Spontaneous Peripheral Ameloblastic Odontoma in a Male Sprague-Dawley Rat.

Peripheral ameloblastic odontoma is a rare variant of odontogenic tumor occurring in the extraosseous region. The present report describes a spontaneous tumor in male Sprague-Dawley (SD) rats. The clinically confirmed nodule in the right mandibular region was first observed when the rat was 42 weeks and remained until the terminal sacrifice date when the animal was 48 weeks of age. At necropsy, a well demarcated nodule, approximately 2.5 × 2.0 × 2.0 cm, protruded from the ventral area of the right mandible. The nodule was not attached to mandibular bone and was not continuous with the normal teeth. Histopathologically, the tumor was characterized by the simultaneous occurrence of an ameloblastomatous component and composite odontoma-like elements within the same tumor. The epithelial portion formed islands or cords resembling the follicle or plexiform pattern typical of ameloblastoma and was surrounded by mesenchymal tissue. Formation of eosinophilic and basophilic hard tissue matrix (dentin and enamel) resembling odontoma was observed in the center of the tumor. Mitotic figures were rare, and areas of cystic degeneration were present. Immunohistochemically, the epithelial component was positive for cytokeratin AE1/AE3 (CK AE1/AE3), and the mesenchymal component and odontoblast-like cells were positive for vimentin, in the same manner as in normal teeth. On the basis of these findings, the tumor was diagnosed as a peripheral ameloblastic odontoma in an extraosseous mandibular region in a SD rat. In the present study, we report the uncommon spontaneous peripheral ameloblastic odontoma in the SD rat. We also discuss here the morphological characteristics, origin, histochemical, and immunohistochemical features for the diagnosis of this tumor.

The spectrum of eosinophilic infiltration of the cecum and its relationship to other disorders of multiple granulomas and arteritis in Sprague-Dawley rat.

Spontaneous multiple granulomas were present in the animal under the SPF condition and without chemical treatment, in a 19-week-old male Sprague-Dawley control-group rat. Here we describe multiple granulomas and prominent diffuse infiltration by eosinophils in the cecal submucosa, and arteritis in the mesenteric arteries. The multiple granulomas were characterized by central eosinophilic degeneration or necrosis, prominent eosinophils, many multi-nucleated giant cells and abundant fibroblasts. They were restricted to the cecal submucosa. The mesenteric arteritis consisted of fibrinoid necrosis of the intima and media, intense inflammatory cell infiltration and fibrosis in the arterial wall. An affected artery in the cecum was continuous with the mesenteric artery. The foregoing tissue changes in this rat correlate with the high absolute blood eosinophil count found in this animal.

A spontaneous epithelial-myoepithelial carcinoma of the submandibular gland in a sprague-dawley rat.

The present report describes a rare case of spontaneous tumor of the salivary gland in a male Sprague-Dawley rat. The clinically confirmed mass rapidly developed in the cervical region between 19 and 21 weeks of age, and the animal was subsequently euthanized. At necropsy, a well-circumscribed nodule approximately 7 × 6 cm in diameter was found at the site of the salivary gland. The cut surface of the nodule was lobulated and soft and had a pinkish tan fish-flesh appearance. One large cyst (approximately 3 × 2 cm in size) containing reddish fluid was also present in the nodule. Histopathologically, the tumor, with a partially lobulated structure, was surrounded by a thin fibrous capsule. The majority of tumor cells formed a diffuse solid sheet structure that mainly consisted of small ovoid or spindle-shaped cells. In the tumor periphery, some cells were arranged in nest-like structures. Small duct-like structures lined with a monolayer of cuboidal epithelial cells resembling an intercalated duct or large polygonal clear cells with a myoepithelial component were also observed. Mitotic figures and necrotic foci were frequently observed in solid areas. Immunohistochemically, the tumor cells were positive for cytokeratin, epithelial membrane antigen, vimentin, p63, α-smooth muscle actin and calponin. The cells were negative for calcitonin, synaptophysin and chromogranin A. On the basis of these findings, the tumor was diagnosed as an epithelial-myoepithelial carcinoma originating from the luminal epithelial cells and myoepithelial cells in the submandibular gland.

Single and 90-day repeated oral dose toxicity studies of fermented Rhus verniciflua stem bark extract in Sprague-Dawley rats.

Fermented Rhus verniciflua stem bark (FRVSB) extract, an urushiol-free extract of Rhus verniciflua Stokes (RVS) fermented with Fomitella fraxinea, has various biological activities. The present study was carried out to investigate the potential toxicity of the FRVSB extract following single and repeated oral administration to Sprague-Dawley rats. In the single dose toxicity study, the FRVSB extract was administered orally to male and female rats at single doses of 0, 2500, 5000, and 10,000mg/kg. No animals died and no toxic changes were observed in clinical signs, body weight, and necropsy findings during the 15-day period following administration. In the repeated dose toxicity study, the FRVSB extract was administered orally to male and female rats for 90days at doses of 0, 556, 1667, and 5000mg/kg/day. There were no treatment-related adverse effects in clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at any dose tested. The approximate lethal dose of the FRVSB extract was >10,000mg/kg in both genders, the oral no-observed-adverse-effect level of the FRVSB extract was >5000mg/kg/day in both genders, and no target organs were identified.

Evaluation of general toxicity and genotoxicity of the silkworm extract powder.

The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent α-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.

A 6-week oral toxicity study of oral cholera vaccine in sprague-dawley rats.

The present study was carried out to examine the toxicity and target organs of oral cholera vaccine (OCV) after repeated oral administration in Sprague-Dawley rats for 6 weeks (3 administrations, once every 2 weeks). OCV is an inactivated oral cholera vaccine that contains Vibrio cholerae and confers protection against cholera caused by V. cholera serogroups O1 (Inaba and Ogawa serotypes) and O139 (strain 4260B). The animals were orally administered either OCV placebo (negative control) or OCV at a dose equivalent to 240 times the anticipated human dose. Throughout the administration period, no significant change was detected in clinical signs, body weight, food or water consumption, urinalysis results, hematological and clinical biochemistry test results, organ weights, necropsy, or histopathological examination results. Minor changes were found in hematological and clinical biochemistry tests; however, these changes were within normal ranges. The above results suggest that oral administration of OCV in rats did not induce any toxicologically meaningful changes, and the target organs could not be determined. This study was conducted in accordance with the guidelines established by Good Laboratory Practice (2009-183, KFDA, December 22, 2009) and the OECD Principles of Good Laboratory Practice (1997).

Acute and 90-day subchronic toxicity studies of Silk peptide E5K6, in Sprague-Dawley rats.

Acute and 90-day subchronic oral toxicity studies of Silk peptide E5K6 were performed in Sprague-Dawley rats. In the acute toxicity study, Silk peptide E5K6 was administered orally to male and female rats at a single dose of 2000 and 5000 mg/kg. Mortality, clinical signs and body weight changes were monitored for 14 days. There were no treatment-related changes in these parameters. Therefore, the Approximate Lethal Dose (ALD) of Silk peptide E5K6 in male and female rats is higher than 5000 mg/kg. In the subchronic toxicity study, Silk peptide E5K6 was administered orally to male and female rats for 90 days at a single dose of 500, 1000, and 2000 mg/kg. There were no toxicologically significant changes in clinical signs, body weight, food and water consumptions, ophthalmoscopic examination, urinalysis, hematological and serum biochemical examinations, necropsy findings, organ weights and histopathological examination of all of the animals treated with Silk peptide E5K6. These results suggest that the oral No Observed Adverse-Effect Level (NOAEL) of Silk peptide E5K6 is greater than 2000 mg/kg/day in both sexes and the target organs were not established.

Monoterpenes from thyme (Thymus vulgaris) as potential mosquito repellents.

Five monoterpenes (carvacrol, p-cymene, linalool, alpha-terpinene, and thymol) derived from the essential oil of thyme (Thymus vulgaris) were examined for their repellency against the mosquito Culex pipiens pallens. All 5 monoterpenes effectively repelled mosquitoes based on a human forearm bioassay. Alpha-terpinene and carvacrol showed significantly greater repellency than a commercial formulation, N,N-diethyl-m-methylbenzamide (deet), whereas thymol showed similar repellency to that of deet. The duration of repellency after application for all these monoterpenes was equal to or higher than that of deet. These findings indicate that a spray-type solution containing 2% alpha-terpinene may serve as an alternative mosquito repellent.