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991.
Olivier Guillaud Jérôme Dumortier Rodolphe Sobesky Dominique Debray Philippe Wolf Claire Vanlemmens François Durand Yvon Calmus Christophe Duvoux Sébastien Dharancy Nassim Kamar Karim Boudjema Pierre Henri Bernard Georges-Philippe Pageaux Ephrem Salamé Jean Gugenheim Alain Lachaux Dalila Habes Sylvie Radenne Jean Hardwigsen Olivier Chazouillères Jean-Marc Trocello France Woimant Philippe Ichai Sophie Branchereau Olivier Soubrane Denis Castaing Emmanuel Jacquemin Didier Samuel Jean-Charles Duclos-Vallée 《Journal of hepatology》2014
992.
Mohamed Mokhtar Patrick M. Gosselin Lacasse François-Xavier Patrice Hildgen 《Pharmaceutical development and technology》2019,24(2):211-221
Our work aimed at evaluating the use of permeability glycoprotein (P-gp) inhibiting nanoparticles (NPs) as a part of a suitable oral solid dosage to improve bioavailability. Famotidine (Pepcid®), a stomach acid production inhibitor, was used as a drug model to test our hypothesis. Famotidine-loaded NPs were prepared by solvent emulsion evaporation using PEG grafted on a polylactide acid (PLA) polymer backbone (PLA-g-PEG), with a 5% molar ratio of PEG versus lactic acid monomer and PEG of either 750 or 2000?Da molecular weight. Tablet formulation was composed of 40% Famotidine-loaded NPs, 52.5% microcrystalline cellulose as filler, 7% pre-gelatinized starch as binder/disintegrant, and 0.5% magnesium stearate as lubricant. Tablets containing 1.6?mg of Famotidine were prepared at an average weight of 500?mg, thickness of 6.2–6.5?mm, hardness of 5–8?kp, and disintegration time of <1?min. Our results suggest that Famotidine-loaded NPs using grafted PEG-g-PLA polymers can be formulated as an oral solid dosage form while effectively inhibiting P-gp mediated Famotidine efflux, irrespective of PEG molecular weights. This could therefore represent an attractive formulation alternative to enhance oral permeability and bioavailability of drugs that are P-gp substrates. 相似文献
993.
Lemieux Léandre Gagné Simoneau Martin Tessier Jean-François Billot Maxime Blouin Jean Teasdale Normand 《Age (Dordrecht, Netherlands)》2014,36(2):823-837
GeroScience - When tracing a template with mirror-reversed vision (or distorted vision), the sensory information arising from the movement does not match the expected sensory consequences. In such... 相似文献
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Stéphanie Dulucq Cyril Astrugue Gabriel Etienne François-Xavier Mahon Antoine Benard 《British journal of haematology》2020,189(3):452-468
More than 10 years ago, the first pilot observational study of imatinib discontinuation was reported in chronic myeloid leukaemia (CML) patients in deep molecular response (DMR). Several studies have been published since then, in patients treated with frontline imatinib, or second-generation tyrosine kinase inhibitors (TKI) in first or second line but also on second attempt of TKI discontinuation. Our objective was to estimate, through meta-analyses of the literature data, the probability of molecular recurrence (MolRec) in the time periods of 0–6, 6–12, 12–18 and 18–24 months after a first and second TKI discontinuation and the probability of re-acquisition of DMR after MolRec. The Medline and Scopus databases were searched up to April 2019. The studies were selected by three independent reviewers. Random-effect meta-analyses were conducted using the MetaXL software. The probability of MolRec in the time periods 0–6, 6–12, 12–18 and 18–24 months after the first attempt was respectively 35%, 8%, 3% and 3%, whereas the probability of MolRec in the time periods 0-6, 6-12 and 12-18 after the second attempt was 48%, 27% and 12% respectively. Re-acquisition of a DMR was observed in 90% of patients. Most of the MolRec occur during the first six months in case of a first attempt, whereas the second MolRec occurs over a larger window of time. 相似文献
997.
Fran?ois Quemeneur Jon K. Sigurdsson Marianne Renner Paul J. Atzberger Patricia Bassereau David Lacoste 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(14):5083-5087
The lateral mobility of proteins within cell membranes is usually thought to be dependent on their size and modulated by local heterogeneities of the membrane. Experiments using single-particle tracking on reconstituted membranes demonstrate that protein diffusion is significantly influenced by the interplay of membrane curvature, membrane tension, and protein shape. We find that the curvature-coupled voltage-gated potassium channel (KvAP) undergoes a significant increase in protein mobility under tension, whereas the mobility of the curvature-neutral water channel aquaporin 0 (AQP0) is insensitive to it. Such observations are well explained in terms of an effective friction coefficient of the protein induced by the local membrane deformation.Brownian motion plays an essential role in biological processes. Since the pioneering experiments of Perrin (1), the observation of diffusing objects has emerged as a mean to extract the rheological properties of the surrounding medium or the probe particle size. The theoretical investigation of diffusion of proteins within membranes has been studied widely going back to P. G. Saffman and M. Delbrück (SD). They investigated the hydrodynamic drag acting on a membrane inclusion when the membrane is described as a 2D fluid sheet of viscosity embedded within a less viscous fluid of viscosity η (2). In this theory, the diffusion coefficient D0 in the limit of a large viscosity contrast between the membrane and bulk fluid is given by:The length is the length scale over which flow is generated within the bilayer by the inclusion, kBT is the thermal energy, and γ is Euler’s constant. This model predicts a logarithmic dependence of D0 on the protein radius ap, which has been confirmed for some in vitro experiments on membranes containing transmembrane proteins (see ref. 3 and references therein). In contrast, the experiments of Gambin et al. (4) showed significant deviations from the SD theory.A possible origin for the discrepancy observed by Gambin et al. (4) is the significant local membrane deformation due to the interaction between the inclusion and the lipid bilayer (5). Naji et al. suggested in ref. 6 that inclusions experience additional dissipation, either due to internal flows within the membrane or to additional fluid flows produced by the deformed membrane. This work triggered a number of theoretical studies investigating the coupling of inclusion proteins with the membrane that had been pioneered by the Seifert’s group (see ref. 7 and references therein). Such studies have systematically gone beyond the SD model by including additional effects (8–12). So far, a thorough verification of these ideas has not been attempted. To investigate the effect of the protein–lipid coupling on the protein mobility, we study its dependence on membrane tension, because this parameter affects the local membrane deformation.In this work, we compare the mobility of two transmembrane proteins with the same lateral size, aquaporin 0 (AQP0) and a voltage-gated potassium channel (KvAP), reconstituted in giant unilamellar vesicles (GUVs). Whereas AQP0 does not deform locally the bilayer, KvAP locally bends the membrane (13). Using single-particle tracking (SPT), we demonstrate that the curvature-coupled protein KvAP undergoes a significant increase in mobility under tension, whereas the mobility of the curvature-neutral water channel AQP0 is insensitive to it. This difference, which goes beyond the SD model, is explained by an approach that includes the interplay between membrane deformation and friction with the surrounding medium and within the bilayer. This is compelling evidence that the Brownian motion of a shaping-membrane protein is not simply dependent on the inclusion size but also related to the lateral extension of the deformed membrane patch, which depends on tension. 相似文献
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Banar Nikolay Bertels Jeroen Laurent François Boedi Rizky Merdietio De Tobel Jannick Thevissen Patrick Vandermeulen Dirk 《International journal of legal medicine》2020,134(5):1831-1841
International Journal of Legal Medicine - Staging third molar development is commonly used for age assessment in sub-adults. Current staging techniques are, at most, semi-automated and rely on... 相似文献