Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Invasive aspergillosis is a major cause of mortality in allogeneic bone marrow transplant recipients and patients treated for blood malignancies. The diagnostic tools, treatments and preventive strategies, essentially developed for neutropaenic patients, have not been assessed in populations whose immune systems are considered to be competent. Beside the standard picture of chronic Aspergillus infection, the incidence of invasive aspergillosis is increasing in non neutropaenic patients, such as those with chronic lung diseases or systemic disease treated with long-term immunosuppressive drugs and solid organ transplant recipients. This study reviews the specific features of invasive aspergillosis in non neutropaenic subjects (NNS) and discusses the value of the diagnostic tools and treatment in this population. A better understanding of the pathophysiology and the epidemiological characteristics of invasive aspergillosis would provide a means of adapting the staging and classification of the disease for NNS. Invasive aspergillosis is under diagnosed in NNS who may already be colonised when they receive immunosuppressive treatment; this can lead to an adverse outcome in patients who are considered to be a moderate risk population.
ISSN: 0761-8425

hal-01118185
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118185
DOI : 10.1016/j.rmr.2010.01.004
PUBMED : 20965392

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND: The insecticide chlordecone was extensively used in the French West Indies to control banana root borer. Its persistence in soils has led to the widespread pollution of the environment, and human beings are still exposed to this chemical. Chlordecone has been shown to impair neurological and behavioural functions in rodents when exposed gestationally or neonatally. OBJECTIVES: The aim of the study was to evaluate the impact of prenatal and postnatal exposure to chlordecone on the cognitive, visual, and motor development of 7-month-old infants from Guadeloupe. METHODS: Infants were tested at 7 months (n=153). Visual recognition memory and processing speed were assessed with the Fagan Tests of Infant Intelligence (FTII), visual acuity with the Teller Acuity Card, and fine motor development with the Brunet-Lezine. Samples of cord blood and breast milk at 3 months (n=88) were analyzed for chlordecone concentrations. Postnatal exposure was determined through breast feeding and frequency of contaminated food consumption by the infants. RESULTS: Cord chlordecone concentrations in tertiles were associated with reduced novelty preference on the FTII in the highly exposed group (β=-0.19, p=0.02). Postnatal exposure through contaminated food consumption was marginally related to reduced novelty preference (β=-0.14, p=0.07), and longer processing speed (β=0.16, p=0.07). Detectable levels of chlordecone in cord blood were associated with higher risk of obtaining low scores on the fine motor development scale (OR=1.25, p<0.01). CONCLUSION: These results suggest that pre- and postnatal low chronic exposure to chlordecone is associated with negative effects on cognitive and motor development during infancy.
ISSN: 0013-9351

hal-00875939
https://hal.archives-ouvertes.fr/hal-00875939
DOI : 10.1016/j.envres.2012.07.006
PUBMED : 22910562

Éditeur(s) : HAL CCSD
Résumé : International audience
OBJECTIVES: Semen composition is influenced by HIV-1 infection, yet the impact of semen components on HIV infection of primary target cells has only been studied in samples from HIV-uninfected donors. DESIGN: We compared the effect of seminal plasma from chronically HIV-infected (SP+) versus uninfected donors (SP-) on HIV-1 infection of PBMCs and CD4+T cells. METHODS: Primary cells were infected with HIV-1 in the presence of SP+ or SP- and analyzed for infection level, metabolic activity, HIV receptor expression, proliferation and activation. SP+ and SP- were compared for infection-enhancing peptides, cytokines and prostaglandin E2 levels. RESULTS: SP- efficiently enhanced HIV-1 R5 infection of CD4+ T cells, whereas SP+ enhancing activity was significantly reduced. RANTES concentrations were elevated in SP+ relative to SP-, while the concentrations of infectivity-enhancing peptides (SEVI, SEM1, SEM2) were similar. CCR5 membrane expression levels were reduced on CD4+T cells shortly post-exposure to SP+ compared with SP- and correlated to R5-tropic HIV-1 infection levels, and CCR5 ligands' concentrations in semen. SP+ and SP- displayed similar enhancing activity on PBMC infection by X4-tropic HIV-1. Addition/depletion of RANTES from seminal plasmas modulated their effect on PBMC infection by R5-tropic HIV-1. CONCLUSIONS: Semen from HIV-infected donors exhibit a significantly reduced enhancing potential on CD4+ T cell infection by R5-tropic HIV-1 when compared with semen from uninfected donors. Our data indicate that elevated seminal concentrations of RANTES in HIV+ men can influence the ability of semen to enhance infection.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0
AIDS

hal-01274885
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01274885
DOI : 10.1097/QAD.0000000000001048
PUBMED : 26854806

Éditeur(s) : HAL CCSD
Résumé : National audience
Endometriosis is a common gynecological estrogen-dependent disorder, affecting more than 10 % of women in reproductive age. This disease results in chronic pelvic pain and infertility and is characterized by the presence of functional endometrial tissue outside of uterine cavity. To date, the diagnosis of endometriosis takes many years because of the lack of non-invasive diagnostic tools. Interestingly, "Omics" technologies demonstrated their relevance for the search, identification and characterization of potential disease biomarkers with significant achievements in many areas in the field of human health. Use a panel of Omics approaches seems to be a good way to improve our knowledge about endometriosis. Despite several studies on the subject, the potential biomarkers obtained are still not used in the clinical practice, as it calls for large-scale validation. Combined approaches based on strong interdisciplinary collaborations should improve our knowledge of endometriosis, and allow the identification of specific predictive markers, thus leading to the development of therapeutic solutions for a non-invasive and early diagnosis of this debilitating disease. Copyright © 2017 John Libbey Eurotext.
Medecine Therapeutique Medecine de la Reproduction, Gynecologie et Endocrinologie

hal-01467551
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467551
DOI : 10.1684/mte.2016.0632

Éditeur(s) : EURAQUA 1992
Résumé : Aquaculture is an important part of the Common Fisheries Policy. Indeed, the Community incentives policy for the farming of sea or fresh water fish, shellfish and molluscs must contribute to supplying the Common Market with fisheries products and to reducing the chronic negative trade balance in this area. The collection of statistics on the economic and social aspects of Aquaculture in the European Community is not a straightforward process. [NOT CONTROLLED OCR]

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/1992/acte-4280.pdf
http://archimer.ifremer.fr/doc/00000/4280/

Éditeur(s) : HAL CCSD Paris, Masson et Cie
Résumé : National audience
Decreased frequency of pulmonary exacerbations, mainly related to immunomodulatory effects of macrolide antibiotics, has been demonstrated in bronchiectasis and chronic obstructive pulmonary diseases (COPD). Due to its tolerance, azithromycin is the antibiotic of choice for maintenance therapy at the dose of 250 mg per day or 500 mg × 3 per week (for body weight >55 kg). Maintenance therapy with macrolide could be proposed in selected patients with bronchiectasis or COPD with more than 3 acute exacerbations in the previous year or decreased lung function despite compliance with optimum treatment. The risk of sudden cardiac death with azithromycin is rare and controversial. It should be avoided in patients with a high baseline risk of cardiovascular disease, QT>450 msec, pulse rate>100 bpm and potential drug interactions, particularly those known to cause QT prolongation. It is recommended to search for hearing deficit (audiometry) and sputum culture positive for mycobacteria. Patients must also be aware that it can rapidly lead to macrolide resistance in commensal or pathogenic flora. Follow-up evaluation every 3 month can be proposed with medical history (hearing deficit) and electrocardiography. After one year, the treatment should be stopped in the absence of reduction in the frequency of exacerbations.
Points essentielsLes macrolides administrés au long cours permettent, grâce en partie à leurs propriétés anti-inflammatoires, de diminuer la fréquence des exacerbations dans la DDB et la BPCO.Du fait de sa tolérance, l’azithromycine est le macrolide de choix, pouvant être utilisé à la dose de 250 mg/j ou 500 mg 3 fois par semaine chez les patients de plus de 55 kg.Un traitement par macrolides au long cours pourrait être proposé à des patients atteints de DDB ou de BPCO ayant eu plus de 3 exacerbations l’année précédente ou ayant une dégradation de leur fonction respiratoire malgré un traitement de fond bien conduit.Du fait d’un risque rare et controversé de mort subite d’origine cardiaque, il ne doit pas être proposé en cas de pathologie cardiovasculaire évoluée, d’intervalle QT > 450 ms, de traitement pouvant allonger l’intervalle QT, de tachycardie > 100/min.Il est recommandé de s’assurer de l’absence de troubles auditifs (audiogramme) et de mycobactérie atypique dans les cultures des expectorations. Les patients doivent aussi être informés du risque d’apparition de résistance aux macrolides de la flore commensale et pathogène.Une surveillance clinique, avec en particulier la recherche de troubles auditifs et électrocardiographique, peut être proposée tous les 3 mois. L’absence de diminution de la fréquence des exacerbations, lors du bilan annuel, justifie l’arrêt du traitement.
ISSN: 0032-7867

hal-01073027
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01073027
DOI : 10.1016/j.lpm.2013.08.006
PUBMED : 24631048

Éditeur(s) : HAL CCSD
Résumé : Climate change is one of the biggest public health threats in the 21th century. An increase in temperatures will lead to an increase in mortality attributable to temperature. In addition, some populations and territories are particularly vulnerable to the impact of increases in heat. It is thus necessary to identify these populations and territories as well as examine future heat-Related health impacts in order to recommend equity-Oriented policies today and in the future. The general objective of this thesis is to document current and future heat-Related vulnerability factors in the context of climate change. In order to address this general objective, the thesis involved four components: a) to conduct a systematic review and a meta-Analysis to assess the heterogeneity in the heat-Mortality associations with respect to individual and contextual population characteristics; b) to identify whether and how the magnitude of mean temperature effects on all-Cause mortality were modified by chronic air pollution exposure, social deprivation, and a combination of these two dimensions; c) to develop a method to quantify the climate change impacts on heat-Related mortality using climate modeling; d) to assess historical and future social disparities in years of life lost caused by ambient temperature in Montreal and Paris, and compare these estimates as well as the impact of climate change on social disparities between the two cities. This thesis highlights which populations are more vulnerable to heat and shows that several differences exist with regard to guidelines from international public health institutions for the identification of vulnerable populations. This thesis also identified chronic air pollution exposure as a new vulnerability factor in heat-Related mortality and that it has a double interaction with social deprivation. Furthermore, in this thesis a novel method to quantify future heat-Related mortality was developed which emphasized the strong evidence of an increase in heat-Related mortality under climate change. This method was then applied to estimate the increase in daily years of life lost social disparities in both Montreal and Paris under climate change which showed that this increase would be greater in Montreal compared to Paris in the future. Thus, this thesis which used a variety of epidemiologic methods has clarified which populations are particularly vulnerable to heat impacts and challenges guidelines for the identification of vulnerable populations from international public health institutions. It has also highlighted the climate change impacts on health inequalities and aims to reorient equity-Focused policies.
Les changements climatiques constituent l’un des enjeux les plus importants en santé publique du XXIème siècle. En effet, une hausse des températures provoquera une hausse de la mortalité attribuable à la chaleur. En outre, certaines populations et territoires sont particulièrement vulnérables aux effets de la chaleur. Il est donc nécessaire de les identifier clairement ainsi que les impacts futurs pour orienter avec équité les politiques publiques aujourd’hui et à l’avenir. L’objectif de cette thèse est de documenter les facteurs de vulnérabilité à la chaleur dans le présent et les éléments permettant leur prise en compte pour l’avenir dans le contexte des changements climatiques. Quatre étapes ont été menées pour répondre à cet objectif : a) Mener une revue systématique et une méta-Analyse des facteurs de vulnérabilité face aux risques de mortalité en lien avec la chaleur ; b) Analyser si l’exposition chronique à la pollution atmosphérique modifie la relation entre la chaleur et la mortalité dans un contexte urbain (Paris) et explorer la double interaction avec la défaveur sociale ; c) Développer une méthode de quantification des impacts liés à la chaleur en lien avec les changements climatiques en intégrant une grande diversité de simulations climatiques ; d) Estimer les inégalités d’années de vies perdues attribuables à la chaleur et leurs projections futures dans deux contextes distincts (Montréal et Paris) et comparer ces inégalités. Cette thèse a permis de mettre en évidence sur la base de la littérature épidémiologique les groupes de population qui sont les plus vulnérables face aux effets de la chaleur et de montrer qu’il y a plusieurs divergences par rapport aux recommandations émises par les institutions de santé publique vis-À-Vis de l’identification de populations vulnérables. Cette thèse a permis également d’identifier l’exposition chronique à la pollution atmosphérique comme nouveau facteur de vulnérabilité à la chaleur et que cette vulnérabilité était encore plus prononcée lorsqu’il s’agissait de populations défavorisées socialement. Puis, une méthode permettant de quantifier l’impact des changements climatiques sur les décès attribuables à la chaleur et ses sources d’incertitudes a été développée, et a permis de mettre en évidence que la probabilité que les changements climatiques conduisent à une augmentation de la mortalité en lien avec la chaleur est très forte. Cette méthode a ensuite été utilisée pour estimer que l’augmentation de la température conduira à une augmentation des inégalités sociales d’années de vie perdues à la fois à Montréal et à Paris, l’effet des changements climatiques sur l’accroissement de ces inégalités étant plus fort à Montréal qu’à Paris. Cette thèse, en se basant sur diverses méthodes épidémiologiques, a permis dans l’ensemble de clarifier quelles populations étaient particulièrement à risque face aux effets de la chaleur et de questionner les recommandations émises par les organismes tels que l’OMS. Elle a également permis de montrer l’effet des changements climatiques sur l’évolution de vulnérabilités face à la chaleur pour inciter dès aujourd’hui la mise en place de politiques publiques équitables et limiter l’impact des changements climatiques sur l’accroissement des inégalités de santé.
https://tel.archives-ouvertes.fr/tel-01456772

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2015PA11T003
tel-01456772
https://tel.archives-ouvertes.fr/tel-01456772
https://tel.archives-ouvertes.fr/tel-01456772/document
https://tel.archives-ouvertes.fr/tel-01456772/file/VA_BENMARHNIA_TARIK_05022015.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Dietary exposure to pesticide residues may present a risk to public health, especially for sensitive populations such as pregnant women. To characterize this risk, this study assessed chronic dietary exposure to pesticide residues based on the French ELFE cohort. A self-administered food frequency questionnaire (FFQ) about the last three months of pregnancy filled in by pregnant women in 2011 was used in combination with occurrence data from French Total Diet Studies completed by the results of national monitoring programs on pesticide residues in food. The dietary intake of pesticides (μg/kg of body weight/day) was estimated for 14,099 pregnant women with a complete FFQ, for 317 substances under two occurrence scenarios to handle left-censored data: a lower-bound scenario (LB), where undetected results were set to zero, and an upper-bound scenario (UB), where undetected results were set to the detection limit if the substance was expected to be found in food and zero if it was not. The risk was assessed for 284 substances with a toxicological reference value (TRV) and a good coverage level of the diet potentially contributing to pesticide intake. The cumulative risk was also assessed for seven effects on nervous and thyroid systems using the hazard index and the Cumulative Assessment Groups defined by EFSA. Substances with the highest exposure levels under the LB scenario were, in decreasing order, imazalil, piperonyl butoxide, chlorpropham, thiabendazole, iprodione and propargite. Under the LB scenario, only for lindane did women have a statistically significant probability of exceeding the TRV (2.4%). Under the UB scenario, risk could not be excluded for nine other substances. A better management of left-censored data and more sensitive analyses of the main food contributors might help to refine the UB exposure and risk assessments. A statistically significant cumulative risk was found for neurochemical effects related to high intake levels of three organophosphate insecticides (chlorpyrifos, pirimiphos-methyl and dimethoate) mainly detected in fruits and cereals
ISSN: 0160-4120

hal-01319892
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01319892
DOI : 10.1016/j.envint.2016.04.007
PUBMED : 27187793

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Coral reef resource systems are complex adaptive social-ecological systems providing vital and valuableecosystem services for human societies such as food provision, coastal protection and recreational activities.Their sustainability is questioned in many places around the world as they experience combined effects ofmultiple chronic anthropogenic and natural drivers at local to global scales. From a management perspective,there is a crucial need to understand how the impact of these drivers cascade through the social-ecologicalsystem components. This study develops a transdisciplinary and participatory approach to investigating thesocial-ecological dynamics of a Polynesian coral reef coastal system. A preliminary conceptual model using theDriver-Pressure-State-Impact (DPSI) framework is first being built through participatory modeling workshops.Then, pressure-state relationships are assessed with the help of empirical datasets as a first step towards thevalidation of the DPSI model. Results shows striking social-ecological interactions with different patterns in thelagoon and in the fore reef. Local management should be: (1) less resource-focused to account more specificallyto the existing typology of actors; (2) more spatially-explicit to better distinguish management objectives andactions for the lagoon and the fore reef sub-systems; and (3) more coordinated with terrestrial agencies for acoherent land-sea connection and integration that would both (i) account for existing land-sea interactions and(ii) better reflect the Polynesian cultural heritage that considers nature from ridge to reef as a whole. Suchconceptual models of social-ecological systems are a useful tool to build exploratory scenarios to ultimatelysupport planning decision-making processes.
ISSN: 0308-597X

hal-01491968
https://hal-univ-perp.archives-ouvertes.fr/hal-01491968
DOI : 10.1016/j.marpol.2017.01.014

Éditeur(s) : HAL CCSD
Résumé : Molds are common contaminants in indoor environments. Health effects associated with these microscopic fungi are multiple, including irritations, allergic reactions, infections and toxicity. Depending on the exposure level and the vulnerability of the populations, fungi may represent different public health risks. For example, damp and moldy dwellings are associated with chronic, respiratory diseases such as asthma and allergic rhinitis. However, the lack of valid tools for accurately measuring the environmental fungal exposure is one of the main challenges to better understanding the role of fungal products and particles in human health. In this thesis, diverse sampling techniques and analytical methods were evaluated for measuring the fungal contamination in the air, on surfaces and in settled dust. A quantitative PCR-based index was notably tested and compared with other approaches to assess fungal exposure in dwellings. By collecting and analyzing settled floor dust, this index successfully distinguished between contaminated and non-contaminated homes in Brittany, France. Quantitative PCR and this index are promising techniques for fungal exposure assessment in indoor environments. Further validation of these methods may lead to disease prevention approaches, particularly for vulnerable populations.
Les moisissures sont des micro-organismes présents dans tous les environnements intérieurs. Les effets sur la santé associés à ces champignons microscopiques sont multiples : irritations, réactions immunoallergiques, infections et effets toxiques. Selon le niveau d'exposition et la vulnérabilité des populations, les moisissures peuvent représenter des risques plus ou moins importants pour la santé publique. Les logements humides et moisis ont par exemple été associés à des maladies chroniques respiratoires telles que l'asthme et les rhinites allergiques. Cependant, le manque d'outils valides permettant d'évaluer quantitativement l'exposition fongique environnementale constitue une des principales difficultés pour mieux appréhender le rôle des particules et des composés fongiques sur la santé humaine. Lors de ce travail de thèse, diverses techniques d'échantillonnage et méthodes d'analyses ont été évaluées afin de mesurer la contamination fongique de l'air, des surfaces et des poussières. Un indice moléculaire basé sur la technique de PCR quantitative a notamment été testé et comparé à d'autres approches pour mesurer l'exposition fongique dans des logements. Après analyse des poussières domestiques collectées au sol, cet indice a permis de discriminer les habitats avec ou sans moisissures visibles. La quantification de groupes fongiques par PCR quantitative s'avère une technique prometteuse pour la mesure de l'exposition aux moisissures dans les environnements intérieurs. Outre le développement et la validation d'outils de mesure, une démarche globale de prévention du risque fongique semble nécessaire, particulièrement chez les populations vulnérables.
https://tel.archives-ouvertes.fr/tel-00768444

Droits : info:eu-repo/semantics/OpenAccess
tel-00768444
https://tel.archives-ouvertes.fr/tel-00768444
https://tel.archives-ouvertes.fr/tel-00768444/document
https://tel.archives-ouvertes.fr/tel-00768444/file/MA_heust_Delphine.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Studies performed in the last decades have highlighted the need to better understand the contribution of the endothelium, vascular function, oxidative stress, inflammation, coagulation, hemolysis and vascular adhesion mechanisms to the pathophysiology of acute vaso-occlusive like events and chronic organ damages in sickle cell disease (SCD). Although SCD is a hemorheological disease, a few works focused on the contribution of blood viscosity, plasma viscosity, red blood cell deformability and aggregation in the pathophysiology of SCD. After a brief description of basic hemorheology, the present review focuses on the role of the hemorheological abnormalities in the causation of several SCD complications, mainly in sickle cell anemia and hemoglobin (Hb) SC disease. Several genetic and cellular modulators of blood rheology in SCD are discussed, as well as unresolved questions and perspectives.
ISSN: 0268-960X

hal-01668334
https://hal.univ-antilles.fr/hal-01668334
DOI : 10.1016/j.blre.2015.08.005

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The Blake excursion was among the first recognized with directional and intensity behavior known mainly from marine sediment and Chinese loess. Age estimates for the directional shifts in sediments are poorly constrained to about 118−100 ka, i.e., at the marine isotope stage (MIS) 5e/5d boundary. Moreover, sediments at Lac du Bouchet maar, France and along the Portuguese margin reveal what may be a "post-Blake" excursion at about 105−95 ka. The excursional directions are associated with a prominent paleointensity minimum between about 125 and 95 ka in global stacked records. Lava flow recordings of the Blake excursion(s) have, however, been questionable because precise ages required for correlation with these sediment records are lacking. To establish new, independent records of the Blake excursion, and link these into a larger Quaternary GITS, we have undertaken 40Ar/39Ar incremental heating and unspiked K-Ar experiments on groundmass from the transitionally magnetized Inzolfato flow on Lipari Island. We also obtained 40Ar/39Ar incremental heating results for a lava flow on Amsterdam Island originally thought to record the Mono Lake excursion and from the transitionally magnetized El Calderon basalt flow, New Mexico that was K-Ar dated by Champion et al. (1988) at 128 ± 66 ka. Unspiked K-Ar ages of four samples from the Inzolfato flow are 102.5 ± 4.7, 101.3 ± 3.3, 97.1 ± 2.6, and 96.8 ± 3.1 ka and thus indistinguishable from one another. 40Ar/39Ar results are more complex, with three samples yielding discordant age spectra. Based on incremental heating data obtained in both the UW-Madison and Gif-sur-Yvette 40Ar/39Ar laboratories, a fourth sample yields six concordant age plateaus and a weighted mean age of 105.2 ± 1.4 ka that we take as the best estimate of time since the flow erupted. Five 40Ar/39Ar incremental heating experiments on the Amsterdam Island lava yield a plateau age of 120 ± 12 ka, whereas ages from two sites in the Calderon flow are 112 ± 23 and 101 ± 14 ka, together giving a weighted mean of 104 ± 12 ka. The age of 120 ± 12 ka from Amsterdam Island, though imprecise, correlates with the Blake excursion. In contrast, the 104-105 ka age obtained from both Lipari and New Mexico indicates that these lavas record a younger period of dynamo instability, most probably associated with the post-Blake excursion. These radioisotopic ages are consistent with the astronomical ages of two paleointensity minima in the PISO-1500 global stack. Our findings indicate that the Blake and post-Blake excursions are both global features of past geodynamo behavior and support the hypothesis that Brunhes chron excursions are temporally clustered into two groups of at least a half-dozen each spanning over 220 to 30 ka and 720 to 520 ka.
ISSN: 1871-1014

hal-01054336
https://hal.archives-ouvertes.fr/hal-01054336
DOI : 10.1016/j.quageo.2012.12.005

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Several epidemiologic studies have shown an interactive effect of heavy smoking and heavy alcohol drinking on the development of hepatocellular carcinoma. It has also been recently described that chronic hepatocyte death can trigger excessive compensatory proliferation resulting later in the formation of tumors in mouse liver. As we previously demonstrated that both benzo[a]pyrene (B[a]P), an environmental agent found in cigarette smoke, and ethanol possess similar targets, especially oxidative stress, to trigger death of liver cells, we decided to study here the cellular and molecular mechanisms of the effects of B[a]P/ethanol coexposure on cell death. After an 18-h incubation with 100nM B[a]P, primary rat hepatocytes were supplemented with 50mM ethanol for 5 or 8h. B[a]P/ethanol coexposure led to a greater apoptotic cell death that could be linked to an increase in lipid peroxidation. Plasma membrane remodeling, as depicted by membrane fluidity elevation and physicochemical alterations in lipid rafts, appeared to play a key role, because both toxicants acted with specific complementary effects. Membrane remodeling was shown to induce an accumulation of lysosomes leading to an important increase in low-molecular-weight iron cellular content. Finally, ethanol metabolism, but not that of B[a]P, by providing reactive oxygen species, induced the ultimate toxic process. Indeed, in lysosomes, ethanol promoted the Fenton reaction, lipid peroxidation, and membrane permeabilization, thereby triggering cell death. To conclude, B[a]P exposure, by depleting hepatocyte membrane cholesterol content, would constitute a favorable ground for a later toxic insult such as ethanol intoxication. Membrane stabilization of both plasma membrane and lysosomes might be a potential target for further investigation considering cytoprotective strategies.
ISSN: 0891-5849

hal-01018147
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01018147
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01018147/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01018147/file/Cooperative-interaction_final.pdf
PUBMED : 24681337

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND AND AIMS: Infection by hepatitis C virus is a worldwide health problem. An inadequate Th2 cytokine response promotes the fibrosis-cirrhosis fate. Immune-modulating molecules favoring a Th2 profile, such as HLA-G molecules of the HLA class Ib family, may play a role in chronic hepatitis. HLA-G contributes to the escape of tumors, and their involvement in viral infections has been increasingly described. The aim of this work was to study the expression of HLA-G in the liver, its cellular source and its regulation in cases of chronic C hepatitis. METHODS: HLA-G cells in blocks of liver derived from patients infected with HCV were labeled by immunohistochemistry and enumerated. Double immunofluorescence allowed the identification of the cellular source. HLA-G secretion by a human mast cell line was quantified by ELISA after various stimulations. After treatment with IFN-α real-time PCR was performed to determine the kinetics of cytokine expression profiles, followed by heat map clustering analysis. RESULTS: The number of HLA-G + cells was significantly associated with the area of fibrosis. For the first time, we identify the HLA-G+ cells as being mast cells. HLA-G secretion was significantly induced in human mast cells stimulated by IL-10 or interferons of class I. The transcriptome of the secretome of this cell line stimulated by IFN-α revealed that i) the HLA-G gene is upregulated late, ii) T lymphocytes and NK cells are recruited. CONCLUSIONS: These findings suggest an autocrine loop in the genesis of HCV liver fibrosis, based on mast cells expressing HLA-G.
ISSN: 0168-8278

hal-00874106
https://hal.archives-ouvertes.fr/hal-00874106
https://hal.archives-ouvertes.fr/hal-00874106/document
https://hal.archives-ouvertes.fr/hal-00874106/file/Amiot-Expression-HLA-G-revised.pdf
DOI : 10.1016/j.jhep.2013.09.006

Résumé : En Guadeloupe, la prévalence du diabète est deux fois plus élevée qu'en France hexagonale, avec une prédominance féminine. En dehors des facteurs environnementaux, la vitamine D et certains polymorphismes de gènes impliqués dans son métabolisme seraient associés à un risque de pathologies métaboliques. Les androgènes sont également associés aux anomalies du métabolisme glucidique, soit directement, soit via leur transporteur SHBG (Sex Hormone Binding Protein). Nous avons émis les hypothèses de recherche suivantes: 11 le statut en vitamine D et les polymorphismes des gènes impliqués dans son métabolisme pourraient être associés aux paramètres métaboliques chez des sujets Afro-Caribéens (AC). Ils expliqueraient l'importance des pathologies cardiométaboliques en Guadeloupe. 2/ la SHBG pourrait être associée aux anomalies du métabolisme glucidique, indépendamment des stéroïdes sexuels. Nos travaux sont présentés dans 4 études. Nous avons mis en évidence une prévalence élevée du déficit en vitamine D chez les sujets AC diabétiques de type 2. Nous avons trouvé une association significative entre le statut vitaminique D et le risque cardiométabolique chez ces sujets, mais aussi dans une population de sujets en hémodialyse chronique. Les polymorphismes des gènes impliqués dans le métabolisme de la vitamine D sont aussi associés à ce risque. Chez les sujets dysmétaboliques, une relation entre la SHBG, la graisse intra-hépatique, les hépatokines et les paramètres métaboliques a été mise en évidence, indépendamment des stéroïdes sexuels. En conclusion, la vitamine D et la SHBG pourraient être des marqueurs d'intérêt pour le dépistage des sujets à haut risque cardiométabolique.
In Guadeloupe, the prevalence of diabetes is two times higher than in Metropolitan France, with a female predominance. Apart from environmental factors, vitamin D and polymorphisms of genes involved in vitamin D metabolism would be associated with increased risk of metabolic diseases. Androgens are also associated with abnormal glucose metabolism, directly or through the Sex Hormone Binding Protein (SHBG). Our main hypotheses were: 11 Vitamin D status and polymorphisms of genes involved in its metabolism may be associated with metabolic pammeters in Afro-Caribbean (AC). They could explain the importance of cardiometabolic diseases in Guadeloupe. 2/ SHBG may be associated with abnormal glucose metabolism, independently of sex steroids. Our research is presente
http://www.theses.fr/2012AGUY0536/document

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Transmembrane CD95L (Fas ligand) can be cleaved to release a promigratory soluble ligand, cl-CD95L, which can contribute to chronic inflammation and cancer cell dissemination. The motility signaling pathway elicited by cl-CD95L remains poorly defined. Here, we show that in the presence of cl-CD95L, CD95 activates the Akt and RhoA signaling pathways, which together orchestrate an allosteric activation of the Na+/H+ exchanger NHE1. Pharmacologic inhibition of Akt or ROCK1 independently blocks the cl-CD95L-induced migration. Confirming these pharmacologic data, disruption of the Akt and ROCK1 phosphorylation sites on NHE1 decreases cell migration in cells exposed to cl-CD95L. Together, these findings demonstrate that NHE1 is a novel molecular actor in the CD95 signaling pathway that drives the cl-CD95L-induced cell migration through both the Akt and RhoA signaling pathways.
ISSN: 2045-2322

hal-01334067
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334067
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334067/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334067/file/Cleaved%20FAS%20ligand%20CC-BY.pdf
DOI : 10.1038/srep28008

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Purpose The purpose of this review was to examine the comprehensively accumulated data regarding potential therapeutic aspects of exogenous administration of interleukin 33 (IL-33) or its antagonists in allergic, cancerous, infectious, and inflammatory diseases. Methods A selected review was undertaken of publications that examined the protective and exacerbating effects of IL-33 or its inhibitors in different diseases. Mechanisms of action are summarized to examine the putative role of IL-33 in various diseases. Findings IL-33 promoted antibacterial, antiviral, anti-inflammatory, and vaccine adjuvant functions. However, in TH2-biased respiratory, allergic, parasitic, and inflammatory conditions, IL-33 exhibited disease-sensitizing effects. The alarmin cytokine IL-33 induced protective effects in diseases via recruitment of regulatory T cells; antiviral CD8+ cells, natural killer cells, γδ T cells, and nuocytes; antibacterial and antifungal neutrophils or macrophages; vaccine-associated B/T cells; and inhibition of nuclear factor–κB–mediated gene transcription. In contrast, IL-33 exacerbated the disease process by increasing TH2 cytokines, IgE and eosinophilic immune responses, and inhibition of leukocyte recruitment in various diseases. Implications The protective or exacerbated aspects of use of IL-33 or its inhibitors are dependent on the type of infection or inflammatory condition, duration of disease (acute or chronic), organ involved, cytokine microenvironment, dose or kinetics of IL-33, and genetic predisposition. The alarmin cytokine IL-33 acts at cellular, molecular, and transcriptional levels to mediate pluripotent functions in various diseases and has potential therapeutic value to mitigate the disease process
ISSN: 0149-2918

hal-01295637
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01295637
PUBMED : 26992663
DOI : 10.1016/j.clinthera.2016.02.021

Éditeur(s) : Université des Antilles Études caribéennes
Résumé : There is substantial social unrest underlying the prevailing neocolonial political and societal structure in Martinique. It is burdened with chronic high rate of unemployment rate and continuing rising cost of imported food and other basic necessities of life. Banana is the foremost plantation crop grown in Martinique. There is also an ecological disaster arising from the widespread use of carcinogenic chlordecone for controlling banana pests for more than 3 decades. Although this practice had stopped in 2003, the recalcitrant pesticide remained largely in the soil. The challenge to create meaningful new jobs under these social-economic and environmental constraints is thus formidable.
C’est sous le prisme de la structure politique et sociale néocoloniale qu’il convient d’appréhender l'importante agitation sociale de la Martinique. L’île est marquée par un taux élevé et dépend d’importations alimentaires et autres dont les prix ne cessent d’augmenter. La banane, culture de plantation qui a structuré les logiques économiques de la Martinique, est à l’origine d’une catastrophe écologique en raison de l'utilisation généralisée de chlordécone cancérogène pour lutter contre les parasites pendant plus de trois décennies. Bien que cette pratique ait cessé en 2003, le pesticide récalcitrant est resté en grande partie dans le sol. Le défi est de créer de nouveaux emplois, intéressants, dans ce contexte marqué par de lourdes contraintes socio-économiques et environnementaux.
Martinique

Droits : info:eu-repo/semantics/openAccess
urn:doi:10.4000/etudescaribeennes.6073
http://journals.openedition.org/etudescaribeennes/6073

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
The HIWATE (Health Impacts of long-term exposure to disinfection byproducts in drinking WATEr) project was a systematic analysis that combined the epidemiology on adverse pregnancy outcomes and other health effects with long-term exposure to low levels of drinking water disinfection byproducts (DBPs) in the European Union. The present study focused on the relationship of the occurrence and concentration of DBPs with in vitro mammalian cell toxicity. Eleven drinking water samples were collected from five European countries. Each sampling location corresponded with an epidemiological study for the HIWATE program. Over 90 DBPs were identified; the range in the number of DBPs and their levels reflected the diverse collection sites, different disinfection processes, and the different characteristics of the source waters. For each sampling site, chronic mammalian cell cytotoxicity correlated highly with the numbers of DBPs identified and the levels of DBP chemical classes. Although there was a clear difference in the genotoxic responses among the drinking waters, these data did not correlate as well with the chemical analyses. Thus, the agents responsible for the genomic DNA damage observed in the HIWATE samples may be due to unresolved associations of combinations of identified DBPs, unknown emerging DBPs that were not identified, or other toxic water contaminants. This study represents the first to integrate quantitative in vitro toxicological data with analytical chemistry and human epidemiologic outcomes for drinking water DBPs.
ISSN: 0013-936X

hal-00875923
https://hal.archives-ouvertes.fr/hal-00875923
DOI : 10.1021/es3024226
PUBMED : 22958121

Éditeur(s) : HAL CCSD Wiley-Blackwell
Résumé : International audience
UNLABELLED: Interleukin (IL)-33, a member of the IL-1 cytokine family, positively correlates with acute hepatitis and chronic liver failure in mice and humans. IL-33 is expressed in hepatocytes and is regulated by natural killer T (NKT) cells during concanavalin A (ConA)-induced acute liver injury. Here, we investigated the molecular mechanisms underlying the expression of IL-33 during acute hepatitis. The expression of IL-33 and its regulation by death receptor pathways was investigated after the induction of ConA-acute hepatitis in wildtype (WT), perforin(-/-) , tumor necrosis factor related apoptosis inducing ligand (TRAIL)(-/-) , and NKT cell-deficient (CD1d(-/-) ) mice. In addition, we used a model of acute liver injury by administering Jo2/Fas-antibody or D-galactosamine-tumor necrosis factor alpha (TNFα) in WT mice. Finally, the effect of TRAIL on IL-33 expression was assessed in primary cultured murine hepatocytes. We show that IL-33 expression in hepatocytes is partially controlled by perforin during acute liver injury, but not by TNFα or Fas ligand (FasL). Interestingly, the expression of IL-33 in hepatocytes is blocked during ConA-acute hepatitis in TRAIL-deficient mice compared to WT mice. In contrast, administration of recombinant murine TRAIL associated with ConA-priming in CD1d-deficient mice or in vitro stimulation of murine hepatocytes by TRAIL but not by TNFα or Jo2 induced IL-33 expression in hepatocytes. The IL-33-deficient mice exhibited more severe ConA liver injury than WT controls, suggesting a protective effect of IL-33 in ConA-hepatitis. CONCLUSION: The expression of IL-33 during acute hepatitis is dependent on TRAIL, but not on FasL or TNFα.
ISSN: 0270-9139

hal-00874194
https://hal.archives-ouvertes.fr/hal-00874194
PUBMED : 22961755
DOI : 10.1002/hep.25893