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Inflammation et sénescence dans les BPCO professionnelles: Marqueurs de sénescence et d’inflammation systémiques des bronchopneumopathies d’origine professionnelle
No full textDu point de vue physiopathologique, la BPCO est caractérisée par une inflammation pulmonaire chronique. Mais il n’existe pas, à ce jour, d’étude associant un phénotype clinique, fonctionnel et/ou biologique à certaines BPCO professionnelles. l'objectif principal du projet de recherche SEISMIC-COPD est d’identifier des biomarqueurs d’inflammation et de sénescence spécifiques aux BPCO professionnelles, en prenant exemple sur deux secteurs d’activité à risque, par rapport aux BPCO post-tabagiques par des approches génomiques et protéomiques
A multi-band body-worn distributed radio-frequency exposure meter : design, on-body calibration and study of body morphology
No full textInternational audienceA multi-band Body-Worn Distributed exposure Meter (BWDM) calibrated for simultaneous measurement of the incident power density in 11 telecommunication frequency bands, is proposed. The BDWM consists of 22 textile antennas integrated in a garment and is calibrated on six human subjects in an anechoic chamber to assess its measurement uncertainty in terms of 68% confidence interval of the on-body antenna aperture. It is shown that by using multiple antennas in each frequency band, the uncertainty of the BWDM is 22 dB improved with respect to single nodes on the front and back of the torso and variations are decreased to maximum 8.8 dB. Moreover, deploying single antennas for different body morphologies results in a variation up to 9.3 dB, which is reduced to 3.6 dB using multiple antennas for six subjects with various body mass index values. The designed BWDM, has an improved uncertainty of up to 9.6 dB in comparison to commercially available personal exposure meters calibrated on body. As an application, an average incident power density in the range of 26.7–90.8 μW·m −2 is measured in Ghent, Belgium. The measurements show that commercial personal exposure meters underestimate the actual exposure by a factor of up to 20.6
Effects of DDT and permethrin on rat hepatocytes cultivated in microfluidic biochips: Metabolomics and gene expression study
No full textInternational audienceDichlorodiphenyl-trichloroethane (DDT) and permethrin (PMT) are amongst most prevalent pesticides in the environment. Although their toxicity has been extensively studied, molecular mechanisms and metabolic effects remain unclear, including in liver where their detoxification occurs. Here, we used metabolomics, coupled to RTqPCR analysis, to examine effects of DDT and PMT on hepatocytes cultivated in biochips. At 150 04, DDT caused cell death, cytochrome P450 induction and modulation of estrogen metabolism. Metabolomics analysis showed an increase in some lipids and sugars after 6 h, and a decrease in fatty acids (tetradecanoate, octanoate and linoleate) after 24 h exposure. We also found a change in expression associated with genes involved in hepatic estrogen, lipid, and sugar metabolism. PMT at 150 OA perturbed lipid/sugar homeostasis and estrogen signaling pathway, between 2 and 6 h. After 24 h, lipids and sugars were found to decrease, suggesting continuous energy demand to detoxify PMT. Finally, at 15 M, DDT and PMT appeared to have a small effect on metabolism and were detoxified after 24 h. Our results show a time-dependent perturbation of sugar/lipid homeostasis by DDT and PMT at 150 M. Furthermore, DDT at high dose led to cell death, inflammatory response and oxidative stress
Release and toxicity of adipose tissue-stored TCDD: Direct evidence from a xenografted fat model
No full text1873-6750 Joffin, Nolwenn Noirez, Philippe Antignac, Jean-Philippe Kim, Min-Ji Marchand, Philippe Falabregue, Marion Le Bizec, Bruno Forest, Claude Emond, Claude Barouki, Robert Coumoul, Xavier Journal Article Netherlands Environ Int. 2018 Oct 31. pii: S0160-4120(18)31382-5. doi: 10.1016/j.envint.2018.10.027.International audienceBackgroundPersistent organic pollutants (POPs) are known to accumulate in adipose tissues (AT). This storage may be beneficial by diverting POPs from other sensitive tissues or detrimental because of chronic release of pollutants as indirectly suggested during weight loss. The aim is to study the biological and/or toxic effects that chronic POP release from previously contaminated grafted AT could exert in a naïve mouse.MethodsC57BL/6J male mice were exposed intraperitoneally to 2,3,7,8-tetrachlorodibenzo-p-doxin (TCDD); their epididymal fat pads were collected and grafted on the back skin of uncontaminated recipient mice whose brain, liver, and epididymal ATs were analyzed (TCDD concentration, relevant gene expression). Kinetics of release and redistribution were modeled using Physiologically Based PharmacoKinetics (PBPK).ResultsThe grafts released TCDD over a period of 10 weeks with different kinetics of distribution in the three organs studied. A PBPK model was used to simulate the AT releasing process and the incorporation of TCDD into the major organs. At three weeks post-graft, we observed significant changes in gene expression in the liver and the host AT with signatures reminiscent of inflammation, gluconeogenesis and fibrosis as compared to the control.ConclusionsThis study confirms that AT-stored TCDD can be released and distributed to the organs of the recipient hence leading to distinct changes in gene expression. This original model provides direct evidence of the potential toxic-relevant effects when endogenous sources of contamination are present
Maternal cumulative exposure to extremely low frequency electromagnetic fields and pregnancy outcomes in the Elfe cohort
No full textInternational audienceObjectives : To study the relations between maternal cumulative exposure to extremely low frequency electromagnetic fields (ELF EMF) and the risk of moderate prematurity and small for gestational age within the Elfe cohort. Methods : The Elfe study included 18,329 infants born at 33 weeks of gestation or more in France in 2011 and was designed to follow the children until 20 years of age. Gestational age and anthropometric data at birth were collected in medical records and small for gestational age was defined according to a French customized growth standard. During interviews, mothers were asked to report their job status during pregnancy. If employed, their occupation was coded according to the International Standard Classification of Occupations 1988 and the date on which they stopped their work was recorded. Cumulative exposure to ELF EMF during pregnancy was assessed, for both mothers who worked and those who did not during pregnancy, using a recently-updated job-exposure matrix (JEM). Cumulative exposure was considered as a categorical variable (< 17.5, 17.5–23.8, 23.8–36.2, 36.2–61.6 or ≥ 61.6 μT-days), a binary variable (< 44.1 and ≥ 44.1 μT-days) and a continuous variable. Associations were analyzed by logistic regression, adjusting for the mother's lifestyle factors, sociodemographic characteristics and some mother's medical history during and before pregnancy. Analyses were restricted to single births and to complete values for the pregnancy outcomes (n = 16,733). Results : Cumulative exposure was obtained for 96.0% of the mothers. Among them, 37.5% were classified in the 23.8–36.2 μT-days category, but high exposures were rare: 1.3% in the ≥ 61.6 μT-days category and 5.5% in the ≥ 44.1 μT-days category. No significant association was observed between maternal cumulative exposure and moderate prematurity and small for gestational age in this exposure range. Conclusion : This large population-based study does not suggest that maternal exposure to ELF EMF during pregnancy is highly associated with risks of moderate prematurity or small for gestational age
Socioeconomic position and outdoor nitrogen dioxide (NO 2 ) exposure in Western Europe: A multi-city analysis
No full textInternational audienceBACKGROUND:Inconsistent associations between socioeconomic position (SEP) and outdoor air pollution have been reported in Europe, but methodological differences prevent any direct between-study comparison.OBJECTIVES:Assess and compare the association between SEP and outdoor nitrogen dioxide (NO2) exposure as a marker of traffic exhaust, in 16 cities from eight Western European countries.METHODS:Three SEP indicators, two defined at individual-level (education and occupation) and one at neighborhood-level (unemployment rate) were assessed in three European multicenter cohorts. NO2 annual concentration exposure was estimated at participants' addresses with land use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE; http://www.escapeproject.eu/). Pooled and city-specific linear regressions were used to analyze associations between each SEP indicator and NO2. Heterogeneity across cities was assessed using the Higgins' I-squared test (I2).RESULTS:The study population included 5692 participants. Pooled analysis showed that participants with lower individual-SEP were less exposed to NO2. Conversely, participants living in neighborhoods with higher unemployment rate were more exposed. City-specific results exhibited strong heterogeneity (I2>76% for the three SEP indicators) resulting in variation of the individual- and neighborhood-SEP patterns of NO2 exposure across cities. The coefficients from a model that included both individual- and neighborhood-SEP indicators were similar to the unadjusted coefficients, suggesting independent associations.CONCLUSIONS:Our study showed for the first time using homogenized measures of outcome and exposure across 16 cities the important heterogeneity regarding the association between SEP and NO2 in Western Europe. Importantly, our results showed that individual- and neighborhood-SEP indicators capture different aspects of the association between SEP and exposure to air pollution, stressing the importance of considering both in air pollution health effects studies
Functional Characterization of Xenopus Thyroid Hormone Transporters mct8 and oatp1c1
No full textInternational audienceAbstract Xenopus is an excellent model for studying thyroid hormone signaling as it undergoes thyroid hormone–dependent metamorphosis. Despite the fact that receptors and deiodinases have been described in Xenopus, membrane transporters for these hormones are yet to be characterized. We cloned Xenopus monocarboxylate transporter 8 (mct8) and organic anion-transporting polypeptide 1C1 (oatpc1c1), focusing on these two transporters given their importance for vertebrate brain development. Protein alignment and bootstrap analysis showed that Xenopus mct8 and oatp1c1 are closer to their mammalian orthologs than their teleost counterparts. We functionally characterized the two transporters using a radiolabeled hormones in vitro uptake assay in COS-1 cells. Xenopus mct8 was found to actively transport both T3 and T4 bidirectionally. As to the thyroid precursor molecules, diiodotyrosine (DIT) and monoiodotyrosine (MIT), both human and Xenopus mct8, showed active efflux, but no influx. Again similar to humans, Xenopus oatp1c1 transported T4 but not T3, MIT, or DIT. We used reverse transcription quantitative polymerase chain reaction and in situ hybridization to characterize the temporal and spatial expression of mct8 and oatp1c1 in Xenopus. Specific expression of the transporter was observed in the brain, with increasingly strong expression as development progressed. In conclusion, these results show that Xenopus thyroid hormone transporters are functional and display marked spatiotemporal expression patterns. These features make them interesting targets to elucidate their roles in determining thyroid hormone availability during embryonic development
Clock-dependent and system-driven oscillators interact in the suprachiasmatic nuclei to pace mammalian circadian rhythms
No full textClock-dependent and system-driven oscillators interact in the suprachiasmatic nuclei to pace mammalian circadian rhythm
Occupational Asbestos Exposure and Incidence of Colon and Rectal Cancers in French Men: The Asbestos-Related Diseases Cohort (ARDCo-Nut)
No full textInternational audienceBackground : The relationships between asbestos exposure and colorectal cancer remain controversial.Objectives : We examined the association between asbestos exposure and colorectal cancer incidence. Methods : Volunteer retired workers previously exposed to asbestos were invited to participate in the French ARDCo screening program between 2003 and 2005. Additional data on risk factors for colorectal cancer were collected from the ARDCo-Nut subsample of 3,769 participants in 2011. Cases of colon and rectal cancer were ascertained each year through 2014 based on eligibility for free medical care following a cancer diagnosis. Survival regression based on the Cox model was used to estimate the relative risk of colon and rectal cancer separately, in relation to the time since first exposure (TSFE) and cumulative exposure index (CEI) to asbestos, and with adjustment for smoking in the overall cohort and for smoking, and certain risk factors for these cancers in the ARDCo-Nut subsample.Results : Mean follow-up was 10.2 years among 14,515 men, including 181 colon cancer and 62 rectal cancer cases (41 and 17, respectively, in the ARDCo-Nut subsample). In the overall cohort, after adjusting for smoking, colon cancer was significantly associated with cumulative exposure (HR = 1.14; 95% CI: 1.04, 1.26 for a 1-unit increase in ln-CEI) and ≥ 20–40 years since first exposure (HR = 4.67; 95% CI: 1.92, 11.46 vs. 0–20 years TSFE), and inversely associated with 60 years TSFE (HR = 0.26; 95% CI: 0.10, 0.70). Although rectal cancer was also associated with TSFE 20–40 years (HR = 4.57; 95% CI: 1.14, 18.27), it was not associated with ln-CEI, but these findings must be interpreted cautiously due to the small number of cases.Conclusions : Our findings provide support for an association between occupational exposure to asbestos and colon cancer incidence in men
Malaria Vector Control Still Matters despite Insecticide Resistance
No full textInternational audienceMosquito vectors’ resistance to insecticides is usually considered a major threat to the recent progresses in malaria control. However, studies measuring the impact of interventions and insecticide resistance reveal inconsistencies when using entomological versus epidemiological indices. First, evaluation tests that do not reflect the susceptibility of mosquitoes when they are infectious may underestimate insecticide efficacy. Moreover, interactions between insecticide resistance and vectorial capacity reveal nonintuitive outcomes of interventions. Therefore, considering ecological interactions between vector, parasite, and environment highlights that the impact of insecticide resistance on the malaria burden is not straightforward and we suggest that vector control still matters despite insecticide resistance