Éditeur(s) : HAL CCSD
Résumé : International audience
Background Chlordecone is a persistent organochlorine insecticide with well-defined estrogenic properties. It was intensively used in the French West Indies until 1993 to control the banana root borer. Because of the long-term contamination of soils and water, the population is currently exposed to chlordecone through food consumption. Chlordecone has been found in the blood of pregnant women and in cord blood. It has been shown to be an endocrine-disrupting chemical and exposure during pregnancy may affect fetal growth. Objectives The objective of our study was to examine the association between prenatal exposure to chlordecone and fetal growth based on the TIMOUN birth cohort conducted in Guadeloupe, with a focus on the potential modification of this relationship by maternal body mass index (BMI) and gestational weight gain (GWG). Methods Chlordecone was determined in cord plasma at birth in 593 babies. Birth weight was the indicator of fetal growth. Maternal pre-pregnancy BMI and GWG were determined. Adherence to GWG recommendations of the US Institute of Medicine based on maternal pre-pregnancy BMI was assessed. Birth weight was analyzed relative to cord blood chlordecone levels using linear and non-linear regression models. Results Overall chlordecone in cord blood was not associated with birth weight, but we found an interaction between chlordecone exposure with GWG and adherence to GWG recommendations. After stratification by GWG, we found a significant U-shaped association between birth weight and chlordecone exposure, within the upper quartiles of GWG or excessive GWG. Conclusion Chlordecone exposure may affect fetal growth, particularly when excessive GWG is present. © 2016 Elsevier Inc.
Environmental Research

hal-01367154
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367154
DOI : 10.1016/j.envres.2016.08.004
PUBMED : 27560981

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Patients with sickle cell anemia (SCA) have usually lower diastolic, systolic and mean blood pressure (BP) than the general population. However, BP values ≥120/70 mmHg considerably increase the risk for acute and chronic complications in SCA. The aim of this study was to identify biological factors associated with relative hypertension in adults with SCA. We compared the hematological, lipid and hemolytic profiles, as well as blood viscosity, between SCA patients with normal BP (<120/70 mmHg, n = 54) and those with relative hypertension (BP≥120/70 mmHg, n = 43). Our results demonstrated that male gender (OR: 3.49; 95%CI 1.20 to 10.16, p<0.05), triglycerides (OR: 9.19; 95% CI 2.29 to 36.95, p<0.01), blood viscosity (OR: 1.35; 95% CI 1.01 to 1.81, p<0.05) and body mass index (OR: 1.37; 95% CI 1.14 to 1.64, p<0.01) were independent risks factors for relative hypertension in SCA. No association was found between the BP status and the positive history of painful vaso-occlusive crisis or acute chest syndrome. An association between triglycerides level and the occurrence of these two major acute complications was detected. Our study suggests that male gender, increased triglycerides level, BMI and blood viscosity could increase the risk for developing relative hypertension in SCA. In addition, our results support a role of moderately elevated triglycerides in the pathophysiology of vaso-occlusive events.
ISSN: 1932-6203

inserm-00838991
http://www.hal.inserm.fr/inserm-00838991
http://www.hal.inserm.fr/inserm-00838991/document
http://www.hal.inserm.fr/inserm-00838991/file/Lamarre_et_al._2013_PloS_ONE_.pdf
DOI : 10.1371/journal.pone.0066004

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
MR and MDHD contributed equally to this work. Summary Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence , we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxi-dase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil-and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.
ISSN: 0007-1048

inserm-01476067
http://www.hal.inserm.fr/inserm-01476067
http://www.hal.inserm.fr/inserm-01476067/document
http://www.hal.inserm.fr/inserm-01476067/file/2016%2C%20Hierso%20-%20Exacerbation%20of%20oxidative%20stress%20during%20sickle%20vaso-occlusive%20crisis.pdf
DOI : 10.1111/bjh.14476

Éditeur(s) : Elsevier
Résumé : The purpose of this study was to determine whether diploid and triploid sea bass differed in terms of main haematological and physiological characteristics. Diploid and triploid fish were produced by sub-optimal pressure treatments and held in communal environments under standard rearing conditions. Total red blood cell count (RBCC), haemoglobin concentration (Hb), hematocrit (Hct), mean cell volume (MCV), mean cellular haemoglobin content (MCH), mean cell haemoglobin concentration (MCHC), plasma metabolites, osmotic pressure, gill Na+/K+-ATPase activity, electrolytes, cortisol, and 3,5,3'-triiodo-L-thyronine (T-3) were measured and compared. Triploidisation in sea bass led to an increase in erythrocyte size (32% in cytoplasm surface area, and 50% in nucleus) and a decrease in erythrocyte number (similar to34%). Haemoglobin and basal plasma cortisol levels were significantly lower in triploid sea bass than in diploids. There were also differences between ploidies in the plasma concentrations of some electrolytes, with triploids showing lower concentrations of K, Fe, Zn, S, and Cu than their diploid counterparts.
Aquaculture (0044-8486) (Elsevier), 2005-02 , Vol. 244 , N. 1-4 , P. 359-367

Droits : 2004 Elsevier B.V. All rights reserved
http://archimer.ifremer.fr/doc/2005/publication-508.pdf
DOI:10.1016/j.aquaculture.2004.11.028
http://archimer.ifremer.fr/doc/00000/508/

Éditeur(s) : HAL CCSD
Résumé : International audience
Introduction: Diabetes mellitus results from the loss of tolerance to insulin and alters glycemia and the glycogen content. Oxidative stress and inflammation are linked to theses alterations, especially with insulin-resistance. The therapy management of diabetes includes nutritional recommendations. Several nutrients are developed to improve glycemia, oxidative stress, inflammation and glycogen content. More interestingly, ?-GOS exhibits anti-inflammatory and insulin-sensitive effects in vitro (Efstathiou and Fathi 2010) and in vivo (Boucher et al. 2003). Thus, ?-GOS is a potential functional food for the treatment of diabetes. But, less is known about the in vivo effect of ?-GOS on inflammatory, glycoxidation markers and glycogen content in diabetes. In this context, the aim of this work was to study the effect of ?-GOS developed by Sojasun technologies (from fermented soy product) compared to a synthetic ?-GOS produced by Sigma on inflammatory, glycoxidation markers and glycogen content in a streptozotocin-induced diabetic rat model. Methods: Twenty-four male Wistar streptozotocin-diabetic rat (STZ) were divided into three group: control group, supplemented with natural ?-GOS (20 mg/kg/day) group and supplemented with synthetic ?-GOS (20 mg/kg/day). The supplementation protocol duration was 8 weeks. At the end of the protocol, blood and skeletal muscle (gastrocnemius) were obtained to measure glucose , insulin, fructosamine in plasma and N-(carboxymethyl)lysine, glycogen synthase activity and glycogen content, in muscle. Results-Discussion: Diabetes was confirmed with the measure of insuline and glucose levels. All the diabetic groups had significantly higher glucose and insuline levels compared to control healthy group (data not shown). Insuline level in plasma and storage of glycogen in muscle were increased only in both ?-GOS groups. Fructosamine, TNF?and glycogen synthase activity was also decreased in the two supplemented groups (synthetic ?-GOS and natural ?-GOS). CML remained unchanged in all groups. Natural ?-OGT and synthetic ?-OGT only differed on muscular glucose level: only natural ?-OGT induced a significant decrease in muscular glucose. To conclude, our results suggest that ?-GOS alters positively glucose level, increases the glycogen content in diabetique population, improves glycemic control in the long term and decreases the inflammatory effects in streptozotocin-diabetic rat . Keywords: ?-GOS, inflammatory and glycoxidation markers, diabetes. Acknowledgment : Brittany region References Efstathiou, T. and D. Fathi. Sojasun Technologies. 2010 Boucher J et al. J Physiol Biochem. 59(3):169-73, 2003
5e congrès international de "Nutrition, Oxygen Biology and Medicine", Paris 5-7 juin 2013
Paris, France

hal-01159375
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01159375

Éditeur(s) : HAL CCSD
Résumé : International audience
INTRODUCTION: Alpha-1 antitrypsin, secreted by the liver, inhibits neutrophil elastase. Its deficiency favours the development of emphysema. Restoring a "protective" serum level in deficient patients should make it possible to inhibit the development of emphysema. STATE OF THE ART: Human plasma-derived alpha-1 antitrypsin is a blood-derived drug sold in France under the name Alfalastin(®). The recommended posology is an I.V. administration of 60mg/kg once a week. Human plasma-derived alpha-1 antitrypsin restores anti-elastase protection in the lower lung and prevents experimental emphysema induced by the elastasis of human neutrophils in hamster. The low number of patients with alpha-1 antitrypsin deficiency is one of the difficulties to perform sufficiently powerful randomised studies. However, randomised studies have reported the efficacy of human plasma-derived alpha-1 antitrypsin perfusions on mortality, FEV1 decline and the frequency of exacerbations. Randomised control trials have demonstrated the efficacy of human plasma-derived alpha-1 antitrypsin perfusions on the loss of lung density assessed by CT scan. CONCLUSION: Augmentation therapy is simple in its conception and implementation, but it is expensive. However, there are currently no other solutions.
Revue Des Maladies Respiratoires

hal-01146841
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146841
DOI : 10.1016/j.rmr.2014.10.001
PUBMED : 25908241

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 IOS Press
Résumé : International audience
Strenuous exercise is associated with an inflammatory response involving the activation of several types of blood cells. In order to document the specific activation of these cell types, we studied the effect of three maximal exercise tests conducted to exhaustion on the quantitative and qualitative pattern of circulating cell-derived microparticles and inflammatory molecules in healthy subjects. This study mainly indicated that the plasma concentration of microparticles from platelets and polymorphonuclear neutrophils (PMN) was increased immediately after the strenuous exercise. In addition, the increase in plasma concentration of microparticles from PMN and platelets was still observed after 2 hours of recovery. A similar pattern was observed for the IL-6 plasma level. In contrast, no change was observed for either soluble selectins or plasma concentration of microparticles from red blood cells, monocytes and endothelial cells. In agreement, sVCAM-1 and sICAM-1 levels were not changed by the exercise. We conclude that a strenuous exercise is accompanied by platelet-and PMN-derived microparticle production that probably reflects the activation of these two cell types.
ISSN: 1386-0291

hal-01163965
https://hal.univ-antilles.fr/hal-01163965
DOI : 10.3233/CH-2010-1361

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 Wiley
Résumé : International audience
Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence, we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxidase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil- and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.
ISSN: 0007-1048

hal-01668325
https://hal.univ-antilles.fr/hal-01668325
DOI : 10.1111/bjh.14476

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1-2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases.
ISSN: 0041-008X

inserm-00813758
http://www.hal.inserm.fr/inserm-00813758
DOI : 10.1016/j.taap.2012.11.008
PUBMED : 23164666

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Whereas it is well established that prenatal exposure to polychlorinated biphenyls (PCBs) can disrupt children's behavior, early postnatal exposure has received relatively little attention in environmental epidemiology. To evaluate prenatal and postnatal exposures to PCB-153, a proxy of total PCB exposure, and their relation to inattention and activity in 5-year-old Inuits from the Cord Blood Monitoring Program. Prenatal exposure to PCBs was informed by cord plasma PCB-153 levels. We used a validated pharmacokinetic model to estimate monthly infants' levels across the first year of life. Inattention and activity were assessed by coding of video recordings of children undergoing fine motor testing. We used multivariable linear regression to evaluate the association between prenatal and postnatal PCB-153 levels and inattention (n=97) and activity (n=98) at 5years of age. Cord plasma PCB-153 was not associated with inattention and activity. Each interquartile range (IQR) increase in estimated infant PCB-153 levels at 2months was associated with a 1.02% increase in the duration of inattention (95% CI: 0.04, 2.00). Statistical adjustment for the duration of breastfeeding slightly increased regression coefficients for postnatal level estimates, some of which became statistically significant for inattention (months: 2-4) and activity (months: 2-5). Our study adds to the growing evidence of postnatal windows of development during which children are more susceptible to neurotoxicants like PCBs.
ISSN: 0160-4120

hal-01134338
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134338
DOI : 10.1016/j.envint.2015.02.004
PUBMED : 25796081

Éditeur(s) : Actes de colloques Ifremer, Tahiti, French Polynesia, 20 Feb - 4 Mar 1989, n°9, chap. 17, pp.171-181
Résumé : Symptoms recalling a nutritional pathology and more precisely a process of lipid peroxydation were observed during the last years in seabass Dicentrarchus labrax and other fishes cultured in tropical marine condition, Ocyurus chrysurus and Lutjanus analis . They included dark coloration, skin ulceration, lethargy, anorexy, emaciation. Histological examinations showed hepatic fatty degenerative lesions, pancreatitis, muscular degeneration and retinal atrophy. Additional vitamins E and C in the food suppressed that pathological symptoms. The previously evoked clinical or histological signs were not achieved in spite of an increase of the level of hepatic, muscular or blood malondialdehyde and of the conjugated dienes of the perivisceral fat. In the same time, hepatic and muscular tocopherol decreased. These experiments also showed the feasibility and the interest of different analyses in the characterization of such a pathology: hemolysis test and activity of enzymes such as erythrocytic catalase or superoxyde dismutase and plasma glutathione peroxydase. Another nutritional disease is worth describing again, the Granulomatous Hypertyrosinaemia. It was essentially investigated in turbot Scophtalmus maximus but other fish species such as sea bream Chrysophris aurata are often affected.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/1989/acte-1501.pdf
http://archimer.ifremer.fr/doc/00000/1501/

Éditeur(s) : HAL CCSD
Résumé : International audience
Introduction: Type 1 diabetes mellitus, a T cell-mediated autoimmune disease, is a complex process that results from the loss of tolerance to insulin and other beta-cell-specific antigens. Diabetes is associated with an increased risk of death from infectious disease. Hyperglycaemia, oxidative stress and inflammation have been identified as the main factor contributing to the development of diseases associated with diabetes mellitus. However, experimental evidence indicates individual susceptibility to develop complications of diabetes. Various genetic and environmental factors have been studied so far, but precise causation has yet to be established. Numerous studies in rodents and human subjects have been performed in order to elucidate the role of B and T cells, which determine the risk of development and progression of diabetes. Moreover, the therapy management of diabetes includes nutritional recommendations and exercise training. The effects of exercise training on glycemia, oxidative stress, inflammation and immune response are well known and favorable to limit the development of diabetes and its complications. More interestingly, ?-galacto-oligosaccharides (?-GOS) are prebiotics that selectively alter the composition of gut microbiota and exhibit strong antioxidant, anti- inflammatory and insulin-sensitive effects in vitro (Efstathiou and Fathi 2010) and in vivo (Boucher J et al. 2003). Thus, ? -GOS is a potential functional food for the treatment of diabetes. But, less is known about the effect of training and ? –GOS on immune response in diabetes. In this context, the aim of this work was to study the immune response in a streptozotocin-induced type 1 diabetes with two therapeutic means: training and ?-galacto-oligosaccharides (?-GOS) alone or combined. Methods: Forty-two male Wistar rats were divided into control placebo, streptozotocin-diabetic rat (STZ) groups supplemented or not with ?-GOS (20 mg/kg/day) for 8 weeks and/or following endurance training. The training program was individualized and consisted in a 1h/day, 5days/week running during 8 weeks on a motor-driven treadmill. At the end of the protocol, blood was obtained by venous puncture into heparin-containing tubes for further analyses (glucose, insulin, fructosamine and immune responses) Results: Relative to the control group, STZ rats exhibited hyperglycemia, insulin deficiency and a trend to higher plasma fructosamine levels, a marker of glycated proteins. They also exhibited a decrease in T and B cells and an increase in natural killers (NK). ?-GOS treatment reduced plasma fructosamine levels and increased B cells compared to STZ rats. Training induced a decrease in plasma glucose, T cells and an increase in B cells in STZ rats. The combined effect of ?-GOS and training didn’t potentiate the immune response on B and T cells but inhibited the effects of training on NK. Discussion: Our results suggest that training and ?-GOS alter positively plasma glucose and/or fructosamine and the immune response. But the effects of combined treatments only concern limited parameters. ? -GOS effects could be partly attributable to its immunomodulating activity. Keywords: ?-GOS, training, immune cells, diabetes. References Efstathiou, T. and D. Fathi. Sojasun Technologies. 2010 Boucher J et al. J Physiol Biochem. 59(3):169-73, 2003
18th Annual Congress of the European College of Sport Sciences, Barcelone, Spain, 26-29 juin.
Barcelone, Spain

hal-01159378
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01159378

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Do mild analgesics affect the endocrine system of the human adult testis? SUMMARY ANSWER: Mild analgesics induce multiple endocrine disturbances in the human adult testis in vitro. WHAT IS KNOWN ALREADY: Mild analgesics have recently been incriminated as potential endocrine disruptors. Studies of the effects of these widely used molecules on the androgenic status of men are limited and somewhat contradictory. This prompted us to investigate whether these compounds could alter the adult human testicular function. We therefore assessed in parallel the effects of paracetamol, aspirin and indomethacin on organo-cultured adult human testis and on the NCI-H295R steroid-producing human cell line. STUDY DESIGN, SIZE, DURATION: Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with 10(-4) or 10(-5) M paracetamol, aspirin or indomethacin for 24-48 h. The effect of 10(-5) M ketoconazole, used as an anti-androgenic reference molecule, was also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testes were obtained from prostate cancer patients, who had not received any hormone therapy. The protocol was approved by the local ethics committee of Rennes, France and informed consent was given by the donors. Only testes displaying spermatogenesis, as assessed by transillumination, were used in this study. Hormone levels in the culture media were determined by radioimmunoassay (testosterone, insulin-like factor 3), Enzyme-Linked Immunosorbent Assay (inhibin B) or Enzyme Immunosorbent Assay [prostaglandin (PG) D2, and PGE2]. Tissues were observed and cells counted using classical immunohistochemical methods. MAIN RESULTS AND THE ROLE OF CHANCE: The three mild analgesics caused multiple endocrine disturbances in the adult human testis. This was particularly apparent in the interstitial compartment. Effective doses were in the same range as those measured in blood plasma following standard analgesic treatment. The production of testosterone and insulin-like factor 3 by Leydig cells was altered by exposure to all these drugs. Inhibin B production by Sertoli cells was marginally affected by aspirin only. Our experiments also revealed that mild analgesics display direct anti-PG activity, which varied depending on the drug used, the dose and the duration of exposure. Nevertheless, associations between the alteration of the PG and testosterone profiles were not systematically observed, suggesting that a combination of mechanisms of endocrine disruption is at play. LIMITATIONS, REASONS FOR CAUTION: Our studies were performed in vitro. WIDER IMPLICATIONS OF THE FINDINGS: We provide the first evidence that direct exposure to mild analgesics can result in multiple endocrine disturbances in the human adult testis. Caution, concerning the consumption of mild analgesics by men, should be strengthened, particularly in high-risk population subgroups such as elite athletes.
ISSN: 0268-1161

inserm-00866016
http://www.hal.inserm.fr/inserm-00866016
PUBMED : 23670170
DOI : 10.1093/humrep/det112

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The levels and duration of physical activity that can be considered as completely safe in patients with sickle cell anemia (SCA) is unknown. The present study compared the hemorheological and hematological profile, cell density distribution and basic biochemistry between a group of 17 patients with SCA and 21 healthy subjects before and after a 20 min duration submaximal cycling exercise at the same absolute workload. Blood was sampled at rest and 3 min after the end of exercise for measurement of biological parameters. Exercise did not affect the hematocrit and blood viscosity in the two groups. Plasma viscosity was not different between the two groups at rest and similarly increased with exercise. The proportion of intermediary dense cells (with density between 1.11 and 1.12 g/ml) decreased with exercise in the SCA group resulting in an increase in the proportion of red blood cells with a density > 1.12 g/ml. No change was observed in the control group. The present study suggests that mild-moderate exercise is not very harmful for SCA patients. The hemorheological and hematological changes very mild, except for the formation of dense cells but no clinically significant signs of medical complication were present in any of the patients.
ISSN: 0007-1048

hal-00640629
https://hal.archives-ouvertes.fr/hal-00640629
https://hal.archives-ouvertes.fr/hal-00640629/document
https://hal.archives-ouvertes.fr/hal-00640629/file/PEER_stage2_10.1111%252Fj.1365-2141.2011.08728.x.pdf
DOI : 10.1111/j.1365-2141.2011.08728.x

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 Springer Verlag
Résumé : International audience
Bone Morphogenetic Protein 9 (BMP9) has been recently found to be the physiological ligand for the activin receptor-like kinase 1 (ALK1), and to be a major circulating vascular quiescence factor. Moreover, a soluble chimeric ALK1 protein (ALK1-Fc) has recently been developed and showed powerful anti-tumor growth and anti-angiogenic effects. However, not much is known concerning BMP9. This prompted us to investigate the human endogenous sources of this cytokine and to further characterize its circulating form(s) and its function. Analysis of BMP9 expression reveals that BMP9 is produced by hepatocytes and intrahepatic biliary epithelial cells. Gel filtration analysis combined with ELISA and biological assays demonstrate that BMP9 circulates in plasma (1) as an unprocessed inactive form that can be further activated by furin a serine endoprotease, and (2) as a mature and fully active form (composed of the mature form associated with its prodomain). Analysis of BMP9 circulating levels during mouse development demonstrates that BMP9 peaks during the first 3 weeks after birth and then decreases to 2 ng/mL in adulthood. We also show that circulating BMP9 physiologically induces a constitutive Smad1/5/8 phosphorylation in endothelial cells. Taken together, our results argue for the role of BMP9 as a hepatocyte-derived factor, circulating in inactive (40%) and active (60%) forms, the latter constantly activating endothelial cells to maintain them in a resting state.
ISSN: 1420-682X

hal-00681969
https://hal.archives-ouvertes.fr/hal-00681969
DOI : 10.1007/s00018-011-0751-1
PUBMED : 21710321

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Hydroxycarbamide (HC) treatment has been shown to improve the clinical course of patients with sickle cell anaemia (SCA), a haemoglobinopathy resulting from a single base substitution in the bêta-globin gene (HBB). SCA is characterized by chronic haemolytic anaemia and recurrent vascular occlusions leading to multisystemic complications. Several beneficial biological effects of HC have been documented (Halsey et al, 2003) but its impact on the concentration of circulating microparticles (MPs), a subtype of extracellular vesicles released from cytoplasmic membrane of activated or apoptotic cells and detected at high levels in sickle plasma, remains controversial (Hebbel et al, 2016). The aim of the present study was to compare the MP pattern in a group of SCA patients treated by HC and followed for 2 years.
ISSN: 0007-1048

hal-01668320
https://hal.univ-antilles.fr/hal-01668320
https://hal.univ-antilles.fr/hal-01668320/document
https://hal.univ-antilles.fr/hal-01668320/file/Garnier%20et%20al%20BJH-2017-00655.pdf
DOI : 10.1111/bjh.14810

Éditeur(s) : HAL CCSD
Résumé : International audience
Paracetamol and NSAIDs, in particular acetylsalicylic acid (aspirin) and ibuprofen, are among the most used and environmentally released pharmaceutical drugs. The differences in international trends in the sale and consumption of mild analgesics reflect differences in marketing, governmental policies, habits, accessibility, disease patterns and the age distribution of each population. Biomonitoring indicates ubiquitous and high human exposure to paracetamol and to salicylic acid, which is the main metabolite of acetylsalicylic acid. Furthermore, evidence suggests that analgesics can have endocrine disruptive properties capable of altering animal and human reproductive function from fetal life to adulthood in both sexes. Medical and public awareness about these health concerns should be increased, particularly among pregnant women.
Nature Reviews Endocrinology

hal-01359566
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359566
DOI : 10.1038/nrendo.2016.55
PUBMED : 27150289