Prise en charge du pneumothorax spontané aux urgences du C.H.U d'Angers (évaluation des pratiques professionnelles de Juin 2009 à mai 2013)

INTRODUCTION : La conduite à tenir devant un pneumothorax spontané n est pas consensuelle. La décision de drainage thoracique ou d exsufflation dépend du lieu de prise en charge et du praticien. Le but de ce travail était d évaluer de façon rétrospective de juin 2009 à mai 2013, l adéquation au protocole (07/2008) de la prise en charge d un pneumothorax spontané primitif ou secondaire à une BPCO aux urgences d Angers. MATERIEL et METHODES : Les dossiers médicaux et les radiographies thoraciques ont été relus ; un questionnaire a été envoyé a tous les médecins ayant travaillé sur cette période. L adéquation au protocole du service était définie par plusieurs critères qui devaient tous être vérifiés selon le sous-type de pneumothorax : gravité, aspect radiologique, geste(s) technique(s) réalisé(s) en urgence et hospitalisation. RESULTATS : 161 pneumothorax spontanés primitifs ou secondaires à une BPCO ont été analysés. L adéquation globale de prise en charge était de 24,49%. Les taux de conformité les plus importants étaient ceux des pneumothorax graves et/ou mal tolérés (59,38%) ou des pneumothorax spontanés avec un petit décollement apical de moins de 2 cm (80%). L adéquation était de 8,33% pour les pneumothorax avec un décollement axillaire total et était nulle pour ceux avec un décollement apical de plus de 2 cm isolé. Une valeur intermédiaire a été calculée pour les pneumothorax secondaires non graves (44,44%). CONCLUSION : Des justifications humaines, matérielles ou logistiques expliquent une prise en charge globale du pneumothorax aux urgences d Angers qui n est pas conforme au protocole en vigueur au moment de l étude.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Pharmacokinetics, Tissue Distribution and Therapeutic Effect of Cationic Thermosensitive Liposomal Doxorubicin Upon Mild Hyperthermia

Purpose: To evaluate pharmacokinetic profile, biodistribution and therapeutic effect of cationic thermosensitive liposomes (CTSL) encapsulating doxorubicin (Dox) upon mild hyperthermia (HT). Methods: Non-targeted thermosensitive liposomes (TSL) and CTSL were developed, loaded with Dox and characterized. Blood kinetics and biodistribution of Dox-TSL and Dox-CTSL were followed in B16BL6 tumor bearing mice upon normothermia (NT) or initial hyperthermia conditions. Efficacy study in B16BL6 tumor bearing mice was followed with Dox-TSL or Dox-CTSL upon NT or HT. Efficacy study in LLC tumor bearing mice was performed upon two HT conditions. Intravital microscopy was performed on B16BL6 tumors implanted in dorsal-skin fold window-bearing mice. Results: Targeting did not cause faster blood clearance of CTSL compared to TSL. Highest uptake of liposomes was observed in spleen, kidneys and liver. Applying HT prior to CTSL administration increased drug delivery to the tumor and CTSL delivered ∼1.7 fold higher Dox concentration compared to TSL. Efficacy in B16BL6 murine melanoma showed that HT had a significant effect on CTSL in tumor suppression and prolonged survival. Efficacy in LLC Lewis lung carcinoma tumor model demonstrates that two HT treatments hold promises for a successful treatment option. Conclusion: CTSL have potency to increase drug efficacy in tumors due to their targeted and drug release functions

Attraction Basins as Gauges of Robustness against Boundary Conditions in Biological Complex Systems

One fundamental concept in the context of biological systems on which researches have flourished in the past decade is that of the apparent robustness of these systems, i.e., their ability to resist to perturbations or constraints induced by external or boundary elements such as electromagnetic fields acting on neural networks, micro-RNAs acting on genetic networks and even hormone flows acting both on neural and genetic networks. Recent studies have shown the importance of addressing the question of the environmental robustness of biological networks such as neural and genetic networks. In some cases, external regulatory elements can be given a relevant formal representation by assimilating them to or modeling them by boundary conditions. This article presents a generic mathematical approach to understand the influence of boundary elements on the dynamics of regulation networks, considering their attraction basins as gauges of their robustness. The application of this method on a real genetic regulation network will point out a mathematical explanation of a biological phenomenon which has only been observed experimentally until now, namely the necessity of the presence of gibberellin for the flower of the plant Arabidopsis thaliana to develop normally

Combining ChIP-chip and Expression Profiling to Model the MoCRZ1 Mediated Circuit for Ca2+/Calcineurin Signaling in the Rice Blast Fungus

Significant progress has been made in defining the central signaling networks in many organisms, but collectively we know little about the downstream targets of these networks and the genes they regulate. To reconstruct the regulatory circuit of calcineurin signal transduction via MoCRZ1, a Magnaporthe oryzae C2H2 transcription factor activated by calcineurin dephosphorylation, we used a combined approach of chromatin immunoprecipitation - chip (ChIP-chip), coupled with microarray expression studies. One hundred forty genes were identified as being both a direct target of MoCRZ1 and having expression concurrently differentially regulated in a calcium/calcineurin/MoCRZ1 dependent manner. Highly represented were genes involved in calcium signaling, small molecule transport, ion homeostasis, cell wall synthesis/maintenance, and fungal virulence. Of particular note, genes involved in vesicle mediated secretion necessary for establishing host associations, were also found. MoCRZ1 itself was a target, suggesting a previously unreported autoregulation control point. The data also implicated a previously unreported feedback regulation mechanism of calcineurin activity. We propose that calcium/calcineurin regulated signal transduction circuits controlling development and pathogenicity manifest through multiple layers of regulation. We present results from the ChIP-chip and expression analysis along with a refined model of calcium/calcineurin signaling in this important plant pathogen

EQUIPEMENT ET MATERIEL TECHNIQUE, DES MEDECINS GENERALISTES EN FRANCHE-COMTE

BESANCON-BU Médecine pharmacie (250562102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Spatially restricted hyaluronan production by Has2 drives epithelial tubulogenesis in vitro

Generation of branched tubes from an epithelial bud is a fundamental process in development. We hypothesized that induction of hyaluronan synthase (Has) and production of hyaluronan (HA) drives tubulogenesis in response to morphogenetic cytokines. Treatment of J3B1A mammary cells with transforming growth factor-β1 or renal MDCK and mCCD-N21 cells with hepatocyte growth factor induced strong and specific expression of Has2. Immunostaining revealed that HA was preferentially produced at the tips of growing tubules. Inhibition of HA production, either by 4-methylumbelliferone (4-MU) or by Has2 mRNA silencing, abrogated tubule formation. HA production by J3B1A and mCCD-N21 cells was associated with sustained activation of ERK and S6 phosphorylation. However, silencing of either CD44 or RHAMM (receptor for HA-mediated motility), the major HA receptors, by RNA interference, did not alter tubulogenesis, suggesting that this process is not receptor-mediated