Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
As climate change continues to impact socio-ecological systems, tools that assist conservation managers to understand vulnerability and target adaptations are essential. Quantitative assessments of vulnerability are rare because available frameworks are complex and lack guidance for dealing with data limitations and integrating across scales and disciplines. This paper describes a semi-quantitative method for assessing vulnerability to climate change that integrates socio-ecological factors to address management objectives and support decision-making. The method applies a framework first adopted by the Intergovernmental Panel on Climate Change and uses a structured 10-step process. The scores for each framework element are normalized and multiplied to produce a vulnerability score and then the assessed components are ranked from high to low vulnerability. Sensitivity analyses determine which indicators most influence the analysis and the resultant decision-making process so data quality for these indicators can be reviewed to increase robustness. Prioritisation of components for conservation considers other economic, social and cultural values with vulnerability rankings to target actions that reduce vulnerability to climate change by decreasing exposure or sensitivity and/or increasing adaptive capacity. This framework provides practical decision-support and has been applied to marine ecosystems and fisheries, with two case applications provided as examples: (1) food security in Pacific Island nations under climate-driven fish declines, and (2) fisheries in the Gulf of Carpentaria, northern Australia. The step-wise process outlined here is broadly applicable and can be undertaken with minimal resources using existing data, thereby having great potential to inform adaptive natural resource management in diverse locations.
ISSN: 0308-597X

hal-01380403
https://hal-univ-perp.archives-ouvertes.fr/hal-01380403
DOI : 10.1016/j.marpol.2016.09.024

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Worrying trends regarding human reproductive endpoints (e.g. semen quality, reproductive cancers) have been reported and there is growing circumstantial evidence for a possible causal link between these trends and exposure to endocrine disrupting chemicals (EDCs). However, there is a striking lack of human data to fill the current knowledge gaps. To answer the crucial questions raised on human reproductive health, there is an urgent need for a reproductive surveillance system to be shared across countries. METHODS: A multidisciplinary network named HUman Reproductive health and Global ENvironment Network (HURGENT) was created aiming at designing a European monitoring system for reproductive health indicators. Collaborative work allowed setting up the available knowledge to design such a system. Furthermore we conducted an overview of 23 potential indicators, based upon a weight of evidence (WoE) approach according to their potential relation with EDC exposure. RESULTS: The framework and purposes of the surveillance system are settled as well as the approach to select suitable reproductive indicators. The indicators found with the highest scores according to the WoE approach are prostate and breast cancer incidence, sex ratio, endometriosis and uterine fibroid incidence, indicators related to the testicular dysgenesis syndrome, precocious puberty incidence and reproductive hormone levels. CONCLUSION: Not only sentinel health endpoints, but also diseases with high burdens in public health are highlighted as prior indicators in the context of EDC exposure. Our work can serve as a basis to construct, as soon as possible, the first multi-country reproductive monitoring system
European Journal of Public Health

hal-01197348
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01197348
DOI : 10.1093/eurpub/ckv153
PUBMED : 26330492

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
The Société de pneumologie de langue française defines acute exacerbation of chronic obstructive pulmonary disease (AE COPD) as an increase in daily respiratory symptoms, basically duration ≥ 48h or need for treatment adjustment. Etiology of EA COPD are mainly infectious, viral (rhinovirus, influenzae or parainfluenzae virus, coronavirus, adenovirus and respiratory syncytial virus) or bacterial (Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis). Pollutant exposure can also lead to AE COPD, such as NO2, SO2, ozone or particulates (PM10 and PM2.5). In 30% the etiology remains unknown. Differential diagnoses of AE COPD include infectious pneumonia, pneumothorax, acute heart failure and pulmonary embolism. Presences of signs of severity impose hospitalization: signs of respiratory distress, shock, acute confusion but also fragile patients, insufficient home support or absence of response to initial treatment. AE COPD treatments consist on increase in bronchodilators, chest physiotherapy, and antibiotics if sputum is frankly purulent. Systemic corticosteroids should not be systematic.Recommended dose is 0.5 mg/kg on short course (7 days). During hospitalization, oxygen supplementation and thromboprophylaxis could be prescribed. The main interest in noninvasive ventilation is persistent hypercapnia despite optimal medical management. During ambulatory management or hospitalization, clinical assessment at 48-72h is mandatory. L’exacerbation aiguë de bronchopneumopathie chronique obstructive (EA BPCO) représente un événement important dans l’histoire naturelle de la BPCO, notamment en cas d’hospitalisation. Les EA BPCO interviennent dans la gravité et l’évolution de la BPCO ; et leur prévention est un des objectifs principal des traitements de fond.
La Société de pneumologie de langue française définie l’exacerbation aiguë de bronchopneumopathie chronique obstructive (EA BPCO) comme une majoration des symptômes respiratoires au-delà des variations quotidiennes, en pratique, d’une durée ≥ 48h ou justifiant une modification thérapeutique. L’étiologie de ces EA BPCO est principalement infectieuse, virale (rhinovirus, virus influenzae et parainfluenzae, coronavirus, adénovirus et virus respiratoire syncytial) ou bactérienne (principalement Haemophilus influenzae, Streptococcus pneumoniae et Moraxella catarrhalis). Elles peuvent également résulter de l’exposition à certains polluants comme le NO2, le SO2, l’ozone et la pollution particulaire (PM10 et PM2,5). L’étiologie reste indéterminée dans près de 30 % des cas. Les diagnostics différentiels des EA BPCO incluent les pneumopathies infectieuses, les pneumothorax, les poussées d’insuffisance cardiaque et les embolies pulmonaires. La présence de signes de gravité conditionnent l’hospitalisation : signes d’insuffisance respiratoire aiguë, de choc ou de défaillance neurologique, mais aussi en cas de patient fragile, d’absence de soutien familial à domicile ou d’absence de réponse au traitement initial. Le traitement d’une EA BPCO consiste en une majoration des bronchodilatateurs, une kinésithérapie respiratoire, une antibiothérapie en cas d’expectoration franchement purulente.La prescription de corticoïdes systémiques ne doit pas être systématique. La dose recommandée est de 0,5 mg/kg sur une courte période (7 jours). Lors d’une hospitalisation, une oxygénothérapie et une thromboprophylaxie peuvent être prescrite. La ventilation noninvasiveest principalement indiquée en cas de persistance d’une hypercapnie malgré un traitement médical optimal. Que le patient soit pris en charge en ambulatoire ou en hospitalisation, une réévaluation clinique à 48-72h est indispensable.
ISSN: 0755-4982

hal-01117949
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117949
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117949/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117949/file/Prise%20en%20charge%20des%20exacerbations_accepted.pdf
DOI : 10.1016/j.jeurea.2015.02.002

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
Hand disinfection with alcohols-based hand rubs (ABHRs) are known to be the most effective measure to prevent nosocomial infections in healthcare. ABHRs contain on average 70% by weight of one or more alcohols. During the hand rubbing procedure, users are exposed to these alcohols not only through dermal contact, but also via inhalation, due to the physical and chemical properties of alcohols volatilizing from alcoholic solutions or gels into the air. Ethanol ingestion is well known to increase risks of several diseases (affecting the pancreas, liver, cardiovascular system…), but there is a lack of knowledge about the effects of exposure to other alcohols (including n- or isopropanol) via inhalation and dermal contact, despite the worldwide use of ABHRs. This work aims at discussing possible health effects related to unintentional alcoholization (via inhalation and dermal contact) from professional ABHR usage to suggest the need for more research in this area (but not to question the value of ABHRs). Based upon an average of 30 hand rubbings per healthcare professional per day, it can be assumed that a healthcare worker may be exposed to a maximum 5,500 mg/m(3) per work shift, five times above the recommended occupational time weighted average limit. Thus, in order to answer the question posed in the title, studies on spatial and temporal variability of alcohol emission from ABHRs in real world situations and studies on certain high risk individuals are needed.
ISSN: 1660-4601

hal-01122305
https://hal.archives-ouvertes.fr/hal-01122305
PUBMED : 20948945
DOI : 10.3390/ijerph7083038
PUBMEDCENTRAL : PMC2954566

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 Public Library of Science
Résumé : International audience
BACKGROUND: The male genital tract is suspected to constitute a viral sanctuary as persistent HIV shedding is found in the semen of a subset of HIV-infected men receiving effective antiretroviral therapy (HAART). The origin of this persistent shedding is currently unknown. Phylogenetic studies indicated that HIV in semen from untreated men arises from local sources and/or passive diffusion from the blood. We previously demonstrated in human and macaque low levels and localized infection of several semen-producing organs by HIV/SIV. Using a macaque model, this study investigates the impact of short term HAART (2-4 weeks) initiated either during the asymptomatic chronic stage or 4 h post-intravenous inoculation of SIVmac251 on the infection of male genital organs. METHODOLOGY/PRINCIPAL FINDINGS: Short term HAART during the chronic stage decreased blood viral load. No major impact of HAART was observed on SIV DNA levels in male genital organs using a sensitive nested PCR assay. Using in situ hybridization, SIV RNA+ cells were detected in all male genital tract organs from untreated and treated animals with undetectable blood viral load following HAART. Infected CD68+ myeloid cells and CD3+ T lymphocytes were detected pre- and post-HAART. In contrast, short term HAART initiated 4 h post-SIV exposure led to a drastic decrease of the male genital tissues infection, although it failed to prevent systemic infection. In both cases, HAART tended to decrease the number of CD3+ T cells in the male organs. CONCLUSIONS: Our results indicate that the established infection of male genital organs is not greatly impacted by short term HAART, whereas the same treatment during pre-acute phase of the infection efficiently impairs viral dissemination to the male genital tract. Further investigations are now needed to determine whether infection of male genital organs is responsible for long term persistent HIV shedding in semen despite HAART.
ISSN: 1932-6203

hal-00876945
https://hal.archives-ouvertes.fr/hal-00876945
https://hal.archives-ouvertes.fr/hal-00876945/document
https://hal.archives-ouvertes.fr/hal-00876945/file/Impactsur Short-Term-accepted.pdf
DOI : 10.1371/journal.pone.0037348

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
CK chondrites are highly oxidized meteorites containing abundant magnetite and trace amounts of Fe,Ni metal. Although the group is predominately composed of equilibrated meteorites (types 4-6), in recent years a significant number of new samples have been classified as being either CK3 or CK3-anomalous. These unequilibrated CKs often display a close affinity with members of the CV oxidized subgroup. CKs and CVs (oxidized subgroup) may therefore form a continuum and by implication could be derived from a single common parent body. To investigate the relationship between these two groups a detailed study of the oxygen isotope composition, opaque mineralogy and major and trace element geochemistry of a suite of CV and CK chondrites has been undertaken. The results of oxygen isotope analysis confirm the close affinity between CV and CK chondrites, while excluding the possibility of a linkage between the CO and CK groups. Magnetites in both CV and CK chondrites show significant compositional similarities, but high Ti contents are a diagnostic feature of the latter group. The results of major and trace element analysis demonstrate that both CV and CK chondrites show overlapping variation. Supporting evidence for a single common source for both groups comes from their similar cosmic-ray exposure age distributions. Recent reflectance spectral analysis is consistent with both the CVs and CKs being derived from Eos family asteroids, which are believed to have formed by the catastrophic disruption of a single large asteroid. Thus, a range of evidence appears to be consistent with CV and CK chondrites representing samples from a single thermally stratified parent body. In view of the close similarity between CV and CK chondrites some modification of the present classification scheme may be warranted, possibly involving integration of the two groups. One means of achieving this would be to reassigned CK chondrites to a subgroup of the oxidized CVs. It is recognized that a full evaluation of this proposal may require further study of the still poorly understood CK3 chondrites.
ISSN: 0016-7037

hal-00474633
https://hal.archives-ouvertes.fr/hal-00474633
DOI : 10.1016/j.gca.2009.11.029

Éditeur(s) : HAL CCSD
Résumé : National audience
Epidemiological researches in the field of DOHaD are in favor of a role of early environment, including chemical (pesticides), physical (air pollution), nutritional or psychosocial environment, on child and adult health. Disentangling the different factors of environment that may affect health, especially over time, and identifying critical periods of exposure remains a major challenge. The biological mechanisms involved remain elusive in human beings. Nevertheless, it seems that whatever the nature of the exposure, epigenetic mechanisms are currently discussed to explain how the environment may alter biological systems over time.
Les résultats épidémiologiques dans le domaine de la DOHaD (developmental origins of health and disease) sont en faveur d’un rôle de l’environnement précoce sur la santé immédiate mais aussi future, qu’il s’agisse de l’environnement physique, chimique, nutritionnel ou encore psychosocial. Faire la part des différents facteurs de l’environnement susceptibles de modifier la santé, notamment sur le long terme, et des périodes critiques d’exposition reste un enjeu majeur. De même, les multiples mécanismes biologiques impliqués restent encore, pour une grande part, à identifier chez l’homme. Il semble néanmoins que, quelle que soit la nature de l’exposition considérée, des mécanismes épigénétiques sont actuellement évoqués pour expliquer comment l’environnement est susceptible de modifier des systèmes biologiques sur le long terme.
Médecine Sciences: M/S

hal-01274219
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01274219
DOI : 10.1051/medsci/20163201005
PUBMED : 26850603

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
More than half the pregnant women in the Western world report taking mild analgesics. These pharmaceutical compounds have been associated with congenital cryptorchidism in humans, the best-known risk factor for low semen quality and testicular germ cell cancer. Furthermore, some of these mild analgesics exert potent anti-androgenic effects in the male rat and several endocrine-disrupting compounds, known to alter masculinization, have also been shown to be potent inhibitors of prostaglandin (PG) synthesis similar to mild analgesics. Using a 3-day ex vivo organotypic model system based on gestational day 14.5 rat testes, we herein show that testosterone production was inhibited by paracetamol, at doses of 0.1 μm to 100 μm. Similar results were obtained for aspirin (1-100 μm) and indomethacin (10 μm). The production of the other Leydig cell hormone, Insl3, was not disrupted by exposure to paracetamol. Investigations of the gross anatomy of the testis as well as Leydig cells number and rate of gonocyte apoptosis after the 3 days of ex vivo differentiation showed no significant effect of the analgesics tested compared with controls. These data indicate therefore that mild analgesics specifically inhibit testosterone production in rat foetal testes in vitro and that these compounds had no effect on gonocyte survival. Parallel determinations of prostaglandin D2 (PGD2) production indicated that the effects of paracetamol and aspirin on PGD2 and testosterone were not connected, whereas the effects of indomethacin were correlated. We conclude that mild analgesics exert direct and specific anti-androgenic effects in rat foetal testis in our experimental setup and that the mechanism of action is probably uncoupled from the inhibition of PG synthesis.
ISSN: 0105-6263

hal-00876956
https://hal.archives-ouvertes.fr/hal-00876956
DOI : 10.1111/j.1365-2605.2012.01282.x
PUBMED : 22612476

Éditeur(s) : HAL CCSD Springer
Résumé : The analysis of three different regions of the South- Pyrenean fold-and-thrust belt reveals that during the Tertiary compression the hydrological system was compartmentalised in time and space. During the early-middle Eocene, when the thrust front affected marine soft-sediments in the Ainsa basin, the thrust fault zones were dominated by formation fluids derived from Eocene marine waters trapped in the underlying Eocene marls, although influences of meteoric waters were also present. During the middle-late Eocene, when the thrust front emplaced marine rocks over continental redbeds in the eastern Catalan basin (L'Escala thrust), the thrust fault zones were dominated by meteoric fluids. These fluids flowed preferentially along these faults, draining laterally the meteoric fluids and acting as barriers hindering their flowing towards more external parts of the belt. During the Oligocene, the most external part of the fold-and-thrust belt in the eastern Catalan basin developed on top of a salt detachment horizon. The thrust front affected continental materials of late Eocene-Oligocene age. At this moment, the thrusts were conduits for meteoric fluids arriving from the surface and also for evolved meteoric fluids migrating over short distance upwards after being in contact with the underlying evaporitic beds. Most of the fractures show a similar sequence of microfractures. Microfractures of stage 1 formed when the sediment was poorly lithified. Microfractures of stage 2 represent the main episode of vein formation which developed when a progressive induration of the host sediment occurred. During microfracture stage 3, formed in an extensional regime, the host sediment was more indurated. The repetition of this sequence of microfractures in different fracture generations of the same outcrop indicates that the sediment induration was restricted to the vicinity of the vein. Away from the veins, the sediment remained poorly lithified during the entire deformation cycle. Calcite cement within the host rock precipitated later than the syn-compressive veins, when the sediment was more indurated. Elemental geochemistry and stable isotopes of the calcite veins indicates that early generation of microfractures is infilled by local fluids (either marine or meteoric), whereas external fluids (meteoric or evolved meteoric) infilled the main compressive stage of microfractures. The hot temperature of these fluids (157°C to 183°C in the Atiart-Arro example) indicates their circulation through deep parts of the thrust belt. The progressive increase of the 87Sr/86Sr ratio through time is due to the progressive uplift, exposure and erosion of the internal Pyrenean Axial Zone.
Thrust belts and foreland basins, from fold kinematics to hydrocarbon systems

hal-00408001
https://hal.archives-ouvertes.fr/hal-00408001
DOI : 10.1007/978-3-540-69426-7_5

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
: Indoor dust samples cannot always be analyzed immediately after collection. However, little information is currently available on how storage conditions may affect measurements. This study was designed to determine how sample storage conditions may affect the concentration of semi-volatile organic compounds (SVOCs) in the dust. A composite dust was prepared using a Standard Reference Material (SRM 2585) with real indoor dust samples. The composite dust was stored in various types of packaging, at different temperatures (-18°C, 5°C, 20°C and 35°C) and in different light conditions. The concentration of SVOCs was measured after various storage durations. No effect on SVOC concentrations was observed for the composite dust stored in an amber glass vial at -18°C for 36 months. At 5°C, 20°C and 35°C, losses occurred for the more volatile compounds. The experimental storage conditions clearly showed that temperature and duration affected the concentrations of SVOCs in the composite dust. The type of packaging material (polyethylene zip bag or polyethylene garbage bag) did not seem to have a systematic effect on the preservation of SVOCs in the composite dust. Maximum storage duration times are proposed for each compound at various temperatures. For most compounds, samples can be stored for two months at 20°C. For samples that cannot be analyzed immediately, we recommend to store them in the dark at -18°C to ensure a good recovery of all tested compounds. This article is protected by copyright. All rights reserved.
ISSN: 0905-6947

inserm-00866171
http://www.hal.inserm.fr/inserm-00866171
DOI : 10.1111/ina.12066
PUBMED : 24033516

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Diesel exhaust particles (DEPs) are common environmental air pollutants primarily affecting the lung. DEPs or chemicals adsorbed on DEPs also exert extra-pulmonary effects, including alteration of hepatic drug detoxifying enzyme expression. The present study was designed to determine whether organic DEP extract (DEPe) may target hepatic drug transporters that contribute in a major way to drug detoxification. Using primary human hepatocytes and transporter-overexpressing cells, DEPe was first shown to strongly inhibit activities of the sinusoidal solute carrier (SLC) uptake transporters organic anion-transporting polypeptides (OATP) 1B1, 1B3 and 2B1 and of the canalicular ATP-binding cassette (ABC) efflux pump multidrug resistance-associated protein 2, with IC50 values ranging from approximately 1 to 20 μg/mL and relevant to environmental exposure situations. By contrast, 25 μg/mL DEPe failed to alter activities of the SLC transporter organic cation transporter (OCT) 1 and of the ABC efflux pumps P-glycoprotein and bile salt export pump (BSEP), whereas it only moderately inhibited those of sodium taurocholate co-transporting polypeptide and of breast cancer resistance protein (BCRP). Treatment by 25 μg/mL DEPe was next demonstrated to induce expression of BCRP at both mRNA and protein level in cultured human hepatic cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B3, OATP2B1, OCT1 and BSEP. Such changes in transporter expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a reference activator of the aryl hydrocarbon receptor (AhR) pathway. This suggests that DEPe, which is enriched in known ligands of AhR like polycyclic aromatic hydrocarbons, alters drug transporter expression via activation of the AhR cascade. Taken together, these data established human hepatic transporters as targets of organic chemicals containing in DEPs, which may contribute to their systemic effects through impairing hepatic transport of endogenous compound or drug substrates of these transporters.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01138535
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01138535
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01138535/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01138535/file/Regulation%20of%20human%20hepatic%20drug.pdf
DOI : 10.1371/journal.pone.0121232

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7-17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8-9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10-12 GW, or in second trimester xenografted testes (14-17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow â €' early window' of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology. © The Author(s) 2017.
ISSN: 2045-2322

hal-01517095
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01517095
DOI : 10.1038/srep44184
PUBMED : 28281692

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The Hengshan–Wutaishan area forms part of the Trans-North-China Belt developed in response to the final amalgamation of the North China Craton. The Hengshan–Wutaishan domain and the adjacent Fuping massif constitute the largest and the most representative rock exposure of the belt. A structural study allows us to redefine the lithological and tectonic units that compose the architecture of the Hengshan–Wutaishan domain and to propose that the Trans-North-China Belt was built up through a polyphase tectonic evolution within the period 1900–1800 Ma. The first event (D1) corresponds to the emplacement of lower and upper nappes herein called the Orthogneiss and Volcanites Unit (OVU) and the Low Grade Mafic Unit (LGMU), respectively. The OVU mainly consists of rocks formed in an arc system and metamorphosed under amphibolite facies conditions whereas the LGMU represents oceanic crust rocks with an arc component that underwent greenschist facies metamorphism. The syn-metamorphic D1 deformation is characterized by a NW–SE stretching and mineral lineation with a top-to-the SE sense of shear that corresponds to the sense of nappe motion. U–Th–Pb EPM chemical dating on monazite from three metapelites of the OVU gives isochron ages of 1884 ± 11 Ma, 1886 ± 5 Ma and 1887 ± 4 Ma interpreted as the age of the prograde amphibolite facies metamorphism coeval with nappe stacking during the D1 event. The D2 event corresponds to a widespread crustal melting of the OVU and underlying basement rocks in Hengshan related to the exhumation of deep structures about 20–30 Ma after nappe emplacement. The migmatite contains blocks of retrograded eclogite or HP-granulitic restites, and is characterized by the development of a pervasive foliation and lineation. A late D2 event represents the folding stage of the migmatitic foliation during the completion of a dome. The Orthogneiss and Volcanics Unit and the Low Grade Mafic Unit are unconformably covered by weakly metamorphosed to unmetamorphosed sediments belonging to the Hutuo Supergroup. These rocks were deformed by a ductile D3 event, characterized by a NW–SE trending stretching lineation, south verging folds associated with an axial planar slaty cleavage and an E–W crenulation lineation. Lastly, a left-lateral wrenching along the Zhujiafang Shear Zone separates the northern and southern parts of Hengshan. Our structural study shows that there is no significant difference between the southern part of Hengshan and the lower part of Wutaishan, both areas belong to OVU and show a structural continuity. We suggest that this polyphase deformation developed in response to a north-westward subduction of an old ocean, named the Lüliang Ocean, beneath the Western Block, followed by collision with a micro-continent named the Fuping Block at not, vert, similar1890–1880 Ma.
ISSN: 0301-9268

insu-00151594
https://hal-insu.archives-ouvertes.fr/insu-00151594
https://hal-insu.archives-ouvertes.fr/insu-00151594/document
https://hal-insu.archives-ouvertes.fr/insu-00151594/file/Trap-PrecambrainResearch-2007.pdf
DOI : 10.1016/j.precamres.2007.03.001

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Technologies for wireless telecommunication systems using millimeter waves (MMW) will be widely deployed in the near future. Forthcoming applications in this band, especially around 60 GHz, are mainly developed for high data-rate local and body-centric telecommunications. At those frequencies, electromagnetic radiations have a very shallow penetration into biological tissues, making skin keratinocytes, and free nerve endings of the upper dermis the main targets of MMW. Only a few studies assessed the impact of MMW on neuronal cells, and none of them investigated a possible effect on neuronal differentiation. We used a neuron-like cell line (PC12), which undergoes neuronal differentiation when treated with the neuronal growth factor (NGF). PC12 cells were exposed at 60.4 GHz for 24 h, at an incident power density averaged over the cell monolayer of 10 mW/cm2. Using a large scale cell-by-cell analysis based on high-content screening microscopy approach, we assessed potential effects of MMW on PC12 neurite outgrowth and cytoskeleton protein expression. No differences were found in protein expression of the neuronal marker β3-Tubulin nor in internal expression control β-Tubulin. On the other hand, our data showed a slight increase, although insignificant, in neurite outgrowth, induced by MMW exposure. However, experimental controls demonstrated that this increase was related to heating
ISSN: 0304-3940

hal-01281481
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01281481
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01281481/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01281481/file/Effects%20of%2060-GHz%20Millimeter%20Waves%20on%20Neurite.pdf
DOI : 10.1016/j.neulet.2016.02.038

Éditeur(s) : HAL CCSD American Academy of Pediatrics
Résumé : International audience
Vitamin D is an essential hormone for calcium gut absorption. It is also involved in child growth, cancer prevention, immune system responses, and tooth formation. Due to inadequate vitamin D intake and/or decreased sunlight exposure, vitamin D deficiency has resurfaced in developed countries despite known inexpensive and effective preventive methods. Vitamin D deficiency is a common cause of rickets, a condition that affects bone development in children and that can have serious dental complications. Deficiency during pregnancy can cause enamel hypoplasia of primary teeth. Enamel regeneration is currently impossible; hypoplasia is therefore irreversible, and once affected, teeth are prone to fast caries development. Deficiency during early childhood can affect permanent teeth and ensuing caries can sometimes lead to tooth loss at a young age. Oral manifestations of rickets should be diagnosed early by both physicians and dentists to prevent severe dental complications. This case study presents 2 young girls with rickets in early childhood who suffered from subsequent serious tooth decay.
ISSN: 0031-4005

hal-01545477
https://hal.archives-ouvertes.fr/hal-01545477
DOI : 10.1542/peds.2013-0733

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Nonylphenol (NP) is an endocrine disruptor with harmful effects including feminization and carcinogenesis on various organisms. This substance is a degradation product of nonylphenol ethoxylates (NPEO) that is used in several industrial and agricultural processes. In this paper, we examined the assessment of NP exposure on chick embryo development, using a concentration consistent with the environmental concentrations of NP. With this aim, NP (between 0.1 and 50μg/egg) was injected into the yolk of egg through a small needle hole in the shell. We report the effect of NP on chick reproductive system development although the effect we observed is lower than those observed by exposition to other endocrine disruptors. However, histological analysis highlighted a decrease of intraluminal seminiferous surface area in 64.12% of case (P=0.0086) and an heterogeneous organization of the renal tubules when 10μg/egg were injected. Moreover, an impairment of liver development with an abnormal bile spillage was observed when higher concentration of NP was injected (50μg/egg).
Environment International

hal-00878651
https://hal.archives-ouvertes.fr/hal-00878651
https://hal.archives-ouvertes.fr/hal-00878651/document

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: An environmental health inequality is a major public health concern in Europe. However just few studies take into account a large set of characteristics to analyze this problematic. The aim of this study was to identify and describe how socioeconomic, health accessibility and exposure factors accumulate and interact in small areas in a French urban context, to assess environmental health inequalities related to infant and neonatal mortality.Methods: Environmental indicators on deprivation index, proximity to high-traffic roads, green space, and healthcare accessibility were created using the Geographical Information System. Cases were collected from death certificates in the city hall of each municipality in the Nice metropolitan area. Using the parental addresses, cases were geocoded to their census block of residence. A classification using a Multiple Component Analysis following by a Hierarchical Clustering allow us to characterize the census blocks in terms of level of socioeconomic, environmental and accessibility to healthcare, which are very diverse definition by nature. Relation between infant and neonatal mortality rate and the three environmental patterns which categorize the census blocks after the classification was performed using a standard Poisson regression model for count data after checking the assumption of dispersion.Results: Based on geographic indicators, three environmental patterns were identified. We found environmental inequalities and social health inequalities in Nice metropolitan area. Moreover these inequalities are counterbalance by the close proximity of deprived census blocks to healthcare facilities related to mother and newborn. So therefore we demonstrate no environmental health inequalities related to infant and neonatal mortality.Conclusion: Examination of patterns of social, environmental and in relation with healthcare access is useful to identify census blocks with needs and their effects on health. Similar analyzes could be implemented and considered in other cities or related to other birth outcomes.
ISSN: 1476-069X

halshs-01366285
https://halshs.archives-ouvertes.fr/halshs-01366285
https://halshs.archives-ouvertes.fr/halshs-01366285/document
https://halshs.archives-ouvertes.fr/halshs-01366285/file/art_10.1186_s12940-016-0163-7.pdf
PUBMED : 27449640

Éditeur(s) : HAL CCSD
Résumé : International audience
The Alboran Domain, situated at the western end of the Mediterranean subduction system, is characterized by theRonda Peridotites, one of the world largest exposures of sub-continental mantle. Using U-Pb (LA-ICP-MS) and Ar-Ar dating, we precisely dated two tectonic events associated with the Tertiary exhumation of the Ronda Peridotites.First, shearing along the Crust-Mantle Extensional Shear Zone caused, at ca. 22.5 Ma, mantle exhumation, localpartial melting in the deep crust and coeval cooling in the upper crust. Second, the Ronda Peridotites Thrusttriggered the final crustal emplacement of the peridotites onto the continental crust at ca. 21 Ma, as testified bygranitic intrusions in the thrust hanging-wall. The tectonic evolution of the western Alboran Domain is thereforecharacterized by a fast switch from a continental lithosphere extension in a backarc setting, with sub-continentalmantle exhumation, to a rift inversion by thrusting driven by shortening of the subduction upper plate
European Geosciences Union General Assembly 2017
Vienne, Austria

insu-01510393
https://hal-insu.archives-ouvertes.fr/insu-01510393

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life. OBJECTIVES: Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals. METHODS: We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10-12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures. RESULTS: We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose-response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight. CONCLUSIONS: Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life. https://doi.org/10.1289/EHP1014.
Environmental Health Perspectives

hal-01579609
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579609
DOI : 10.1289/EHP1014
PUBMED : 28796631