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International audience; OBJECTIVE: To determine the true community prevalence of human cystic (CE) and alveolar (AE) echinococcosis (hydatid disease) in a highly endemic region in Ningxia Hui, China, by detecting asymptomatic cases. METHODS: Using hospital records and "AE-risk" landscape patterns we selected study communities predicted to be at risk of human echinococcosis in Guyuan, Longde and Xiji counties. We conducted community surveys of 4773 individuals from 26 villages in 2002 and 2003 using questionnaire analysis, ultrasound examination and serology. FINDINGS: Ultrasound and serology showed a range of prevalences for AE (0-8.1%; mean 2%) and CE (0-7.4%; mean 1.6%), with the highest prevalence in Xiji (2% for CE, 2.5% for AE). There were significant differences in the prevalence of CE, AE and total echinococcosis between the three counties and villages (with multiple degrees of freedom). While hospital records showed 96% of echinococcosis cases attributable to CE, our survey showed a higher prevalence of human AE (56%) compared to CE (44%). Questionnaire analysis revealed that key risk factors for infection were age and dog ownership for both CE and AE, and Hui ethnicity and being female for AE. Drinking well-water decreased the risk for both AE and CE. CONCLUSION: Echinococcosis continues to be a severe public health problem in this part of China because of unhygienic practices/habits and poor knowledge among the communities regarding this disease.

ConferenceConference: 11th European Symposium on the Quality of Eggs and Egg ProductsLocation: Doorwerth, NETHERLANDSDate: MAY 23-26, 2005; The hen's egg plays a crucial role in the embryonic development of the bird. It serves first as a source of energy and nutrients of high digestibility and, second, protects the embryonic bird against external aggressions. The unique structure of an egg with yolk containing the embryo surrounded by albumen and shell as physical barriers, is the first element of this protection. The second one consists of the specific composition of yolk, albumen and shell with many molecules possessing elevated biological properties. Thus, these molecules represent a major source of active principles usable by medical, pharmaceutical, cosmetic, nutraceutical and biotechnological industries. In this review, we will focus particularly on nutritional, health, and biotechnological activities of egg molecules and on the approaches, which are proposed by European research groups, to exploit this bioactive potential.

National audience

International audience; Okadaic Acid (OA) the major diarrheic shellfish poisoning (DSP) toxin is known as a tumor promoter and seems likely implicated in the genesis of digestive cancer. Little is known regarding genotoxicity and carcinogenicity of Domoic Acid (DA), the major Amnesic Shellfish Poisoning (ASP) toxin. Both OA and DA occur in seafood and are of human health concerns. Micronuclei (MN) arise from abnormalities in nuclear division during mitosis due to a failure of the mitotic spindle or by complex chromosomal configurations that pose problems during anaphase. In order to evaluate the ability of okadaic acid (OA) and domoic acid (DA) to induce DNA damage we performed the micronucleus assay using the Caco-2 cell line. To discriminate between a clastogenic or aneugenic effect of OA and DA, the micronucleus assay was conducted by cytokinesis-block micronucleus assay using cytochalasin B with Giemsa staining and/or acridine orange staining, in parallel to fluorescence in situ hybridization (FISH) using a concentrated human pan-centromeric chromosome paint probe. Our results showed that OA and DA significantly increased the frequency of MN in Caco-2 cells. The MN caused by OA are found in mononucleated cells and binucleated cells, whereas those caused by DA are mainly in binucleated cells. The results of FISH analysis showed that OA induced centromere-positive micronuclei and DA increased the percentage of MN without a centromeric signal. In conclusion, both OA and DA bear mutagenic potential as revealed in Caco-2 cells by induction of MN formation. Moreover, OA induced whole chromosome loss suggesting a specific aneugenic potential, whereas DA seems simply clastogenic. At present, one cannot rule out possible DNA damage of intestinal cells if concentrations studied are reached in vivo, since this may happen with concentrations of toxins just below regulatory limits in case of frequent consumption of contaminated shell fishes.

National audience

A fortified street food to prevent nutrient deficiencies in homeless Existing food aid programs have failed to prevent insufficient dietary intakes and micronutrient deficiencies in the population of homeless in Paris. To improve these programs, we designed a fortified food easy to consume in the street. Its economic interest was estimated by linear programming. We further tested its acceptability among the target population. A chocolate-flavoured spread naturally rich in potassium and n-3 fatty acids was fortified with calcium, zinc, vitamins C, D, E, B12, thiamine, niacin and folic acid. This spread presents multiple advantages for homeless nutrition : resistance to bacterial contamination, viscosity adapted to people having limited chewing capacity, high energy density, and high nutritional quality/ price ratio. Indeed, adding 1 packet of Vitapoche ® to a classical food basket increases, for a low cost (21 eurocents/ packet), the energy content of the basket, and significantly improves its nutritional quality. This represents an economic advantage for the donor, as well as for the food aid recipient. The acceptability study was conducted in eight sites providing food aid to homeless. During two weeks in each site, the fortified food was systematically proposed (one packet/ day) to each individual visiting the site. The evaluation of this new food, named Vitapoche ® , showed that homeless would consume the fortified food often or daily, if available. Including fortified street foods in existing food aid programs for homeless is a practical and economic way to help prevent nutritional deficiencies in this population., Pour mieux prévenir la dénutrition et les déficiences vitaminiques et minérales chez les personnes en situation d’exclusion, nous avons mis au point un aliment enrichi facile à consommer dans la rue : le Vitapoche ® . Il s’agit d’une pâte chocolatée résistante à la contamination bactérienne, emballée dans un sachet hermétique. Cette pâte est naturellement riche en potassium et en acides gras oméga-3. Elle a été enrichie en calcium, zinc et vitamines C, B1, B9, PP, B12, E et D, afin que chaque sachet (70 g, 377 kcal) apporte ces nutriments en quantité nécessaire pour la journée. Outre son intérêt nutritionnel évident, le Vitapoche ® présente aussi un double intérêt économique, pour le donateur et pour le bénéficiaire. Une étude d’acceptabilité menée au sein de la population cible à Paris a montré que deux personnes sur trois consommeraient régulièrement du Vitapoche ® si elles pouvaient se le procurer facilement. Le Vitapoche ® n’est pas un substitut de repas. Il n’est pas destiné à remplacer l’aide alimentaire déjà existante, mais il la complète, afin d’en optimiser la qualité nutritionnelle., Darmon Nicole, Briend André. Prévention des déficiences nutritionnelles chez les personnes sans-abri : intérêt d’un aliment de rue enrichi. In: Cahiers d'Economie et sociologie rurales, N°79, 2e trimestre 2006. Alimentation et pauvreté. L'alimentation comme outil de santé et d'insertion en situations de pauvreté. pp. 53-66.

Unique établissement public français dédié à la recherche et à la santé publique, l’Inserm est investi d’une mission particulière. Ses objectifsprioritaires sont d’assurer l’attractivité et la mobilité des carrières biomédicales en accompagnant les individus dans leur parcoursprofessionnel, d’organiser le continuum de la recherche depuis le domaine fondamental jusqu’au domaine clinique thérapeutiqueet la santépublique, de valoriser les connaissances ainsi produites par un lien permanent avec le monde industriel, et enfin de développer une politiqueeuropéenne et internationale conquérante.

Human papillomavirus type 16 (HPV-16) is the major causative agent of cervical cancer. To date, vaccine strategies against HPV-16 are based on the ability of the E7 oncoprotein to elicit an immune response against this virus. In this study, the use of an inducible or a constitutive system to produce the HPV-16 E7 protein in Lactococcus lactis, a non-pathogenic and non-invasive Gram-positive bacterium, was compared. The highest E7 production was obtained with the inducible system. When mice were immunized intranasally with recombinant lactococci expressing either inducible or constitutive E7, an antigen-specific cellular response (i.e. secretion of IL2 and IFN-γ cytokines) was evoked and was substantially higher in mice receiving L. lactis expressing E7 with the inducible system. As bacterial antigen location may influence the immune response, recombinant L. lactis strains that produced E7 in three cellular locations, intracellular, secreted or cell-wall-anchored were evaluated. The highest immune response was elicited by administration of L. lactis producing an inducible cell-wall-anchored form of E7 protein. These promising results represent a step towards the development of a new, safe mucosal vector to treat HPV-related cervical cancer.

En raison des incertitudes épidémiologiques relatives aux maladies à prions, il est urgent de découvrir et de développer des thérapeutiques anti-prions chez l’homme. L’efficacité des molécules candidates est essentiellement testée in vitro sur des cellules de neuroblastome. Pour plusieurs molécules, dont la quinacrine, il a été observé une discordance entre l’effet anti-prion in vitro et l’absence d’efficacité clinique dans le traitement de la maladie de Creutzfeldt-Jakob. Pour documenter l’hypothèse selon laquelle l’absence d’efficacité de la quinacrine était d’ordre pharmacocinétique (et donc prévisible), la disposition de la quinacrine (disparition de la quinacrine du compartiment sanguin, qui résulte par exemple de processus de distribution et d’élimination du principe actif) a été étudiée à la fois in vivo et in vitro afin de déterminer les doses qu’il conviendrait d’administrer in vivo pour obtenir des concentrations efficaces dans la biophase. Le modèle de brebis naturellement atteintes de tremblante a été utilisé. Dans un premier temps, un essai thérapeutique contrôlé sur des brebis en phase clinique de tremblante a permis de confirmer ce qui était connu chez l’homme, c’est-à-dire l’absence d’efficacité clinique de la quinacrine. Sur le modèle in vitro reproduisant les conditions princeps de culture pour lesquelles 50 % de l’effet anti-prion avait été observé, avec une concentration nominale de quinacrine de 300 nM (nanomoles par litre), nous avons redéterminé les EC50 (concentration qui permet d’inhiber à 50 % la formation de PrP pathogène) pour les biophases potentielles de l’action anti-prion en mesurant sélectivement, par HPLC (chromatographie liquide haute performance), les véritables concentrations extracellulaire (120 nM) et intracellulaire (6700 nM) de quinacrine dans les neuroblastomes en culture. Les concentrations de quinacrine dans le Liquide Cérébro-Spinal (LCS) et le tissu nerveux cérébral, représentatifs in vivo respectivement des biophases extracellulaire et intracellulaire, ont été mesurées chez la brebis après une administration de quinacrine. Les concentrations de quinacrine dans le liquide cérébro-spinal (< 2,1 nM et 55 nM, obtenues respectivement pour des doses thérapeutique et toxique) sont restées très inférieures aux concentrations nécessaires pour obtenir in vitro un effet antiprion (120 nM). Les concentrations totales de quinacrine dans le tissu nerveux (1040 nM) après une dose thérapeutique sont restées inférieures aux concentrations de quinacrine actives in vitro (6700 nM) et, seule une dose toxique de quinacrine a permis d’atteindre des concentrations intracellulaires actives (53800 nM). En définitive, quelle que soit la biophase intra- ou extracellulaire, les schémas posologiques non toxiques sont incapables de maintenir des concentrations antiprion efficaces de quinacrine. A l’avenir, pour éviter des études in vivo dont on peut prévoir d’emblée qu’elles sont vouées à l’échec, notamment chez l’homme, il est recommandé de mesurer les EC50 anti-prions dans les biophases in vitro, pour évaluer si les effets anti-prion observés in vitro sont extrapolables in vivo., Given the epidemiological uncertainty of the prion diseases, there is an urgent need to discover and to develop antiprion therapeutics in humans. The efficacy of candidate molecules is predominantly tested in vitro in neuroblastoma cells. For several molecules, including quinacrine, a discrepancy has been observed between a proven antiprion action in vitro and its lack of clinical efficacy in the Creutzfeldt-Jakob disease. To further investigate the possible pharmacokinetic origin of the lack of clinical efficacy of quinacrine (and then predictable), we studied the quinacrine disposition both in vivo and in vitro. Ultimately, our experiment was aimed at determining the dosage regimen, which should be administered in vivo to obtain efficacious concentrations in the biophase. We used a model of naturally scrapie-affected ewes. First, we performed a standard clinical trial in scrapie-affected ewes and, we confirmed the absence of therapeutic benefit of quinacrine, as previously shown in humans. In in vitro experiments reproducing the princeps culture conditions in which 50% of antiprion action has been observed, namely a nominal quinacrine concentration of 300 nM, we re-evaluated the EC50 for the potential biophases of quinacrine effect. Quinacrine was assayed by HPLC. We showed that the actual extracellular and intracellular quinacrine neuroblastoma concentrations were 120 nM and 3700 nM, respectively. Quinacrine concentrations in cerebrospinal fluid concentrations and brain tissue, corresponding to the extracellular and intracellular biophases respectively, were measured in healthy ewes after quinacrine administration. The cerebrospinal fluid quinacrine concentrations (

The presence of Staphylococcus intermedius in food remains unclear because routine laboratory analysis does not discriminate between S. intermedius and Staphylococcus aureus, a major cause of food poisoning. Both species share many phenotypic characteristics, including coagulase and thermonuclease production. In both species, some strains can produce enterotoxin and therefore can be the cause of food poisoning outbreaks. Although the ID32 Staph System (bioMérieux, SA, Marcy l'Etoile, France), based on a miniaturized phenotypic characterization, gives satisfactory results for discriminating between these two species, some rapid molecular PCR-based methods have been developed to identify S. aureus specifically, but they do not identify S. intermedius. Here, we developed a rapid, accurate, and discriminative multiplex PCR method that targets species-specific sequences in the nuc gene, which encodes thermonuclease in the two species. The test includes an internal positive control that targets a highly conserved region of 16S ribosomal RNA gene (rDNA). A total of 116 strains were used to validate our test. The test gave no signal on the following Staphylococcus species: S. epidermidis, S. chromogenes, S. hyicus, S. warneri, S. xylosus, S. lentus, and S. sciuri. It allowed a 100% successful discrimination between S. aureus (44 strains tested) and S. intermedius (57 strains) isolated from different origins.

Food-borne diseases are of major concern worldwide. To date, around 250 different food-borne diseases have been described, and bacteria are the causative agents of two thirds of food-borne disease outbreaks. Among the predominant bacteria involved in these diseases, Staphylococcus aureus is a leading cause of gastroenteritis resulting from the consumption of contaminated food. Staphylococcal food poisoning is due to the absorption of staphylococcal enterotoxins preformed in the food. Here, we briefly review the latest data on staphylococcal enterotoxins and some papers exemplifying the interactions between S. aureus and the food matrix; environmental factors affecting staphylococcal enterotoxin production are discussed.

Introduction. The effects of fruit and vegetable consumption concerning pathol- ogies have already been underlined by many studies in which, in particular, apple consump- tion could be correlated with a significant protective effect. This document presents a review of the results which were obtained at the conclusion of these studies. Apple fractions useful for nutrition. The contributions of apple to glucids, polyphenols, minerals, organic anions and vitamins were successively analyzed and studied according to the effects of these elements on human health. Apple potential effects on health. The apple's protective effects concern- ing cardiovascular risks were first exposed, and more specific effects were then reviewed: effects on the insulinic statute and the antioxidant statute, antiacidosic effects and impact on digestive fermentations into the colon. Conclusion. From a preventive nutrition point of view, apple has very interesting potential. A great number of health effects which are allotted to it would depend on interactions between various nutriments such as, for example, interactions between fibers and certain polyphenols. These interactions are still little known; their study seems promising and could be transposed to many foods of vegetable origin. France / apples / proximate composition / nutrition physiology / human nutrition / health protection

La 3e conférence internationale sur les glucosinolates, intitulée « Glucosinolates and beyond », a rassemblé plus d’une centaine de participants à Wageningen aux Pays-Bas, du 12 au 15 Octobre 2014. Le programme a été organisé en quatre sessions couvrant la recherche fondamentale sur l’origine et la biosynthèse des glucosinolates au cours de l’évolution, et les applications concrètes en santé humaine et agriculture. Près de 90 communications orales et posters, portant sur les récents progrès et les questions émergentes pour les recherches futures ont été présentés.

Le Cuivre est un oligo-élément essentiel qui participe à de nombreuses fonctions physiologiques dont le métabolisme du Fe, la fonction immunitaire et la protection contre les stress oxydants. Le foie joue un rôle central dans le métabolisme et l’homéostasie du Cu : selon les apports et le statut de l’animal, le Cu est stocké, excrété via la bile ou distribué vers les organes. Les besoins nutritionnels en Cu du porc en croissance sont inférieurs à 10 mg/kg d’aliment et peuvent théoriquement être couverts par les seules matières premières, sans supplémentation. Cependant, utilisé pour ses propriétés de facteur de croissance, le Cu est introduit à 150 à 250 ppm dans l’aliment du porcelet en post-sevrage et permet d’en améliorer la vitesse de croissance. Cette pratique est sans incidence sur la qualité des produits consommés par l’Homme, si elle est limitée à la seule période de post-sevrage. Elle a cependant pour conséquence d’augmenter les quantités de Cu appliquées lors de l’épandage des lisiers de porc et conduit à une accumulation de cet élément dans les sols. L’une des solutions pour réduire les rejets de Cu est d’en limiter les apports alimentaires au niveau du besoin. Cette approche nécessite de bien connaître et de hiérarchiser les composants alimentaires susceptibles d’influer significativement sur la disponibilité du Cu. Certains agents complexants, comme les phytates, les fibres ou les matières grasses ainsi que certains éléments minéraux, comme le Zn et le Ca sont en effet des facteurs de variation possibles de la disponibilité du Cu. Leur impact sur les besoins reste cependant à évaluer, de même que les critères d’évaluation du statut en Cu restent à préciser., Copper is essential for many physiological functions including iron metabolism, immunity and protection of tissues from oxidative stress. Liver plays a key role in maintaining copper homeostasis and adjustment to fluctuation of copper supply is mainly achieved by liver storage and biliary secretion. The copper requirements of the growing pig are below 10 mg/kg feed. They are normally covered by the feedstuff copper provision and any supplementation is theoretically superfluous. However, because of the growth promoting effect of copper, 150 to 250 ppm supplements are often added in diets of weaned piglet. When this supply of copper is omitted at the end of the post-weaning period, such a dietary copper supply does not influence the copper content of the meat consumed by humans. However, it induces an increase of copper content in pig slurry and, consequently, an accumulation of copper in soils. The reduction of dietary copper supply close to the requirements is the main way to better control this environmental risk. However, to achieve this goal, the dietary factors that may significantly influence the availability of copper should be accurately known and ranked. Some chelating agents, such as phytates, fibres or fat as well as the level of other minerals such as Zn and Ca may interfere on copper availability. However their actual impact remains to be assessed. In addition, relevant indicators of copper status should be chosen to implement these investigations.

Différents points d’impact des mesures de suspension des farines et graisses animales ont été identifiés. En matière de technologie des aliments, les répercussions prévisibles sont liées au retrait des graisses animales avec un risque de plus grande friabilité des granulés et des difficultés d’incorporation de quantités importantes de graisses. Au plan nutritionnel, s’il existe des solutions techniques pour remplacer les farines et les graisses animales, on peut cependant prévoir des difficultés d’utilisation de certaines matières premières (tourteau de soja à taux plus élevés, huile de palme, huiles de récupération…), des perturbations de la consommation d’aliments, voire des baisses de performances (volailles surtout) et une surexcrétion d’eau (dinde, poule pondeuse) avec ses conséquences sanitaires. L’impact sur la qualité des produits animaux provient essentiellement du remplacement des graisses animales par des matières grasses d’origine végétale le plus souvent insaturées qui peut se traduire par des défauts de présentation des carcasses et une moins bonne conservation des produits animaux plus sensibles à l’oxydation. Concernant la sécurité alimentaire pour le consommateur, on peut s’attendre à un accroissement des risques potentiels d’ordre chimique (contaminants, mycotoxines et autres substances toxiques produites par les plantes) et biologique (bactéries pathogènes) associés à l’importation de matières premières de provenances multiples, souvent mal contrôlées et dépourvues de traçabilité. Certains de ces risques sont cependant encadrés par des réglementations spécifiques de l’Union Européenne. On peut s’attendre également à des difficultés de traçabilité pour les filières fonctionnant avec des signes officiels de qualité ou des certifications, en regard de l’importation de matières premières standard et OGM non différenciées. En revanche, il n’y a pas de risques identifiés associés aux plantes OGM ayant à ce jour reçu une autorisation de commercialisation. Enfin en matière d’environnement, il faut prévoir un arrêt du recyclage (phosphates " cachés " des farines de viande et d’os) et des prélèvements accrus sur des ressources non renouvelables (phosphates minéraux), ainsi que des risques de rejets plus importants de phosphore (biodisponibilité plus faible du phosphore végétal) et d’éléments traces métalliques (absents des farines animales) provenant des phosphates minéraux., Different consequences of the suspension of the use of meat and bone meals and fats of animal origin have been identified. In terms of food technology, the predictable implications are related to the withdrawal of animal fats with a risk of greater brittleness of the pellet and difficulty of incorporating large amounts of fats. From the nutritional point of view, even though technical solutions exist for the substitution of meat and bone meals and fats of animal origin, one must expect difficulties in the use of some raw materials (soybean meal at high level, palm oil, recycled oils...), altered consumption of the feeds, a possible decrease in performance (in particular with poultry) and an over-excretion of water (turkeys, laying liens) with sanitary consequences. The impact on the quality of the animal products comes essentially from the replacement of animal fats by vegetable oils which are the most often unsaturated and may cause faulty presentation of the carcasses and a poorer conservation, since the products are more sensitive to oxidation. For the consumer and in terms of food safety point, there may be higher potential chemical (contaminants, mycotoxins and other toxic substances produced by plants) and biological (pathogenic bacteria) risks associated with importing raw materials from different origins which are often poorly inspected and are not traceable. Some of these risks are covered by specific regulations of the European Union. There may also be traceability difficulties for those sectors which use official signs of quality or certifications, concerning the importing of non-differentiated raw materials (standard or GMO). There are not, however, identified risks associated with the GMO that have currently been authorised for commercialisation. Finally, concerning the environment, recycling must be stopped ('hidden phosphates' in meat and bone meal) and there must be an increased sampling of the non-renewable resources (mineral phosphates). In addition, there may be an increased rejection of phosphorus (lower bioavailability of plant phosphorus) and traces of metals (not present in meat meals) which come from mineral phosphates.

International audience; (CE, 29 déc. 1999, Synd. national du commerce extérieur des produits congelés et surgelés et autres, Req. n° 206945)

International audience; After a brief survey of metabolic pathways and nutrient fluxes involved in mammary lipogenesis, this review summarises the known effects of diet on ruminant milk fat composition. Special attention is given to fatty acids that could play a positive role for human health, such as butyric acid, oleic acid, C18 to C22 polyunsaturated fatty acids and conjugated linoleic acid (CLA). The efficiency of the transfer of C18:2, C18:3, C20:5, C22:5 and C22:6, from the duodenum to the milk, is reviewed. The main dietary factors taken into account are the nature of forages, including pasture, and the supplementation of dairy rations with protected or unprotected vegetable or fish oils. Dose-response curves of milk CLA are reviewed for different fat supplements, as well as the non-linear relationship between milk CLA and trans C18:1. The potential of dietary factors to increase the mean CLA content in cow milk fat is about 300% above basal values. There is, however, a need to evaluate how the different feeding strategies could change the other aspects of milk fat quality.; Plasticité de la matière grasse du lait de ruminant : contrôle nutritionnel des acides gras saturés, polyinsaturés, trans et conjugués. Après un bref rappel des voies métaboliques et des flux de nutriments qui concourrent à la lipogenèse mammaire, cette revue est consacrée aux principaux effets des facteurs alimentaires sur la composition des lipides du lait de ruminant. Un intérêt particulier est porté aux acides gras qui peuvent avoir des effets positifs sur la santé humaine, tels que les acides butyrique, oléique, linoléique conjugué (CLA) et les acides gras polyinsaturés, de 18 à 22 atomes de carbone. L'efficacité du transfert des C18:2, C18:3, C20:5, C22:5 et C22:6, du duodénum au lait est estimée à partir des données de la bibliographie. Les principaux facteurs alimentaires considérés sont la nature des fourrages, dont l'herbe pâturée, et la supplémentation des rations pour vaches laitières avec des huiles végétales ou de poisson, protégées ou non. L'augmentation potentielle de la teneur en CLA de la matière grasse du lait de vache par les facteurs alimentaires est d'environ 300 % au-dessus du niveau de base. Des courbes dose-réponse du CLA du lait sont établies à partir des différentes publications sur les effets de suppléments lipidiques, ainsi que la relation non linéaire qui existe entre le CLA et le C18:1 trans du lait. Il reste toutefois à évaluer les conséquences des différentes stratégies alimentaires sur les autres aspects de la qualité du lait.

L’administration de toute substance chimique à l’animal doit se faire sans risque pour sa santé et doit préserver totalement la santé du consommateur. Pour satisfaire à ces critères exigeants de sécurité, il est devenu primordial de prédire, avec précision, le devenir de ces substances dans l’organisme et d’en apprécier les capacités toxiques. Nous évoquerons les plus récents apports des biosciences permettant d’atteindre cet objectif. Nous présentons des modèles biologiques génétiquement optimisés (in vitro et in vivo) particulièrement adaptés à ces tâches., Administration of any chemical to animals should preserve its own health and should be totally safe for consumers. To comply with safety criteria, it became crucial to precisely predict the future of these molecules in the body and to define their toxic potencies. We will present biotechnologies that can help to reach that goal, We present genetically engineered models (in vitro et in vivo) suitable for these tasks.

Après la présentation de l’importance des sécrétions digestives pour transformer les aliments en nutriments absorbables et assimilables par l’organisme, les principes généraux de la régulation de leur synthèse et de leur libération sont décrits en soulignant la complexité des mécanismes. Des exemples sont donnés pour montrer l’effet de quelques facteurs (repas, nature des protéines, âge, digestibilité...) sur les sécrétions gastriques et pancréatiques et tenter de proposer une explication des mécanismes en cause. Quelques illustrations font état des apports possibles en nutrition et dans le domaine clinique chez l’animal et l’homme. En conclusion, les résultats récemment obtenus permettent, à l’aide des nouvelles techniques mises à notre disposition et associées à des méthodes classiques, d’ouvrir de nouvelles voies d’investigation dans le but d’intervenir sur la régulation des sécrétions pour mieux les adapter à l’aliment distribué, en tenant compte de l’environnement d’élevage., The role of digestive secretions is important in transforming food into nutrients that are able to be absorbed and assimilated by the organism. The general principles of the regulation of their synthesis and release are described, underlining the complexity of the mechanisms involved. Examples are given to show the effect of some factors (meals, protein sources, age, digestibility) on gastric and pancreatic secretions and to suggest an explanation of the mechanisms involved. Some illustrations show the possible applications in nutrition or clinical field, in animals and humans. In conclusion, the results obtained using new techniques at our disposal and combining them with classical methods, allow us to open up new ways of investigation. These will probably bring to light new knowledge which can be used in the regulation of secretions in order to adapt them better to the food given, taking the rearing environment into account.

Cryptosporidium, protozoaire parasite décrit en 1907 par Tyzzer, fut longtemps considéré comme un organisme commensal, rare et spécifique d’hôte. Après 1981, tous les auteurs s’accordèrent à penser que l’espèce C.parvum était commune à tous les mammifères, y compris l’homme, causant des diarrhées néonatales chez les ruminants, des diarrhées à guérison spontanée chez l’homme immunocompétent et des diarrhées cholériformes incurables chez l’homme immunodéficient. La cryptosporidiose était alors considérée comme une zoonose, l’homme s’infectant au contact des animaux malades ou au contact d’animaux de compagnie porteurs sains. Cependant, la cryptosporidiose peut se transmettre directement d’homme à homme comme le démontrent certaines épidémies dans des hôpitaux ou dans des centres aérés, ou indirectement par l’eau de boisson et les aliments souillés. Des recherches effectuées après plusieurs épidémies en Amérique du Nord et au Royaume Uni ont montré que toutes les eaux de surface (lacs, rivières...) sont contaminées par des cryptosporidies. Cette pollution serait principalement due à l’agriculture et à la faune sauvage. Les eaux d’égouts de populations infectées sont aussi source de contamination. Les procédés de traitement des eaux usées, filtration et désinfection, ne sont pas totalement efficaces pour éliminer complètement Cryptosporidium et des oocystes sont retrouvés dans l’eau de boisson. Depuis 1985, les recherches s’intensifient pour mettre au point des techniques fiables afin de déceler la présence des oocystes dans l’eau de boisson, de les identifier et de les inactiver., Described in 1907, Cryptosporidium, a protozoan parasite, was considered as a rare, commensal and specific organism. After 1981, C.paruum was recognized as a common source of contamination in all mammals including humans. Symptoms are neonatal diarrhea in ruminants and self limiting or life threatening diarrhea in immunocompetent or immunodeficient hosts, respectively. The first reports indicated that infected animals were the source of human infections and that cryptosporidiosis was a zoonotic disease. Nevertheless, cryptosporidiosis may be transmitted directly from person to person and indirectly by water. Pollution of all types of surface water, lakes, reservoirs, rivers etc can result from agriculture but sewage from infected populations are also a source of contamination. The sewage treatment processes, filtration and desinfection, are not fully effective and oocysts have been found in drinking water in North America and the United Kingdom. From 1985, studies have been carried out to enumerate, identify and inactivate Cryptosporidium oocysts in water.

12 pages; International audience; Background: Emerging infectious diseases in wildlife are major threats for both human health and biodiversity conservation. Infectious diseases can have serious consequences for the genetic diversity of populations, which could enhance the species' extinction probability. The Ebola epizootic in western and central Africa induced more than 90% mortality in Western lowland gorilla population. Although mortality rates are very high, the impacts of Ebola on genetic diversity of Western lowland gorilla have never been assessed. Methodology/Principal Findings: We carried out long term studies of three populations of Western lowland gorilla in the Republic of the Congo (Odzala-Kokoua National Park, Lossi gorilla sanctuary both affected by Ebola and Lossi's periphery not affected). Using 17 microsatellite loci, we compared genetic diversity and structure of the populations and estimate their effective size before and after Ebola outbreaks. Despite the effective size decline in both populations, we did not detect loss in genetic diversity after the epizootic. We revealed temporal changes in allele frequencies in the smallest population. Conclusions/Significance: Immigration and short time elapsed since outbreaks could explain the conservation of genetic diversity after the demographic crash. Temporal changes in allele frequencies could not be explained by genetic drift or random sampling. Immigration from genetically differentiated populations and a non random mortality induced by Ebola, i.e., selective pressure and cost of sociality, are alternative hypotheses. Understanding the influence of Ebola on gorilla genetic dynamics is of paramount importance for human health, primate evolution and conservation biology.

International audience; Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors, including variants in the CFH gene and the ARMS2 LOC387715/HTRA1locus. Our purpose was to perform a case-control study in two populations among individuals who did not carry risk variants for CFHY402H and LOC387715 A69S (ARMS2), called ‘‘study’’ individuals, in order to identify new genetic risk factors. Based on a candidate gene approach, we analyzed SNP rs5888 of the SCARB1 gene, coding for SRBI, which is involved in the lipid and lutein pathways. This study was conducted in a French series of 1241 AMD patients and 297 controls, and in a North American series of 1257 patients with advanced AMD and 1732 controls. Among these individuals, we identified 61 French patients, 77 French controls, 85 North American patients and 338 North American controls who did not carry the CFH nor ARMS2 polymorphisms. An association between AMD and the SCARB1 gene was seen among the study subjects. The genotypic distribution of the rs5888 polymorphism was significantly different between cases and controls in the French population (p,0.006). Heterozygosity at the rs5888 SNP increased risk of AMD compared to the CC genotypes in the French study population (odds ratio (OR) = 3.5, CI95%: 1.4–8.9, p,0.01) and after pooling the 2 populations (OR = 2.9, 95% CI: 1.6–5.3, p,0.002). Subgroup analysis in exudative forms of AMD revealed a pooled OR of 3.6 for individuals heterozygous for rs5888 (95% CI: 1.7–7.6, p,0.0015). These results suggest the possible contribution of SCARB1, a new genetic factor in AMD, and implicate a role for cholesterol and antioxidant micronutrient (lutein and vitamin E) metabolism in AMD

National audience

All dietary proteins are potential sources of bioactive peptides, with a large range of beneficial effects on health. However, although technical progress has allowed significant breakthroughs in the identification of peptides issued from in vivo protein digestion, some links in the chain between protein ingestion and the physiological effect of the derived peptides are still lacking. For instance, true quantification of the peptides at each step of the degradation would be useful to explore a potential activity at the gut level. For peptides having peripheral effects, the major uncertainty is on their ability to cross the gut epithelium and to present a sufficiently long half-life in the plasma to be able to trigger a physiologic response. Finally, clear clinical evidence supporting the health effects of food-derived bioactive peptides are still weak. This review article takes stock of current knowledge in this research field.

3. International Symposium on Human Health Effects of Fruits and Vegetables - FAVHEALTH 2009, 2009/10/18-21, Avignon (France); International audience; Objective: Consumption of fruit and vegetables (F&V) may play a role in the fight against overweight. The aim of the current study was to validate the link between consumption of F&V with overweight and biological impact. The Algerian context is a very rapid transition with a high prevalence of overweight and low consumption of F&V. Methodology: Qualitative and quantitative surveys were conducted on 421 persons in urban (200) and rural (200) areas. Experimentation on 40 persons in Adj El Mechri (South Algeria): Distribution of 400 g/capita/day of fruit and vegetables during 2 months. Results: (i) Link between consumption of F&V and the prevalence of overweight is not as obvious as it seems. Three types of people emerge: (a) urban people with a high level of F&V consumption and a normal body mass index, (b) the illiterate urban people with a low consumption of F&V and prone to obesity, (c) the rural elderly, primary school level people with a pre-obese status. (ii) Some physiological and behavioural impacts of increased consumption of F&V were validated: vitamins E and B9 have increased; blood pressure was improved; pre-obese people lost weight while obese persons have increased their weight because the quantity of F&V consumed was added to the usual ration. (iii) Increased availability of F&V was appreciated and did not disrupt the behaviours. Low consumption of F&V was due to their limited access (low income, high prices, low availability and lack of variety).

L’obésité, considérée comme pandémique, est associée à l’apparition de troubles cognitifs et émotionnels chez l’Homme comme chez l’animal. La prévalence de l’obésité augmente de manière drastique chez les enfants et les adolescents. Or l’adolescence est une période primordiale pour la maturation des structures cérébrales (notamment l’hippocampe et l’amygdale) qui vont sous-tendre les processus cognitifs pour le restant de la vie de l’individu. Cependant, aucune étude n’avait investigué la potentielle vulnérabilité de cette période développementale aux effets de l’obésité sur la mémoire, comparativement à l’âge adulte. Nous avons donc effectué cette comparaison chez le rongeur, en modélisant l’obésité par une exposition à un régime hyper-lipidique (HL) pendant une période incluant l’adolescence versus à l’âge adulte uniquement (i.e. excluant l’adolescence). Nous mettons en évidence que l’obésité induite à l’adolescence provoque des altérations mnésiques, qui ne sont pas retrouvés lorsque l’obésité est induite à l’âge adulte. La majorité des études sur les effets de l’obésité ayant mis en évidence une altération des mémoires dépendantes de l’hippocampe, nous nous sommes tout d’abord focalisés sur les fonctions hippocampiques. Nous avons ensuite exploré le système amygdalien, impliqué dans les mémoires émotionnelles et peu étudié dans le cadre de l’obésité. Ces deux systèmes fonctionnels ont été appréhendés au travers d’approches comportementales visant à évaluer les performances mnésiques, mais également d’approches d’imagerie cellulaire et d’électrophysiologie afin d’évaluer la plasticité cellulaire au sein de ces structures. Nous mettons en évidence que l’obésité induite à l’adolescence impacte la mémoire et la plasticité de ces systèmes de manière bidirectionnelle en dégradant les fonctions hippocampiques et en exacerbant les fonctions amygdaliennes. Concernant les mécanismes impliqués dans ces effets nous mettons en évidence l’existence d’une exacerbation de la réponse inflammatoire spécifiquement au niveau de l’hippocampe chez les animaux exposés au régime HL à l’adolescence, ce qui pourrait expliquer les déficits des fonctions hippocampiques. Enfin, nous montrons que la dérégulation de l’axe corticotrope chez ces animaux est responsable des effets comportementaux et cellulaires observés au niveau des fonctions amygdaliennes. L’ensemble de ces résultats montre l’urgence de développer les études sur l’obésité juvénile, dont les effets importants sur les fonctions cognitives et émotionnelles pourraient engendrer une altération importante de la qualité de vie et une prise en charge accrue de ces sujets tout au long de leur vie., The obesity pandemic is linked to cognitive and emotional disorders in humans. Obesity prevalence in adolescence is increasing at an alarming rate. Adolescence is a crucial period for maturation of brain structures, like hippocampus and amygdala, particularly important for neurocognitive shaping required for whole life duration. However, no study investigated a potential higher vulnerability of this specific developmental period to the effects of obesity on memory. For this purpose we compared, in rodent models, the effects of high-fat diet (HFD)-induced obesity during adolescence (from weaning to adulthood) or at adulthood. We were able to demonstrate that adolescence is more vulnerable than adulthood to the effects of obesity on memory. Most of the studies interested in the effects of obesity on memory found deficits in hippocampal dependent memories. We therefore first focused on hippocampal functioning. We also extended this investigation to another memory system depending on amygdala, since little was known about the effects of obesity on this structure. Using behavioral approaches to evaluate memory performances, but also cellular imaging and electrophysiology to assess cellular plasticity, we evidenced that juvenile obesity affects both memory and plasticity in a bidirectional way, impairing hippocampal function and enhancing amygdala function. Looking for mechanisms to explain these effects, we found a potentiated inflammatory response specifically in the hippocampus that could explain decreased hippocampal function. We also demonstrated that deregulation of hypothalamo-pituitary-adrenal axis is responsible for increased amygdala plasticity and memory. Altogether these results suggest that obesity during adolescence predisposes to later maladaptive cognitive and emotional functions. This is a major concern as it could induce a significant impairment in quality of life of these individuals and contribute considerably to their social and occupational dysfunction.

Apo-lycopenal formation and absorption in the digestive tract of healthy men.. 9. Gordon Research Conference on Carotenoids, 22-27 mai 2016, Lucca, Italie.

A poluição causada pelo fumo proveniente de fogos florestais pode afectar a saúde humana, em particular a do pessoal envolvido nas operações de combate ao fogo. Visando contribuir para o conhecimento científico sobre a exposição de bombeiros ao fumo durante fogos florestais, foram recolhidos dados de exposição individual ao monóxido de carbono, dióxido de azoto, compostos orgânicos voláteis e matéria particulada, no decorrer de queimas experimentais realizadas em 2008 na região centro de Portugal. O estudo incidiu sobre um grupo de dez bombeiros munidos de equipamentos portáteis de medição em contínuo dos níveis de exposição aos poluentes referidos. Os níveis medidos são muito elevados, excedendo os valores-limite de qualidade do ar impostos pela União Europeia para protecção da saúde humana e os valores recomendados pela Organização Mundial de Saúde, o que aponta para a necessidade de definição e implementação de medidas de protecção respiratória dos bombeiros durante operações de combate a fogos florestais, para evitar a exposição a níveis susceptíveis de causarem danos na saúde. Smoke pollution due to forest fire events is an important public health issue for the communities directly affected, and particularly for the personnel involved in firefighting operations. Aiming to contribute to the scientific knowledge concerning firefighter's exposure to forest fires smoke, data of individual exposure to carbon monoxide, nitrogen dioxide, volatile organic compounds, and particulate matter were obtained during experimental field fires in 2008 in the central region of Portugal. The study focused on a group of ten firefighters equipped with portable "in continuum" measuring devices of exposure to these pollutants. Measured values are very high, exceeding the air quality limit values imposed by the European Union to protect human health and the recommended values by World Health Organization. These measurements indicate that urgent measures are needed to prevent exposure to levels likely to cause harm to health, namely those concerning the respiratory protection in firefighting operations during forest fires. La pollution, causée par la fumée provenant des feux de forêt, peut affecter la santé humaine, en particulier la santé du personnel impliqué dans les opérations de combat aux feux. Pour contribuer à la connaissance scientifique concernant l'exposition des pompiers à la fumée, émis pendant les feux de forêt, des données ont été recueillies à partir de l'exposition individuelle au monoxyde de carbone, au dioxyde d'azote, aux composés organiques volatils et aux particules, au cours de travaux expérimentaux effectués en 2008 dans la région centrale du Portugal. Un groupe de dix pompiers équipés d'équipement portable, mesurant en continu l'exposition à ces polluants, a été choisi pour cette étude. Les niveaux mesurés sont très élevés, dépassant les valeurs-limites imposées par l'Union Européenne pour la protection de la santé humaine et dépassant les valeurs recommandées par l'Organisation Mondiale de la Santé, ce qui souligne la nécessité de mesures de protection respiratoire des pompiers, pendant les opérations de combat lors des incendies de forêt, pour éviter l'exposition à des niveaux qui peuvent endommager la santé.

Life Cycle Assessment (LCA) is a tool developed to evaluate the environmental impact of a product or a system. After a decade of research in the LCA field, significant progress has been achieved but methodologies for the assessment of toxicological impacts on human health are still in the development phase. This dissertation contributes to the research required in this field. More specifically, its main objective is to develop a Life Cycle Impact Assessment (LCIA) procedure for human health respecting the guidance developed under the umbrella of the Society of Environmental Toxicology and Chemistry (SETAC). This means that we aim to implement an original procedure to quantify the potential carcinogenic and noncarcinogenic effects of toxic releases on human health (chapters 2 and 3), and to develop a new method describing the fate of atmospheric releases and the resulting exposure on humans (chapter 4). A framework summarized in figure 5.1 is also proposed to combine the effect assessment with the fate and exposure assessment, in order to derive a so-called human damage factor (chapter 5). A set of heavy metals (cadmium, chromium(VI), chromium(III), copper, methylmercury, beryllium, lead and inorganic arsenic) and of criteria air pollutants (CO, SO2, NOx and fine particles) is chosen for a full application of the procedure developed in this dissertation. The use of this procedure to the Cycleaupe case study is also part of the objectives of this research. This study aims to determine whether systems using rainwater or reducing water consumption are "friendlier" from an environmental perspective than conventional toilet flushing (chapter 6). Figure 5.1. Overview of the framework proposed in this thesis for assessing the damage induced on human health by a toxic released into air. In chapters 2 and 3, a new paradigm based on the effect dose ED10h is derived from the Risk Assessment concept of benchmark dose. It is proposed and explored for the first time in LCIA. The ED10h is defined as the best estimate of the dose which induces a 10% added risk over background for humans. Carcinogenic and noncarcinogenic risks towards humans are characterized by drawing a straight line from the ED10h down to the origin of the dose-response function. The slope of this straight line is called the slope factor and is denoted βED10. The linear dose-response function without threshold, which is assumed in this ED10-approach, is discussed. The ED10h is calculated for chemicals with bioassay data available in the Integrated Risk Information Service (IRIS) database provided by the US Environmental Protection Agency (US EPA). New correlations between the ED10h and the more widely available tumor dose TD50a (for carcinogenic effects) and the No Observable Adverse Effect Level NOAEL (for noncarcinogenic effects) are determined. They are applied to quantify the slope factor of more than 900 chemicals. A weighting of the different health outcomes associated with chemicals is proposed, based upon the Disability Adjusted Life Years per affected person (DALYp) concept. For carcinogenic endpoints, the DALYp is calculated for different types of tumors, using data reported in the literature. This shows that all cancers have more or less the same severity and an average DALYp of 11.1 years of life lost per affected person is derived. For noncarcinogenic effects, a simplified classification of the adverse effects into three categories is chosen and a DALYp of 11.1, 1.1 and 0.11 years of life lost per affected person is respectively assigned to each of the three categories. Finally, the slope factor βED10 and the DALYp for each substance are combined together in an original way to derive its effect factor. This effect factor is expressed in years of life lost per absorbed mass. Appendix 1.1 summarizes the effect factors calculated for more than 900 toxic releases. Effect factors for carcinogenic outcomes range from 1.3·10-9 for cinnamyl anthranilate up to 3.4·10-1 [yr lost / mg absorbed] for 2,3,7,8-tetrachlorodibenzo-p-dioxin. Effect factors for noncarcinogenic endpoints range from 4.2·10-12 for 1-Chloro-1,1-difluoroethane to 1.4·10-3 [yr lost / mg absorbed] for beryllium. In chapter 4, a semi-empirical approach is developed to evaluate the fate and exposure for atmospheric releases of metals, carbon monoxide (CO), sulfur dioxide (SO2), nitrogen oxides (NOx) and fine particles. For that purpose, we apply for the first time in LCA the concept of exposure efficiency, which is defined as the ratio between the dose absorbed by the population and the emission inducing that absorption. Three types of exposure efficiency are defined for a world release into air of a given compound. A specific exposure efficiency is directly based on the rural and urban concentrations inhaled by humans. A continental exposure efficiency is defined by considering an uniform world continental concentration over urban and rural inhabited regions (marine and desert regions are excluded). A global exposure efficiency issimilarly defined from the global world concentration of a substance. Exposure efficiencies are calculated for fine particles, CO, NOx and SO2. The specific exposure efficiency ranges from 3.9·10-6 to 2.4·10-5 [mg absorbed / mg emitted], demonstrating that only a very small fraction of an air release is inhaled by humans. The exposure efficiency for metals after inhalation is assumed to be equal to the exposure efficiency for fine particles, since airborne metals are attached to particulate matter. If atmospheric deposition on an agricultural soil occurs, humans can be exposed through a transfer into food products. A first evaluation of this transfer indicates that it can increase the exposure efficiency of metals released into air by a factor 5 up to 70. Specific exposure efficiencies are selected in this thesis to describe the fate and exposure of atmospheric releases. We show for the first time that specific exposure efficiencies are higher by a factor 3 than continental exposure efficiencies, indicating that the use of one-box continental models tend to underestimate the exposure efficiency that can be expected in the real world. This is due to the fact that higher emissions occur in highly populated regions. As a first approximation, the factor 3 could be used as a corrective factor to derive the specific exposure efficiency from the exposure efficiency predicted by one-box continental models. In chapter 5, exposure efficiencies presented in chapter 4 and effect factors presented in chapters 2 and 3 are multiplied to derive the so-called Human Damage Factors (HDF). The damage factors are expressed in years of life lost per emitted mass. Using that factor, the emission of a substance can be converted into its potential damage induced on humans. The damage factors are calculated for NOx, SO2, CO and fine particles, as well as for the selected set of metals released into air or into agricultural soils (see appendix 1.2 for the summarized results). When the transfer into food products is not accounted for, the damage factors for the studied metals range from 1.7·10-11 for chromium(VI) up to 1.3·10-8 [yr lost / mg emitted] for beryllium. Lead has the highest damage factor (1.9·10-8 [yr lost / mg emitted]) if transfer into food products is considered. Damage factors ranging from 2.7·10-10 to 6.6·10-10 [yr lost / mg emitted] are found for NOx, SO2 and fine particles, while carbon monoxide is characterized by a damage factor 103-folds lower. Per emitted mass, metals inhaled by humans induce damages of the same order of magnitude than NOx, SO2 and fine particles; when atmospheric deposition on agricultural soils and its subsequent transfer into food are accounted for, metals present higher damage factors. An indirect validation of the damage factors is presented for SO2, NOx, CO, fine particles and some metals, by applying their damage factors to their total emissions over Switzerland and Europe. The evaluated damages are plausible and in accordance with results reported in other studies. In chapter 6, a Life Cycle Analysis is performed to compare five scenarios for toilets flushing. This LCA is the first one carried out on the whole water cycle, including both thesimilarly defined from the global world concentration of a substance. Exposure efficiencies are calculated for fine particles, CO, NOx and SO2. The specific exposure efficiency ranges from 3.9·10-6 to 2.4·10-5 [mg absorbed / mg emitted], demonstrating that only a very small fraction of an air release is inhaled by humans. The exposure efficiency for metals after inhalation is assumed to be equal to the exposure efficiency for fine particles, since airborne metals are attached to particulate matter. If atmospheric deposition on an agricultural soil occurs, humans can be exposed through a transfer into food products. A first evaluation of this transfer indicates that it can increase the exposure efficiency of metals released into air by a factor 5 up to 70. Specific exposure efficiencies are selected in this thesis to describe the fate and exposure of atmospheric releases. We show for the first time that specific exposure efficiencies are higher by a factor 3 than continental exposure efficiencies, indicating that the use of one-box continental models tend to underestimate the exposure efficiency that can be expected in the real world. This is due to the fact that higher emissions occur in highly populated regions. As a first approximation, the factor 3 could be used as a corrective factor to derive the specific exposure efficiency from the exposure efficiency predicted by one-box continental models. In chapter 5, exposure efficiencies presented in chapter 4 and effect factors presented in chapters 2 and 3 are multiplied to derive the so-called Human Damage Factors (HDF). The damage factors are expressed in years of life lost per emitted mass. Using that factor, the emission of a substance can be converted into its potential damage induced on humans. The damage factors are calculated for NOx, SO2, CO and fine particles, as well as for the selected set of metals released into air or into agricultural soils (see appendix 1.2 for the summarized results). When the transfer into food products is not accounted for, the damage factors for the studied metals range from 1.7·10-11 for chromium(VI) up to 1.3·10-8 [yr lost / mg emitted] for beryllium. Lead has the highest damage factor (1.9·10-8 [yr lost / mg emitted]) if transfer into food products is considered. Damage factors ranging from 2.7·10-10 to 6.6·10-10 [yr lost / mg emitted] are found for NOx, SO2 and fine particles, while carbon monoxide is characterized by a damage factor 103-folds lower. Per emitted mass, metals inhaled by humans induce damages of the same order of magnitude than NOx, SO2 and fine particles; when atmospheric deposition on agricultural soils and its subsequent transfer into food are accounted for, metals present higher damage factors. An indirect validation of the damage factors is presented for SO2, NOx, CO, fine particles and some metals, by applying their damage factors to their total emissions over Switzerland and Europe. The evaluated damages are plausible and in accordance with results reported in other studies. In chapter 6, a Life Cycle Analysis is performed to compare five scenarios for toilets flushing. This LCA is the first one carried out on the whole water cycle, including both the water supply and the wastewater treatment. The drinking water supply system, the rainwater recuperation system and the wastewater treatment system are included in the system boundaries. Results demonstrate that economic toilets (3.5 [l/flushing]) lead to a significant reduction of the energy requirements compared to conventional toilets (9 [l/flushing]). A conventional water supply and a rainwater recuperation with a storage tank of 10 m3 are characterized by similar energy consumption. A rainwater storage tank of 20 m3, designed to be completely independent of the conventional water supply system, is energetically disadvantageous. Calorific losses, linked to the temperature increase of flushing water within the house, have a significant contribution to the energy requirement. The advantage of economic toilets is confirmed when looking at the inventory emissions. An initial LCIA was performed using the critical surface-time CST95 method of Jolliet and Crettaz [1997]. It showed that the conventional scenario using economic toilets (CONVeco) is the most advantageous for all impact classes. When applying the human damage factors developed in this thesis (see chapter 5), the conventional scenario (CONVeco) is still characterized by lower impacts on humans than the recuperation scenario (REC10eco). However, the substances having the major effect on human health differ from those found with the CST95 method; reasons for that change are discussed.

Background Major depression disorder (MDD) is a common condition in patients suffering from acute coronary syndrome (ACS), and depression is a risk factor for mortality following an ACS. Growing evidence suggests that there is an intricate interplay between atherosclerosis, inflammation and depression. The aim of this study was to investigate the role of atherosclerosis-induced inflammation in the mediation of MDD. Methods 87 patients without depression were recruited at the time of an ACS, evaluated at 3 and 7 days and followed at 1, 3 and 9 months for the occurrence of a MDD as assessed by structured interviews (MINI). At each time point, they were monitored for inflammatory markers (high sensitivity C Reactive Protein {hsCRP} and fibrinogen), cardiovascular risk factors and atherosclerosis burden. Association between possible predictive characteristics and depression was assessed using a multivariable logistic regression model. Results The overall incidence of MDD, in this population, was 28.7% [95% CI: 19.5 – 39.4] during the 9-month follow up period. Elevated hsCRP was not associated with depression onset after an ACS (adjusted OR: 1.07 [0.77 - 1.48]; p = 0.70), and similarly no association was found with fibrinogen. Furthermore, we found no association between hsCRP, fibrinogen or atherosclerosis burden at any time-point, and the occurrence of a MDD (or HDRS-17 and MADRS). The only factor associated with depression occurrence after an ACS was a previous personal history of depression (adjusted OR: 11.02 [2.74 to 44.34]; p = 0.0007). Conclusions The present study shows that after an ACS, patients treated with optimal medications could have a MDD independent of elevated hsCRP or fibrinogen levels. Personal history of depression may be a good marker to select patients who should be screened for depression after an ACS. Electronic supplementary material The online version of this article (doi:10.1186/s12872-015-0015-3) contains supplementary material, which is available to authorized users.

International audience; In their native state, milk lipids are present in the form of dispersed droplets called Milk Fat Globules (MFG, average diameter of 4 µm in human and bovine milks), which have been recently pointed out as key elements of early nutritional programming. Understanding the specific digestive fate of MFG is thus a priority in neonatal nutrition. The MFG are unique biophysical elements differing from other lipoproteic objects by their external trilayered membrane inherited from their secretory past. To play their major biological function, i.e. deliver energy to the newborn, the MFG have to be hydrolyzed in the gastro-intestinal tract by lipases. This hydrolysis is typically a heterogeneous phase reaction, in which the lipase has to diffuse and get adsorbed onto the lipid phase before the formation of the enzyme-substrate complex, and the onset of the proper catalytic action. Very few techniques allow assessing the mechanisms involved in the enzymatic hydrolysis of complex supramolecular substrates such as MFG. To get a better insight of these mechanisms, 4-D imaging of gastric and pancreatic lipases enzymes using synchrotron SOLEIL UV fluorescence microscopy was applied during simulated static in vitro newborn digestion. This methodology allowed mapping the adsorption and diffusion of lipases onto/within human or bovine MFG or biomimetic droplets devoid of membrane proteins. These data were completed with simultaneous transmission light imaging of MFG disintegration during hydrolysis. The high sensitivity of the DISCO beamline allowing the detection of digestive lipases auto-fluorescence, is a unique tool to unravel their mechanisms of adsorption onto complex substrate using free-label imaging and has generated useful data for infant formula optimization.

The objective of this study is to better understand and model the effect of dairy matrix structure on the hydrolysis and transit rates of milk proteins during digestion. 4 dairy matrices having a similar composition but differing by their internal structure were manufactured: 2 solutions, 1 acid gel and 1 stirred acid gel which all contained a small amount of Cr-EDTA complexes, a non-absorbable and non-hydrolysable water soluble marker. These 4 matrices were given to six adult mini-pigs and, for each experiment, 9 samples corresponding to 8 different times after the meal ingestion and 1 time before the meal were collected after the pylori, i.e. at the stomach exit. Effluents were analysed by ELISA to determine their residual concentration in β-lactoglobulin and caseins (intact proteins and large fragments) and by atomic absorption to measure the Cr2+ concentration. Statistical analyses performed on ELISA data for proteins are presented. They allow distinguishing the gelled from the liquid matrices, the stirred acid gel being equally distributed among the two groups. A first mathematical model describing the gastric emptying of Cr-EDTA is also presented. This model provides a good fitting of the Cr-EDTA concentrations and allows estimating several unknown digestion parameters (level of gastric juice flow and half-life of the chromium complex in the stomach) with a good accuracy.

Réalisation d'une analyse de risques relative au houblon du Japon et élaboration de recommandations de gestion

Une nouvelle étude conteste les mesures utilisées pour estimer l’innocuité des OGM avant leur mise sur le marché.

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// Fillipe Luiz Rosa do Carmo 1 , 2 , Houem Rabah 2 , 3 , Barbara Fernandes Cordeiro 1 , Sara Heloisa da Silva 1 , Rafaela Miranda Pessoa 4 , Simone Odilia Antunes Fernandes 4 , Valbert Nascimento Cardoso 4 , Valerie Gagnaire 2 , Martine Deplanche 2 , Bruna Savassi 1 , Alessandra Figueiroa 1 , Emiliano Rosa Oliveira 1 , Caio Cesar Fonseca 1 , Maria Izabel Alves Queiroz 1 , Nubia Morais Rodrigues 1 , Savio Henrique de Cicco Sandes 1 , Alvaro Cantini Nunes 1 , Luisa Lemos 1 , Juliana de Lima Alves 1 , Ana Maria Caetano Faria 1 , Enio Ferreira 1 , Yves Le Loir 2 , Gwenael Jan 2 , * and Vasco Azevedo 1 , * 1 Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brasil 2 STLO, INRA, Agrocampus Ouest, UMR1253, Science & Technologie du Lait & de l'Oeuf, Rennes, France 3 Bba, Pole Agronomique Ouest, Regions Bretagne et Pays de la Loire, Rennes, France 4 Department of Clinical and Toxicological Analysis, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil * These authors share senior authorship Correspondence to: Gwenael Jan, email: gwenael.jan@inra.fr Keywords: mucositis; probiotic; surface protein; immunomodulation; inflammation Received: June 11, 2019 Accepted: October 21, 2019 Published: December 31, 2019 ABSTRACT Propionibacterium freudenreichii CIRM-BIA 129 ( P. freudenreichii wild type, WT) is a probiotic bacterium, which exerts immunomodulatory effects. This strain possesses extractable surface proteins, including SlpB, which are involved in anti-inflammatory effect and in adhesion to epithelial cells. We decided to investigate the impact of slpB gene mutation on immunomodulation in vitro and in vivo . In an in vitro assay, P. freudenreichii WT reduced expression of IL-8 (p

International audience; Despite consented efforts in prevention, mycotoxins remain a problem of human health concern in several parts of the world including developed countries. Within the same range of toxins concentrations in the blood some people develop a disease while others do not. Could this inequality in front of mycotoxins effects be explained by environment factors and/or genetic predisposition? Among recent advances in environmental health research Correlation between chronic diseases and mycotoxins in humans deserves attention through several questions: Are genetic factors involved in disease causation of mycotoxins? How much are these factors currently taken into account for mycotoxins risk assessment and how much should we involve them? Answers are still to come. Genetic and environment factors deserve therefore more attention when dealing with regulatory limits, since among the general population, those who are at risk and will develop specific diseases are likely those bearing genetic predispositions. We have addressed these questions for the specific case of ochratoxin A in humans by investigating in Tunisia, county of Jelma, in four rural families forming a household of 21 persons all exposed to ochratoxin A in diet. Our results confirm that ochratoxin A induces chronic tubular nephropathy in humans and mainly point at those having the HLA haplotype A3, B27/35, DR7 to be more sensitive to the disease for quantitatively similar or lower exposure. Persons with such haplotype were found to bear chronic interstitial nephropathy with tubular karyomegalic cells while others were apparently healthy. Godin et al. (1996) in France have also found in sibling (a sister and her brother from urban area) that have similar HLA haplotype B35-patern, OTA-related renal tubulopathy with mild proteinuria including beta2-microglobulinuria. Several mechanisms are discussed that could be put ahead to explain how the HLA haplotype could lead to tubular cells lyses and renal failure. In the mean time it is urgent to search for mass screening biomarkers for mycotoxins in humans and related genetic factors to set-up more appropriate regulation.

Facing health, environmental, economic and social issues, urban agriculture is currently on the rise in cities of industrialized countries. Among the different forms of urban agriculture, community gardens are characterized by their multi-functionality (source of food, education, social link…) and were identified as promising to promote healthy lifestyles (e.g. increased fruit and vegetable consumption, increased physical activity). However, only few studies are conducted in a European context, and evidence tends to be based on cross-sectional designs which do not allow causality assessment. A recent observational study conducted in the city of Marseille, France, suggested that having access to a community garden could encourage socio-economically disadvantaged women to adopt dietary practices that more closely meet dietary recommendations. Although this investigation highlighted valuable information on the role of gardening in food practices in a French context, causality still could not be inferred due to a transversal design. Moreover, given the widening gap in socio-economic inequalities in health in Europe, including in France, more research is needed on the possible differential impacts of such experiment on individuals, depending on their socioeconomic positions and incomes.The objective of this study is to design a protocol for a quasi-experimental evaluation allowing to assess the impact of access to a community garden on nutritional quality and sustainability of food practices, and if this impact varies between low- and middle-income populations.Methods/Design:This study will be based on a natural experiment (access to a community garden) evaluated within a quasi-experimental design. Gardeners who recently had access to a community garden will be recruited in two socio-economically contrasted neighborhoods of Montpellier, France, to constitute a low-income and a middle-income natural experiment groups. Volunteers living in the same neighborhoods but with no access to a community garden will be recruited as comparison groups (control). Data collection at recruitment (baseline) and at follow up at 1 year (endline) will include household monthly food supply (food purchase receipts, garden productions, gifts, food aid), food waste behavior, and socio-demographic characteristics. Qualitative approaches will be used to explore intermediate variables on a causal path between access to the garden and food practices changes, such as gardener’s motives for sustainable food systems and sustainable food choices, length of time with access to a garden, personal history of gardening, or self-efficacy.The primary outcome will be the sustainability of food practices, assessed through the nutritional quality and environmental impact of household’s food purchases, the later being estimated through food waste, diet-related greenhouse gas emissions and the animal-to-plant ratio. This protocol is part of the SURFOOD-Foodscapes project (Sustainable Urban Food Systems – The effects of urban foodscape on food styles in Montpellier Metropole).Discussion: Change of outcomes after 1 year will be compared between the natural experiment and control groups, to evaluate the effect of access to a community garden on the sustainability of food practices. Differences induced will be compared between the low- and middle-income groups in order to assess the impact on social inequalities in health. This study will provide valuable information for urban strategies to favor healthy and sustainable food practices, based on a robust quasi-experimental design allowing causality evaluation.