Éditeur(s) : HAL CCSD Ferrata Storti Foundation
Résumé : International audience
BACKGROUND: Abnormal interactions between red blood cells, leukocytes and endothelial cells play a critical role in the occurrence of the painful vaso-occlusive crises associated with sickle cell disease. We investigated the interaction between circulating leukocytes and red blood cells which could lead to aggregate formation, enhancing the incidence of vaso-occlusive crises. DESIGN AND METHODS: Blood samples from patients with sickle cell disease (n=25) and healthy subjects (n=5) were analyzed by imaging and classical flow cytometry after density gradient separation. The identity of the cells in the peripheral blood mononuclear cell layer was determined using antibodies directed specifically against white (anti-CD45) or red (anti-glycophorin A) blood cells. RESULTS: Aggregates between red blood cells and peripheral blood mononuclear cells were visualized in whole blood from patients with sickle cell disease. The aggregation rate was 10-fold higher in these patients than in control subjects. Both mature red blood cells and reticulocytes were involved in these aggregates through their interaction with mononuclear cells, mainly with monocytes. The size of the aggregates was variable, with one mononuclear cell binding to one, two or several red blood cells. Erythroid Lu/basal cell adhesion molecule and α(4)β(1) integrin were involved in aggregate formation. The aggregation rate was lower in patients treated with hydroxycarbamide than in untreated patients. CONCLUSIONS: Our study gives visual evidence of the existence of circulating red blood cell-peripheral blood mononuclear cell aggregates in patients with sickle cell disease and shows that these aggregates are decreased during hydroxycarbamide treatment. Our results strongly suggest that erythroid Lu/basal cell adhesion molecule proteins are implicated in these aggregates through their interaction with α(4)β(1) integrin on peripheral blood mononuclear cells.
ISSN: 0390-6078

inserm-00821120
http://www.hal.inserm.fr/inserm-00821120
http://www.hal.inserm.fr/inserm-00821120/document
http://www.hal.inserm.fr/inserm-00821120/file/1841.full.pdf
DOI : 10.3324/haematol.2010.026294

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 Elsevier
Résumé : International audience
Despite the dramatic reductions in children's blood lead levels (BLLs), there is considerable evidence that low-level lead exposure is associated with intellectual deficits and behavioral problems, without apparent threshold. There are limited data, however, about the contribution of residential sources of lead to contemporary children's blood lead levels. The aim of this study is to calculate the contributions of residential sources of lead to assess the potential impact of setting new standards for lead levels in residential dust, soil and water. We enrolled 484 French children aged from 6 months to 6 years, and collected data on social, housing and individual characteristics. Lead concentrations in blood and environmental samples (water, soils, and dusts) were measured using inductively coupled plasma mass spectrometry. Data were analyzed using a multivariate generalized additive model accounting for the sampling design and the sampling weights. We found that exceedingly low concentrations of lead in dust, soil and water were significant predictors of children's BLLs, after adjustment for potential confounding variables. Lead-contaminated floor dust was the main source of lead in blood. BLLs (GM: 14μg/L) increased by 65%, 13%, 25%, and 5% when lead content in floor dust, loose soil, hard soil and water increased from their 25th percentile to their 95th percentile, respectively. We also observed that the steepest increase in BLLs occurred at the lowest levels of lead-contaminated floor dust, which indicates that lead contamination should be kept as low as possible. Impact of different possible standards on children's BLLs was also tabulated and indicated that unless standards are set low, they will only benefit a small proportion of children who have the highest exposures.
ISSN: 1438-4639

inserm-00821999
http://www.hal.inserm.fr/inserm-00821999
DOI : 10.1016/j.ijheh.2013.02.007
PUBMED : 23528234

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
The decline in children's Blood Lead Levels (BLL) raises questions about the ability of current lead poisoning screening criteria to identify those children most exposed. The objectives of the study were to evaluate the performance of current screening criteria in identifying children with blood lead levels higher than 50 µg/L in France, and to propose new criteria. Data from a national French survey, conducted among 3831 children aged 6 months to 6 years in 2008-2009 were used. The sensitivity and specificity of the current criteria in predicting blood lead levels higher than or equal to 50 µg/L were evaluated. Two predictive models of BLL above 44 µg/L (for lack of sufficient sample size at 50 µg/L) were built: the first using current criteria, and the second using newly identified risk factors. For each model, performance was studied by calculating the area under the ROC (Receiver Operating Characteristic) curve. The sensitivity of current criteria for detecting BLL higher than or equal to 50 µg/L was 0.51 (0.26; 0.75) and specificity was 0.66 (0.62; 0.70). The new model included the following criteria: foreign child newly arrived in France, mother born abroad, consumption of tap water in the presence of lead pipes, pre-1949 housing, period of construction of housing unknown, presence of peeling paint, parental smoking at home, occupancy rates for housing and child's address in a cadastral municipality or census block comprising more than 6% of housing that is potentially unfit and built pre-1949. The area under the ROC curve was 0.86 for the new model, versus 0.76 for the current one. The lead poisoning screening criteria should be updated. The risk of industrial, occupational and hobby-related exposure could not be assessed in this study, but should be kept as screening criteria
ISSN: 1660-4601

hal-01239804
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01239804
DOI : 10.3390/ijerph121214989
PUBMED : 26633457

Éditeur(s) : HAL CCSD
Résumé : Red blood cell hemodynamics influence blood rheology and thus circulatory function. Different authors showed that red blood cells are heterogeneous in blood flow. This heterogeneity could be explained by physical characteristics such as morphology, aggregability and deformability, but also by cellular and molecular environment. All these notions are found in sickle cell disease where sickle red blood cells become more rigid, leading to vascular occlusions, increased with an inflammatory context. In a preceding study, our results showed that velocity heterogeneity allow RBC classification, leading to different RBC sub-groups, using a dynamical approach and flow studies. In order to have a better understanding of the physiological meaning of such an heterogeneity, dynamical velocity experiences have been conducted in the case of normal and sickle red blood cells with different endothelial activations by proinflammatory cytokines, under a constant venular flow. Thus, normal and sickle red blood cells are classified into different sub-groups, showing their heterogeneity. Moreover, sub-population velocities and distribution evolve differently according to vascular state or treatment. These results show that red blood cell velocities and rheology depend on vascular environment and red blood cell morphology. However, the physiological meaning of this behavior should be explained by cellular and molecular effects of such activation.
https://hal.archives-ouvertes.fr/hal-00201461

hal-00201461
https://hal.archives-ouvertes.fr/hal-00201461
https://hal.archives-ouvertes.fr/hal-00201461/document
https://hal.archives-ouvertes.fr/hal-00201461/file/RBCV_Marianne_v1.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background: Blood Lead Levels (BLLs) have substantially decreased in recent decades in children in France. However, further reducing exposure is a public health goal because there is no clear toxicological threshold. The identification of the environmental determinants of BLLs as well as risk factors associated with high BLLs is important to update prevention strategies. We aimed to estimate the contribution of environmental sources of lead to different BLLs in children in France.Methods: We enrolled 484 children aged from 6 months to 6 years, in a nationwide cross-sectional survey in 2008-2009. We measured lead concentrations in blood and environmental samples (water, soils, household settled dusts, paints, cosmetics and traditional cookware). We performed two models: a multivariate generalized additive model on the geometric mean (GM), and a quantile regression model on the 10th, 25th, 50th, 75th and 90th quantile of BLLs. Results: The GM of BLLs was 13.8 μg/L (=1.38 µg/dL) (95% Confidence Intervals (CI): 12.7-14.9) and the 90th quantile was 25.7 μg/L (CI: 24.2-29.5). Household and common area dust, tap water, interior paint, ceramic cookware, traditional cosmetics, playground soil and dust, and environmental tobacco smoke were associated with the GM of BLLs. Household dust and tap water made the largest contributions to both the GM and the 90th quantile of BLLs. The concentration of lead in dust was positively correlated with all quantiles of BLLs even at low concentrations. Lead concentrations in tap water above 5 µg/L were also positively correlated with the GM, 75th and 90th quantiles of BLLs in children drinking tap water.Conclusions: Preventative actions must target household settled dust and tap water to reduce the BLLs of children in France. The use of traditional cosmetics should be avoided whereas ceramic cookware should be limited to decorative purposes.
ISSN: 0160-4120

Droits : info:eu-repo/semantics/OpenAccess
hal-01099719
https://hal.archives-ouvertes.fr/hal-01099719
https://hal.archives-ouvertes.fr/hal-01099719/document
https://hal.archives-ouvertes.fr/hal-01099719/file/Manuscript_Etchevers_EI_V3_no%20%20changes%20marked.pdf
DOI : 10.1016/j.envint.2014.10.007

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Heterogeneous patterns of malaria transmission are thought to be driven by factors including host genetics, distance to mosquito breeding sites, housing construction, and socio-behavioural characteristics. Evaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) techniques has been a major asset to this approach. To assess time and space distribution of malaria disease in Bandiagara, Mali, within a transmission season, data were used from an ongoing malaria incidence study that enrolled 300 participants aged under six years old ". Methods: Children's households were georeferenced using a handheld global position system. Clinical malaria was defined as a positive blood slide for Plasmodium falciparum asexual stages associated with at least one of the following signs: headache, body aches, fever, chills and weakness. Daily rainfall was measured at the local weather station. Landscape features of Bandiagara were obtained from satellite images and field survey. QGIS™ software was used to map malaria cases, affected and non-affected children, and the number of malaria episodes per child in each block of Bandiagara. Clusters of high or low risk were identified under SaTScan W software according to a Bernoulli model. Results: From June 2009 to May 2010, 296 clinical malaria cases were recorded. Though clearly temporally related to the rains, Plasmodium falciparum occurrence persisted late in the dry season. Two " hot spots " of malaria transmission also found, notably along the Yamé River, characterized by higher than expected numbers of malaria cases, and high numbers of clinical episodes per child. Conversely, the northeastern sector of the town had fewer cases despite its proximity to a large body of standing water which was mosquito habitat. Conclusion: These results confirm the existence of a marked spatial heterogeneity of malaria transmission in Bandiagara, providing support for implementation of targeted interventions. Background Malaria is one of the leading causes of morbidity and mortality in the world, with an estimated 3.3 billion people at risk of malaria [1]. The incidence of malaria worldwide is estimated to be 216 million cases per year, with 81% of these cases occurring in sub-Saharan Africa. Malaria kills approximately 655,000 people per year; 91% of deaths occur in sub-Saharan Africa [1], mostly in children under five years of age. In Mali, West Africa, malaria represents 36.5% of consultation motives in health center, it is a leading cause of morbidity and mortality children of less than five years of age and the first reason of anaemia in pregnant women [2]. Malaria transmission is seasonal. Malaria parasite transmission and clinical disease are characterized by important microgeographic variation, often between adjacent villages, households or families [3-8]. This local heterogeneity is driven by a variety of factors including human genetics [9,10], distance to potential breeding sites [11,12], housing construction
ISSN: 1475-2875

hal-01307672
https://hal-amu.archives-ouvertes.fr/hal-01307672
https://hal-amu.archives-ouvertes.fr/hal-01307672/document
https://hal-amu.archives-ouvertes.fr/hal-01307672/file/1475-2875-12-82.pdf
DOI : 10.1186/1476-072X-2-5

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) : Academic Press Ltd- Elsevier Science Ltd
Résumé : Antioxidant defences and induced oxidative stress tissue damage of the blue shrimp Litopenaeus stylirostris, under challenge with Vibrio nigriputchritudo, were investigated for a 72-h period. For this purpose, L stylirostris were first infected by immersion with pathogenic V. nigripulchritudo strain SFn1 and then antioxidant defences: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), Total antioxidant status (TAS), glutathiones and induced tissue damage (MDA and carbonyl proteins) were determined in the digestive gland at 0, 12, 24, 48 and 72 h post-infection (h.p.i.). In the meantime, TAS was also measured in the blood. Infection level of the shrimps during the challenge was followed by determining V. nigripulchritudo prevalence and load in the haemolymph of the shrimps. Changes in all these parameters during the 72-h.p.i. period were recorded for control shrimps and shrimps previously fed for one month with probiotic Pediococcus aciditactici MA18/5M at 10(7) CFU g(-1) of feed. Our results showed that immersion with V nigripulchritudo led to maximal infection level in the haemolymph at 24 h.p.i. preceding the mortality peak recorded at 48 h.p.i. Significant decreases in the antioxidant defences were detected from 24 h.p.i. and beyond that time infection leaded to increases in oxidative stress level and tissue damage.. Compared to control group, shrimps fed the probiotic diet showed lower infection (20% instead of 45% at 24 h.p.i. in the control group) and mortality (25% instead of 41.7% in the control group) levels. Moreover, infected shrimp fed the probiotic compared to uninfected control shrimps exhibited very similar antioxidant status and oxidative stress level. Compared to the infected control group, shrimps fed the probiotic sustained higher antioxidant defences and lower oxidative stress level. This study shows that bacterial infection leads to oxidative stress in L. stylirostris and highlighted a beneficial effect of P. acidilactici, suggesting both a competitive exclusion effect leading to a reduction of the infection level and/or an enhancement of the antioxidant status of the shrimps. (C) 2010 Elsevier Ltd. All rights reserved.
Fish & Shellfish Immunology (1050-4648) (Academic Press Ltd- Elsevier Science Ltd), 2010-04 , Vol. 28 , N. 4 , P. 622-631

Droits : 2010 Elsevier Ltd All rights reserved.
http://archimer.ifremer.fr/doc/00003/11419/7984.pdf
DOI:10.1016/j.fsi.2009.12.024
http://archimer.ifremer.fr/doc/00003/11419/

Éditeur(s) : HAL CCSD
Résumé : International audience
Objective Macrophages may play a significant role in the initiating stages leading to chronic inflammation/infection in cystic fibrosis (CF), via an inability to act as a suppressor cell. In a previous study demonstrating impaired function of CF macrophage, we have shown high production of soluble CD14 (sCD14). The aim of the present work is to determine origin and function of sCD14 in blood monocyte-derived macrophages from stable adult CF patients. Methods To study origin, sCD14 is measured by ELISA in supernatant of macrophages from healthy subjects (non-CF) treated with PI-PLC or cholesterol. The involvement of sCD14 in inflammation, was investigated by analysis of NF-kB and caspase 1 pathways in non-CF macrophages treated by sCD14. Measurement of gene expression was done by qPCR and proteins were quantified by ELISA and Western blot. Results Treatment with PI-PLC increased sCD14 level in the supernatant of non-CF macrophages whereas cholesterol did not modified it. Furthermore high secretion of sCD14 from CF macrophages was decreased by an inhibitor of PI-PLC. Treatment with sCD14 increased pro-IL-1β, IL-8 and TNF-α expression resulting from NF-kB activation through IkBa phosphorylation, this effect was inhibited by NF-kB inhibitors. Also, activation of caspase 1 by cleavage of pro-caspase 1 allowed the secretion of mature IL-1β, inhibited by an inhibitor of caspase 1. However, inflammasome complex involved in caspase 1 activation remains to be determined. Conclusion This data show that origin of sCD14 is partly due to the action of lipases cutting the GPI tail that serves as a membrane anchor to CD14. Furthermore sCD14 have a role in chronic inflammation in CF
the 38th European Cystic Fibrosis Conference
Vienne, Austria

hal-01162773
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162773
DOI : 10.1016/S1569-1993(15)30203-4

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
Lead in childhood is well known to be associated with poor neurodevelopment. As part of a study on maternal anemia and offspring neurodevelopment, we analyzed blood lead level (BLL) with no prior knowledge of lead exposure in 225 mothers and 685 offspring 1 to 2 years old from Allada, a semi-rural area in Benin, sub-Saharan Africa, between May 2011 and May 2013. Blood samples were analyzed by inductively coupled plasma mass spectrometry. Environmental assessments in households and isotopic ratio measurements were performed for eight children with BLL extgreater 100 µg/L. High lead levels (BLL extgreater 50 µg/L) were found in 44% of mothers and 58% of children. The median BLL was 55.1 (interquartile range 39.2-85.0) and 46.6 (36.5-60.1) µg/L, respectively. Maternal BLL was associated with offspring's consumption of piped water and animals killed by ammunition. Children's BLL was associated with presence of paint chips in the house and consumption of animals killed by ammunition. In this population, with 98% of children still breastfed, children's BLL was highly associated with maternal BLL on multivariate analyses. Environmental measures and isotopic ratios supported these findings. Offspring may be highly exposed to lead in utero and probably via breastfeeding in addition to lead paint exposure
ISSN: 1660-4601

hal-01296778
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01296778
DOI : 10.3390/ijerph13030316
PUBMED : 26978384

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND: Evidence of human sexual transmission during Zika virus emergence is a matter of concern, particularly in procreation, but to date, kinetics of seminal shedding and the effects of infection on human reproductive function have not been described. To investigate the effects of Zika virus infection on semen and clearance of Zika virus from semen and body fluids, we aimed to study a cohort of Zika virus-infected men. METHODS: This prospective observational study recruited men presenting with acute Zika virus infection at Pointe-à-Pitre University Hospital in Guadeloupe, French Caribbean, where a Zika virus outbreak occurred between April and November, 2016. Blood, urine, and semen were collected at days 7, 11, 20, 30, 60, 90, and 120 after symptom onset, and semen characteristics, such as total sperm count, sperm motility, vitality, and morphology, and reproductive hormone concentrations, such as testosterone, inhibin, follicle-stimulating hormone, and luteinising hormone, were assessed. At days 7, 11, and 20, semen was processed to isolate motile spermatozoa. Zika virus RNA was detected by RT-PCR using whole blood, serum, urine, seminal plasma, semen cells, and motile spermatozoa fractions. Zika virus was isolated from different sperm fractions on Vero E6 cultures. FINDINGS: 15 male volunteers (mean age 35 years [SD 5; range 25-44) with acute Zika virus infection and positive Zika virus RNA detection in blood or urine were enrolled. Total sperm count was decreased from median 119 × 10(6) spermatozoa (IQR 22-234) at day 7 to 45·2 × 10(6) (16·5-89·6) at day 30 and 70 × 10(6) (28·5-81·4) at day 60, respectively, after Zika virus infection. Inhibin values increased from 93·5 pg/mL (IQR 55-162) at day 7 to 150 pg/mL (78-209) at day 120 when total sperm count recovered. In motile spermatozoa obtained after density gradient separation, Zika virus RNA was found in three of 14 patients at day 7, four of 15 at day 11, and four of 15 at day 20, and replication-competent virus was found in the tested patient. Seminal shedding kinetics seemed heterogeneous among patients. Whole blood was the fluid most frequently positive for Zika virus RNA (62 of 92 samples) and three patients remained positive at day 120. INTERPRETATION: Semen alterations early after acute Zika virus infection might affect fertility and could be explained by virus effects on the testis and epididymis. Frequency of shedding and high viral load in semen, together with the presence of replicative virus in a motile spermatozoa fraction, can lead to Zika virus transmission during sexual contact and assisted reproduction procedures. Whole blood seems to be the best specimen for Zika virus RNA detection, diagnosis, and follow-up. FUNDING: Agence de la Biomédecine/Agence Régionale de Santé de la Guadeloupe/Inserm-REACTing.
ISSN: 0140-6736

hal-01647078
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647078
DOI : 10.1016/S1473-3099(17)30444-9
PUBMED : 28838639

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
29 inorganic compounds (Al, As, B, Ba, Be, Bi, Ca, Cd, Ce, Co, Cr, Cu, Fe, Gd, K, Mg, Mn, Mo, Na, Nd, Ni, Pb, Sb, Se, Sr, Ti, U, V and Zn) were measured in the tap water of 484 representative homes of children aged 6 months to 6 years in metropolitan France in 2008-2009. Parents were asked whether their children consumed tap water. Sampling design and sampling weights were taken into account to estimate element concentrations in tap water supplied to the 3,581,991 homes of 4,923,058 children aged 6 months to 6 years. Median and 95th percentiles of concentrations in tap water were in mu g/L: Al: <10, 483, As: 02, 2.1; B: <100, 100; Ba: 30.7, 149.4; Ca: 85,000, 121,700; Cd: <0.5, <0.5; Ce: <0.5, <0.5; Co: <0.5, 0.8; Cr: <5, <5; Cu: 70, 720; K: 2210, 6740; Fe: <20, 46; Mn: <5, <5; Mo: <0.5,1.5; Na: 14,500, 66,800; Ni: <2,10.2; Mg: 6500,21,200; Pb: <1, 5.4; Sb: <0.5, <0.5; Se: <1, 6.7; Sr: 256.9, 1004; TI: <0.5, <0.5; U: <0.5, 2.4; V: <1, 1; Zn; 53, 208. Of the 2,977,123 young children drinking tap water in France, some were drinking water having concentrations above the 2011 World Health Organization drinking water quality guidelines: respectively 498 (CI 95%: 0-1484) over 700 mu g/L of Ba; 121,581 (CI 95%: 7091-236,070) over 50 mg/L of Na; 2044 (CI 95%: 0-6132) over 70 mu g/L of Ni, and 78,466 (17,171-139,761) over 10 mu g/L of Pb. Since it is representative, this tap water contamination data can be used for integrated exposure assessment, in conjunction with diet and environmental (dust and soil) exposure data. (C) 2016 Elsevier Ltd. All rights reserved.
ISSN: 0160-4120

hal-01390976
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390976
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390976/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390976/file/Le%20Bot%202016%20EI%20revision1%20.pdf
DOI : 10.1016/j.envint.2016.06.009

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND:In French Guiana, a French overseas territory in South America, 6 to 10 thousands undocumented persons work illegally in gold mining sites in the Amazonian forest. Precarious life conditions lead to poor health but few data exist on the health status of illegal gold miners in French Guiana. The objective of this article was to describe the sociodemographic and health status of this vulnerable population.METHOD:A prospective cross-sectional survey was conducted in 2015 on gold mine supply sites at the border between French Guiana and Suriname. Health status was assessed through medical examination, past medical history, haemoglobin concentration, and HIV and malaria testing. A questionnaire was used to collect data about the migration itinerary and life conditions on mining sites.RESULTS:Among the 421 adults included in the study, 93.8% (395/421) were Brazilian, mainly from Maranhão (55.7%, 220/395), the poorest Brazilian state. The sex ratio was 2.4. Overall, 48% of persons never went to school or beyond the primary level. The median time spent in gold mining was quite long (10 years), with a high turn-over. One third of the surveyed population (37.1%, 156/421) had high blood pressure, and only two had a medical follow-up. Most persons had experienced malaria (89.3%, 376/421). They declared frequent arboviroses and digestive disorders. Active leishmaniasis was observed in 8.3% of gold miners. Among women, 28.5% were anemic. Concerning HIV, 36.6% (154/421) of persons, mainly men, never got tested before and 6 were tested positive, which represented an HIV prevalence of 1.43% (95%CI =0.29-2.5).CONCLUSION:These findings support the hypothesis that mining in remote areas is linked to several specific illnesses. Theoretically, gold miners would be presumed to start their economical migration to French Guiana as a healthy group. However, their strenuous working and living conditions there lead to poor health caused by infectious and non infectious diseases. This description of their health status is precious for health policy planners in French Guiana given the importance of controlling communicable disease, and the severity and range of specific illnesses acquired by this neglected population.TRIAL REGISTRATION:Clinical trial registration PRS N° NCT02903706 . Retrospectively registered 09/13/2016.
ISSN: 1471-2458

inserm-01566314
http://www.hal.inserm.fr/inserm-01566314
http://www.hal.inserm.fr/inserm-01566314/document
http://www.hal.inserm.fr/inserm-01566314/file/2017%2C%20Douine%20-%20Illegal%20gold%20miners%20in%20French%20Guiana.pdf
DOI : 10.1016/S0140-6736(10)62169-1

Éditeur(s) : HAL CCSD Portland Press
Résumé : International audience
Lutheran (Lu) blood group and Basal Cell Adhesion Molecule (BCAM) antigens both reside on two glycoprotein (gp) isoforms, Lu and Lu(v13), that differ by the size of their cytoplasmic tail. They are receptors of laminin-10/11 and are expressed in red blood cells (RBCs), epithelial cells of multiple tissues and vascular endothelial cells. To gain more insights into the biological function of Lu/BCAM gps, we looked for potential partners of their cytoplasmic tail. We isolated Ubc9 (Ubiquitin-conjugating enzyme 9) protein by screening a human kidney library using the yeast two-hybrid system. Lu/Ubc9 interaction was validated by GST pull-down and co-immunoprecipitation experiments. Endogenous Ubc9 formed a complex with endogenous or recombinant Lu gp in A498 and MDCK epithelial cells, respectively. Substitution of lysine 585 by alanine in the Lu gp, abolished in vitro and ex vivo interaction of Lu gp with Ubc9 protein. Lu K585A mutant transfected in MDCK cells exhibited a normal basolateral membrane expression but was overexpressed at the surface of polarized MDCK cells as compared to wild-type Lu. Pulse-chase experiments showed extended half-life of Lu K585A gp at the plasma membrane, suggesting an impaired endocytosis of this mutant leading to protein accumulation at the membrane. Furthermore, we showed that the ability of MDCK-Lu K585A cells to spread on immobilized laminin was dramatically decreased. Our data supports a physiological role for the direct interaction between Lu gp and Ubc9 protein, and reveals a role for this enzyme in regulating the stability of Lu gp at the cell membrane.
ISSN: 0264-6021

hal-00478614
https://hal.archives-ouvertes.fr/hal-00478614
https://hal.archives-ouvertes.fr/hal-00478614/document
https://hal.archives-ouvertes.fr/hal-00478614/file/PEER_stage2_10.1042%252FBJ20060861.pdf
DOI : 10.1042/BJ20060861

Résumé : La drépanocytose est une hémoglobinopathie aux formes et aux sévérités cliniques très hétérogènes qui affectent de nombreux organes chez les patients touchés. Pour cette raison le terme de syndrome drépanocytaire majeur est généralement employé. Tous les syndromes drépanocytaires majeurs ont en commun une mutation ponctuelle du gène β-globine appelée mutation βs . Cette mutation βs conduit à la synthèse de la protéine d'hémoglobine S (HbS) caractérisée par sa capacité à polymériser dans sa forme désoxygénée. La polymérisation de l'HbS est l'élément déclencheur de la falciformation du globule rouge et conduit à de nombreuses altérations hématologiques et hémorhéologiques. Ces dernières sont à l'origine de troubles de l'hémodynamique, de l'oxygénation sanguine et de la perfusion tissulaire en oxygène. Il en résulte de nombreuses complications aigues (crise vaso-occlusive, accident vasculaire cérébral, syndrome thoracique aigu etc.) et/ou chroniques (glomérulopathie, ostéonécrose de la tête fémorale etc.) causés par un défaut d'oxygénation des tissus.
Sickle cell anemia is a hemoglobinopathy forms and severities very heterogeneous clinical affecting many organs in affected patients. For this reason the term major sickle cell syndrome is generally used. All major sickle cell syndromes have a common point mutation in the gene called β-globin mutation βs. This βs mutation leads to the synthesis of the protein hemoglobin S (HbS) is characterized by its ability to polymerize in its deoxygenated form. The polymerization of HbS is the trigger for the sickling of red blood cells and leads to many Hematological and hemorheological. These are at the origin of disorders hemodynamics, blood oxygenation and tissue perfusion with oxygen. This results in many acute complications (vaso-occlusive crisis, stroke, acute chest syndrome, etc..) And / or chronic (glomerulopathy, osteonecrosis of the femoral head etc.). Caused by a defect of tissue oxygenation.

http://www.theses.fr/2012AGUY0563/document

Éditeur(s) : HAL CCSD
Résumé : International audience
Objective Oxidative stress, excess production of reactive oxygen species (ROS) and intense colonization of the respiratory tract by microorganisms are described in CF patients, leading to an influx in macrophages. This results in activation of NADPH oxidase that yields ROS, initiating the oxidative burst responsible for pathogen destruction. We showed that phagocytosis was altered in CF macrophages, yet oxidative status in this cell was not defined. The objective of this study is to draw a link between oxidative stress and plasma membrane integrity in CF macrophages, since lipid peroxidation is known to alter cell membrane. Methods Peripheral blood monocytes-derived macrophages were obtained from CF patients and healthy subjects. Plasma membrane fluidity was assessed with di4-ANEPPDHQ and oxidative status was measured with ROS indicating probes. Results In CF macrophages, membrane fluidity was increased whereas lipid peroxidation was diminished. Surprisingly, general oxidative status remained similar to the one observed in non-CF macrophages. Also, CF macrophages did not abolish chemically induced-oxidative stress. In non-CF macrophages, treatment with cholesterol slightly increased membrane fluidity whereas LPS treatment had no effect. Conclusion CF macrophages displayed an increased membrane fluidity associated with a decreased lipid peroxidation. This raises the hypothesis that membrane alteration in CF macrophages may be due to other mechanism than oxidative stress. Nevertheless, since the killing capacity of CF macrophage is defective, a deregulation of O•−2 production is very likely, suggesting alteration of NADPH oxidase or mitochondrial dysfunction
the 38th European Cystic Fibrosis Conference
Vienne, Austria

hal-01162769
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162769
DOI : 10.1016/S1569-1993(15)30217-4

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Early in life, cystic fibrosis (CF) patients are infected with microorganisms. The role of macrophages has largely been underestimated in literature, whereas the focus being mostly on neutrophils and epithelial cells. Macrophages may however play a significant role in the initiating stages of this disease, via an inability to act as a suppressor cell. Yet macrophage dysfunction may be the first step in cascade of events leading to chronic inflammation/infection in CF. Moreover, reports have suggested that CFTR contribute to altered inflammatory response in CF by modification of normal macrophage functions. OBJECTIVES: In order to highlight possible intrinsic macrophage defects due to impaired CFTR, we have studied inflammatory cytokines secretions, recognition of pathogens and phagocytosis in peripheral blood monocyte-derived macrophages from stable adult CF patients and healthy subjects (non-CF). RESULTS: In CF macrophage supernatants, concentrations of sCD14, IL-1β, IL-6, TNF-α and IL-10 were strongly raised. Furthermore expression of CD11b and TLR-5 were sorely decreased on CF macrophages. Beside, no difference was observed for mCD14, CD16, CD64, TLR-4 and TLR1/TLR-2 expressions. Moreover, a strong inhibition of phagocytosis was observed for CF macrophages. Elsewhere CFTR inhibition in non-CF macrophages also led to alterations of phagocytosis function as well as CD11b expression. CONCLUSIONS: Altogether, these findings demonstrate excessive inflammation in CF macrophages, characterized by overproduction of sCD14 and inflammatory cytokines, with decreased expression of CD11b and TLR-5, and impaired phagocytosis. This leads to altered clearance of pathogens and non-resolution of infection by CF macrophages, thereby inducing an exaggerated pro-inflammatory response.
ISSN: 1932-6203

inserm-00872278
http://www.hal.inserm.fr/inserm-00872278
http://www.hal.inserm.fr/inserm-00872278/document
http://www.hal.inserm.fr/inserm-00872278/file/Impaired_Functions.accepted.pdf
DOI : 10.1371/journal.pone.0075667

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : PURPOSE OF REVIEW: Malaria represents one of the most important selective factors affecting human populations. Several inherited diseases of red blood cells lead to resistance at the erythrocytic stage. Among patients who experience hereditary elliptocytosis related to mutations of erythrocyte membrane proteins, molecular studies have shown the prevalence of particular spectrin mutations in patients from black ethnic extraction, leading one to question the selection of new malaria-resistant genes. RECENT FINDINGS: Prospective epidemiological and molecular studies in West Africa have confirmed the prevalence (between 0.6 and 1.6%) of particular spectrin mutations related to hereditary elliptocytosis. These studies have also revealed the frequency of alpha-spectrin chain polymorphisms, associated in cis with elliptocytogenic spectrin mutations and defining particular spectrin allele haplotypes. Culture studies of Plasmodium falciparum in elliptocytes bearing such elliptocytogenic alleles of spectrin showed that these alleles are supplementary genetic factors of malaria resistance in vitro. SUMMARY: Certain instances of spectrin mutations or polymorphisms have not yet been shown to constitute new factors of innate resistance to malaria in vivo. Epidemiological surveys of hereditary elliptocytosis and parasite culture studies, however, have argued that the relationships between parasite and spectrin-based skeleton should be examined more closely and the molecular interactions between parasite ligands and particular spectrin chain domains should be characterized.
ISSN: 1065-6251

inserm-00128119
http://www.hal.inserm.fr/inserm-00128119
http://www.hal.inserm.fr/inserm-00128119/document
http://www.hal.inserm.fr/inserm-00128119/file/Dhermy_et_al_figures.pdf
DOI : 10.1097/MOH.0b013e3280d21afd

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
Sickle cell anemia (SCA or SS homozygous sickle cell disease) is an inherited blood disorder caused by single 12 nucleotide substitution in the ␤-globin gene that renders their hemoglobin (HbS) much less soluble than normal hemoglobin 13 (HbA) when deoxygenated. The polymerization of HbS upon deoxygenation is the basic pathophysiologic event leading to 14 RBC sickling, hemolysis, vasoocclusion and ultimately to chronic organ damage. The metabolic changes imposed by exercise 15 may initiate sickling and vaso-occlusive episodes. Further, in patients with SCA, exercise limitation may be related to anemia 16 or chronic complications such as pulmonary vascular disease, congestive heart failure and chronic parenchymal lung disease. 17 Few studies have investigated the cardiorespiratory responses of patients with SCA during either symptom-limited maximal 18 exercise test on cyclo-ergometer or during a six minute walk test. Therefore, patients are advised to start exercise slowly and 19 progressively, to maintain adequate hydration during and after exercise, to avoid cold exposure or sudden change in temperature, 20 and to avoid sports associated with mechanical trauma. There are, however, lack of evidence to allow practitioners to prescribe 21 an exercise program for patients with SCA, and individuals are usually encouraged to exercise on a symptom-limited basis. 22 Finally, this review will also highlight the basic principles that are often used for exercise practice and could be used for exercise 23 prescription and rehabilitation in patients with sickle cell anemia.
ISSN: 1386-0291

hal-01163966
https://hal.univ-antilles.fr/hal-01163966
DOI : 10.3233/CH-2011-1465