HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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Crecimiento, eficiencia alimentaria y calidad de canal de conejos en crecimiento alimentados con dietas conteniendo dos productos derivados de la producción de linaza suplementados con dos niveles de vitamina E
No full textInternational audienceGrowth, feed efficiency and polyunsaturated fatty acid profile (omega-6 and omega-3) were evaluated in fattening rabbits fed diets containing two novel products derived from the flaxseed oil production. A total of 400 rabbits were distributed among the five experimental diets (CTL: control, PL-O: mixture of high fat flaxseed chaff and wheat flour (70:30); PL-E: PL + Vitamin E, HL-O: high fat extruded flaxseed meal, HL-E: HL + Vitamin E) at 36 days of age. At 71 days of age, 20 animals/diet were euthanized to quantify the fatty acid profile in the longissimus dorsi muscle. Growth (≈ 40 g/rabbit/day), feed consumption (≈ 129 g/day), and the health risk index (morbidity + mortality ≈ 44.5%) were similar among the five diets. The proportion of omega-6 polyunsaturated fatty acids was higher in the CTL diet with respect to the other diets (≈ 2.0 points). The diets containing PL and HL had a fatty acid profile with a higher percentage of omega-3 polyunsaturated fatty acids (≈ 3.7 points) relative to the CTL diet, resulting in a higher omega-6/omega-3 ratio in the CTL diet relative to the other diets (≈ 4.3 units)
Triméthoprime et sulfadoxine : pharmacodynamique et pharmacocinétique dans le cadre de la lutte anti-dopage chez le cheval
No full textOur stuty is part of a the medication control approach, which is a significant concern in horseraces and equestrians sports. Following a single intravenous injection to eight horses of trimethoprim at 2.7mg/kg and sulfadoxine at 13.4mg/kg, the detection times for trimethoprim, its metabolite, and sulfadoxine in plasma were 216 hours, 143 hours, and over 524 hours, respectively, for a detection limit of 0.05ng/mL. Detections times in urine were 1680 hours for the metabolite and 984 hours for both antibiotics, for a detection limit of 1ng/mL. A shorter withdrawal time of 102 hours would ensure the absence of antibacterial effects of the molecules. The concentrations monitoring allowed us to initiate a preliminary study of the efficacy of this antibiotic combination. Following the administration of trimethoprim and sulfadoxine in horses, the ratio between the two antibiotics is significantly lower than the optimal value of 1/19 described as synergistic in vitro in the literature. The study of plasma concentrations in relation to the Minimum Inhibitory Concentrations (MIC) of pathogens suggests that the two molecules are not effective individually. Therefore, it is necessary to better characterize the interaction between the two molecules at different ratios to predict the efficacy of this combination.Notre étude s’inscrit dans une approche de contrôle des médications qui est un enjeu important dans le milieu des courses hippiques et des sports équestres. Après une injection unique par voie IV à huit chevaux de triméthoprime à 2,7mg/kg et de sulfadoxine à 13,4mg/kg, les temps de détection du triméthoprime, de son métabolite et de la sulfadoxine dans le plasma étaient respectivement de 216h, 143h et plus de 524h pour une limite de détection de 0,05ng/mL. Les temps de détection dans les urines étaient de 1680h pour le métabolite et de 984h pour les deux antibiotiques pour une limite de détection de 1ng/mL. Un temps de retrait plus court de 102h permettrait d’assurer l’absence d’effet antibactérien des molécules. Le suivi des concentrations nous a permis d’effectuer les prémices d’une étude d’efficacité de cette association d’antibiotique. Suite à l’administration de triméthoprime et de sulfadoxine chez le cheval, le ratio entre les deux antibiotiques est bien inférieur à la valeur optimale de 1/19 décrite comme synergique in vitro dans la littérature. La comparaison des concentrations plasmatiques aux CMI des pathogènes semble indiquer que, les deux molécules ne sont pas efficaces individuellement. Il faudrait donc mieux caractériser l’interaction entre les deux molécules à différents ratios pour prédire l’efficacité de cette combinaison
A new tool to assess the economic impact of q fever on dairy cattle farms
No full textSource Agritrop Cirad (https://agritrop.cirad.fr/612176/)International audienceTo support farmers in their decisions related to Q fever, a dedicated economic assessment tool is developed. The present work describes the calculator, its economic rationale, and the supporting assumptions. The calculator integrates a yearly compartmental model to represent population dynamism and the main interactions between disorders linked to Q fever, especially reproductive disorders (abortion, retained foetal membranes, purulent vaginal discharge and endometritis, extra services, and calving–conception delays). The effects of the nontangible cost of the disease on human health, the welfare of the animals, and the workload of farmers were not integrated into the model. The model shows high-level sensitivity to the prevalence of Q fever in the herd prevaccination and to the costs of abortion and extra days of calving–conception intervals. Breakeven points, i.e., cost values that allow us to achieve positive vaccination benefits, are also reported. For herds with moderate or high prevalence rates of Q fever prevaccination (>30%), a vaccination benefit is observed. The vaccine should be considered a type of insurance in herds with low prevalence rates of Q fever prevaccination (≤20%). The calculator was developed to aid decision-making at the farm level, and no conclusion can be extrapolated as a generic trend based on the present work
Looking for a needle in a haystack: de novo phenotypic target identification reveals Hippo pathway-mediated miR-202 regulation of egg production
No full textInternational audienceUnderstanding microRNA (miRNA) functions has been hampered by major difficulties in identifying their biological target(s). Currently, the main limitation is the lack of a suitable strategy to identify biologically relevant targets among a high number of putative targets. Here we provide a proof of concept of successful de novo (i.e. without prior knowledge of its identity) miRNA phenotypic target (i.e. target whose derepression contributes to the phenotypic outcomes) identification from RNA-seq data. Using the medaka mir-202 knock-out (KO) model in which inactivation leads to a major organism-level reproductive phenotype, including reduced egg production, we introduced novel criteria including limited fold-change in KO and low interindividual variability in gene expression to reduce the list of 2853 putative targets to a short list of 5. We selected tead3b, a member of the evolutionarily-conserved Hippo pathway, known to regulate ovarian functions, due to its remarkably strong and evolutionarily conserved binding affinity for miR-202-5p. Deleting the miR-202-5p binding site in the 3′ UTR of tead3b, but not of other Hippo pathway members sav1 and vgll4b, triggered a reduced egg production phenotype. This is one of the few successful examples of de novo functional assignment of a miRNA phenotypic target in vivo in vertebrates
Welfare issues in goat farming and management
No full textInternational audienceGoats are raised in a wide range of production systems all around the world. Whatever the system, different aspects of the farming management can affect the welfare of goats, namely management of the relationships with social peers and humans, kids’ management, outdoor access, and milking, reproduction and genetics management. In this chapter, each of these management aspects is discussed with regard to the risks of impairing the welfare of goats and the strategies to mitigate their stress by better fitting the farming management to the behavioural and physiological needs of goats. In addition to stress mitigation, this chapter also highlights the possibility throughout management practices to elicit positive emotional experiences to induce positive welfare in goats. In tandem, the positive effects of facilitating positive welfare of goats on the quality of life at work for the farmer are reported, illustrating the interrelationships between human wellbeing and animal welfare. Recent scientific knowledge in behavioural and social needs of goats and their cognitive abilities should be better taken into account to develop good practice guidelines and specific regulations to ensure more welfare-friendly goat farming systems
The cytokine response to innate stimuli in blood of calves at birth and the occurrence of infectious diarrhoea
No full textInternational audienceNewborn calves are susceptible to diarrhoea caused by infections. The capacity of calves to mobilize their innate immune defenses is key to explain the disease susceptibility at this early stage of life. To phenotype this innate response, whole blood cells collected from 623 Holstein calves aged 1 to 2 weeks were exposed for 24h at 38.5°C to synthetic agonists mimicking exposure to pathogens (R848, LPS and MDP, ligands of TLR7/8, TLR4 and NOD2, respectively). The production of 15 cytokines and chemokines was quantified using Luminex technology. A subset of cytokines and chemokines (CCL3, CCL4, IP10, IL-1RA, TNFα, IL-1α, IL-1β, IL-10 and IFNγ) had increased levels of expression after treatment of blood cells with agonists, R848 being the most potent. Using contingency approaches on the values of these cytokines between individuals/agonist treatments,we showed convergence between groups of strong responders for all conditions as well as for groups of weak responders. Nevertheless the distribution of individuals in these “high” versus “weak” categories varied with the agonist. A multivariate redundancy analysis showed that there were significant relationships between the cytokines produced in the blood and the clinical status of the calves (symptoms, pathogens). However, the significant associations were dependent upon the agonist used to reveal the cytokine signature and the clinical parameter monitored. To conclude, calves at birth show different abilities in their response to innate stimuli, which to some extent could explain the occurrence of intestinal infections. We are investigating the genetic control for the innate immune phenotype
Species barrier as molecular basis for adaptation of synthetic prions with N‐terminally truncated PrP
No full textInternational audienceMammalian prions are neurotropic pathogens formed from PrP Sc assemblies, a misfolded variant of the host‐encoded prion protein PrP C . Multiple PrP Sc conformations or strains self‐propagate in host populations or mouse models of prion diseases, exhibiting distinct biological and biochemical phenotypes. Constrained interactions between PrP Sc and PrP C conformations confer species specificity and regulate cross‐species transmission. The pathogenicity of fibrillar assemblies derived from bacterially expressed recombinant PrP (rPrP) has been instrumental in demonstrating the protein‐only nature of prions. Yet, their ability to encode different strains and transmit between species remains poorly studied, hampering their use in exploring structure‐to‐strain relationships. Fibrillar assemblies from rPrP with hamster, mouse, human, and bovine primary structures were generated and tested for transmission and adaptation in tg7 transgenic mice expressing hamster PrP C . All assemblies, except the bovine ones, were fully pathogenic on the primary passage, causing clinical disease, PrP Sc brain deposition, and spongiform degeneration. They exhibited divergent adaptation processes and strain properties upon subsequent passage. Assemblies of hamster origin propagated without apparent need for adaptation, those of mouse origin adapted abruptly, and those of human origin required serial passages for optimal fitness. Molecular analyses revealed the presence of endogenously truncated PrP Sc species in the resulting synthetic strains that lack the 90–140 amino acid region considered crucial for infectivity. In conclusion, rPrP assemblies provide a facile means of generating novel prion strains with adaptative/evolutive properties mimicking genuine prions. The PrP amino acid backbone is sufficient to encode different strains with specific adaptative properties, offering insights into prion transmission and strain diversity
Population pharmacokinetic modelling of cetirizine concentrations in human breast milk—A contribution from the ConcePTION project
No full textInternational audienceAbstract Cetirizine is an antihistamine commonly used to treat allergic rhinitis and other allergic conditions. Cetirizine is often prescribed to breastfeeding mothers although there is limited information on infant exposure via breast milk. The aim of this study was to develop a popPK model based on data from a lactation study to predict cetirizine breast milk concentrations and estimate the relative infant dose (RID) in a breastfed infant. A popPK model was developed in NONMEM on data from a human lactation study including 35 women using cetirizine or levocetirizine while breastfeeding. Serial samples of breast milk were collected (n = 205) and the cetirizine concentrations quantified using a validated LC–MS/MS method. A one‐compartment model of cetirizine in breast milk was developed and employed to calculate the relative infant dose (RID). Covariates related to the maternal characteristics and breastfeeding patterns were evaluated in the model; only milk sampling pumping duration was found to be a significant covariate, with an increasing pumping duration leading to an increased apparent milk volume of distribution (V m ). The mean RID was 1.99% with the highest RID being 3.36% at C max . PopPK modelling could be used to estimate infant exposure to cetirizine via breast milk. The low predicted exposure in infants supports that cetirizine is compatible with breastfeeding
Interaction entre deux mycotoxines préoccupantes, l'aflatoxine B1 et le déoxynivalénol : étude de la génotoxicité, des rôles des cytochromes P450 et du stress ribotoxique
No full textMycotoxins are fungal secondary metabolites that account among the most common food contaminants. Humans are exposed to several mycotoxins concomitantly. In that context, two mycotoxins appear particularly preoccupying because of their prevalence and toxicity: aflatoxin B1 (AFB1) and deoxynivalenol (DON). AFB1 mainly contaminates cereals (maize, rice, sorghum ...), legumes like peanuts, and spices (black pepper, paprika, cilantro ...). It is bio-activated in the liver by cytochromes P450 (CYP450) 1A2 and 3A4 into a genotoxic compound, AFB1-8,9-exo-epoxyde (AFBO). Relatively to that genotoxicity, AFB1 is associated with the aetiology of hepatocellular carcinoma. DON contaminates cereals (wheat, maize, barley, oat, rye, sorghum ...) and it is responsible for alterations of intestinal, immune and hepatic functions. It is also known to exacerbate the genotoxicity of compounds that induce DNA damage like a bacterial toxin (colibactin), agents used in chemotherapy (etoposide, cisplatin) and a pesticide (captan). AFB1 being a known genotoxic agent, this PhD work took interest in its genotoxicity in mixture with DON. For the liver is the main target of AFB1 and a target of DON, this study was conducted with hepatic in vitro models. Using two markers of DNA damage response, γ-H2AX and 53BP1, we have demonstrated that DON inhibits the genotoxicity induced by AFB1. The role of the enzymes responsible for the bio-activation of AFB1 in that inhibition phenotype was investigated. The result is that DON inhibits the protein expression and the enzymatic activities of CYP1A2 and CYP3A4. It suggests that the inhibition of AFB1 genotoxicity by DON is caused by an inhibition of its bio-activation into AFBO. Using cycloheximide, another ribosome inhibitor, allowed to demonstrate that ribosome inhibition by DON has a role in the observed phenotype. Ultimately, this study indicates that DON interacts with the genotoxicity of AFB1, emphasizing the importance of studying food contaminants in mixture. It also suggests to study the possible modifications of cell metabolism induced in the presence of DON, relatively to its inhibition of CYP1A2 and CYP3A4.Les mycotoxines sont des métabolites secondaires fongiques qui comptent parmi les contaminants alimentaires les plus répandus. L’Homme est exposé à plusieurs d’entre elles de façon concomitante. Dans ce contexte, deux mycotoxines apparaissent particulièrement préoccupantes en raison de leur prévalence et de leur toxicité : l’aflatoxine B1 (AFB1) et le déoxynivalénol (DON). L’AFB1 contamine principalement les céréales (maïs, riz, sorgho …), des légumineuses comme l’arachide et les épices (poivre noir, paprika, coriandre …). Elle est bio-activée dans le foie par les cytochromes P450 (CYP450) 1A2 et 3A4 en un composé génotoxique, l’AFB1-8,9-exo-époxyde (AFBO). En lien avec cette génotoxicité, l’AFB1 est associée à l’étiologie du carcinome hépatocellulaire. Le DON contamine principalement les céréales (blé, maïs, orge, avoine, seigle, sorgho …) et est responsable d’altérations des fonctions intestinales, immunitaires et hépatiques. Il est également connu pour exacerber la génotoxicité de composés induisant des dommages à l’ADN comme une toxine bactérienne (la colibactine), des agents utilisés en chimiothérapie (étoposide, cisplatine) et un pesticide (le captane). L’AFB1 étant un génotoxique alimentaire avéré, cette étude s’est intéressée dans la même optique à son interaction avec le DON. Puisque le foie est la cible principale de l’AFB1 et une cible du DON, cette étude a été menée sur modèles cellulaires hépatiques. En utilisant deux marqueurs de la réponse aux dommages à l’ADN, γ-H2AX et 53BP1, nous avons montré que le DON inhibe la génotoxicité induite par l’AFB1. L’implication des enzymes responsables de la bio-activation de l’AFB1 a été investiguée. Il en résulte que le DON inhibe l’expression protéique et l’activité enzymatique du CYP1A2 et du CYP3A4, suggérant que l’inhibition de la génotoxicité de l’AFB1 est due à une inhibition de sa bio-activation en AFBO. L’utilisation de cycloheximide, une autre ribotoxine, et de de-epoxy-deoxynivalenol, un dérivé non ribotoxique du DON, a permis de montrer que le stress ribotoxique induit par le DON a un rôle dans le phénotype observé. En définitive, cette étude indique que le DON interagit avec la génotoxicité de l’AFB1, soulignant l’importance d’étudier les contaminants alimentaires en mélange. Elle suggère aussi une étude des possibles modifications du métabolisme cellulaire induites en présence de DON, en lien avec l’inhibition du CYP1A2 et du CYP3A4
