Conclusions. Among high-risk patients, a first measurement of BDG >80 pg/mL was strongly associated with the occurrence of IC. Neither a cutoff of 250 pg/mL nor repeated measurements of fungal biomarkers seemed to be useful to predict the occurrence of IC. The cumulative risk of IC in the placebo group if BDG >80 pg/mL was 25.39%, which calls into question the efficacy of empirical therapy in this subgroup