Régulation de la mucosécrétion colique humaine par les récepteurs par -2 (protéinase activated receptors) (Implication de la voie Adam17/EGFR)

Dans le côlon humain, la mucine secrétée majeure est MUC2 ; MUC5AC apparaît lors d'inflammation et de cancers. Premièrement l'auteur a mis au point une q-PCR pour étudier l'expression des transcrits MUC2 et MUC5AC dans 2 modèles in vitro, la lignée cancéreuse colique humaine HT29-C1.16E et des cultures d'explants de muqueuse colique humaineNANTES-Ecole Nat.Vétérinaire (441092302) / SudocSudocFranceF

A Diagnosis Support System for Veterinary Necropsy based on Bayesian Networks

International audienceVeterinary autopsy requires a high level of expertise and skills that not all veterinarians necessarily master, especially in the context of the desertification of rural areas. The development of support systems is a challenging issue, since such a tool, to be considered relevant and accepted by practitioners in their diagnosis process, must avoid any black box effect. The diagnosis support system we introduce here, IVAN (“Innovative Veterinary Assisted Necropsy”), aims to engage the user in an explicit, understandable, validable and reviewable process, able to cope with the specific issues of cattle necropsy. Besides, it provides uncertainty management to deal with approximate lesion descriptions. IVAN relies on a Bayesian network to infer relevant proposals at each step of the diagnostic process. IVAN was trained on a set of real autopsy cases from autopsy reports, and its performance was assessed using another set of reports. In addition, the tool had to provide results in short r esponse time and be able to run the application on mobile device and web server. In addition to demonstrating the feasibility of the approach, IVAN is a first step towards other support systems in other species and in broader contexts than autopsy

IVAN (Innovative Veterinary Assisted Necropsy): A Diagnosis Support System for Veterinary Necropsy Based on Bayesian Network

International audienc

Un cas de botulisme bovin massif : investigation épidémiologique

National audienceDepuis quelques années, de plus en plus de foyers de botulisme bovin de type D sont signalés en Europe avec une forte suspicion d’implication de fumiers de volaille, mais sans que les circonstances exactes d’exposition des bovins aux toxines de Clostridium botulinum n’aient pu être identifiées. En juin 2015, le service de Médecine des Animaux d’Elevage d’Oniris a été sollicité pour identifier l’origine d’un foyer sévère de botulisme bovin survenu dans une exploitation ayant des ateliers de bovins et de volailles. En l’espace de 2 mois, 80 des 110 vaches laitières étaient mortes après avoir manifesté des signes cliniques de botulisme, sans que l’origine du foyer n’ait pu être déterminée. Les autopsies avaient montré une absence de lésions significatives et les prélèvements de contenus intestinaux avaient identifié la présence de C. botulinum de type D/C. Les investigations épidémiologiques et les analyses réalisées suggèrent fortement que ce foyer soit dû à l’ingestion d’un ensilage d’herbe insuffisamment acidifié, contaminé par des spores de C. botulinum de type D/C. La quantité importante d’ensilage contaminée (plus de 20 m3) n’est pas compatible avec la contamination de l’ensilage par des spores provenant d’une carcasse piégée dans l’ensilage. Les spores pourraient provenir d’un tas de fumier de volaille stocké dans la pâture avant que l’ensilage d’herbe n’ait été réalisé, les spores ayant été dispersées dans la pâture avant ensilage par le vent ou l’eau de ruissellement. Par ailleurs, la présence de carcasses de volailles dans le fumier de volaille est peu probable au vu de la gestion minutieuse des carcasses dans cet élevage, ce qui interroge sur un potentiel portage asymptomatique de C. botulinum de type D/C par les volailles. Ce cas illustre l’importance des conditions de conservation des ensilages et des conditions de stockage des fumiers de volaille, même en cas bonne gestion des cadavres de volaille, pour prévenir l’apparition de foyers de botulisme bovi

Un foyer de botulisme bovin à Clostridium botulinum de type D/C : suspicion d’une contamination massive de l’ensilage d’herbe à partir de fumier de volailles

National audienc

Refractory hypoglycaemia in a dog infected with Trypanosoma congolense

A 20 kg German shepherd dog was presented to a French veterinary teaching hospital for seizures and hyperthermia. The dog had returned 1 month previously from a six-month stay in Senegal and sub-Saharan Africa. Biochemistry and haematology showed severe hypoglycaemia (0.12 g/L), anaemia and thrombocytopenia. Despite administration of large amounts of glucose (30 mL of 30% glucose IV and 10 mL of 70% sucrose by gavage tube hourly), 26 consecutive blood glucose measurements were below 0.25 g/L (except one). Routine cytological examination of blood smears revealed numerous free extracytoplasmic protozoa consistent with Trypanosoma congolense. PCR confirmed a Trypanosoma congolense forest-type infection. Treatment consisted of six injections of pentamidine at 48-hour intervals. Trypanosomes had disappeared from the blood smears four days following the first injection. Clinical improvement was correlated with the normalization of laboratory values. The infection relapsed twice and the dog was treated again; clinical signs and parasites disappeared and the dog was considered cured; however, 6 years after this incident, serological examination by ELISA T. congolense was positive. The status of this dog (infected or non-infected) remains unclear. Hypoglycaemia was the most notable clinical feature in this case. It was spectacular in its severity and in its refractory nature; glucose administration seemed only to feed the trypanosomes, indicating that treatment of hypoglycaemia may in fact have been detrimental

Long-Term Toxicity of [213]Bi-Labelled BSA in Mice

International audienceBackgroundShort-term toxicological evaluations of alpha-radioimmunotherapy have been reported in preclinical assays, particularly using bismuth-213 ([213]Bi). Toxicity is greatly influenced not only by the pharmacokinetics and binding specificity of the vector but also by non-specific irradiation due to the circulating radiopharmaceutical in the blood. To assess this, an acute and chronic toxicity study was carried out in mice injected with [213]Bi-labelled Bovine Serum Albumin ([213]Bi-BSA) as an example of a long-term circulating vector.MethodBiodistribution of [213]Bi-BSA and [125]I-BSA were compared in order to evaluate [213]Bi uptake by healthy organs. The doses to organs for injected [213]Bi-BSA were calculated. Groups of nude mice were injected with 3.7, 7.4 and 11.1 MBq of [213]Bi-BSA and monitored for 385 days. Plasma parameters, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine, were measured and blood cell counts (white blood cells, platelets and red blood cells) were performed. Mouse organs were examined histologically at different time points.ResultsHaematological toxicity was transient and non-limiting for all evaluated injected activities. At the highest injected activity (11.1 MBq), mice died from liver and kidney failure (median survival of 189 days). This liver toxicity was identified by an increase in both ALT and AST and by histological examination. Mice injected with 7.4 MBq of [213]Bi-BSA (median survival of 324 days) had an increase in plasma BUN and creatinine due to impaired kidney function, confirmed by histological examination. Injection of 3.7 MBq of [213]Bi-BSA was safe, with no plasma enzyme modifications or histological abnormalities.ConclusionHaematological toxicity was not limiting in this study. Liver failure was observed at the highest injected activity (11.1 MBq), consistent with liver damage observed in human clinical trials. Intermediate injected activity (7.4 MBq) should be used with caution because of the risk of long-term toxicity to kidneys

Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas.

International audienceSpontaneously occurring melanomas are frequent in dogs. They appear at the same localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They display variable behaviors: tumors at oral localizations are more frequent and aggressive than at other anatomical sites. Interestingly, dog melanomas are associated with strong breed predispositions and overrepresentation of black-coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles are at high risk of developing oral melanoma, while schnauzers or Beauce shepherds mostly developped cutaneous melanoma. Clinical and histopathological analyses were performed on a cohort of 153 cases with a 4-yr follow-up. Histopathological characterization showed that most canine tumors are intradermal and homologous to human rare morphological melanomas types - 'nevocytoid type' and 'animal type'-. Tumor cDNA sequencing data, obtained from 95 dogs for six genes, relevant to human melanoma classification, detected somatic mutations in oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF. Altogether, these findings support the relevance of the dog model for comparative oncology of melanomas, especially for the elucidation of non-UV induced pathways

Interest of circulating tumor DNA as a biomarker for canine cancers: illustration in histiocytic sarcoma, oral malignant melanoma and multicentric lymphoma

Circulating tumor DNA (ctDNA) has become an attractive biomarker in human oncology and may be informative in cancer-affected dogs. By performing ddPCR or PARR methods, we detected tumor-specific point mutations, copy number alterations and chromosomal rearrangements in the plasma of cancer-affected dogs. It allowed the detection of ctDNA in 2/8 (25%) oral malignant melanoma cases, 12/13 (92.3%) lymphoma cases and 21/23 (91.3%) histiocytic sarcoma (HS) cases. The value of ctDNA to diagnose HS was explored in 133 dogs including 49 with HS. In this cohort, screening recurrent PTPN11 mutations in plasma had a specificity of 98.8%, and a sensitivity between 42.8-77% according to HS clinical presentation, being higher in internal forms, especially with pulmonary location. Regarding lymphoma, the follow-up of four dogs showed that the minimal residual disease detection by targeting lymphoma-specific antigen receptor rearrangement in the plasma was concordant with the clinical evaluation. Moreover, ctDNA analysis appeared interesting to assess treatment response and to predict relapse.This study shows that ctDNA is detectable in the plasma of cancer-affected dogs and is a relevant biomarker for diagnosis and clinical follow-up. With a growing interest in integrating natural canine tumors to explore new therapies, this biomarker appears promising in comparative oncology research