Three Cases of Exclusively Extragenital Canine Transmissible Venereal Tumor (cTVT)

Background: Canine Transmissible Venereal Tumor (cTVT) is a neoplasia that affects mainly the genital organs of dogs, but can rich extragenital sites as well. It´s a tumor characterized microscopically by the presence of vacuolized round cells. Transmission occurs by implantation of these cells in non-affected tissues and the treatment is based on vincristine chemotherapy.Cases: Case 1. A 5-year-old intact male Poodle, presenting an increase volume of nasal plane came for veterinary care at a private veterinary clinic. The animal had bilateral bloody nasal secretion and dyspnea. The external genitalia had no alterations. The cytological evaluation confirmed cTVT. Treatment with vincristine sulfate weekly showed a rapid responsewith improvement of the respiratory condition, total remission of the mass and absence of neoplastic cells in cytology. Case 2. A 5-year-old mixed-breed canine bitch, weighing 6.7 kg, was brought to the State University of Santa Cruz Veterinary Hospital (UESC-VH), showing an increase volume in the nasal plan region, with complaints about sneezing, nasal bleeding,respiratory distress with approximately 4 months of evolution. The owner informed that the mother of these female dog, that lived in the same environment, died a month before the beginning of clinical signs of the bitch of this case, and showed a reddish vaginal mass with intense bleeding. Intranasal exfoliative cytology showed moderately cellular sample compatible with cTVT. The treatment with vincristine sulphate for 6 weeks, showed completely remission of all clinical signs. Case 3. A 3-year-old mixed-breed male dog was brought to the UESC-VH with a reddish, friable mass located in the left eye. The citology confirmed the clinical suspicion of cTVT. After six weekly sessions of chemotherapy with vincristine sulfate, the tumor regressed and a new cytological evaluation was performed, without visible of tumor cells. By the end of the treatment, the dog was diagnosed with phitisis bulbi, and one year later, due to recurrent ulcerative keratitis, the enucleation was performed and the histopathological examination of the eye did not identify the presence of tumor cells.Discussion: Two of the dogs cited in this report had freely streets access, without supervision of the owners, and they are likely to have contracted cTVT on one of those occasions. The animal’s care style acts as a risk factor for the development of neoplasia. Regarding the third animal, the close contact with another female dog, who had compatible vaginal cTVTclinical signs was probably the factor that determined the transmission. None of the animals cited in this report had lesions on their external genitalia. The extragenital presentation may be attributed to the social behavior of licking and sniffing the genitalia of carrier animals, which may lead to the natural implantation of the viable cells of the cTVT into the ocular and nasal mucosa. About the clinical signs manifested, in the cases of involvement of the nasal structures, the main signs described in literature are bloody nasal secretion, sneezing, dyspnea and increased nasal plane volume, and are similar to those observed in the animals cited in this report. In the case of ocular cTVT, the increase volume with impairment and deformity of all ocular structures, as well as pain and pruritus corroborate with the clinical findings observed in the literature. The cytopathological test was the diagnostic tool used in all cases cited in this report and the cytopathological findings corroborates with those described in the literature. Vincristine sulfate is the drug of choice for the treatment of cTVT cases, and in the dogs of this report, this drug was successfully used leading to complete remission of lesions and clinical signs, as observed in other studies.Keywords: nasal mucosa, ocular mucosa, venereal disease, round cells

Kisspeptin treatment improves fetal-placental development and blocks placental oxidative damage caused by maternal hypothyroidism in an experimental rat model

Maternal hypothyroidism is associated with fetal growth restriction, placental dysfunction, and reduced kisspeptin/Kiss1R at the maternal-fetal interface. Kisspeptin affects trophoblastic migration and has antioxidant and immunomodulatory activities. This study aimed to evaluate the therapeutic potential of kisspeptin in the fetal-placental dysfunction of hypothyroid Wistar rats. Hypothyroidism was induced by daily administration of propylthiouracil. Kisspeptin-10 (Kp-10) treatment was performed every other day or daily beginning on day 8 of gestation. Feto-placental development, placental histomorphometry, and expression levels of growth factors (VEGF, PLGF, IGF1, IGF2, and GLUT1), hormonal (Dio2) and inflammatory mediators (TNFα, IL10, and IL6), markers of hypoxia (HIF1α) and oxidative damage (8-OHdG), antioxidant enzymes (SOD1, Cat, and GPx1), and endoplasmic reticulum stress mediators (ATF4, GRP78, and CHOP) were evaluated on day 18 of gestation. Daily treatment with Kp-10 increased free T3 and T4 levels and improved fetal weight. Both treatments reestablished the glycogen cell population in the junctional zone. Daily treatment with Kp-10 increased the gene expression levels of Plgf, Igf1, and Glut1 in the placenta of hypothyroid animals, in addition to blocking the increase in 8-OHdG and increasing protein and/or mRNA expression levels of SOD1, Cat, and GPx1. Daily treatment with Kp-10 did not alter the higher protein expression levels of VEGF, HIF1α, IL10, GRP78, and CHOP caused by hypothyroidism in the junctional zone compared to control, nor the lower expression of Dio2 caused by hypothyroidism. However, in the labyrinth zone, this treatment restored the expression of VEGF and IL10 and reduced the GRP78 and CHOP immunostaining. These findings demonstrate that daily treatment with Kp-10 improves fetal development and placental morphology in hypothyroid rats, blocks placental oxidative damage, and increases the expression of growth factors and antioxidant enzymes in the placenta