Dog-specific hemorrhagic changes induced by liposomal formulations, in the liver and the gallbladder.

Although several liposomal drugs, including liposomal doxorubicin, have been approved, the etiology of the pathological responses caused by their physicochemical properties remains unknown. Herein, we investigated the pathological changes in the liver and the gallbladder of dogs following a single injection of liposomal doxorubicin (1 or 2.5 mg/kg) or an empty liposomal formulation (i.

Dedifferentiated retroperitoneal liposarcoma spontaneously occurring in an aged SD rat.

Liposarcoma is a rare neoplasm in rats and is characterized by the presence of lipoblasts containing multiple cytoplasmic vacuoles. We encountered a rare type of liposarcoma in a male SD (Crj:CD(SD)IGS) rat during a long-term study to gather background data. At necropsy at 105 weeks of age, there was a large amount of fatty tissue covering the mesentery, pancreas, and retroperitoneum; a white nodule in the right kidney; and paleness of the liver.

Spontaneous carcinosarcoma originating from the renal pelvis ina rat.

Carcinosarcoma is a rare neoplasm composed of malignant epithelial and stromal elements, and, for rats, carcinosarcomas in the kidney have not been reported. In a long-term study to gather background data, we encountered a spontaneous carcinosarcoma originating from the renal pelvis with metastasis to the lung. At necropsy, a mass was observed in the abdominal cavity, and white nodules were scattered in lung lobes.

Application of a compact magnetic resonance imaging system for toxicologic pathology: evaluation of lithium-pilocarpine-induced rat brain lesions.

Magnetic resonance imaging (MRI) is a useful noninvasive tool used to detect lesions in clinical and veterinary medicine. The present study evaluated the suitability of a new easy-to-use compact MRI platform (M2 permanent magnet system, Aspect Imaging, Shoham, Israel) for assisting with preclinical toxicologic pathology examination of lesions in the rat brain. In order to induce brain lesions, male Sprague-Dawley rats were treated once with lithium chloride (127 mg/kg, intraperitoneal [i.

Practical approaches for evaluating adrenal toxicity in nonclinical safety assessment.

The adrenal gland has characteristic morphological and biochemical features that render it particularly susceptible to the actions of xenobiotics. As is the case with other endocrine organs, the adrenal gland is under the control of upstream organs (hypothalamic-pituitary system) in vivo, often making it difficult to elucidate the mode of toxicity of a test article. It is very important, especially for pharmaceuticals, to determine whether a test article-related change is caused by a direct effect or other associated factors.

Granulomatous nephritis consistent with malakoplakia in a cynomolgus monkey.

Malakoplakia is a rare form of chronic granulomatous inflammation in mammals, and usually affects the urinary tract in humans. In this report, we present a case of granulomatous nephritis consistent with malakoplakia in a 4-year-old male cynomolgus monkey. Gross examination showed that the kidney was markedly enlarged and adhered to the surrounding organs.

Brunner's gland lesions in rats induced by a vascular endothelial growth factor receptor inhibitor.

Vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitors are reported to cause reversible mucosal hyperplasia (adenosis) in the duodenum of rats; however, the pathogenesis is not fully elucidated. Using lenvatinib, a VEGF RTK inhibitor, we characterized the histologic time course of this duodenal change in rats. At 4 weeks, there was degeneration and necrosis of Brunner's gland epithelium accompanied by neutrophil infiltration around the affected glands.

Spontaneous gingivitis related to hair penetration in rats.

Maxillary gingivae from male and female Crl:CD(SD) rats at 12, 16, 21, and 34 weeks of age were examined histologically. The incidence of gingivitis was approximately 40%, with no age or sex predilection, and was most frequent between the first and second molar. Lesions were characterized by acute focal neutrophilic infiltration into the gingival mucosa, occasionally with inflammatory exudate.

Histopathological characteristics of luteal hypertrophy induced by ethylene glycol monomethyl ether with a comparison to normal luteal morphology in rats.

Ethylene glycol monomethyl ether (EGME) is a known reproductive toxicant that induces luteal hypertrophy in rat ovaries. In this study, we characterized the histopathological features of corpora lutea (CL) from EGME-treated rats and compared them with normal CL formation and regression. Normally cycling female Sprague-Dawley rats were treated with 5-bromo-2'-deoxyuridine (BrdU) intraperitoneally on the morning of estrus and their ovaries were examined 1 (metestrus), 4 (estrus), 8 (estrus), or 12 (estrus) days later to observe the transition of BrdU-labeled cells within in the CL.

Identification of urinary biomarkers useful for distinguishing a difference in mechanism of toxicity in rat model of cholestasis.

This (1)H nuclear magnetic resonance metabonomics study was aimed to determine urinary biomarkers of cholestasis resulting from inhibition of biliary secretion of bile or obstruction of bile flow. To inhibit biliary secretion of bile, cyclosporine A was administered to male Sprague-Dawley rats. Obstruction of bile flow was induced by administration of 4,4'-methylene dianiline, alpha-naphthylisothiocyanate or bile duct ligation.

Collaborative work on evaluation of ovarian toxicity. 11) Two- or four-week repeated-dose studies and fertility study of ethylene glycol monomethyl ether in female rats.

The objective of this study was to determine the optimal period of administration for detection of ovarian toxicity in rat repeated-dose toxicity studies. A well-known ovarian toxicant, ethylene glycol monomethyl ether (EGME), was administered to female rats at dose levels of 0, 30, 100, or 300 mg/kg for 2 or 4 weeks (repeated-dose toxicity studies). The same doses were administered to female rats for 2 weeks prior to mating, during mating, and until Day 6 of pregnancy (fertility study).

Participation of a fusogenic protein, glyceraldehyde-3-phosphate dehydrogenase, in nuclear membrane assembly.

We found an autoimmune serum, K199, that strongly suppresses nuclear membrane assembly in a cell-free system involving a Xenopus egg extract. Four different antibodies that suppress nuclear assembly were affinity-purified from the serum using Xenopus egg cytosol proteins. Three proteins recognized by these antibodies were identified by partial amino acid sequencing to be glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fructose-1,6-bisphosphate aldolase, and the regulator of chromatin condensation 1.

5-Fluorouracil-induced intestinal toxicity: what determines the severity of damage to murine intestinal crypt epithelia?

To elucidate the relationship between 5-fluorouracil (5-FU) distribution and 5-FU-induced apoptosis and/or cell cycle arrest, microautoradiography was applied to murine intestinal crypts exposed to [14C] 5-FU by intravenous infusion. The histologic location of apoptotic cells in the crypt did not correlate to that of 5-FU. The temporal profiles of apoptotic and/or mitotic indexes corresponded to those of orally administered 5-FU in a previous study.