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763.More information
Le Québec de l'entre-deux-guerres connaît une importante croissance du capitalisme industriel. C'est l'approfondissement et l'accélération d'un développement déjà bien amorcé depuis le dernier tiers du XIXe siècle. Les rapports sociaux caractéristiques de cette phase du capitalisme se généralisent en conséquence : prolétarisation des classes populaires et urbanisation. Les médecins québécois de l'époque prennent conscience avec beaucoup d'inquiétude que les transformations de la structure sociale se déploient à leurs dépens. La classe ouvrière qui s'entasse dans les villes dépend de salaires rarement suffisants pour payer les honoraires d'un médecin ou les frais d'une hospitalisation. Pour le praticien, cela signifie le rétrécissement d'un marché qui autrefois avait fait de la médecine une profession prospère. La part de charité dans le travail médical s'accroît inversement. La médecine libérale, …
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764.More information
Keywords: praticien-chercheur, gestionnaire-chercheur, travail social, médecine, organisation communautaire
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767.More information
SummaryGlucocorticoids are implicated as a pathophysiological mediator of obesity and its accompanying metabolic and cardiovascular complications. Obese patients exhibit normal circulating cortisol levels, related to increased glucocorticoid production and degradation. However, it has been demonstrated that local production of active cortisol from inactive cortisone driven by 11β-hydroxysteroid dehydrogenase type 1 is exaggerated in adipose tissue of obese subjects. Such local hypercortisolism may be responsible for increased adipocyte differentiation and enhanced secretion of free fatty acids and other substances involved in the metabolic and cardiovascular complications observed in obesity.
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768.More information
SummaryChronic pain is frequently associated with profound alterations of neuronal systems involved in pain processing and should be considered as a real disease state of the nervous system. Unfortunately, some forms of chronic pain remain difficult to be satisfactorily treated. In the search for new therapeutic strategies, the gene-based approaches are of potential interest as they offer the possibility to introduce a therapeutic protein into some relevant structures and to drive its continuous production in the near vicinity of targeted cells. Recently, these techniques have been experimented in several animal models of chronic pain, showing that transfer at the spinal level of some genes, in particular those of opioid precursors proopiomelanocortin or proenkephalin A, leading to the overproduction of products that they encode, attenuated persistent pain of both inflammatory and neuropathic origin. Thus, in polyarthritic rat, a model of chronic inflammatory pain, we demonstrated that herpes simplex virus vector mediated overexpression of proenkephalin A in primary sensory neurons at the lumbar level elicited both antihyperalgesic and anti-inflammatory activities. Apart from opioids, numerous other molecules involved in pain processing are of potential therapeutic interest for gene-based protocols. For instance, targeting some molecules involved in pain induction and perpetuation, such as proinflammatory cytokines, raises an interesting possibility to block the «development» of pain. The clinical application of these approaches remains to be established, and, presently, one of the main problems to be solved is the innocuity of virus-derived vectors. However, the experimental use of gene-based techniques might be particularly useful for the evaluation of the therapeutic interest of some recently identified molecules involved in pain processing and might finally lead to the development of new “classical” pharmacological tools.
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770.More information
SummaryBiliary function is essential for intestinal absorption of fat, homeostasis of cholesterol and elimination of diverse metabolic end-products. Bile is elaborated in hepatocyte canaliculi and modified by cholangiocytes through both secretion and absorption processes. The main determinant of bile formation is an osmotic filtration process resulting from active transport of bile acids and other osmotic solutes. Most of the membrane transporters ensuring bile formation have now been identified. The expression of these membrane transporters is regulated in particular through transcriptional mechanisms under the control of nuclear receptors activated by ligands, such as bile acids, which act as endogenous steroids synthesized from cholesterol in hepatocytes. Monogenic cholestatic diseases illustrate the key role of membrane transporters in biliary function. Bile acids are potent modulators of transporters and thus trigger an adaptative response to cholestasis. The extent of this adaptative response could explain the compelling phenotypic variability of cholestatic diseases in childhood and adults. The firstline medical treatment is currently ursodeoxycholic acid. In case of failure of this medical treatment, liver transplantation is required. Recent progress in the molecular pathogenesis of bile formation and cholestatic liver diseases is expected to provide the design for drugs targeted to the molecular abnormalities responsible of cholestatic diseases.