L'utilisation de la dompéridone comme substrat marqueur de l'activité in vitro des CYP3A4 et CYP3A5

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Études in vitro et in vivo évaluant le rôle du métabolisme des médicaments par les CYP450s comme facteurs de variabilité interindividuelle dans la réponse aux médicaments

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Energy dissipation in concentrated monodisperse colloidal suspensions of silica particles in polyethylene glycol

Highly concentrated colloidal suspensions exhibit a discontinuous shear-thickening behaviour. The transition from a low to a high viscosity state is associated to a large energy dissipation. This effect could find applications in structural damping while the viscosity increase brings added stiffness. In the present work, highly concentrated suspensions of monodisperse spherical silica particles in polyethylene glycol were selected for their strong thickening at low critical shear rates. Their damping properties were characterized by measuring the energy dissipated per cycle at low frequency (below 2 Hz) during oscillatory tests using a rheometer. The influence of parameters such as particle concentration, size and frequency was investigated. Damping was found to overcome that of benchmark elastomeric materials only in high frequencies and high strain domains

Pre- and post-transition behavior of shear-thickening fluids in oscillating shear

The dynamic shear-thickening behavior of concentrated colloidal suspensions of fumed silica in polypropylene glycol has been investigated. Dynamic frequency sweeps showed that, for any given solids concentration, the complex viscosity at different imposed strain amplitudes followed a unique power-law-type behavior up to the onset of strain thickening. Moreover, similar behavior was also observed in the post-transition state, i.e., the viscosities again superimposed at frequencies beyond the transition frequency. In an attempt to develop a parametric description of this behavior, both the Delaware-Rutgers rule and the concept of a critical shear stress for the onset of shear thickening in steady-state experiments were considered. However, neither approach could account for the observed trends over the entire range of strains and frequency investigated. Plots of the critical shear strains for the onset and the end-point of the transition as a function of frequency were, therefore, used to describe the state of the suspensions for an arbitrary combination of strain and frequency. Finally, Fourier transform (FT) rheology was used to evaluate the extent of non-linearity in the response of the suspensions to dynamic shear, and it was shown that the observed behavior was not significantly influenced by wall slip at the tool-specimen interfac

Assessing drug distribution in tissues expressing P-glycoprotein through physiologically based pharmacokinetic modeling: model structure and parameters determination

<p>Abstract</p> <p>Background</p> <p>The expression and activity of P-glycoproteins due to genetic or environmental factors may have a significant impact on drug disposition, drug effectiveness or drug toxicity. Hence, characterization of drug disposition over a wide range of conditions of these membrane transporters activities is required to better characterize drug pharmacokinetics and pharmacodynamics. This work aims to improve our understanding of the impact of P-gp activity modulation on tissue distribution of P-gp substrate.</p> <p>Methods</p> <p>A PBPK model was developed in order to examine activity and expression of P-gp transporters in mouse brain and heart. Drug distribution in these tissues was first represented by a well-stirred (WS) model and then refined by a mechanistic transport-based (MTB) model that includes P-gp mediated transport of the drug. To estimate transport-related parameters, we developed an original three-step procedure that allowed extrapolation of <it>in vitro </it>measurements of drug permeability to the <it>in vivo </it>situation. The model simulations were compared to a limited set of data in order to assess the model ability to reproduce the important information of drug distributions in the considered tissues.</p> <p>Results</p> <p>This PBPK model brings insights into the mechanism of drug distribution in non eliminating tissues expressing P-gp. The MTB model accounts for the main transport mechanisms involved in drug distribution in heart and brain. It points out to the protective role of P-gp at the blood-brain barrier and represents thus a noticeable improvement over the WS model.</p> <p>Conclusion</p> <p>Being built prior to <it>in vivo </it>data, this approach brings an interesting alternative to fitting procedures, and could be adapted to different drugs and transporters.</p> <p>The physiological based model is novel and unique and brought effective information on drug transporters.</p

The effect of processing conditions on the morphology, thermomechanical, dielectric, and piezoelectric properties of P(VDF-TrFE)/BaTiO3 composites

In this study (0-3) P(VDF-TrFE)/BaTiO3 composites containing up to 60vol% of ceramic phase were prepared by solvent casting or compression molding. Their thermomechanical, dielectric, and piezoelectric properties were investigated, and discussed in the light of the properties of the basic components, the processing route and the resulting morphology. The crystalline structure of the P(VDF-TrFE) matrix was found to be highly dependent on the processing route, while the structure of BaTiO3 was not affected by any of the processing steps. The mechanical properties of the solvent cast materials showed a maximum at 30vol% BaTiO3, while they increased monotonically with BaTiO3 content for compression molded materials. This difference was attributed to a higher amount of porosity and inhomogeneities in the solvent cast composites. Permittivity as high as 120 and piezoelectric coefficient d 33 up to 32pC/N were obtained for compression molded composites, and the observed decrease in d 33 with aging time was attributed to the effect of mechanical stress release in the polymer matri

Individual and population dietary specialization decline in fin whales during a period of ecosystem shift

Abstract This study sought to estimate the effect of an anthropogenic and climate-driven change in prey availability on the degree of individual and population specialization of a large marine predator, the fin whale (Balaenoptera physalus). We examined skin biopsies from 99 fin whales sampled in the St. Lawrence Estuary (Canada) over a nine year period (1998–2006) during which environmental change was documented. We analyzed stable isotope ratios in skin and fatty acid signatures in blubber samples of whales, as well as in seven potential prey species, and diet was quantitatively assessed using Bayesian isotopic models. An abrupt change in fin whale dietary niche coincided with a decrease in biomass of their predominant prey, Arctic krill (Thysanoessa spp.). This dietary niche widening toward generalist diets occurred in nearly 60% of sampled individuals. The fin whale population, typically composed of specialists of either krill or lipid-rich pelagic fishes, shifted toward one composed either of krill specialists or true generalists feeding on various zooplankton and fish prey. This change likely reduced intraspecific competition. In the context of the current “Atlantification” of northern water masses, our findings emphasize the importance of considering individual-specific foraging tactics and not only population or group average responses when assessing population resilience or when implementing conservation measures

Magneto-mechanical actuation of ferromagnetic shape memory alloy/epoxy composites

Ferromagnetic shape memory alloys (MSMA) exhibit magnetic field- and stress-induced twinning when processed into single crystals, but are brittle and difficult to shape. Embedding slender single crystalline MSMA elements into a polymer matrix can thus provide composites with adjustable magnetic strain actuation behavior. Ni-Mn-Ga single crystalline rods were characterized for their magneto-mechanical behavior and embedded in two different types of epoxy matrices with different volumetric fractions. The magnetic actuation of the composites was measured and shown to depend on the Ni-Mn-Ga volumetric fraction and the matrix stiffness. This behavior was well predicted by finite element simulations of the composite using a simple material model for the strain of the MSMA as a function of the magnetic field and applied stresses. Guidelines for composite behavior prediction could thus be proposed. (C) 2015 Elsevier Ltd. All rights reserved

Gesundheit und Lebensstil 16- bis 20 Jaehriger in der Schweiz (2002) : SMASH 2002 : Swiss multicenter adolescent survey on health 2002

[Table des matières] Zusammenfassung. 1. Einleitung: Rahmen und Zielsetzungen der Studie. 2. Stichprobe und Methode. 3. Resultate. 3.1. Stichprobenbeschreibung. 3.2. Psychosoziales Umfeld und persönliche Beziehungen. 3.3. Allgemeine und Psychische Gesundheit. 3.4. Gesundheitsverhalten. 3.5. Sexualität. 3.6. Beabsichtigte und nicht Beabsichtigte Gewalt. 3.7. Behandlung und Nutzung der Gesundheitsdienste. 4. Illustrationsverzeichnisse. 5. Index. 6. Anhang: Fragebogen SMASH 2002