HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Retour au travail après maladies chroniques, l’exemple de la lombalgie chronique: Apport de l’ergonomie dans les représentations partagées entre médecins et préventeurs dans le processus de retour au travail après maladies chroniques
No full textLa lombalgie chronique est une affection dont les causes sont multifactorielles. Les éléments anatomiques ne suffisent pas à expliquer l’intensité de la douleur ou le handicap qui en découle. En plus des éléments biomécaniques, les aspects psychosociaux et socioprofessionnels de la situation doivent être pris en compte. La prise en charge des lombalgiques chroniques est complexe et ne peut être que pluridisciplinaire. Il existe un manque de données sur les divergences des représentations du travail que construisent les différents acteurs médico-sociaux impliqués dans le maintien en emploi des patients : d’où l’importance de l’amélioration et de la coordination des pratiques. L’objectif principal du projet PARTAG de recherche est d’améliorer la vision partagée des lombalgies chroniques entre les acteurs, d’horizons variés, impliqués dans le processus de retour au travail, pour favoriser leur collaboration
Étude de l’asthme chez les personnels hospitaliers et de ménage: Rôle des expositions professionnelles ou domestiques aux produits de nettoyage et de désinfection dans l’asthme
No full textL’asthme professionnel représente 5 à 10 % des asthmes en France. Il est défini comme « un asthme déclenché ou aggravé par une substance inhalée sur les lieux du travail ». Plus de 400 substances ont été identifiées comme pouvant intervenir dans l’asthme professionnel, parmi lesquelles : l’ammoniac, l’eau de javel, le formaldéhyde, etc. Parmi les métiers exposés figurent ceux liés au nettoyage, notamment en milieu hospitalier, milieu dans lequel l’exposition professionnelle aux désinfectants ou aux produits de nettoyage est d’autant plus élevée que ces substances permettent de prévenir la survenue d’infections nosocomiales. Si les données montrent une augmentation progressive des nouveaux cas d’asthme professionnel, le rôle des produits chimiques dans le déclenchement de l’asthme n’est pas encore très clair. Le projet de recherche « NETA » (2009-2013) traite de l’exposition aux produits de nettoyage et aux désinfectants en milieu hospitalier et de son lien avec l’asthme
Fibrose hépatique : lien force mécanique et génotoxicité: Bioactivation des contaminants de l’environnement au cours de la fibrose hépatique : lien force mécanique et génotoxicité
No full textNational audienceEn 2012, en France, il y a eu 6.867 nouveaux cas de cancer du foie chez l’homme et 1.586 chez la femme. On soupçonne que les maladies du foie sont associées à un dysfonctionnement sévère des fonctions hépatiques et susceptibles d’entraîner une sensibilité accrue des patients vis-à-vis des contaminants environnementaux. Comment évaluer cette susceptibilité individuelle au cours de maladies chroniques, qui se prolongent dans le temps ? L’objectif du projet Mécagénotox est de caractériser et modéliser la capacité du foie humain à bioactiver (transformer en espèces plus toxiques) les contaminants environnementaux dans ces situations particulièrement sensibles de fibrose
Structural and Functional Profiling of Environmental Ligands for Estrogen Receptors.: Profiling of estrogen receptors environmental ligands
No full textInternational audienceBackground: Individuals are exposed daily to environmental pollutants which may act as endocrine-disrupting chemicals (EDCs) causing a range of developmental, reproductive, metabolic or neoplastic diseases. With their mostly hydrophobic pocket that serves as a docking site for endogenous and exogenous ligands, nuclear receptors (NRs) can be primary targets of small molecule environmental contaminants. However, most of these compounds are chemically unrelated to natural hormones so their binding modes and associated hormonal activities are hardly predictable.Objectives: We conducted a correlative analysis of structural and functional data to gain insight into the mechanisms by which twelve members of representative families of pollutants bind to and activate the estrogen receptors ERα and ERβ. Methods: We have used a battery of biochemical, structural, biophysical and cell-based approaches to characterize the interaction between ERs and their environmental ligands. Results: Our study reveals that the chemically diverse compounds bind to ERs via varied sets of protein ligand interactions reflecting their differential activities, binding affinities and specificities. We show that xenoestrogens bind to both ERs with affinities ranging from sub nanomolar to micromolar values and act in a subtype-dependent fashion as full agonists or partial agonists/antagonists by using different combinations of the activation functions 1 and 2 of ERα and ERβ. Conclusions: The precise characterization of the interactions between major environmental pollutants and two of their primary biological targets provides rational guidelines for the design of safer chemicals and will increase the accuracy and usefulness of structure-based computational methods, allowing for activity prediction of chemicals in risk assessment
Chemical, microbiological, and spatial characteristics and impacts of contaminants from urban catchments: CABRRES project
No full textInternational audienc
Large-Scale Metagenomic-Based Study of Antibiotic Resistance in the Environment
No full textInternational audienceAntibiotic resistance, including multiresistance acquisition and dissemination by pathogens, is a critical healthcare issue threatening our management of infectious diseases [ 1-3 ]. Rapid accumulation of resistance phenotypes implies a reservoir of transferable antibiotic resistance gene determinants (ARGDs) selected in response to inhibition of antibiotic concentrations, as found in hospitals [ 1, 3-5 ]. Antibiotic resistance genes were found in environmental isolates, soil DNA [ 4-6 ], secluded caves [ 6, 7 ], and permafrost DNA [ 7, 8 ]. Antibiotics target essential and ubiquitous cell functions, and resistance is a common characteristic of environmental bacteria [ 8-11 ]. Environmental ARGDs are an abundant reservoir of potentially transferable resistance for pathogens [ 9-12 ]. Using metagenomic sequences, we show that ARGDs can be detected in all (n = 71) environments analyzed. Soil metagenomes had the most diverse pool of ARGDs. The most common types of resistances found in environmental metagenomes were efflux pumps and genes conferring resistance to vancomycin, tetracycline, or β-lactam antibiotics used in veterinary and human healthcare. Our study describes the diverse and abundant antibiotic resistance genes in nonclinical environments and shows that these genes are not randomly distributed among different environments (e.g., soil, oceans or human feces)
Epidemiological study of prostate cancer (EPICAP): a population-based case-control study in France.
No full textInternational audienceBACKGROUND: Prostate cancer is the most common cancer in male in most Western countries, including France. Despite a significant morbidity and mortality to a lesser extent, the etiology of prostate cancer remains largely unknown. Indeed, the only well-established risk factors to date are age, ethnicity and a family history of prostate cancer. We present, here, the rationale and design of the EPIdemiological study of Prostate CAncer (EPICAP), a population-based case-control study specifically designed to investigate the role of environmental and genetic factors in prostate cancer. The EPICAP study will particularly focused on the role of circadian disruption, chronic inflammation, hormonal and metabolic factors in the occurrence of prostate cancer. METHODS/DESIGN: EPICAP is a population-based case-control study conducted in the département of Hérault in France. Eligible cases are all cases of prostate cancers newly diagnosed in 2012-2013 in men less than 75 years old and residing in the département of Hérault at the time of diagnosis. Controls are men of the same age as the cases and living in the département of Hérault, recruited in the general population.The sample will include a total of 1000 incident cases of prostate cancer and 1000 population-based controls over a 3-year period (2012-2014).The cases and controls are face-to-face interviewed using a standardized computed assisted questionnaire. The questions focus primarily on usual socio-demographic characteristics, personal and family medical history, lifestyle, leisure activities, residential and occupational history. Anthropometric measures and biological samples are also collected for cases and controls. DISCUSSION: The EPICAP study aims to answer key questions in prostate cancer etiology: (1) role of circadian disruption through the study of working hours, chronotype and duration/quality of sleep, (2) role of chronic inflammation and anti-inflammatory drugs, (3) role of hormonal and metabolic factors through a detailed questionnaire, (4) role of individual genetic susceptibility of genes involved in biological pathways of interest. The EPICAP study will also allow us to study prognostic factors and tumor aggressiveness.Taken together, the EPICAP study will provide a comprehensive framework to go further in the understanding of prostate cancer occurrence and its prognosis
Metabolic detoxification pathways for 5-methoxy-sterigmatocystin in primary tracheal epithelial cells
No full textInternational audience1. The health effects of inhaled mycotoxins remain poorly documented despite their presence in bioaerosols. 5-methoxy-sterigmatocystin is produced in association with sterigmatocystin by some Aspergillus spp., sometimes in larger amounts than sterigmatocystin. Whereas sterigmatocystin can be metabolized through cytochromes P450 (CYP), UDP-glucuronosyltransferases and sulfotransferases in airway epithelial cells, little is known about 5-methoxysterigmatocystin. 2. The 5-methoxy-sterigmatocystin metabolites were analyzed using human recombinant CYP and porcine tracheal epithelial cell (PTEC) primary cultures at an air-liquid interface. The induction of xenobiotic-metabolizing enzymes was examined by real-time quantitative PCR for mRNA expression and 7-ethoxyresorufin O-deethylation activity. 3. CYP1A1 metabolized 5-methoxy-sterigmatocystin into hydroxy-nor-methoxy-sterigmatocystin, nor-methoxy-sterigmatocystin and dihydroxy-methoxy-sterigmatocystin. CYP1A2 led to monohydroxy-methoxy-sterigmatocystin. In PTEC, 5-methoxy-sterigmatocystin metabolism resulted into a glucuroconjugate of 5-methoxy-sterigmatocystin, a sulfoconjugate and a glucuroconjugate of monohydroxy-methoxy-sterigmatocystin. The exposure of PTEC for 24 h to 1 mu M 5-methoxy-sterigmatocystin induced a significant increase in the mRNA levels of CYP1A1, without significant induction of the 7-ethoxyresorufin O-deethylation activity. 4. These data suggest that 5-methoxy-sterigmatocystin is mainly detoxified in airway cells through conjugation, as sterigmatocystin. However, while CYP produced a reactive metabolite of sterigmatocystin, no such metabolite was detected with 5-methoxysterigmatocystin. Nevertheless, 5-methoxy-sterigmatocystin increases the CYP1A1 mRNA levels. The long-term consequences remain unknown
Considerations for test design to accommodate energy-budget models in ecotoxicology: a case study for acetone in the pond snail[i] Lymnaea stagnalis[/i]
No full textToxicokinetic-toxicodynamic (TKTD) modeling offers many advantages in the analysis of ecotoxicity test data. Calibration of TKTD models, however, places different demands on test design compared with classical concentration-response approaches. In the present study, useful complementary information is provided regarding test design for TKTD modeling. A case study is presented for the pond snail Lymnaea stagnalis exposed to the narcotic compound acetone, in which the data on all endpoints were analyzed together using a relatively simple TKTD model called DEBkiss. Furthermore, the influence of the data used for calibration on accuracy and precision of model parameters is discussed. The DEBkiss model described toxic effects on survival, growth, and reproduction over time well, within a single integrated analysis. Regarding the parameter estimates (e. g., no-effect concentration), precision rather than accuracy was affected depending on which data set was used for model calibration. In addition, the present study shows that the intrinsic sensitivity of snails to acetone stays the same across different life stages, including the embryonic stage. In fact, the data on egg development allowed for selection of a unique metabolic mode of action for the toxicant. Practical and theoretical considerations for test design to accommodate TKTD modeling are discussed in the hope that this information will aid other researchers to make the best possible use of their test animals
Radiation-mediated formation of complex damage to DNA: a chemical aspect overview
No full textInternational audienceDuring the last three decades, a considerable amount of work has been undertaken to determine the nature, the mechanism of formation and the biological consequences of radiation-induced DNA lesions. Most of the information was obtained via the development of chemical approaches, including theoretical, analytical and organic synthesis methods. Since it is not possible to present all the results obtained in this review article, we will focus on recent data dealing with the formation of complex DNA lesions produced by a single oxidation event, as these lesions may play a significant role in cellular responses to ionizing radiation and also to other sources of oxidative stress. Through the description of specific results, the contribution of different chemical disciplines in the assessment of the structure, the identification of the mechanism of formation and the biological impacts in terms of repair and mutagenicity of these complex radiationinduced DNA lesions will be highlighted