La création d’une nouvelle génération d’études épidémiologiques en santé mentale

Grâce à une subvention des Instituts de recherche en santé du Canada (IRSC), il se développe actuellement une nouvelle génération d’études en épidémiologie sociale et psychiatrique dans une zone circonscrite se situant dans le sud-ouest de Montréal où vivent 258 000 personnes. Ce programme de recherche repose sur une étude prospective longitudinale visant à identifier les déterminants de la santé mentale de la population, et sur quatre études spécifiques qui abordent des paramètres importants pour la santé mentale : l’écologie sociale et physique des quartiers, le soutien social, le stigma social et les services en santé mentale. Ce programme est complété par l’utilisation de la dernière génération des outils technologiques et informatiques soit un système d’information géographique (SIG) qui permet d’apprécier les effets du contexte sur la santé mentale. Les bases théoriques sur lesquels repose ce modèle sont présentées de même qu’une description sommaire des méthodes utilisées.The authors were granted funding from the Canadian Institute of Health Research (CIHR) to develop a new generation of epidemiological studies in the field of social and psychiatric epidemiology in a catchment area in Montréal, with a population of around 258 000. This research program will begin with a longitudinal study that will identify mental health determinants and will be followed by four specific studies on important aspects of mental health : service organization, social stigma, and neighbourhood ecology and social support actualization. A Geographic information System based on postal codes will also be used as a mean to evaluate the effects of social and physical environment on mental health and its interactions with individual determinants of mental health. This article describes the research program, its theoretical bases and more briefly, its methodology.Gracias a una subvención de los Institutos de Investigación en Salud de Canadá (IRSC), actualmente se está desarrollando una nueva generación de estudios en epidemiología social y psiquiátrica en una zona circunscrita localizada en el sudoeste de Montreal, donde viven 258,000 personas. Este programa de investigación se apoya en un estudio prospectivo longitudinal, que busca identificar las determinantes de la salud mental de la población, y en cuatro estudios específicos que abordan los parámetros importantes para la salud mental: la ecología social y física de los barrios, el apoyo social, el estigma social y los servicios de salud mental. Este programa se completa con la utilización de la última generación de herramientas tecnológicas e informáticas, es decir, un sistema de información geográfico (SIG) que permite apreciar los efectos del contexto en la salud mental. Se presentan las bases teóricas en las que se apoya este modelo así como una descripción somera de los métodos utilizados.Graças a uma subvenção dos Institutos de Pesquisa em Saúde do Canadá (IRSC), é desenvolvida atualmente uma nova geração de estudos em epidemiologia social e psiquiátrica em uma zona circunscrita situando-se no sudoeste de Montreal, onde vivem 258 mil pessoas. Este programa de pesquisa baseia-se em um estudo prospectivo longitudinal visando identificar os determinantes da saúde mental da população, e sobre quatro estudos específicos que abordam parâmetros importantes para a saúde mental: a ecologia social e física dos bairros, o apoio social, o estigma social e os serviços em saúde mental. Este programa é realizado com a utilização da última geração de ferramentas tecnológicas e informáticas, ou seja, um sistema de informação geográfica (SIG) que permite apreciar os efeitos do contexto na saúde mental. As bases teóricas sobre as quais repousa este modelo são apresentadas, além de uma descrição sumária dos métodos utilizados

Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome inhibitors and apoptosis inducers in human breast cancer cells

INTRODUCTION: A physiological feature of many tumor tissues and cells is the tendency to accumulate high concentrations of copper. While the precise role of copper in tumors is cryptic, copper, but not other trace metals, is required for angiogenesis. We have recently reported that organic copper-containing compounds, including 8-hydroxyquinoline-copper(II) and 5,7-dichloro-8-hydroxyquinoline-copper(II), comprise a novel class of proteasome inhibitors and tumor cell apoptosis inducers. In the current study, we investigate whether clioquinol (CQ), an analog of 8-hydroxyquinoline and an Alzheimer's disease drug, and pyrrolidine dithiocarbamate (PDTC), a known copper-binding compound and antioxidant, can interact with copper to form cancer-specific proteasome inhibitors and apoptosis inducers in human breast cancer cells. Tetrathiomolybdate (TM), a strong copper chelator currently being tested in clinical trials, is used as a comparison. METHODS: Breast cell lines, normal, immortalized MCF-10A, premalignant MCF10AT1K.cl2, and malignant MCF10DCIS.com and MDA-MB-231, were treated with CQ or PDTC with or without prior interaction with copper, followed by measurement of proteasome inhibition and cell death. Inhibition of the proteasome was determined by levels of the proteasomal chymotrypsin-like activity and ubiquitinated proteins in protein extracts of the treated cells. Apoptotic cell death was measured by morphological changes, Hoechst staining, and poly(ADP-ribose) polymerase cleavage. RESULTS: When in complex with copper, both CQ and PDTC, but not TM, can inhibit the proteasome chymotrypsin-like activity, block proliferation, and induce apoptotic cell death preferentially in breast cancer cells, less in premalignant breast cells, but are non-toxic to normal/non-transformed breast cells at the concentrations tested. In contrast, CQ, PDTC, TM or copper alone had no effects on any of the cells. Breast premalignant or cancer cells that contain copper at concentrations similar to those found in patients, when treated with just CQ or PDTC alone, but not TM, undergo proteasome inhibition and apoptosis. CONCLUSION: The feature of breast cancer cells and tissues to accumulate copper can be used as a targeting method for anticancer therapy through treatment with novel compounds such as CQ and PDTC that become active proteasome inhibitors and breast cancer cell killers in the presence of copper