HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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A biological pharmacology network to secure the risk of drug–drug interaction with nirmatrelvir/ritonavir
No full textInternational audienceNirmatrelvir/ritonavir is a protease inhibitor antiviral drug indicated in the treatment of severe acute respiratory syndrome coronavirus-2 infections in high-risk patients for a severe disease. Unfortunately, ritonavir, used to boost nirmatrelvir pharmacokinetics, can also inhibit or induce the metabolism of other co-administered drugs substrates. This may lead to a subsequent risk of adverse drug reaction and lack of efficacy. In this study, we aimed at describing the expert advices provided by the biological pharmacology network of the SFPT (i.e., the therapeutic drug monitoring specialists working in the laboratories of the pharmacology departments in France/Belgium). From February to August 2022, we collected all specialized advices provided by the biological pharmacology network of the SFPT. Seven pharmacology departments actively participated in the study (Brussels Saint-Luc Hospital in Belgium, Caen, Dijon, Nantes, Nancy, Rennes and Toulouse in France). We collected the following data: patient's age, date of nirmatrelvir/ritonavir initiation, clinical department requiring the expert advice, patient's treatments, and advice provided. One hundred and six expert advice on 753 drugs were provided during the seven months of data collection. Two centers provided 83% of all the expert advice (around 8/month). Patients originated form a transplantation department in 65% of the cases. The most common request were for cardiac drugs (28%), immunosuppressive drugs (24%) and endocrine drugs (18%). The advice were distributed as follows: treatment continuation, treatment discontinuation during the antiviral course, dosage adjustment, and treatment switch in 59%, 28%, 11%, and 1.6% of the cases, respectively. Only 2 pieces of advice (0.3%) constituted treatment contra-indications. Drug monitoring was proposed in 10% of prescription lines. Expert advice provided by the biological pharmacology network of the SFPT allows securing the combination of nirmatrelvir/ritonavir with other concomitant drugs. Most of eligible patients to the antiviral drug can benefit from it despite the risk of drug–drug interaction
Vancomycin population pharmacokinetic models: Uncovering pharmacodynamic divergence amid clinicobiological resemblance
No full textInternational audienceVancomycin is an antibiotic used for severe infections. To ensure microbiological efficacy, a ratio of AUC/MIC ≥400 is recommended. However, there is significant interindividual variability in its pharmacokinetic parameters, necessitating therapeutic drug monitoring to adjust dosing regimens and ensure efficacy while avoiding toxicity. Population pharmacokinetic (PopPK) models enable dose personalization, but the challenge lies in the choice of the model to use among the multitude of models in the literature. We compared 18 PopPK models created from populations with the same sociodemographic and clinicobiological characteristics. Simulations were performed for a 47 years old man, weighing 70 kg, with an albumin level of 35.5 g/L, a creatinine clearance of 100 mL/min, an eGFR of 106 mL/min/1.73 m 2 , and receiving an intravenous infusion of 1 g × 2/day of VCM over 1 h for 48 h. Simulations of time–concentration profiles revealed differences, leading us to determine the probability of achieving microbiological efficacy (AUC/MIC ≥ 400) with each model. Depending on some models, a dose of 1 g × 2/day is required to ensure microbiological efficacy in over 90% of the population, while with the same dose other models do not exceed 10% of the population. To ensure that 90% of the patients are correctly exposed, a dose of vancomycin ranging from 0.9 g × 2/day to 2.2 g × 2/day is necessary a priori depending on the chosen model. These differences raise an issue in choosing a model for performing therapeutic drug monitoring using a PopPK model with or without Bayesian approach. Thus, it is fundamental to evaluate the impact of these differences on both efficacy/toxicity
LactoTruite, a project to increase the resilience of trout farms towards the emergence of lactococcosis in Brittany
No full textInternational audienceThe aquaculture sector must develop strategies to adapt towards the consequences of global warming, particularly to face the increase of infectious pathologies.. Lactococcosis is a bacterial disease frequently affecting fish farms of the Mediterranean countries, with severe clinical signs at water temperature above 17°C. During summer 2023, Brittany trout farms where strongly affected by a lactococcosis outbreak, generating up to 50% of mortality in some farms and an associated economic loss of several millions of euros. AimsThe aim of this project is to bring short and mid-terms solutions to the fish farmers to understand and fight against the pathology and limit its impact in the future. MethodologyThe first task will be dedicated to an epidemiological study of the disease and its etiological agent. The aims will be to understand how the disease occurs in fish farm, to identify bacterial species involved, their virulence factors and antibioresistance profiles, and to develop robust and discriminant diagnosis tools. The second task will be focused on the optimization of vaccinal and therapeutic (antibiotherapy) schemes using experimental in vivo approachesDuring the third task, the heritability of genetic resistance of rainbow trout against lactococcosis but also another important bacterial diseases, flavobacteriosis, will be evaluated and correlate with growth traits, allowing to estimate potential survival gains obtainable through trout selection. Moreover, we will investigate the immune mechanisms commonly implemented in fish surviving to these both bacterial diseases , with the objective to to evaluate the possibility of leading a genetic selection based on the immune robustness of the fish.Conclusion Epidemiological and descriptive data coupled with the development of concrete solutions will allow to better understand and fight against the lactococcosis pathology that is enhanced by the climate evolution. These tools will help to preserve the trout farming sector and maintain its competitiveness
Évolution des comportements associés au stress et de la tolérance aux manipulations de chiens lors d’un examen clinique en cabinet vétérinaire, Après une habituation et un conditionnement positif
No full textThis study aimed to evaluate the stress experienced by dogs upon entering the veterinary clinic and during the consultation. Two groups were compared: a test group that received familiarization sessions and positive conditioning, and a control group without specific preparation. Stress levels were assessed using a behavioral scale, both upon entering the consultation room and during the clinical examination. The results show a significant reduction in stress at entry for the prepared dogs, suggesting the benefit of familiarization in reducing stress. However, no notable difference was observed during the examination, highlighting the limitations of this approach in addressing stress related to handling during the consultation. The study emphasizes the clinical potential of this method, wichi s relatively easy to implement in practice, while underlining the need for complementary strategies. Suggestions for improvement are proposed for future research.Ce travail avait pour but d’étudier le stress de chiens à l’entrée du cabinet et lors de la consultation vétérinaire. Deux groupes ont été comparés : un groupe test ayant bénéficié de séances de familiarisation et de conditionnement positif, et un groupe témoin sans préparation. Le stress a été mesuré à l’aide d’une grille comportementale, à l’entrée en salle de consultation puis pendant l’examen clinique. Les résultats montrent une diminution significative du stress lors de l’entrée pour les chiens préparés, suggérant l’intérêt de la familiarisation pour réduire le stress. En revanche, aucune différence notable n’a été observée lors de l’examen, soulignant les limites de cette approche face au stress lié aux manipulations durant la consultation. L’étude met en avant le potentiel clinique de cette méthode, relativement facile à développer en pratique, tout en insistant sur la nécessité d’approches complémentaires. Des pistes d’amélioration sont proposées pour de futurs travaux
In vitro fermentations highlight the prebiotic effect of a specific hydrolyzed yeast on canine fecal microbiota
No full textInternational audienceBackground Dogs are increasingly regarded as family members, with owners highly attentive to their health and well-being. In this context, various nutraceuticals, including a specific hydrolyzed yeast protein source (Yela ProSecure; YPS; Lallemand SAS, Blagnac, France), have been proposed to support gut health. This study aimed to assess the effect of the indigestible fraction of YPS (YPSi) on canine gut microbiota. Methods Faecal samples were obtained from three healthy adult dogs of the same breed, lineage, and diet. Fecal material was diluted (2.5% w/v) in anaerobic buffer media, and treatments were tested in triplicate for each donor: Control vs. YPSi (10g/L) vs. inulin (10 g/L, positive control). 24-hour incubations were performed under strict anaerobiosis at 39°C, 150-rpm, to mimic digestive tract conditions. Endfermentation products (gas, short-chain fatty acids (SCFAs), ammonia) were measured. One-way ANOVA evaluated treatment effects on all fermentative parameters. 16S rRNA sequencing was performed on DNA extracts, and analysis was conducted using DADA2 and Phyloseq R packages. Results The addition of substrate (inulin or YPSi) increased bacterial fermentations, as evidenced by the significant increase in gas production and SCFAs. Inulin selectively increased acetate, while YPSi significantly increased the production of all SCFAs and ammonia. SCFAs are beneficial to the host due to their anti-inflammatory properties and as source of energy for colonocytes. Inulin significantly reduced bacterial diversity, while a greater diversity is considered to support a better stability and resilience in case of perturbation. YPSi impacted the composition of the microbiota by promoting important carbohydrate degrading taxa such as Bacteroidales, Ruminococcaceae, and Clostridiaceae, and specialized genera involved in butyrate production such as Butyricicoccus. Conclusions YPSi non-selectively promotes the dog fecal microbiota and boosts its fermentative activities. These effects more pronounced than with inulin, highlight an interesting prebiotic effect of YPSi for dog
Development of bioinformatics tools for metabolomics and fluxomics
No full textInternational audienceThe development of bioinformatic tools dedicated to metabolomics and fluxomics allows for a more detailed exploration of the functional organisation of biological systems. These approaches facilitate the integration and analysis of complex metabolic data on a large scale. The tools designed contribute to improving annotation, isotopic profiling and quantification of metabolites in mass spectrometry and NMR. They also offer new methods for estimating metabolic fluxes more accurately and robustly
Préparation d’échantillons pour l’utilisation combinée de RMN et LC-HRMS en métabolomique
No full textInternational audienceEn métabolomique non ciblée, la chromatographie liquide couplée à la spectrométrie de masse haute résolution (LC-HRMS) et la résonance magnétique nucléaire (RMN) sont couramment utilisées. Leur utilisation combinée reste relativement rare bien qu’elles soient complémentaires permettant d’augmenter la couverture du métabolome et fiabiliser l’annotation.Préparer un seul échantillon à analyser avec les deux techniques malgré leurs contraintes spécifiques permettrait d’assurer l’homogénéité des analyses et pallier un éventuel manque de quantité. Le tampon phosphate 0,2 M est habituellement utilisé pour les analyses RMN, évitant ainsi les décalages trop importants de déplacements chimiques. Cependant, les phosphates sont déconseillés pour l’analyse LC-HRMS en electrospray en raison de leur cristallisation dans la source, entrainant une perte du signal et une altération de l’appareil. L’un des objectifs de ce projet est de développer un protocole de préparation unique des échantillons compatibles avec les deux techniques. Dans un premier temps, le tampon est réduit à 0,05 M en phosphates afin de tester sa capacité à tamponner l’urine, une matrice à large gamme de pH. Les écarts de pH entre les échantillons réduits à des valeurs acceptables limitent les décalages de déplacements chimiques en RMN, partiellement corrigés grâce à des algorithmes de réalignement (CluPa, par exemple). Les échantillons ont ensuite été analysés en LC-HRMS, correspondant à une centaine d’injections. La stabilité du signal mesuré des métabolites et le maintien du voltage du détecteur n’ont pas été altérés. Une réduction de la concentration en phosphates serait un bon compromis pour l’analyse d’un échantillon unique en LC-HRMS et RMN
Création d’un jeu pédagogique pour permettre l’acquisition de compétences sur la gestion d’une alerte liée à une toxi-infection alimentaire collective
No full textThis veterinary thesis presents the design of an educational escape game focused on a foodborne outbreak (FBO) involving Campylobacter spp., with the objective of teaching the methodology for alert management, using a FBO case in veterinary public health as an example. The scenario takes place during a cocktail reception organized by a catering service for the launch of a business project. Following the event, several guests develop digestive disorders, mainly diarrhea, sometimes associated with hematochezia, vomiting, as well as fever and headaches. The epidemiological investigation, at the core of the game, identifies tzatziki as the implicated food, contaminated through cross-contamination between raw chicken and cucumbers. This scenario highlights hygiene deficiencies in both kitchen equipment and staff practices, underlining the importance of adhering to good hygiene practices in the prevention of FBOs. This serious game aims to strengthen veterinary students’ skills in alert management through a realistic simulation, while enhancing their engagement thanks to a playful, immersive, and collaborative approach.Cette thèse vétérinaire présente la conception d’un escape game pédagogique centré sur une toxi-infection alimentaire collective (TIAC) impliquant Campylobacter spp., dans le but de faire acquérir la méthodologie de la gestion d’alerte en prenant l’exemple d’une TIAC en santé publique vétérinaire. Le scénario se déroule lors d’un apéritif dînatoire organisé par un traiteur, à l’occasion du lancement d’un projet d’entreprise. À la suite de l’événement, plusieurs convives développent des troubles digestifs, principalement de la diarrhée, parfois associée à de l’hématochézie, des vomissements, ainsi que de la fièvre et des céphalées. L’enquête épidémiologique, au coeur du jeu, permet d’identifier le tzatziki comme aliment impliqué, contaminé par une transmission croisée entre du poulet cru et des concombres. Ce scénario met en lumière des défauts d’hygiène du matériel et du personnel de cuisine, soulignant l’importance de la maîtrise des bonnes pratiques dans la prévention des TIAC. Ce jeu sérieux vise à renforcer les compétences des étudiants vétérinaires en matière de gestion d’alerte via une mise en situation qui se veut réaliste, tout en stimulant leur engagement grâce à une approche ludique, immersive et collaborative
Prise en charge des rapaces dénutris en centres de soins
No full textWildlife care centers regularly take in birds of prey suffering from malnutrition. Their management is challenging, as a significant number die during their stay. The contribution of refeeding syndrome (RS), described in human and veterinary medicine in cats, to these deaths has been considered. To address these issues, a literature review on this syndrome and raptor nutrition was conducted, along with a questionnaire for French care centers to assess current practices. With the dual objective of studying RS in raptors and improving the management of these cases, a refeeding protocol, combined with biological monitoring, was developed and applied to nine raptors between May and July 2025 at the ENVT care center. The results of this study identify relevant clinical and biological parameters for monitoring, question the appropriate level of intervention in this wildlife context, and propose a refeeding protocol adapted to the most malnourished raptors.Les centres de soins de la faune sauvage accueillent très régulièrement des rapaces en état de dénutrition. Leur prise en charge est un challenge puisqu’une partie importante décède au cours de leur hospitalisation. La contribution d’un syndrome de nutrition inappropriée (SRI), décrit en médecine humaine et vétérinaire chez les félins domestiques, à ces décès a été envisagée. Pour tenter de répondre à ces problématiques, un état des lieux bibliographique de ce syndrome et de la nutrition des rapaces a été réalisé, ainsi qu’un questionnaire à destination des centres de soins français, visant à évaluer les pratiques actuelles. Dans un double objectif d’étudier le SRI chez les rapaces et d’améliorer la gestion de ces patients, un protocole de réalimentation, associé à un suivi biologique, a été élaboré et appliqué à neuf rapaces entre mai et juillet 2025 au centre de soins de l’ENVT. Les résultats de cette étude identifient des paramètres cliniques et biologiques pertinents pour le suivi, questionnent le niveau d’interventionnisme approprié dans ce contexte de faune sauvage, et proposent un protocole de réalimentation adapté aux rapaces les plus dénutris