Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
OBJECTIVES: Many women who work during pregnancy are occupationally exposed to toxicants. The developing central nervous system is highly vulnerable to neurotoxicants such as solvents. Although the neurotoxicity of solvents to adults is well established, very few studies have examined their effects on children's behaviour following prenatal exposure. METHODS: Women from the Perturbateurs endocriniens: Étude Longitudinale sur les Anomalies de la Grossesse, l'Infertilité et l'Enfance (PELAGIE) mother-child cohort (including 3005 working women) were recruited in Brittany (France) between 2002 and 2006, at the beginning of pregnancy, to assess occupational exposure to solvents at that time. Child behaviour was documented at age 2 by mothers (n=1278) assessing components of attention deficit/hyperactivity, aggression, opposition and emotionality. We used a multiple linear regression analysis to evaluate the association between occupational solvent exposure and children's behaviour. Complementary sensitivity analyses allowed us to handle missing data, due mostly to attrition. RESULTS: 20% of women reported occasional exposure and 31% regular exposure to solvents. Children prenatally exposed were more likely to have higher scores of attention deficit/hyperactivity and aggression, and dose-response relations were observed. CONCLUSIONS: The dose-response effect and the high prevalence of children potentially exposed to solvents from their mother's workplace exposure underline the public health relevance of this result. Our results should be replicated in further studies designed to identify which solvents are most deleterious and to assess child behaviour at school age.
ISSN: 1351-0711

inserm-00795043
http://www.hal.inserm.fr/inserm-00795043
http://www.hal.inserm.fr/inserm-00795043/document
http://www.hal.inserm.fr/inserm-00795043/file/Occupationnal_solvent_exposure_child_behavior_HAL.pdf
DOI : 10.1136/oemed-2012-100892

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: The use of pesticides and the related environmental contaminations can lead to human exposure to various molecules. In early-life, such exposures could be responsible for adverse developmental effects. However, human health risks associated with exposure to complex mixtures are currently under-explored. OBJECTIVE: THIS PROJECT AIMS AT ANSWERING THE FOLLOWING QUESTIONS: What is the influence of exposures to multiple pesticides on the metabolome? What mechanistic pathways could be involved in the metabolic changes observed? METHODS: Based on the PELAGIE cohort (Brittany, France), 83 pregnant women who provided a urine sample in early pregnancy, were classified in 3 groups according to the surface of land dedicated to agricultural cereal activities in their town of residence. Nuclear magnetic resonance-based metabolomics analyses were performed on urine samples. Partial Least Squares Regression-Discriminant Analysis (PLS-DA) and polytomous regressions were used to separate the urinary metabolic profiles from the 3 exposure groups after adjusting for potential confounders. RESULTS: The 3 groups of exposure were correctly separated with a PLS-DA model after implementing an orthogonal signal correction with pareto standardizations (R2 = 90.7% and Q2 = 0.53). After adjusting for maternal age, parity, body mass index and smoking habits, the most statistically significant changes were observed for glycine, threonine, lactate and glycerophosphocholine (upward trend), and for citrate (downward trend). CONCLUSION: This work suggests that an exposure to complex pesticide mixtures induces modifications of metabolic fingerprints. It can be hypothesized from identified discriminating metabolites that the pesticide mixtures could increase oxidative stress and disturb energy metabolism.
ISSN: 1932-6203

inserm-00863407
http://www.hal.inserm.fr/inserm-00863407
http://www.hal.inserm.fr/inserm-00863407/document
http://www.hal.inserm.fr/inserm-00863407/file/journal.pone.0064433.pdf
PUBMED : 23704985

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND: The exposure of children to lead has decreased in recent years, thanks notably to the banning of leaded gasoline. However, lead exposure remains a matter of public health concern, because no toxicity threshold has been observed, cognitive effects having been demonstrated even at low levels. It is therefore important to update exposure assessments. A national study was conducted, in 2008-2009, to determine the blood lead level (BLL) distribution in children between the ages of six months and six years in France. We also assessed the contribution of environmental factors. METHODS: This cross-sectional survey included 3831 children recruited at hospitals. Two-stage probability sampling was carried out, with stratification by hospital and French region. Sociodemographic characteristics were recorded, and blood samples and environmental data were collected by questionnaire. Generalized linear model and quantile regression were used to quantify the association between BLL and environmental risk factors. RESULTS: The geometric mean BLL was 14.9μg/l (95% confidence interval (CI)=[14.5-15.4]) and 0.09% of the children (95% CI=[0.03-0.15]) had BLLs exceeding 100μg/l, 1.5% (95% CI=[0.9-2.1] exceeding 50μg/l. Only slight differences were observed between French regions. Environmental factors significantly associated with BLL were the consumption of tap water in homes with lead service connections, peeling paint or recent renovations in old housing, hand-mouth behavior, passive smoking and having a mother born in a country where lead is often used. CONCLUSIONS: In children between the ages of one and six years in France, lead exposure has decreased over the last 15 years as in the US and other European countries. Nevertheless still 76,000 children have BLL over 50μg/l and prevention policies must be pursued, especially keeping in mind there is no known toxicity threshold.
ISSN: 1438-4639

hal-01009847
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01009847
PUBMED : 24262290
DOI : 10.1016/j.ijheh.2013.10.002

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
ABSTRACT: BACKGROUND: The amount of lead in the environment has decreased significantly in recent years, and so did exposure. However, there is no known safe exposure level and, therefore, the exposure of children to lead, although low, remains a major public health issue. With the lower levels of exposure, it is becoming more difficult to identify lead sources and new approaches may be required for preventive action. This study assessed the usefulness of lead isotope ratios for identifying sources of lead using data from a nationwide sample of French children aged from six months to six years with blood lead levels (B-Pb) [greater than or equal to] 25 ug/L. METHODS: Blood samples were taken from 125 children, representing about 600,000 French children; environmental samples were taken from their homes and personal information was collected. Lead isotope ratios were determined using quadrupole ICP-MS (inductively coupled plasma - mass spectrometry) and the isotopic signatures of potential sources of exposure were matched with those of blood in order to identify the most likely sources. RESULTS: In addition to the interpretation of lead concentrations, lead isotope ratios were potentially of use for 57% of children aged from six months to six years with blood lead level [greater than or equal to] 25 ug/L (7% of overall children in France, about 332,000 children), with at least one potential source of lead and sufficiently well discriminated lead isotope ratios. Lead isotope ratios revealed a single suspected source of exposure for 32% of the subjects and were able to eliminate at least one unlikely source of exposure for 30% of the children. CONCLUSIONS: In France, lead isotope ratios could provide valuable additional information in about a third of routine environmental investigations.
ISSN: 1476-069X

inserm-00624817
http://www.hal.inserm.fr/inserm-00624817
http://www.hal.inserm.fr/inserm-00624817/document
http://www.hal.inserm.fr/inserm-00624817/file/1476-069X-10-75.pdf
DOI : 10.1186/1476-069X-10-75

Éditeur(s) : HAL CCSD
Résumé : National audience
Introduction Le paludisme est en nette diminution en Guyane actuellement. Des foyers de transmission persistent en population autochtone, mais cette pathologie touche aujourd’hui majoritairement les orpailleurs clandestins travaillant en Guyane. Cette étude avait pour objectifs d’évaluer le portage de Plasmodium par bassin d’orpaillage et les connaissances, attitudes et pratiques(CAP) des orpailleurs clandestins vis-à-vis du paludisme.
17es Journées Nationales d’Infectiologie
Lille, France

Droits : info:eu-repo/semantics/OpenAccess
inserm-01410986
http://www.hal.inserm.fr/inserm-01410986
http://www.hal.inserm.fr/inserm-01410986/document
http://www.hal.inserm.fr/inserm-01410986/file/2016%2C%20Douine%20-%20PADS%202-06.pdf
PUBMED : 27495620

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
: Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28°C as compared to 37°C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology.
ISSN: 0041-008X

inserm-01067804
http://www.hal.inserm.fr/inserm-01067804
http://www.hal.inserm.fr/inserm-01067804/document
http://www.hal.inserm.fr/inserm-01067804/file/pintot_et_al._manuscript.pdf
DOI : 10.1016/j.taap.2014.07.020

Éditeur(s) : HAL CCSD SAGE Publications (UK and US)
Résumé : International audience
Molecular evolutionary analysis is an efficient method to predict and/or validate amino acid substitutions that could lead to a genetic disease and to highlight residues and motifs that could play an important role in the protein structure and/or function. We have applied such analysis to amelotin (AMTN), a recently identified enamel protein in the rat, mouse, and humans. An in silico search for AMTN provided 42 new mammalian sequences that were added to the 3 published sequences with which we performed the analysis using a dataset representative of all lineages (circa 220 million years of evolution), including 2 enamel-less species, sloth and armadillo. During evolution, of the 209 residues of human AMTN, 17 were unchanged and 34 had conserved their chemical properties. Substituting these important residues could lead to amelogenesis imperfecta (AI). Also, AMTN possesses a well-conserved signal peptide, 2 conserved motifs whose function is certainly important but unknown, and a putative phosphorylation site (SXE). In addition, the sequences of the 2 enamel-less species display mutations revealing that AMTN underwent pseudogenization, which suggests that AMTN is an enamel-specific protein.
ISSN: 0022-0345

hal-01545488
https://hal.archives-ouvertes.fr/hal-01545488
DOI : 10.1177/0022034512460551

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
People are exposed to multiple pollutants, especially indoors. In the perspective of a cumulative risk assessment, a multi-residue analytical method was developed to assess the contamination of indoor suspended particulate matter by 55 semi-volatile organic compounds (SVOCs) including musk fragrances, organochlorines (OCs), organophosphates (OPs), polycyclic aromatic hydrocarbons (PAHs), polybromodiphenylethers (PBDEs), polychlorobiphenyls (PCBs), phthalates and pyrethroids. It is based on thermal desorption (TD) coupled with gas chromatography/mass spectrometry (GC/MS). Once the thermal desorption conditions were optimized, the method was validated in terms of quantification limits and accuracy using a standard reference material (SRM 2585). Instrumental quantification limits were 10pg (some OCs, some pyrethroids, musk fragrances, OPs, PAHs, PBDEs and PCBs), 100pg (phthalates and other OCs) and 1000pg (other pyrethroids) corresponding respectively to method quantification limits of 1, 10, and 100pg/m(3) for a sampled air volume of 20m(3). Calibration quadratic curves for ranges of 10-1000, 100-10,000, and 1000-100,000pg, depending on the substance, exhibit determination coefficients above 0.999. Recoveries were between 61 and 96% for chlorinated pesticides, PAHs, PBDEs and PCBs present in the SRM 2585. A test of the method on indoor particulate matter samples (PM(10)) collected on quartz fiber filters in French dwellings demonstrated its ability to quantify SVOCs from a small amount of PM.
ISSN: 0021-9673

hal-00732133
https://hal.archives-ouvertes.fr/hal-00732133
DOI : 10.1016/j.chroma.2012.07.025
PUBMED : 22840824

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
OBJECTIVES: To investigate whether the glutathione S-transferase polymorphisms GSTM1 and/or GSTT1 contribute to prostate cancer risk in a Caribbean population of African descent in Guadeloupe. METHODS: We performed a hospital-based case-control study with 134 prostate cancer patients and 134 cancer-free, age-matched control subjects. Epidemiologic data were collected using a standard questionnaire. Logistic regression was used to estimate odds ratios (ORs) and compute confidence intervals (CIs). Genotypes were determined by multiplex polymerase chain reaction. RESULTS: The frequency of the GSTM1-positive genotype was 81% in patients and 73% in control subjects, with an adjusted OR of 1.4 (95% CI 0.7 to 2.5). The frequency of the GSTT1-positive genotype was 78% in patients and 63% in control subjects, with an adjusted OR of 2.6 (95% CI 1.4 to 4.9). CONCLUSIONS: A functional GSTT1 polymorphism may be associated with prostate cancer susceptibility in a Caribbean population of African descent.
ISSN: 0090-4295

hal-00688449
https://hal.archives-ouvertes.fr/hal-00688449
DOI : 10.1016/j.urology.2007.02.039
PUBMED : 17572208

Éditeur(s) : HAL CCSD SAGE Publications (UK and US)
Résumé : International audience
In this article, we focus on hypomaturation autosomal-recessive-type amelogenesis imperfecta (type IIA2) and describe 2 new causal Matrix metalloproteinase 20 (MMP20) mutations validated in two unrelated families: a missense mutation p.T130I at the expected homozygous state, and a compound heterozygous mutation having the same mutation combined with a nucleotide deletion, leading to a premature stop codon (p.N120fz*2). We characterized the enamel structure of the latter case using scanning electron microscopy analysis and microanalysis (Energy-dispersive X-ray Spectroscopy, EDX) and confirmed the hypomaturation-type amelogenesis imperfecta as identified in the clinical diagnosis. The mineralized content was slightly decreased, with magnesium substituting for calcium in the crystal structure. The anomalies affected enamel with minimal inter-rod enamel present and apatite crystals perpendicular to the enamel prisms, suggesting a possible new role for MMP20 in enamel formation.
ISSN: 0022-0345

hal-01545484
https://hal.archives-ouvertes.fr/hal-01545484
DOI : 10.1177/0022034513488393

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Environmental exposures, including dietary contaminants, may influence the developing immune system. This study assesses the association between maternal pre-parturition consumption of seafood and wheeze, eczema, and food allergy in preschool children. Fish and shellfish were studied separately as they differ according to their levels of omega-3 polyunsaturated fatty acids (which have anti-allergic properties) and their levels of contaminants. METHODS: The PELAGIE cohort included 3421 women recruited at the beginning of pregnancy. Maternal fish and shellfish intake was measured at inclusion by a food frequency questionnaire. Wheeze, eczema, and food allergy were evaluated by a questionnaire completed by the mother when the child was 2 years old (n = 1500). Examination of the associations between seafood intake and outcomes took major confounders into account. Complementary sensitivity analyses with multiple imputation enabled us to handle missing data, due mostly to attrition. RESULTS: Moderate maternal pre-parturition fish intake (1 to 4 times a month) was, at borderline significance, associated with a lower risk of wheeze (adjusted OR = 0.69 (0.45-1.05)) before age 2, compared with low intake (< once/month). This result was not, however, consistent: after multiple imputation, the adjusted OR was 0.86 (0.63-1.17). Shellfish intake at least once a month was associated with a higher risk of food allergy before age 2 (adjusted OR = 1.62 (1.11-2.37)) compared to low or no intake (< once/month). Multiple imputation confirmed this association (adjusted OR = 1.52 (1.05-2.21)). CONCLUSIONS: This study suggests that maternal pre-parturition shellfish consumption may increase the risk of food allergy. Further large-scale epidemiologic studies are needed to corroborate these results, identify the contaminants or components of shellfish responsible for the effects observed, determine the persistence of the associations seen at age 2, and investigate potential associations with health effects observable at later ages, such as allergic asthma.
ISSN: 1476-069X

Droits : info:eu-repo/semantics/OpenAccess
inserm-00926282
http://www.hal.inserm.fr/inserm-00926282
http://www.hal.inserm.fr/inserm-00926282/document
http://www.hal.inserm.fr/inserm-00926282/file/1476-069X-12-102.pdf
DOI : 10.1186/1476-069X-12-102

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BackgroundMalaria is endemic in French Guiana, an overseas territory of France on the Guiana Shield. Since 2005, notified malaria cases are decreasing. However, new data show that malaria affects many Brazilian gold miners working illegally in French Guiana, the majority of whom are not counted in official data. In addition, one major concern is the usual practice of improper self-treatment in this mining population, raising fear of the development of antimalarial resistance. This prospective study, conducted in 2015, aimed to estimate the prevalence of Plasmodium spp. in illegal gold miners working in French Guiana. MethodsThe recruitment of gold miners was carried out in resting sites along the French Guiana-Suriname border, where they go for supplies, medical care or leisure. After recording agreement, three malaria diagnostic methods were performed: rapid diagnostic test, microscopy and PCR,ResultsAmong 421 persons recruited in the study, malaria prevalence, detected by nested-PCR, was 22.3% (CI=[18.3-26.3], n=94/421) of which 84% were asymptomatic. ConclusionThis significant malaria reservoir in a mobile and illegal population with difficult access to a health care system raises the threat of artemisinin resistance and puts the population of the Guiana Shield at risk of new transmission foci while countries of the region aim at malaria elimination. Even though French legislation may hamper dealing with this population, France must face the reality of malaria in illegal gold miners in order to meet its commitment to malaria elimination.
ISSN: 1475-2875

hal-01346800
https://hal.archives-ouvertes.fr/hal-01346800
https://hal.archives-ouvertes.fr/hal-01346800/document
https://hal.archives-ouvertes.fr/hal-01346800/file/2016%2C%20Douine%20-%20Prevalence%20of%20Plasmodium%20spp.%20in%20illegal%20gold%20miners%20in%20French%20Guiana%20in%202015.pdf
DOI : 10.1186/s12936-016-1367-6

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Despite intensive research over several decades, the etiology of multiple sclerosis (MS) remains poorly understood, although environmental factors are supposedly implicated. Our goal was to identify spatial clusters of MS incident cases at the small-area level to provide clues to local environmental risk factors that might cause or trigger the disease. Methods: A population-based and multi-stage study was performed in the French Brittany region to accurately ascertain the clinical onset of disease during the 2000-2004 period. The municipality of residence at the time of clinical onset was geocoded. To test for the presence of MS incidence clusters and to identify their approximate locations, we used a spatial scan statistic. We adjusted for socioeconomic deprivation, known to be strongly associated with increased MS incident rates, and scanned simultaneously for areas with either high or low rates. Sensitivity analyses (focusing on relapsing-remitting forms and/or places of residence available within the year following clinical onset) were performed. Results: A total of 848 incident cases of MS were registered in Brittany, corresponding to a crude annual incidence rate of 5.8 per 100,000 inhabitants. The spatial scan statistic did not find a significant cluster of MS incidence in either the primary analysis (p value >= 0.56) or in the sensitivity analyses (p value >= 0.16). Conclusion: The findings of this study indicate that MS incidence is not markedly affected across space, suggesting that in the years preceding the first clinical expression of the disease, no environmental trigger is operative at the small-area population level in the French Brittany region.
ISSN: 1476-072X

hal-01616063
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616063
DOI : 10.1186/s12942-017-0108-6
PUBMED : 28934989

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
BACKGROUND: Exposure to solvents during pregnancy has long been suspected of increasing the risk of congenital malformations, but the lack of prospective assessment of specific solvent exposures has prevented definitive conclusions. METHODS: In a cohort of 3421 pregnant women in Brittany (2002-2006), occupational solvent exposure was assessed from self-report during pregnancy and from a job-exposure matrix. Congenital malformations were diagnosed among live births, stillbirths, and medical pregnancy terminations. In a nested case-control sample, urinary concentrations of 10 metabolites of glycol ethers and chlorinated solvents were measured in maternal samples collected during early pregnancy (n = 79 cases, 580 controls). RESULTS: Dose-response trends linked occupational solvent exposure (both self-reported and based on a job-exposure matrix) to the risk of major congenital malformations--especially oral clefts, urinary tract malformations, and male genital malformations. Detection of some glycol ether metabolites and trichloroacetic acid in urine was associated with increased risks of oral clefts and of urinary tract and limb defects. CONCLUSIONS: This prospective study, using three independent methods of exposure assessment, suggests several specific associations between solvent exposure during early pregnancy and congenital malformations. Results based on urinary biomarkers, although limited by small numbers, identify work situations that require further investigation.
ISSN: 1044-3983

hal-00875918
https://hal.archives-ouvertes.fr/hal-00875918
DOI : 10.1097/EDE.0b013e31826c2bd8
PUBMED : 23007043

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
A thorough phytochemical study of Stereocaulon evolutum was conducted, for the isolation of structurally related atranorin derivatives. Indeed, pilot experiments suggested that atra-norin (1), the main metabolite of this lichen, would interfere with the lifecycle of hepatitis C virus (HCV). Eight compounds, including one reported for the first time (2), were isolated and characterized. Two analogs (5, 6) were also synthesized, to enlarge the panel of atra-norin-related structures. Most of these compounds were active against HCV, with a half-maximal inhibitory concentration of about 10 to 70 µM, with depsides more potent than monoaromatic phenols. The most effective inhibitors (1, 5 and 6) were then added at different steps of the HCV lifecycle. Interestingly, atranorin (1), bearing an aldehyde function at C-3, inhibited only viral entry, whereas the synthetic compounds 5 and 6, bearing a hydroxy-methyl and a methyl function, respectively, at C-3 interfered with viral replication.
ISSN: 1932-6203

hal-01134343
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134343
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134343/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134343/file/Depsides-PloS.pdf
DOI : 10.1371/journal.pone.0120405

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Cancer cells display alterations in many cellular processes. One core hallmark of cancer is the Warburg effect which is a glycolytic reprogramming that allows cells to survive and proliferate. Although the contributions of environmental contaminants to cancer development are widely accepted, the underlying mechanisms have to be clarified. Benzo[a]pyrene (B[a]P), the prototype of polycyclic aromatic hydrocarbons, exhibits genotoxic and carcinogenic effects, and it is a human carcinogen according to the International Agency for Research on Cancer. In addition to triggering apoptotic signals, B[a]P may induce survival signals, both of which are likely to be involved in cancer promotion. We previously suggested that B[a]P-induced mitochondrial dysfunctions, especially membrane hyperpolarization, might trigger cell survival signaling in rat hepatic epithelial F258 cells. Here, we further characterized these dysfunctions by focusing on energy metabolism. We found that B[a]P promoted a metabolic reprogramming. Cell respiration decreased and lactate production increased. These changes were associated with alterations in the tricarboxylic acid cycle which likely involve a dysfunction of the mitochondrial complex II. The glycolytic shift relied on activation of the Na+/H+ exchanger 1 (NHE1) and appeared to be a key feature in B[a]P-induced cell survival related to changes in cell phenotype (epithelial-to-mesenchymal transition and cell migration).
ISSN: 2045-2322

Droits : http://creativecommons.org/licenses/by/
hal-01359569
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569/file/The%20environmental%20carcinogen-CCBY%20%281%29.pdf
DOI : 10.1038/srep30776

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: There is increasing evidence that reproductive abnormalities are increasing in frequency in both human population and among wild fauna. This increase is probably related to exposure to toxic contaminants in the environment. The use of sentinel species to raise alarms relating to human reproductive health has been strongly recommended. However, no simultaneous studies at the same site have been carried out in recent decades to evaluate the utility of wild animals for monitoring human reproductive disorders. We carried out a joint study in Guadeloupe assessing the reproductive function of workers exposed to pesticides in banana plantations and of male wild rats living in these plantations. METHODS: A cross-sectional study was performed to assess semen quality and reproductive hormones in banana workers and in men working in non-agricultural sectors. These reproductive parameters were also assessed in wild rats captured in the plantations and were compared with those in rats from areas not directly polluted by humans. RESULTS: No significant difference in sperm characteristics and/or hormones was found between workers exposed and not exposed to pesticide. By contrast, rats captured in the banana plantations had lower testosterone levels and gonadosomatic indices than control rats. CONCLUSION: Wild rats seem to be more sensitive than humans to the effects of pesticide exposure on reproductive health. We conclude that the concept of sentinel species must be carefully validated as the actual nature of exposure may varies between human and wild species as well as the vulnerable time period of exposure and various ecological factors.
Environmental health : a global access science source [electronic resource]

hal-00669505
https://hal.archives-ouvertes.fr/hal-00669505
DOI : 10.1186/1476-069X-7-40
PUBMED : 18667078

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
To improve a previously constructed broadly neutralizing hepatitis B virus (HBV)-specific preS1 humanized antibody (HzKR127), we further humanized it through specificitydetermining residue (SDR) grafting. Moreover, we improved affinity by mutating two residues in heavy-chain complementarity-determining regions (CDR), on the basis of the crystal structure of the antigen–antibody complex. HzKR127-3.2 exhibited 2.5-fold higher affinity and enhanced virus-neutralizing activity compared to the original KR127 antibody and showed less immunogenic potential than HzKR127. Enhanced virus-neutralizing activity was achieved by the increased association rate, providing insights into engineering potent antibody therapeutics for HBV immunoprophylaxis. HzKR127-3.2 may be a good candidate for HBV immunoprophylaxis.
ISSN: 1873-3468

hal-01110668
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01110668
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01110668/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01110668/file/Enhanced%20humanization_accepted.pdf
DOI : 10.1016/j.febslet.2014.11.046