Diagnosis, Prognosis, and Treatment of Canine Hemangiosarcoma: A Review Based on a Consensus Organized by the Brazilian Association of Veterinary Oncology, ABROVET.

Hemangiosarcoma is a mesenchymal neoplasm originating in the endothelial cells of blood vessels; they can be classified as non-visceral and visceral types. Non-visceral hemangiosarcomas can affect the skin, subcutaneous tissues, and muscle tissues; visceral hemangiosarcomas can affect the spleen, liver, heart, lungs, kidneys, oral cavity, bones, bladder, uterus, tongue, and retroperitoneum. Among domestic species, dogs are most affected by cutaneous HSA. Cutaneous HSA represents approximately 14% of all HSA diagnosed in this species and less than 5% of dermal tumors, according to North American studies. However, Brazilian epidemiological data demonstrate a higher prevalence, which may represent 27 to 80% of all canine HSAs and 13.9% of all skin neoplasms diagnosed in this species. Cutaneous HSA most commonly affects middle-aged to elderly dogs (between 8 and 15 years old), with no gender predisposition for either the actinic or non-actinic forms. The higher prevalence of cutaneous HSA in some canine breeds is related to lower protection from solar radiation, as low skin pigmentation and hair coverage lead to greater sun exposure. Actinic changes, such as solar dermatosis, are frequent in these patients, confirming the influence of solar radiation on the development of this neoplasm. There are multiple clinical manifestations of hemangiosarcoma in canines. The diagnostic approach and staging classification of cutaneous HSAs are similar between the different subtypes. The definitive diagnosis is obtained through histopathological analysis of incisional or excisional biopsies. Cytology can be used as a presurgical screening test; however, it has little diagnostic utility in cases of HSA because there is a high risk of blood contamination and sample hemodilution. Surgery is generally the treatment of choice for dogs with localized non-visceral HSA without evidence of metastatic disease. Recently, electrochemotherapy (ECT) has emerged as an alternative therapy for the local ablative treatment of different neoplastic types; the use of radiotherapy for the treatment of dogs with cutaneous HSA is uncommon. There is greater consensus in the literature regarding the indications for adjuvant chemotherapy in subcutaneous and muscular HSA; doxorubicin is the most frequently used antineoplastic agent for subcutaneous and muscular subtypes and can be administered alone or in combination with other drugs. Other therapies include antiangiogenic therapy, photodynamic therapy, the association of chemotherapy with the metronomic dose, targeted therapies, and natural products. The benefits of these therapies are presented and discussed. In general, the prognosis of splenic and cardiac HSA is unfavorable. As a challenging neoplasm, studies of new protocols and treatment modalities are necessary to control this aggressive disease.

Testicular subcutaneous allografting followed by immunosuppressive treatment promotes maintenance of spermatogonial cells in rainbow trout (Oncorhynchus mykiss).

Germ cell transplantation and testis graft represent promising biotechnologies that can be applied for the reproduction of commercial or endangered species. However, mechanisms of rejection from the host immune system might remove the transplanted donor cells/tissues and limit the surrogate production of gametes. In this work, we administered emulsion containing-immunosuppressants to verify whether they are capable to prevent immune rejection and promote survival of testis allografts in rainbow trout. In the first part of this study, we demonstrated in vitro that tacrolimus and cyclosporine were able to affect viability, inhibit leucocyte proliferation, and suppress il2 expression in vitro. In in vivo experiments, both doses of tacrolimus (0.5 and 1.5 mg/kg) and the lower dose of cyclosporine (20 mg/kg) significantly inhibited the expression of il2 in head kidney, three days post-injection. A higher dose of cyclosporine (40 mg/kg) was able to inhibit il2 expression for up to seven days post-injection. In the second part, testis allografts were conducted in fish treated weekly with emulsion containing-tacrolimus. Immunohistochemical, conventional histology, and qRT-PCR (vasa) analysis demonstrated the presence of spermatogonial cells by the fifth week, in animals treated with 0.5 mg/kg of tacrolimus similar as found in autografted group. In the group treated with the highest tacrolimus dose (1.5 mg/kg) and in the non-treated group (without immunosuppressant), no germ cells or their respective markers were detected. il2 expression in head kidney was also suppressed in grafted animals treated with tacrolimus compared to non-treated group. These results suggest that tacrolimus may be a promising immunosuppressant for testis allografts or germ cell transplantation in rainbow trout. Co-administration combining tacrolimus (at lower dose) with other immunosuppressive drugs for inhibiting other activation pathways of the immune system, as performed in human organ transplantation, could be an alternative approach to optimize the immunosuppressive effects in host organisms.

The pathogenicity of two Neospora caninum goat strains in a BALB/c mouse model.

Goats are frequently described as an intermediate host for the protozoan Neospora caninum, manifesting the disease mainly by recurrent abortions with placentitis and encephalitis in fetuses. Several reports of natural and experimental infections in cattle and mice show differences in the immune response, and the outcome of the infection can be variable depending on the species affected and by the behavior of the infective strain. This study describes for the first time two Neospora caninum strains isolated from naturally infected goats from the state of Minas Gerais, Brazil. One placenta and one brain from different goats were processed for a first bioassay in gerbils (Meriones unguiculatus). Subsequently, a second bioassay was performed by inoculating the processed brain samples from gerbils into Interferon gamma (IFN-γ) knockout mice (KO mice). Tachyzoites collected from the peritoneal fluid of the KO mice were inoculated into VERO cell monolayers, where they presented a very slow growth rate. The tachyzoites were also inoculated into BALB/c mice with a dose of 106 tachyzoites per animal. After a 5-week follow up, the animals infected with both of the strains developed a strong polarized Th1 response with increased serum and spleen gene expression levels of pro-inflammatory cytokines (mainly IFN-γ and TNF-α) in the first week. Tissue lesions were mild in the animals infected with both strains. Despite the strong immune response preventing an infection in the visceral organs, the parasite was able to reach the brain, causing progressive brain lesions from the second to fifth week post infection. The NC-goat1-infected mice presented with severe meningoencephalitis, but the NC-goat2-infected animals had considerable histological brain lesions only at week 5. Immunohistochemical analysis of the mouse brains revealed a different pattern of inflammatory cells compared to the naturally infected goats. A severe inflammatory infiltrate of CD3+ T lymphocytes was found in the NC-goat1-infected mice. A more discrete infiltrate of CD3+ T cells was found in the NC-goat2-infected animals. Additionally, IBA1 IHC revealed an intense microglial reaction and monocyte perivascular cuffs in the NC-goat1-infected animals and lower microglia/monocyte infiltrates in the NC-goat2-infected mice. This work contributes knowledge on the pathogenicity of new Neospora caninum strains in mice, comparable with other well-established mouse models of the disease, and demonstrates the importance of studying goats as an intermediate host of this parasite.

Heat stress, Eimeria spp. and C. perfringens infections alone or in combination modify gut Th1/Th2 cytokine balance and avian necrotic enteritis pathogenesis.

Information on the dynamics of the chicken immune system during bacterial or parasite challenge in the presence or absence of stressful situations may provide a better understanding of the complex mechanisms behind these diseases. Necrotic enteritis (NE) had been controlled previously by the proper use of antimicrobial agents; however, more recently, NE has reemerged in many countries. The imposed restrictions on antimicrobial use and/or the intensive productive programs implemented by producers are challenges the birds, leading to large host adaptive responses that in many instances are like those elicited by stressors. This study analyses the effects of heat stress on Th1/Th2 cytokine balance, pathological features, and Toll-like receptor expression in the small intestine of broiler chickens infected with Clostridium perfringens type A in the presence or absence of Eimeria spp. co-infection. This co-infection model was experimentally used because it reproduces the findings commonly observed in the field during avian NE. For this purpose, broiler chickens infected with C. perfringens and/or Eimeria spp. were reared in isolator chambers subjected or not to heat stress intermittently. It was observed that heat stress directs the expression of Th2-type cytokines, increases Toll-like receptor 4 expression in the intestine and reduces the disease severity induced by Eimeria spp. and C. perfringens infections alone or in combination, most likely as a consequence of stress-induced changes in brain-gut axis activity.