Spontaneous Histiocytic Sarcoma of the Popliteal Lymph Node in a Young Sprague-Dawley Rat

The present report describes a rare case of spontaneous primary histiocytic sarcoma of the popliteal lymph node in a 19-week-old female Sprague-Dawley (SD) rat. At necropsy, a 10 mm-diameter whitish nodule was found at the site of the femoral muscle in the right hindlimb. Histopathologically, the nodule comprised large pleomorphic histiocyte-like cells with abundant eosinophilic or foamy cytoplasm. Multinucleated giant cells, necrotic foci surrounded by palisading arrays of epithelioid histiocyte-like cells and phagocytosis of cell debris or erythrocytes by the neoplastic cells were occasionally observed. Invasion of the tumor cells into the surrounding adipose tissue was found focally, but there were no distal metastases. Immunohistochemically, the neoplastic cells were positive for vimentin, CD68 (ED1) and lysozyme. We concluded that this tumor occurred in the popliteal lymph node, considering the anatomical location of the lesion and the presence of the remnants of lymphoid tissue involved in the tumor

Inhibitory Effects of Anti-VEGF Antibody on the Growth and Angiogenesis of Estrogen-induced Pituitary Prolactinoma in Fischer 344 Rats: Animal Model of VEGF-targeted Therapy for Human Endocrine Tumors

Estrogen-induced pituitary prolactin-producing tumors (PRLoma) in F344 rats express a high level of vascular endothelial growth factor (VEGF) associated with marked angiogenesis and angiectasis. To investigate whether tumor development in E2-induced PRLoma is inhibited by anti-VEGF monoclonal antibody (G6-31), we evaluated tumor growth and observed the vascular structures. With simultaneous treatment with G6-31 for the latter three weeks of the 13-week period of E2 stimulation (E2+G6-31 group), the following inhibitory effects on the PRLoma were observed in the E2+G6-31 group as compared with the E2-only group. In the E2+G6-31 group, a tendency to reduction in pituitary weight was observed and significant differences were observed as (1) reductions in the Ki-67-positive anterior cells, (2) increases in TUNEL-positive anterior cells, and (3) repair of the microvessel count by CD34-immunohistochemistry. The characteristic “blood lakes” in PRLomas were improved and replaced by repaired microvascular structures on 3D observation using confocal laser scanning microscope. These inhibitory effects due to anti-VEGF antibody might be related to the autocrine/paracrine action of VEGF on the tumor cells, because VEGF and its receptor are co-expressed on the tumor cells. Thus, our results demonstrate that anti-VEGF antibody exerted inhibitory effects on pituitary tumorigenesis in well-established E2 induced PRLomas

Effects of Unilateral Nephrectomy on Renal Function in Male Spontaneously Diabetic Torii Fatty Rats: A Novel Obese Type 2 Diabetic Model

The Spontaneously Diabetic Torii (SDT) fatty rat is a new model for obese type 2 diabetes. The aim of the present study was to investigate the effect of 1/2 nephrectomy (Nx) on renal function and morphology and on blood pressure in SDT fatty rats. Male SDT fatty rats underwent 1/2 Nx or a sham operation (Sham). Subsequently, animals were studied with respect to renal function and histological alterations. Induction of 1/2 Nx in SDT fatty rats led to functional and morphological damage to the remnant kidney and to hypertension, which are considered main characteristics of chronic kidney disease, at a younger age compared with the sham group. In conclusion, the SDT fatty rat is useful in investigations to elucidate the pathogenesis of human diabetic nephropathy and in new drug discovery

Ocular Inflammation in Uveal Tract in Aged Obese Type 2 Diabetic Rats (Spontaneously Diabetic Torii Fatty Rats)

We report uveitis observed in an obese type 2 diabetes rat model, Spontaneously Diabetic Torii Leprfa (SDT fatty) rats aged over 50 weeks. The eyes of SDT fatty rats (16 animals: 7 males and 9 females with 50 or 60 weeks of age) were examined histopathologically. Infiltration of inflammatory cells in the uveal tract was observed in 13 of 16 animals. One female showed severe inflammation affecting the entire uveal tract including the iris, ciliary body, and choroid with a variety of inflammatory cells (neutrophils, lymphocytes, and macrophages). Those changes clinically mimic the findings of diabetic iridocyclitis in diabetic patients. Uveitis associated with diabetes can occur in diabetic patients but the pathogenesis still remains unknown. Since increased extramedullary hematopoiesis in the spleen and abscess in the genital and lower urinary tracts were observed in some SDT fatty rats, increased susceptibility to infection, prolongation of inflammatory states, and disorders of the immune system were considered to be possible factors of the uveitis in aged SDT fatty rats. There have been few reports on how diabetes has influence on the development of uveitis associated with bacterial infection. The SDT fatty rat can be an animal model to investigate diabetes-associated uveitis

Effects of peroxisome proliferator-activated receptor-α and -γ agonist, JTT-501, on diabetic complications in Zucker diabetic fatty rats

1. This study has investigated the effects of JTT-501, a peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ agonist, on the pathogenesis of diabetic complications in the Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes. Comparison is made with troglitazone, a PPAR-γ agonist. 2. The ZDF rats exhibited hyperglycaemia and hyperlipidaemia, and developed diabetic complications such as cataract, nephropathy, and neuropathy. Treatment with JTT-501 from the prediabetic stage controlled glycaemia and lipidaemia, and prevented the development of diabetic complications. Troglitazone was less effective in controlling serum cholesterol and neuropathy. 3. ZDF rats developed diabetic osteopenia with reduced bone turnover, and this was prevented by JTT-501 and troglitazone, possibly mediated by increased bone turnover and bone formation. 4. Since JTT-501 controlled glycaemia and lipidaemia in ZDF rats and prevented several diabetic complications, it is suggested that treatment with JTT-501, which activates both PPAR-α and PPAR-γ, could provide a valuable therapeutic approach against diabetic complications in type 2 diabetes