HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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Re‐evaluation of neotame (E 961) as food additive
No full textInternational audienceThe present opinion deals with the re-evaluation of neotame (E 961) as a food additive. Neotame is the chemically manufactured compound N-[N-(3,3-dimethylbutyl)-l-α-aspartyl]-l-phenylalanine 1-methyl ester. The main impurity of neotame (E 961) is also a degradation product (de-esterified form), N-[N-(3,3-dimethylbutyl)-l-α-aspartyl]-L-phenylalanine (NC-00751) and the primary metabolite. No new data were received following the call for biological and toxicological data. A summary of the toxicological studies available in the EFSA opinion of 2007 is presented and studies gathered from the literature are summarised. Neotame is rapidly absorbed and pre-systemically metabolised, systemic intact neotame is likely to be excreted in the urine with its metabolites. The potential aneugenic effects at the site of contact are not expected to occur; overall, there is no concern for genotoxicity of neotame (E 961) at the maximum permitted levels or reported use levels. A review of the other endpoints from the already available toxicological database did not indicate an adverse effect for neotame at the highest doses tested. The Panel established an acceptable daily intake (ADI) of 10 mg/kg bw per day for neotame based on the no observed adverse effect level (NOAEL) of 1000 mg/kg bw per day from a 52-week chronic and 104-week carcinogenicity studies in rats. This ADI replaces the ADI of 2 mg/kg bw per day established by EFSA in 2007. The resulting exposure to methanol and its metabolite formaldehyde from the use of neotame at the ADI of 10 mg/kg bw per day does not raise a concern. The dietary exposure estimates of neotame (E 961) for the different population groups of all exposure scenarios did not exceed the ADI. The Panel concluded that there is no safety concern for neotame (E 961) at the currently permitted and reported uses and use levels. The Panel recommended the European Commission to consider revising the EU specifications of neotame (E 961)
Plastiques utilisés en agriculture et pour l'alimentation : usages, propriétés et impacts. Résumé du rapport de l'expertise scientifique collective
No full textEffet d’une exposition maternelle à un mélange de contaminants alimentaires sur le développement de l’embryon pré-implantatoire
No full textInternational audienceLes femmes enceintes sont quotidiennement exposées à de nombreux perturbateurs endocriniens de type phtalates, parabènes et phénols (PPP). Ces substances présentes dans une grande variété de produits du quotidien (alimentation, emballage, produits d’hygiène) ont des répercussions sur la santé de la progéniture (cardio-métabolique et gonadique). La cohorte mère-enfant SEPAGES caractérise l'exposition des femmes enceintes aux contaminants environnementaux pour étudier leurs effets sur la santé de la femme enceinte et de sa descendance. L’analyse épidémiologique de cette cohorte a permis d’associer la présence de 8 PPP (1 parabène, 3 phénols et 4 phtalates) chez les femmes enceintes à des effets santé sur la descendance (efficacité placentaire, IMC). Pour caractériser les mécanismes impliqués dans la médiation des effets sur la descendance nous avons développé, chez le lapin, un modèle d’exposition aux 8 PPP à des doses mimant l’exposition des femmes de la cohorte SEPAGES (Bozec et al., en cours de soumission). Nous nous intéressons ici à l'impact de l'exposition maternelle aux PPP sur l'embryon au stade pré-implantatoire.Les lapines ont été exposées pendant 70 j quotidiennement per os au mélange de 8 PPP ou à son excipient (C). A 6 jour les blastocystes ont été collectés. Le transcriptome du trophectoderme (TE, futur placenta) et de l’épiblaste (EPI, futur individu) a été réalisé à ce stade par RNAseq.Les embryons PPP présentent un diamètre supérieur aux C (3,1+/-0,1mm vs 2,8+/-0,1mm). Dans le TE PPP comparativement au C, nous identifions 29 gènes différentiellement exprimés (*), dont une diminution de GLUT4, transporteur du glucose, ainsi qu’une sous-représentation de voies impliquées dans le métabolisme des lipides et des carbohydrates. Dans l’EPI PPP, nous identifions 13 gènes* dont une sur-représentation des voies impliquées dans la phosphorylation oxydative.Ces données suggèrent un impact de l’exposition maternelle aux PPP dès le stade pré-implantatoire. Actuellement, des analyses tenant compte du sexe sont en cours. Une intégration de ces données à celles obtenues en fin de vie foetale nous permettra d’identifier des mécanismes clés et précoces dans la médiation des effets des PPP. Support Financier : ANR MEMORI (ANR-21-CE34-0022
Use of stool photographs for fecal scoring and diagnosis of diarrhea in the puppy: validation of the method
No full textBackground- Diarrhea is a common issue in puppies and is associated with poor daily weight gain. To date, objective assessment has relied on a fecal scoring scale applied to fresh feces; however, digital scoring presents a potential alternative. This study aimed to evaluate the use of a puppy fecal grid on stool images for diagnosing diarrhea.Methods- In a first experiment, 40 fresh stools were collected from puppies and scored with a 13-point fecal scale. Feces were then photographed and assessed on picture. Agreement between the two scoring methods was evaluated using a Bland-Altman plot and weighted kappa coefficient. Validity of the method for diarrhea diagnosis was also studied. In a second experiment, four observers scored 98 stool photographs. Intraclass correlation coefficient was calculated to assess inter-observer agreement. Intra-observer reproducibility was also explored with a Bland-Altman plot and weighted kappa coefficient.Results- Our findings showed excellent agreement between the two methods (weighted kappa coefficient of 0.83 (95% CI [0.75, 0.91])). Validity of the photograph method for diarrhea diagnosis was deemed satisfactory. Sensitivity and specificity were both at 84.6%, with positive and negative predictive values at 73.3% and 91.7%, respectively. Our study showed good inter-observer and intra-observer reproducibility (ICC of 0.83 (95% CI [0.76, 0.88]) and weighted kappa coefficient of 0.95 (95% CI [0.93, 0.97], respectively).Conclusions- The puppy fecal scoring scale employed in the present study can reliably be used on stool photographs to objectify diarrhea in puppies. It is a promising solution for veterinary practices and future research studies
Untargeted identification of pesticides metabolites to study their effects on metabolic and Parkinson diseases
No full textInternational audienceThe exposome concept has led to the toxicological assessment of pollutant mixtures. To understand consequences of chronic dietary exposure to pesticide cocktails on Parkinson and metabolic diseases, 2 preclinical studies were performed with mice exposed to the individual admissible daily intake (ADI) of different pesticides in mixture for 20 or 52 weeks. The impact of pesticides may depend on the biotransformation of each one that could be altered when pesticides are in combination. Thus, the characterization of residues (active substance and its metabolites) would not only support exposure but also provide a better insight of the observed effects. However, in a context of low-dose exposure and in the absence of commercial standards, detecting, identifying, and quantifying metabolites is challenging. For the first study of the metabolic effects of pesticide exposure, urinary samples of mice exposed or not to the ADI of pesticides and fed a chow or a western diet were collected upon 20 weeks of exposure. For the second study, urinary samples of a mouse model expressing human alphasynuclein that recapitulates neuronal lesions in subjects with neurodegenererative diseases, and exposed or not to the ADI of a cocktail of pesticides, were collected at different time points of the 52 weeks period of exposure. Samples were analyzed using reversed-phase LC with HRMS detection (TIMS-ToF, Bruker) with a suspect screening approach with a list of suspected compounds, including the studied pesticides, their known metabolites, and putative ones, was screened and identified.For both studies, metabolites of pesticides were identified using MS/MS experiments acquired with the PASEF mode, and using CCS measurements acquired by ion mobility analyses. Comparisons with rare standards enabled level 1 identifications, but in most cases, annotations were achieved with the interpretation of fragment ions and CCS, assisted by in silico tools. By this way, we were able to detect pesticide metabolites following low-dose exposure. Interestingly, different signal intensities of each metabolite between each studied dose or time point and, more importantly, between the different diets or mouse models, were observed. Following the complex identification of pesticides biotransformed products without standard, their HRMS detection and quantification at low doses highlighted a link between the type of diet and the bioavailability of pesticides. Similarly, concentrations of pesticides metabolites were found to be different in the mouse model expressing human alphasynuclein that recapitulates neuronal lesions. Finally, these two studies illustrate that recent advances in mass spectrometry, in particularly ion mobility, allow the detection, identification, and quantification of low-concentration biomarkers of exposure, facilitating a better understanding of the effects of xenobiotics within the context of exposome
Translational Veterinary Immunology: Bridging Discovery and Application
No full textInternational audienc
Etre vétérinaire : rêve, désillusion et représentation
No full textThe aim of this work is to wonder about the veterinarian depiction, and its consequences especially the expectations-reality gap. To this end, an interview series was recorded and gathered in a podcast. In order to contextualise this interview collection, a litterature review about dreaming, rejection and some current trends in the veterinary profession, was conducted.L’objectif de ce travail est d’interroger la représentation du métier de vétérinaire, ainsi que ses répercussions notamment sur le contraste entre une image idéalisée et une réalité décevante. Pour cela, une série d’entretiens a été enregistrée et regroupée en un podcast. Une étude bibliographique portant sur l’écart entre idéalisation et rejet de l’exercice, et sur des tendances actuelles de la profession, a été menée pour mettre en contexte le podcast
Analyse métabolomique comparée entre des modèles cutanés in vitro et in vivo
No full textInternational audienceDans le cadre de l’étude des processus de processus physiopathologiques cutanés, une approche métabolomique LC-HRMS a été mise en œuvre afin de comparer les profils métaboliques issus de deux modèles expérimentaux : un modèle in vitro basé sur des explants de peaux humaines stressées et cultivées dans des conditions contrôlées, et un modèle in vivo reposant sur des prélèvements cutanés humains réaliséssur des peaux stressées. Les écouvillons issus des prélèvements de surface des échantillons et les explants ont été extraits, puis les phases aqueuses ont été analysées par UHPLC (I-Class, Waters) couplée à un spectromètre SYNAPT G2-Si (Waters) par electrospray. Le traitement des données a été effectué avec XCMS (Workflow4Metabolomics), avec alignement, filtrage des blancs et des QC. Après analyses statistiques multivariées, les variables discriminantes présentant un VIP>1 et une p-value <0.05 ont été annotées grâce à CAMERA et notre base de données interne de temps de rétention. Les métabolites annotés ont été identifiés sur un spectromètre LTQ-Orbitrap XL (Thermo Scientific) à l’aide de notre base de données interne MS/MS et des bases externes.Suite aux analyses métabolomiques, environ 3500 variables ont été obtenues en modes positif et négatif après nettoyage des données. Les analyses statistiques ont permis l’obtention de modèles statistiques valides et robustes. L’annotation des variables discriminantes a conduit à l’identification de 56 métabolites à partir du modèle in vitro, et 35 à partir des prélèvements cutanés in vivo
Pharmacocinétique de l'amoxicilline chez le chat
No full textInternational audienceThe pharmacokinetics and plasma protein binding of amoxicillin in cats has not been thoroughly investigated. In a single-group sequential designed experimental study, amoxicillin was administered to six healthy cats intravenously, orally, and subcutaneously. Repeated blood samples were drawn after each administration, and amoxicillin concentrations were determined using High Performance Liquid Chromatography coupled to Triple Quadrupole Mass Spectrometry. Plasma amoxicillin data were subjected to population pharmacokinetic analysis, and pharmacokinetic parameters were estimated. The population clearance was 0.18 L/h•kg, the volume of the central compartment was 0.12 L/kg, the highly perfused compartment was 0.009 L/kg, and the poorly perfused compartment was 0.002 L/kg. The bioavailability was 33% and 69% after oral and subcutaneous administration, respectively. After subcutaneous administration of a slow-release formulation, there was absorption rate-limited pharmacokinetics. The plasma protein binding was 0%-24%. The results increase the understanding of the amoxicillin pharmacokinetics in cats. Further studies combining the results with pharmacodynamic data and in silico simulations are warranted.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited