Alterations in the composition of the intestinal microbiota have been associated with development of type 1 diabetes (T1D), but little is known about changes in intestinal homeostasis that contribute to disease pathogenesis. Here, we analyzed oral tolerance induction, components of the intestinal barrier, fecal microbiota, and immune cell phenotypes in non‐obese diabetic (NOD) mice during disease progression compared to non‐obese diabetes resistant (NOR) mice. NOD mice failed to develop oral tolerance and had defective protective/regulatory mechanisms in the intestinal mucosa, including decreased numbers of goblet cells, diminished mucus production, and lower levels of total and bacteria‐bound secretory IgA, as well as an altered IEL profile. These disturbances correlated with bacteria translocation to the pancreatic lymph node possibly contributing to T1D onset. The composition of the fecal microbiota was altered in pre‐diabetic NOD mice, and cross‐fostering of NOD mice by NOR mothers corrected their defect in mucus production, indicating a role for NOD microbiota in gut barrier dysfunction. NOD mice had a reduction of CD103+ dendritic cells (DCs) in the MLNs, together with an increase of effector Th17 cells and ILC3, as well as a decrease of Th2 cells, ILC2, and Treg cells in the small intestine. Importantly, most of these gut alterations precede the onset of insulitis. Disorders in the intestinal mucosa of NOD mice can potentially interfere with the development of T1D due the close relationship between the gut and the pancreas. Understanding these early alterations is important for the design of novel therapeutic strategies for T1D prevention.

Mast cell tumors represent the most common malignant skin tumor in the dog. This review outlines the incidence, etiology and clinical signs of mast cell tumors. Diagnostic tests, staging and treatments are also discussed.

Melanoma is a fast-growing tumour in dogs and represents 7% of the total malignant neoplasms from the skin and is the most common tumour found in the oral cavity. In these tumours, high expression of cyclooxygenase-2 (COX-2) is associated with a poor prognosis. The aim of this study was to verify if the overexpression of COX-2 is related to the modulation of lymphocytes and if it is associated with the angiogenic and proliferative capacity of the melanoma. Canine melanoma samples (n = 85) were analysed by immunohistochemistry to detect the expression of S-100, Melan-A, PNL-2, COX-2, Factor VIII, Ki-67 and immune cells markers (CD3, CD4, FOXP3 and MAC387); and expression levels of MAC387, NOS and CD206 were determined by immunofluorescence. Our study showed a concurrent difference between the expression of COX-2 and inflammatory cell infiltration: Oral melanomas showed positivity for COX-2 in 34% of the cases and this expression was associated with CD3 positivity in the inflammatory infiltrate and angiogenesis; whereas cutaneous melanomas presented positivity for COX-2 in 42% of the cases and this expression was associated with positive staining for CD3, CD4, FOXP3 and MAC387. These markers are associated with inflammatory cells, angiogenesis and proliferation. Interestingly, melanomas were highly infiltrated by FOXP3+ cells, this is related to angiogenesis, whereas CD3, CD4 and MAC387 expression was only associated with cutaneous melanomas. The macrophage profile analysis showed that both oral and cutaneous melanomas with low COX-2 expression have an M1 phenoptype, whereas the cases with high COX-2 expression demonstrate a hybrid M1/M2 profile pattern. We concluded that the COX-2 is overexpressed in 42% of cutaneous melanomas and in 34% of oral melanomas, with a direct association with angiogenesis, proliferation, and intratumoral lymphocyte infiltration. We propose that COX-2 is a key regulator of immune cell infiltration and may drive tumour associated macrophage activation.

Background: The epidermal growth factor receptors participate in the physiological processes such as regulation of morphogenesis, proliferation and cell migration, but when overexpressed or overactivated they may play an important role in neoplastic progression. Melanoma is the most aggressive skin neoplasm and is characterized by elevated invasion and low survival rates in both humans and dogs. In human melanomas the overexpression of EGFR, HER3 or HER4 is associated with poor prognosis. In canine melanomas the epidermal growth factor receptors expression has not been evaluated. Therefore, this study evaluated the expression of epidermal growth factor receptors by immunohistochemistry and investigated their relationship with morphological characteristics and proliferative indices in cutaneous and oral canine melanoma. Results: In cutaneous melanoma an increased proliferative index was associated with increased cytoplasmic HER4 and reduced EGFR and HER3 protein expression. In oral melanomas, membranous HER2 protein expression correlated with occurrence of emboli, but ERBB2 gene amplification wasn't observed. Conclusion: Thus, our work evidenced the relationship between HER4 and the stimulus to cell proliferation in cutaneous melanomas, in addition to the relationship between HER2 and the occurrence of emboli in oral melanomas.

No abstract

Background: Malignant myoepithelioma is a rare neoplasm in humans and rats, poorly reported in dogs and not previously described in rabbits. This study aims to report a case of malignant mammary myoepithelioma in a domestic rabbit (Oryctolagus cuniculus). Case: A domestic, hybrid, female, entire, nulliparous, 7-year-old rabbit was attended in the Veterinary Hospital Prof. Ricardo Alexandre Hippler at Universidade Vila Velha (UVV) with a history of apathy, lethargy and anorexia. In the clinical examination a 5 cm tumour was observed in the right abdominal mammary gland (M2), along with floating smaller lesions in M1 and M3. There were no palpable abnormalities in the axillary and inguinal lymph nodes. Complete blood count and serum biochemistry were within the normal range. Fine needle aspiration was performed for cytological evaluation of the tumour in M2 and it was suggestive of a malignant glandular neoplasm, with probable epithelial origin. Complete staging included chest and abdominal radiographs, but they were unremarkable. The patient was submitted to a right unilateral mastectomy, involving resection of the inguinal lymph node. The sample was sent to the Laboratory of Animal Pathology of UVV for routine histological evaluation. M2 lesion was compatible with malignant myoepithelioma based on the literature, while nodules in M1 and M3 were classified as mammary cysts. The inguinal lymph node showed no significant abnormalities. An immunohistochemical panel was performed in the Laboratory of Comparative Pathology of the Institute of Biological Sciences at the Universidade Federal de Minas Gerais (UFMG), using immunomarkers (pan-cytokeratin, p63 and vimentin) to characterize the tumour and confirm its diagnosis. Immunohistochemistry revealed expression of p63, and was negative for pan-cytokeratin and vimentin, which confirmed the myoepithelial origin, without involvement of the epithelial compartment. Clinical follow-up was recommended every 2-3 months, including abdominal ultrasonography, chest radiographs, complete blood count and serum biochemistry. Ultrasonography showed thinning of the uterine wall, dilation of 3.7 cm in diameter and presence of endometrial cysts of varied sizes, around 0.7 cm. Neutering was recommended but it was not elected by the pet's responsible. These findings remained stable throughout the follow-up, which was greater than 405 days. Discussion: This is the first report of a malignant myoepithelioma in rabbit, with a detailed description of the clinical, surgical, pathological and immunophenotypic aspects of this neoplasm in this species. This is a tumour characterized by proliferation of epithelioid to spindle-like myoepithelial cells, as observed in this case, forming an extensive and well delimited solid area with marked central necrosis, compatible with what has already been described in the literature in bitches and women. As observed in this case, the neoplastic cells usually exhibit moderate cellular and nuclear pleomorphism, moderate anisocytosis and anisokaryosis, and sever...

Metastatic melanoma is a very aggressive form of cancer in both humans and dogs. Dogs primarily develop oral melanoma of mucosal origin. Although oral melanoma in humans is rare, both diseases are highly aggressive with frequent metastases. This disease represents a “One Health” opportunity to improve molecular and mechanistic understanding of melanoma progression. Accumulating evidence suggests that cyclooxygenase-2 (COX-2) may play a critical role in the malignant behaviour of melanoma. In this study we analysed 85 histologically confirmed melanomas from canine patients and showed that COX-2 is overexpressed in both oral and cutaneous melanomas and that COX-2 expression correlates with established markers of poor prognosis. To determine the role of COX-2 in melanoma we developed two melanoma cell lines with stable integration of an inducible doxycycline-regulated expression vector containing a COX-2 targeted micro-RNA (miRNA). Using this system, we showed that cellular proliferation, migration and invasion are COX-2 dependent, establishing a direct relationship between COX-2 expression and malignant behaviour in canine melanoma. We have also developed a powerful molecular tool to aid further dissection of the mechanisms by which COX-2 regulates melanoma progression.

RESUMO.O presente relata a evisceração e posterior herniação inguinal de segmento de jejuno em equino submetido à orquiectomia. Um eqüino da raça Mangalarga Marchador, macho, 15 anos, foi encaminhado para realização de orquiectomia eletiva em haras no município de Alegre-ES. Após sedação e anestesia local, o paciente foi submetido ao procedimento cirúrgico. Decorridos 15 minutos, foi observado sangramento na região da bolsa escrotal, com visualização de tecido emergindo da ferida cirúrgica na bolsa escrotal direita. Após exame visual verificou-se tratar de porção do intestino delgado insinuandose pelo anel inguinal e ferida cirúrgica. Imediatamente o paciente foi submetido à laparotomia mediana à campo para redução da evisceração, sob anestesia geral intravenosa. O redução foi realizada com êxito, com sutura do anel inguinal externo direito. Decorridas seis horas do término da laparotomia, o paciente apresentou quadro clinico de abdômen agudo, e à palpação retal constatou-se presença de hérnia inguinal direita. Optou-se pela eutanásia do animal, por não haver um centro cirúrgico de grandes animais na região. Na necropsia foi verificado porção de jejuno insinuada no canal inguinal direito, com estrangulamento, apresentando-se com coloração esverdeada. A orquiectomia é uma técnica de execução relativamente simples, podendo ser realizada a campo pelo médico veterinário, porém, apresenta taxas de complicações elevadas, entre 20 a 38% dos casos, principalmente associados a erros de técnica cirúrgica. A evisceração intestinal pós-castração é considerada uma situação de emergência, exigindo uma conduta terapêutica rápida e eficiente. A sua ocorrência é rara, em torno de 0,2 a 2,6 % dos casos de orquiectomia. A palpação retal prévia à orquiectomia pode auxiliar na detecção de um anel inguinal interno dilatado ou qualquer alteração no mesmo, todavia esta prática não é realizada rotineiramente no pré-operatório de orquiectomia na espécie eqüina. Palavras chave: equinos, castração, evisceraçãoEvisceration in a horse submitted to orchiectomy: a case report ABSTRACT. This case report describes an evisceration of a segment of the small intestine in a male, 15-years-old Mangalarga Marchador horse, which was submitted to elective orchiectomy in a stud farm in Alegre, ES, Brazil. Following sedation and local anesthesia, the patient was submitted to the surgical procedure. Fifteen minutes after the end of surgery, hemorrhage from the region of the scrotum was observed, with tissue protruding from the surgical wound in the right scrotal sac. Visual exam revealed that it was a segment of the small intestine protruding from the inguinal ring and surgical wound. The patient was immediately submitted to TIVA (total intravenous anesthesia) and an emergency median laparotomy was performed to reduce the evisceration. The procedure was carried out with success and the right external inguinal ring was sutured. Six hours after the second procedure, the patient presented clinical signs of acute