Science pathologique

Résumé

vignette|redresse|Irving Langmuir (avant 1923). Une science pathologique est un domaine de recherche où et où les . Le terme a été pour la première fois utilisé par Irving Langmuir, chimiste récipiendaire du prix Nobel, durant un colloque en 1953 au . Langmuir a déclaré qu'une science pathologique ne disparaîtrait pas après avoir été abandonnée car jugée fausse par la majorité des scientifiques d'un domaine. Il les qualifia de . Bart Simon liste un certain nombre d'approches dont fait partie la science pathologique : . Sources Références Bibliographie * * * * Liens externes * Catégorie:Pseudo-science

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https://fr.wikipedia.org/wiki/Science_pathologique

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Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery

Harm-Anton Klok

In the past decades, polymeric nanoparticles have emerged as a most promising and viable technology platform for targeted and controlled drug delivery. As vehicles, ideal nanoparticles are obliged to possess high drug loading levels, deliver drug to the specific pathological site and/or target cells without drug leakage on the way, while rapidly unload drug at the site of action. To this end, various "intelligent" polymeric nanoparticles that release drugs in response to an internal or external stimulus such as pH, redox, temperature, magnetic and light have been actively pursued. These stimuli-responsive nanoparticles have demonstrated, though to varying degrees, improved in vitro and/or in vivo drug release profiles. In an effort to further improve drug release performances, novel dual and multi-stimuli responsive polymeric nanoparticles that respond to a combination of two or more signals such as pH/temperature, pH/redox, pH/magnetic field, temperature/reduction, double pH, pH and diols, temperature/magnetic field, temperature/enzyme, temperature/pH/redox, temperature/pH/magnetic, pH/redox/magnetic, temperature/redox/guest molecules, and temperature/pH/guest molecules have recently been developed. Notably, these combined responses take place either simultaneously at the pathological site or in a sequential manner from nanopartide preparation, nanopartide transporting pathways, to cellular compartments. These dual and multi-stimuli responsive polymeric nanoparticles have shown unprecedented control over drug delivery and release leading to superior in vitro and/or in vivo anti-cancer efficacy. With programmed site-specific drug delivery feature, dual and multi-stimuli responsive nanoparticulate drug formulations have tremendous potential for targeted cancer therapy. In this review paper, we highlight the recent exciting developments in dual and multi-stimuli responsive polymeric nanoparticles for precision drug delivery applications, with a particular focus on their design, drug release performance, and therapeutic benefits. (C) 2013 Elsevier Ltd. All rights reserved.

Elsevier Sci Ltd2013

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Monomeric Huntingtin Exon 1 Has Similar Overall Structural Features for Wild-Type and Pathological Polyglutamine Lengths

Hilal Lashuel, John Blaine Warner IV

Huntington’s disease is caused by expansion of a polyglutamine (polyQ) domain within exon 1 of the huntingtin gene (Httex1). A popular hypothesis is that the Httex1 protein undergoes sharp conformational changes as the polyQ length exceeds a threshold of 36 residues. We test this hypothesis by combining novel semi-synthesis strategies with state-of-the-art single molecule Förster resonance energy transfer measurements on biologically relevant Httex1 proteins of five different polyQ lengths. Our results, integrated with atomistic simulations, negate the hypothesis of a sharp, polyQ length-dependent change in the structure of monomeric Httex1. Instead, they support a continuous global compaction with increasing polyQ length and this derives from increased prominence of the globular polyQ domain. More specifically, we show that that monomeric Httex1 adopts tadpole-like architectures for polyQ lengths above and beyond the pathological threshold. Additionally, our results suggest that higher order homo- and / or heterotypic interactions within distinct sub-populations of neurons are likely to be the main source of sharp polyQ length-dependencies of HD. These findings pave the way for uncovering the true structural basis of Httex1-mediated neurotoxicity.

2017

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To properly describe the electrical activity of the left ventricle, it is necessary to model the Purkinje fibers, responsible for the fast and coordinate ventricular activation, and their interaction with the muscular propagation. The aim of this work is to propose a methodology for the generation of a patient-specific Purkinje network driven by clinical measurements of the activation times related to pathological propagations. In this case, one needs to consider a strongly coupled problem between the network and the muscle, where the feedback from the latter to the former cannot be neglected as in a normal propagation. We apply the proposed strategy to data acquired on three subjects, one of them suffering from muscular conduction problems owing to a scar and the other two with a muscular pre-excitation syndrome (Wolff–Parkinson–White). To assess the accuracy of the proposed method, we compare the results obtained by using the patient-specific Purkinje network generated by our strategy with the ones obtained by using a non-patient-specific network. The results show that the mean absolute errors in the activation time is reduced for all the cases, highlighting the importance of including a patient-specific Purkinje network in computational models. Copyright © 2014 John Wiley & Sons, Ltd.

2014

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Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery

Harm-Anton Klok

Elsevier Sci Ltd2013