Molecular characterization of GPR84 in domestic cats.

G protein-coupled receptor 84 (GPR84) was cloned as an orphan receptor, and medium-chain fatty acids were then revealed as endogenous ligands. GPR84 is expressed in immune cells and is believed to protect liver function from lipotoxicity caused by overeating and high-fat diet intake. This study aimed to present the molecular characterization of GPR84 in domestic cats. The deduced amino acid sequence of the feline GPR84 shows high sequence homology (83-89 %) with the orthologues from other mammalians by cDNA cloning of feline GPR84. Remarkably high mRNA expression was observed in the bone marrow by Q-PCR analysis. The inhibition of intracellular cAMP concentration was observed in cells transfected with feline GPR84 and treated with medium-chain fatty acids. Immunostaining of GPR84 and free fatty acid receptor 2 (FFAR2)/GPR43 in the bone marrow, where high mRNA expression was observed, showed reactions in macrophages and myeloid cells. To clarify whether the receptor formed homo/hetero-merization, GPR84 and FFARs were analyzed using Nano-Luc binary technology and NanoLuc bioluminescence resonance energy transfer technologies, which revealed that GPR84 formed more heteromers with FFAR2 than homomers with each other. In addition, when GPR84 and FFAR2/GPR43 were cotransfected in the cell, their localization on the cell membrane was reduced compared with that when single receptors were transfected. These results indicated that GPR84 is a functional receptor protein that is expressed in cat tissues and may have a protein-protein interaction with FFAR2/GPR43 on the cell membrane.

Prostatic stromal tumour of uncertain malignant potential in a dog.

An 11-year-old male Miniature Dachshund dog was presented with dyschezia. Computed tomography examination 35 days after the initial visit revealed a prostate mass (4.0 × 3.5 × 2.7 cm) and prostatectomy and orchiectomy were performed 13 days later. Grossly, the prostate was rubbery and the cut surface of the mass was swollen. The mass was whitish and demarcated from the surrounding tissues. Microscopically, the mass had a capsulate consisting of atypical spindloid stromal cells arranged in a phyllode pattern and also in a fasciculated pattern admixed with acinar ductal cells. Atypical stromal cells contained round-to-oval finely hyperchromatic nuclei that had distinct nuclei and abundant eosinophilic cytoplasm. Immunohistochemically, the atypical stromal cells were positive for vimentin, CD34, desmin, α-smooth muscle actin, progesterone receptor and androgen receptor but negative for cytokeratin AE1/AE3, p63, c-Kit, DOG-1 and SOX10. On the basis of these findings, the tumour was diagnosed as a prostatic stromal tumour of uncertain malignant potential.

Suspected malnutrition-induced reversible feline skin fragility syndrome in a cat with congenital axial deformities.

A stray cat, an intact female Japanese domestic shorthair cat of unknown age (suspected to be a young adult), was rescued. The cat was lethargic and thin and had marked skin fragility, delayed wound healing without skin hyperextensibility, and hind limb proprioceptive ataxia and paresis. Survey radiography, computed tomography, and magnetic resonance imaging revealed congenital vertebral anomalies, including thoracolumbar transitional vertebrae, scoliosis resulting from a thoracic lateral wedge-shaped vertebra, and a kinked tail, and a dilated spinal cord central canal. Through nutritional support, the cat's general condition normalized, followed by a gradual and complete improvement of skin features. Whole-genome sequencing was completed; however, no pathogenic genetic variant was identified that could have caused this phenotype, including congenital scoliosis. A skin biopsy obtained 7 y after the rescue revealed no remarkable findings on histopathology or transmission electron microscopy. Based on clinical course and microscopic findings, malnutrition-induced reversible feline skin fragility syndrome (FSFS) was suspected, and nutritional support was considered to have improved the skin condition. Key clinical message: This is the second reported case of presumed malnutrition-induced reversible FSFS and was accompanied by long-term follow-up.

Syndrome de fragilité cutanée réversible induit par la malnutrition soupçonné chez un chat avec des difformités axiales congénitales. Un chat errant, une femelle intacte de race japonaise à poil court et d'âge inconnu (suspecté être une jeune adulte), a été secourue. La chatte était léthargique et maigre, et avait une fragilité marquée de la peau, un retard dans la guérison de plaies sans hyperextensibilité de la peau, et une ataxie proprioceptive et parésie des membres postérieurs. Des radiographies, un examen par tomodensitométrie, et de l'imagerie par résonnance magnétique ont révélé des anomalies congénitales des vertèbres, incluant des vertèbres transitionnelles thoraco-lombaires, une scoliose résultant d'une vertèbre thoracique en forme de coin, une queue pliée, et un canal central de la moelle épinière dilaté. Grâce à un soutien nutritionnel, la condition générale du chat s'est stabilisée, suivi d'une amélioration graduelle et complète des caractéristiques de la peau. Le séquençage du génome complet a été effectué; toutefois, aucune variation génétique pathogénique n'a été identifiée qui aurait pu causer ce phénotype, incluant la scoliose congénitale. Une biopsie cutanée obtenue 7 j après le sauvetage n'a révélé aucune trouvaille spéciale à l'histopathologie ou par microscopie électronique à transmission. Basé sur le déroulement clinique et l'examen microscopique, le syndrome de fragilité cutanée réversible félin induit par la malnutrition (FSFS) était suspecté, et le soutien nutritionnel a été considéré comme ayant amélioré la condition cutanée.Message clinique clé :Ce cas est le deuxième cas rapporté de FSFS induit par la malnutrition soupçonné et a fait l'objet d'un suivi à long terme.(Traduit par Dr Serge Messier).

Immortalized Canine Adipose-Derived Mesenchymal Stem Cells Maintain the Immunomodulatory Capacity of the Original Primary Cells.

Mesenchymal stem cells (MSCs) are a promising cell source for stem cell therapy of intractable diseases in veterinary medicine, but donor-dependent cellular heterogeneity is an issue that influences therapeutic efficacy. Thus, we previously established immortalized cells that maintain the fundamental properties of primary cells, but functional evaluation had not been performed. Therefore, we evaluated the immunomodulatory capacity of the immortalized canine adipose-derived MSCs (cADSCs) in vitro and in vivo to investigate whether they maintain primary cell functions. C57BL/6J mice were treated with dextran sulfate sodium (DSS) to induce colitis, injected intraperitoneally with immortalized or primary cADSCs on day 2 of DSS treatment, and observed for 10 days. Administration of immortalized cADSCs improved body weight loss and the disease activity index (DAI) in DSS-induced colitic mice by shifting peritoneal macrophage polarity from the M1 to M2 phenotype, suppressing T helper (Th) 1/Th17 cell responses and inducing regulatory T (Treg) cells. They also inhibited the proliferation of mouse and canine T cells in vitro. These immunomodulatory effects were comparable with primary cells. These results highlight the feasibility of our immortalized cADSCs as a cell source for stem cell therapy with stable therapeutic efficacy because they maintain the immunomodulatory capacity of primary cells.

Apocrine carcinoma-and-malignant myoepithelioma in a dog: a case of simultaneous malignant progression of both luminal epithelium and myoepithelium.

A 9-y-old male Boxer dog developed a mandibular skin tumor, which histologically had a locally invasive growth pattern composed of bilayered structures of inner eosinophilic cuboidal tumor cells and outer clear polygonal tumor cells with cytoplasm containing glycogen granules. Both cell populations gradually changed from low-grade morphologic features to highly anaplastic ones. Immunohistochemically, the eosinophilic tumor cells were positive for cytokeratin 8, a useful marker for luminal epithelial cells. In contrast, the clear tumor cells expressed several myoepithelial markers, including α-smooth muscle actin, p63, and cytokeratin 14. Based on these histologic and immunohistochemical characteristics, we diagnosed this apocrine sweat gland tumor as a carcinoma-and-malignant myoepithelioma with high-grade transformation of both luminal and myoepithelial cells. Our case may be a helpful reference for the histogenesis of carcinoma-and-malignant myoepithelioma, in which both the luminal epithelial and myoepithelial components are malignant.

Multiple intra-abdominal fungal granulomas caused by Scedosporium apiospermum effectively treated with voriconazole in a Golden Retriever.

Scedosporium apiospermum is a saprophytic filamentous fungus that is pathogenic to dogs. This report describes a case of S. apiospermum infection that caused multiple large peritoneal fungal granulomas in a dog with a history of jejunojejunostomy. The lesions were firmly attached to multiple organs and could not be surgically removed. In such cases, no precedent for the response to the treatment of this disease exists, and all affected dogs have died. This is the first report of an effective medical treatment for multiple intra-abdominal fungal granulomas using voriconazole.

Case report: Limb-sparing surgery of tibial chondrosarcoma with frozen autologous bone graft using liquid nitrogen in a dog.

Chondrosarcoma is the second most common primary bone tumor after osteosarcoma in dogs. Chondrosarcoma has a good prognosis owing to its low metastatic rate and long survival time, even with amputation alone. However, amputation risks reducing the quality of life in patients with other orthopedic diseases of the non-affected limb, neurological diseases, or large body size. Limb-sparing surgery with frozen autologous bone grafting using liquid nitrogen allows bone quality to be maintained in the normal bone area while killing tumor cells, thereby preserving the affected limb. Thus, it is expected to maintain the quality of life. We describe herein limb-sparing surgery for tibial chondrosarcoma with frozen autologous bone graft using liquid nitrogen in an 8-year and 8-month-old castrated male bulldog weighing 29.2 kg. The patient had chondrosarcoma of the left tibia, suspected cranial cruciate ligament rupture of the right stifle, and degenerative lumbosacral stenosis. In such a case, amputation would increase the burden on the non-affected limb or spine, which could cause difficulty in walking; therefore, we performed limb-sparing surgery. Postoperatively, although a circumduction gait associated with stifle arthrodesis remained, the patient maintained the quality of life for 20 months, and the owner was satisfied with the results.

mTOR pathway as a potential therapeutic target for cancer stem cells in canine mammary carcinoma.

Mammary adenocarcinoma, the most common cancer in female dogs, often exhibits the lymph node and lung metastases and has a higher mortality rate. However, mammary adenocarcinoma has no established treatment, except early surgical excision. Canine mammary carcinoma has many common features with human mammary carcinoma, including clinical characteristics, heterogeneity, and genetic aberrations, making it an excellent spontaneous tumor model for human breast cancer. Diverse cancers comprised heterogeneous cell populations originating from cancer stem cells (CSCs) with self-renewal ability. Therefore, in addition to conventional therapy, therapeutic strategies targeting CSCs are essential for cancer eradication. The present study aimed to extract inhibitors of canine mammary CSCs that suppress their self-renewal ability. Sphere-formation assay, which evaluates self-renewal ability, was performed for the canine mammary cancer cell lines CTBp and CNMp. The spheres formed in this assay were used in inhibitor library screening, which identified various signaling pathways such as proteosome, stress inducer, and mammalian target of rapamycin (mTOR). The present study focused on the mTOR signaling pathway. Western blotting showed higher levels of phosphorylated mTOR in sphere-forming CTBp and CNMp cells than in adherent cells. Drug sensitivity examination using the mTOR inhibitors everolimus and temsirolimus revealed dose-dependent reductions in viability among both sphere-forming cells and adherent cells. Expression of phosphorylated mTOR in adherent and sphere-forming cells decreased by everolimus and temsirolimus treatment. In mice transplanted with CTBp-derived spheres, everolimus treatment significantly decreased tumor volume compared to control. These results reveal that the mTOR signaling pathway may be a potential to be a therapeutic target in both cancer cells and CSCs. Novel therapeutic strategies for canine mammary carcinoma are expected to benefit to human breast carcinoma as well.

Establishment of a BRAF V595E-mutant canine prostate cancer cell line and the antitumor effects of MEK inhibitors against canine prostate cancer.

Canine prostate cancer (cPCa) is a malignant neoplasm with no effective therapy. The BRAF V595E mutation, corresponding to the human BRAF V600E mutation, is found frequently in cPCa. Activating BRAF mutations are recognized as oncogenic drivers, and blockade of MAPK/ERK phosphorylation may be an effective therapeutic target against BRAF-mutated tumours. The aim of this study was to establish a novel cPCa cell line and to clarify the antitumor effects of MEK inhibitors on cPCa in vitro and in vivo. We established the novel CHP-2 cPCa cell line that was derived from the prostatic tissue of a cPCa patient. Sequencing of the canine BRAF gene in two cPCa cell lines revealed the presence of the BRAF V595E mutation. MEK inhibitors (trametinib, cobimetinib and mirdametinib) strongly suppressed cell proliferation in vitro, and trametinib showed the highest efficacy against cPCa cells with minimal cytotoxicity to non-cancer COPK cells. Furthermore, we orally administered 0.3 or 1.0 mg/kg trametinib to CHP-2 xenografted mice and examined its antitumor effects in vivo. Trametinib reduced tumour volume, decreased phosphorylated ERK levels, and lowered Ki-67 expression in xenografts in a dose-dependent manner. Although no clear adverse events were observed with administration, trametinib-treated xenografts showed osteogenesis that was independent of dosage. Our results indicate that trametinib induces cell cycle arrest by inhibiting ERK activation, resulting in cPCa tumour regression in a dose-dependent manner. MEK inhibitors, in addition to BRAF inhibitors, may be a targeted agent option for cPCa with the BRAF V595E mutation.

Pulmonary solid adenocarcinoma in a dog.

A 12-year-old castrated male Beagle dog presented with a 1-month history of progressive loss of appetite and cough. One month after the initial visit, a detailed clinical examination was performed due to weight loss and persistent cough. Computed tomography demonstrated diffuse opacification of the entire right lung and cranial lobe of the left lung. Samples of the pulmonary lesions obtained by fine-needle aspiration (FNA) were highly cellular with scattered and clustered foci of large round cells, suggestive of a round cell tumour. Ten days after the FNA, the dog was euthanized due to decreased activity and severe respiratory symptoms. At necropsy, enlargement of the entire right lung and cranial lobe of the left lung was seen. The external and cut surfaces of the lungs were homogeneously grey-white. Histopathological examination of sections of the right lung and the cranial lobe of the left lung revealed proliferation of large round or polygonal neoplastic cells arranged in nests of variable size separated by a thin fibrous stroma. Neoplastic cells were immunopositive for cytokeratin and thyroid transcription factor-1 but negative for vimentin, CD204, chromogranin A and synaptophysin. On the basis of these findings, the tumour was diagnosed as pulmonary solid adenocarcinoma.

Immortalized Canine Adipose-Derived Mesenchymal Stem Cells as a Novel Candidate Cell Source for Mesenchymal Stem Cell Therapy.

Mesenchymal stem cells are expected to be a cell source for stem cell therapy of various diseases in veterinary medicine. However, donor-dependent cell heterogenicity has been a cause of inconsistent therapeutic efficiency. Therefore, we established immortalized cells from canine adipose tissue-derived mesenchymal stem cells (ADSCs) to minimize cellular heterogeneity by reducing the number of donors, evaluated their properties, and compared them to the primary cells with RNA-sequencing. Immortalized canine ADSCs were established by transduction with combinations of the R24C mutation of human cyclin-dependent kinase 4 (CDKR24C), canine cyclin D1, and canine TERT. The ADSCs transduced with CDK4R24C, cyclin D1, and TERT (ADSC-K4DT) or with CDK4R24C and cyclin D1 (ADSC-K4D) showed a dramatic increase in proliferation (population doubling level >100) without cellular senescence compared to the primary ADSCs. The cell surface markers, except for CD90 of the ADSC-K4DT and ADSC-K4D cells, were similar to those of the primary ADSCs. The ADSC-K4DT and ADSC-K4D cells maintained their trilineage differentiation capacity and chromosome condition, and did not have a tumorigenic development. The ability to inhibit lymphocyte proliferation by the ADSC-K4D cells was enhanced compared with the primary ADSCs and ADSC-K4DT cells. The pathway analysis based on RNA-sequencing revealed changes in the pathways mainly related to the cell cycle and telomerase. The ADSC-K4DT and ADSC-K4D cells had decreased CD90 expression, but there were no obvious defects associated with the decreased CD90 expression in this study. Our results suggest that ADSC-K4DT and ADSC-K4D cells are a potential novel cell source for mesenchymal stem cell therapy.

Infective endocarditis with systemic bacterial embolism caused by Staphylococcus aureus in a free-ranging Amami rabbit (Pentalagus furnessi).

The Amami rabbit (Pentalagus furnessi) is found only on the two islands of Amami-Oshima and Tokunoshima in southwest Japan. It has a primitive appearance and ecology, is an evolutionarily valuable animal and has been assigned to the International Union for Conservation of Nature Red List of Threatened Species. We describe a case with mild purulent wounds on the distal digital skin of both forelimbs and multiple nodular lesions in various organs, including the heart and kidney. Microscopically, the heart lesions were characterized by disruption of the mitral valve and multifocal myocardial necrosis and abscesses due to infection with gram-positive cocci. Similar bacterial infarctions were also found in other organs, including the kidneys. The bacteria were identified as Staphylococcus aureus by immunohistochemical and molecular biological examinations. This first report of infective endocarditis and systemic infarctions caused by S. aureus in an Amami rabbit indicates the importance of monitoring purulent injuries, even if mild, to prevent secondary infections in this species.

Histological, immunohistochemical and ultrastructural features of polyglucosan bodies in uterine smooth muscle of pet rabbits (Oryctolaguscuniculus).

We document the frequency and morphological and immunohistochemical features of inclusion bodies in uterine smooth muscle cells in 56 (76%) of 74 investigated pet rabbits (Oryctolagus cuniculus). Inclusion bodies began to appear at the age of 2 years and their frequency increased with age (P = 0.047, r = 0.33). They ranged from 5 to 20 µm in diameter, were slightly basophilic to amphophilic with well-delimited oval bodies in haematoxylin and eosin-stained tissue sections and formed in the cytoplasm of the uterine smooth muscle cells with displacement of the cell nuclei. The inclusion bodies were positive with periodic acid-Schiff, Best's carmine, Lugol's iodine and Grocott's methenamine silver methods. They were immunoreactive to a monoclonal antibody raised against human polyglucosan and negative with monoclonal antibodies for several intermediate filament proteins. Electron microscopy revealed that they were non-membranous structures composed of electron-dense amorphous material. The morphological, histochemical, immunohistochemical and ultrastructural features of the inclusion bodies in the rabbi uteri were similar to those of human polyglucosan bodies (PGBs). PGBs appear to occur at a high frequency in the uterus of rabbits, which are known to be susceptible to uterine diseases.

Clinical examination and necropsy findings of a mountain hawk-eagle (Nisaetus nipalensis) that died during rehabilitation.

We examined the clinical signs and necropsy findings of a mountain hawk-eagle (Nisaetus nipalensis) that died during rehabilitation. The bird was rescued and treated for open fracture of the right forearm. During rehabilitation, the bird could not stand up or fly. Part of the right secondary and left and right primary feathers were removed during rehabilitation; additional fracture was found in the right tibiotarsus and treated. However, the bird died 92 days after rescue and necropsy was performed. Severe hepatic lipidosis and capture myopathy were confirmed by histopathological examinations. These lesions may be associated with the cause of death of this animal. Accumulation of information is expected to contribute to the improvement of effective rehabilitation techniques for raptors.

Canine Mammary Tumor Cell Lines Derived from Metastatic Foci Show Increased RAD51 Expression but Diminished Radioresistance via p21 Inhibition.

Due to the high incidence of mammary tumors in dogs, it is important to elucidate the pathogenesis of these tumors in veterinary medicine. Radiation therapy is often used to treat mammary tumors that target DNA lesions. RAD51 is a key molecule that repairs DNA damage via homologous recombination. We examined the relationship between RAD51 expression and radiosensitivity in mammary tumor cell lines. CHMp and CHMm from the same individual were selected based on the differences in RAD51 expression. The radiosensitivity of both cell lines was examined using MTT and scratch assays; CHMm, which has high RAD51 expression, showed higher sensitivity to radiation than CHMp. However, the nuclear focus of RAD51 during DNA repair was formed normally in CHMp, but not in most of CHMm. Since irradiation resulted in the suppression of cell cycle progression in CHMp, the expression of p21, a cell cycle regulatory factor, was detected in CHMp after 15 Gy irradiation but not in CHMm. These results indicate that functional expression is more important than the quantitative expression of RAD51 in canine mammary tumor cells in response to DNA damage.

Adenomatous Hyperplasia of Bowman's Capsule Epithelium in a Dog with Metastatic Nasal and Hepatic Neuroendocrine Carcinoma.

A 12-year-old spayed Shiba dog with a nasal neuroendocrine carcinoma and multiple hepatic nodules was necropsied. Histologically, proliferated blast cells with a monolayer or multilayered structure were observed in the kidney. This blast cell proliferation extended from Bowman's capsule epithelium to the proximal tubule in approximately 3% of nephrons. Immunohistochemistry revealed that blast cells were positive for vimentin, Wilm's tumour protein 1 (WT1), paired box 2 (PAX2) and CD10, but negative for cytokeratin (CK) AE1/AE3, CK19, CAM5.2, synaptophysin and chromogranin A. On the basis of these findings, adenomatous hyperplasia of Bowman's capsule epithelium was diagnosed. Multiple yellowish‒white nodules (1-3 cm) were found in the liver and diagnosed as neuroendocrine carcinoma with metastases to the lungs, adrenal glands and pancreaticoduodenal lymph nodes.

In vitro anticancer effects of alpelisib against PIK3CA­mutated canine hemangiosarcoma cell lines.

Hemangiosarcoma (HSA) is a malignant neoplasm that occurs in humans and canines with a poor prognosis owing to metastatic spread, despite effective treatment. The frequency of spontaneous HSA development is higher in canines than in humans. Therefore, canine HSA is a useful model of intractable human disease, which requires early detection and an effective therapeutic strategy. A high frequency of the p110α phosphatidylinositol­4,5­bisphosphate 3­kinase catalytic subunit alpha (PIK3CA) mutations is detected in a comprehensive genome­wide analysis of canine cases of HSA. The present cloned the full­length cDNA of canine PIK3CA and identified a mutation in codon 1047 from canine cases of HSA and cell lines that were established from these. The enforced expression of the 1047th histidine residue (H1047)R or L mutants of canine PIK3CA in HeLa cells enhanced epidermal growth factor receptor (EGFR) signaling via Akt phosphorylation. PIK3CA mutant canine HSA cell lines exhibited the hyperphosphorylation of Akt upon EGF stimulation as well. Alpelisib, a molecular targeted drug against PIK3CA activating mutations, exerted a significant antitumor effect in canine PIK3CA­mutated HSA cell lines. By contrast, it had no significant effect on canine mammary gland tumor cell lines harboring PIK3CA mutations. On the whole, the findings of the present study suggest that alpelisib may be highly effective against PIK3CA mutations that occur frequently in canine HSA.

Primary pulmonary diffuse large B-cell lymphoma associated with feline leukaemia virus infection in a young cat.

CASE SUMMARY: A 4-year-old castrated male domestic shorthair cat with a continuous cough was brought to a private veterinary clinic for detailed examination. Radiography of the thoracic cavity revealed a severe radiopaque region in the caudal lobe of the right lung. At 108 days after the initial visit, CT showed a mass of 27 × 23 × 18 mm in the caudal lobe of the right lung. At that time, no abnormalities in other organs except for the lung were detected on CT and peripheral blood and blood biochemistry tests. The mass in the caudal lobe of the right lung was resected by lobectomy; it had a white surface and was firm. Histopathologically, the mass was non-encapsulated, showing an unclear boundary with surrounding tissues. The mass comprised large, round or polygonal neoplastic cells arranged in a diffuse pattern. Immunohistochemically, neoplastic cells were diffusely positive for CD20, feline leukaemia virus (FeLV) p27 and FeLV glycoprotein 70 but negative for CD3, CD204 and E-cadherin. Based on these findings, diffuse large B-cell lymphoma associated with FeLV infection was diagnosed. Although the cat showed no clinical signs of gastrointestinal or respiratory injury, a routine ultrasonography revealed thickening in the jejunum wall 196 days after lobectomy, and subsequent fine-needle aspiration examination confirmed high-grade lymphoma. RELEVANCE AND NOVEL INFORMATION: This is the first report of primary pulmonary diffuse large B-cell lymphoma associated with FeLV infection in a young cat.

A case of juvenile form of dilated cardiomyopathy in a 6-month-old Shiba Inu dog.

A 6-month-old Shiba Inu dog was brought to the Veterinary Medical Teaching Hospital because of a cough, exercise intolerance, and pulmonary edema. The dog had a Levine 2/6 systolic murmur. Transthoracic echocardiography revealed left atrial and ventricular dilatation (left atrium to aortic ratio: 2.8), mitral and tricuspid valve regurgitation, and severe left ventricular myocardial hypokinesia (fractional shortening was 11.8%). Bubble contrast echocardiography did not reveal a congenital shunt; therefore, the dog was clinically diagnosed with early onset dilated cardiomyopathy. From the first visit, the dog was treated with pimobendan, taurine, torasemide, and isosorbide dinitrate. After 435 days, echocardiography revealed that systolic function had not improved. On Day 465, atrial fibrillation was confirmed via electrocardiogram, and treatment with diltiazem hydrochloride was initiated. The dog continued to appear clinically stable thereafter, until it died suddenly 1087 days after the initial visit. A postmortem histopathological examination identified severe enlargement of the left atrial and ventricular chambers as well as attenuated wavy fibers in the ventricular myocardium, which confirmed dilated cardiomyopathy in a juvenile. This is the first report of a juvenile form of dilated cardiomyopathy in a Shiba Inu dog. This case report provides evidence that the extended prognosis of this dog differed from that in previously reported cases of dilated cardiomyopathy in young dogs. Key clinical message: This is the first reported case of a juvenile form of dilated cardiomyopathy in a Shiba Inu dog. This report provides evidence that the prognosis of this dog differed from that in previously reported cases of dilated cardiomyopathy in young dogs.

Un cas de forme juvénile de cardiomyopathie dilatée chez un chien Shiba Inu de 6 mois. Un chien Shiba Inu de 6 mois a été amené à l'hôpital universitaire de médecine vétérinaire en raison d'une toux, d'une intolérance à l'exercice et d'un oedème pulmonaire. Le chien avait un souffle systolique Levine 2/6. L'échocardiographie transthoracique a révélé une dilatation auriculaire et ventriculaire gauche (rapport oreillette gauche sur aorte : 2,8), une régurgitation des valves mitrale et tricuspide et une hypokinésie myocardique ventriculaire gauche sévère (raccourcissement fractionnel de 11,8 %). L'échocardiographie de contraste par microbulles n'a pas révélé de shunt congénital; par conséquent, le chien a reçu un diagnostic clinique de cardiomyopathie dilatée d'apparition précoce. Dès la première visite, le chien a été traité avec du pimobendane, de la taurine, du torasémide et du dinitrate d'isosorbide. Après 435 jours, l'échocardiographie a révélé que la fonction systolique ne s'était pas améliorée. Au jour 465, la fibrillation auriculaire a été confirmée par électrocardiogramme et un traitement par le chlorhydrate de diltiazem a été instauré. Le chien a continué à apparaître cliniquement stable par la suite, jusqu'à ce qu'il meure subitement 1087 jours après la visite initiale. Un examen histopathologique post mortem a identifié une hypertrophie sévère des cavités auriculaire et ventriculaire gauche ainsi que des fibres ondulées atténuées dans le myocarde ventriculaire, ce qui a confirmé une cardiomyopathie dilatée chez un juvénile. Il s'agit du premier rapport d'une forme juvénile de cardiomyopathie dilatée chez un chien Shiba Inu. Ce rapport de cas fournit des preuves que le pronostic prolongé de ce chien différait de celui des cas précédemment rapportés de cardiomyopathie dilatée chez les jeunes chiens.Message clinique clé :Il s'agit du premier cas rapporté d'une forme juvénile de cardiomyopathie dilatée chez un chien Shiba Inu. Ce rapport fournit des preuves que le pronostic de ce chien différait de celui des cas précédemment rapportés de cardiomyopathie dilatée chez les jeunes chiens.(Traduit par Dr Serge Messier).

Intrahepatic eosinophilic proliferative phlebitis in Japanese black cattle indicate allergies involving mast cell tryptase-dependent activation.

Cow-specific feature hepatic lesion, termed as eosinophilic proliferative phlebitis (EPP), has been mainly detected in Japanese black cattle and identified histologically eosinophilic infiltration and endothelial hyperplasia in portal areas. We previously proposed EPP as a food allergy from the pathological characteristics and a significant increase of serum immunoglobulin E specific to curly dock (Rumex crispus) in allergens testing, however, first report had regarded EPP an atypical type of bovine fascioliasis. In EPP lesions, eosinophilic infiltration was observed to the hypertrophic endothelium and not to the intrahepatic bile duct, and that was related to eotaxin-1 expression. In EPP, the mast cells increased as well as in fascioliasis, and the mast cells producing tryptase without chymase increased with interleukin-4 production. In this context, hyperplasia of periendothelium expressing proteinase-activated receptor-2 (PAR-2) and not angiotensin II was observed. Contrastably, in fascioliasis, unique mast cells producing neither tryptase nor chymase infiltrated, and the periendothelium expressed neither PAR-2 nor angiotensin II. Interestingly, EPP had not occurred liver injury with raised hepatic enzymes like fascioliasis, and suggested to a correlation with severe serum hypo-vitamin A. Overall, this study suggests that EPP is an allergic disease by main difference between adaptive immunity to allergens and innate immunity to parasites.