No abstract

A 90-day oral toxicity study of γ-oryzanol, a rice-derived triterpenoid ferulate, was performed by oral gavage administration to male and female Sprague-Dawley rats at doses of 0, 1000, and 2000 mg/kg body weight/day. All rats administered γ-oryzanol survived throughout the study period. Both male and female rats showed no toxicologically significant changes of the general signs, examination findings, body weight, food consumption, functional observational battery results, ophthalmological findings, urinalysis, hematology tests, clinical chemistry tests, organ weights, and necropsy findings. Moreover, there were no histopathological changes related to administration of γ-oryzanol in males and females from the 2000 mg/kg body weight/day group. In conclusion, the no observed adverse effect level (NOAEL) of γ-oryzanol exceeded 2000 mg/kg body weight/day for both male and female rats under the conditions of this study.

The relationship between tumor necrosis factor (TNF)-alpha level, body temperature, and pulmonary lesion score was determined in 3-week-old pigs inoculated intranasally with swine influenza virus (SIV) subtype H1N2. The expression of TNF-alpha was measured in bronchoalveolar lavage (BAL) fluids by enzyme-linked immunosorbent assay and lung tissues by immunohistochemistry. In BAL fluid, TNF-alpha concentration was maximal at 1 days post-inoculation (dpi), declined markedly by 3 dpi (P<0.05) and steady thereafter. Mean rectal temperatures were above 40 degrees C for the infected groups at 1 dpi and declined markedly by 3 dpi. The body temperatures were correlated with the levels of TNF-alpha in BAL fluids from pigs experimentally infected with SIV (r(s)=0.9754, P<0.05). The pulmonary lesion scores were correlated with the means of positive cells by immunohistochemistry for TNF- alpha (r(s)=0.9949, P<0.001). The results suggest that the expression of TNF-alpha protein plays an important role in induction of pulmonary lesion and clinical sign such as fever in SIV infection.

BackgroundMetastasis to the lung may be the final step in the breast cancer-related morbidity. Conventional therapies such as chemotherapy and surgery are somewhat successful, however, metastasis-related breast cancer morbidity remains high. Thus, a novel approach to prevent breast tumor metastasis is needed.Methodology/Principal FindingAerosol of lentivirus-based small hairpin osteopontin was delivered into mice with breast cancer twice a week for 1 or 2 months using a nose-only inhalation system. The effects of small hairpin osteopontin on breast cancer metastasis to the lung were evaluated using near infrared imaging as well as diverse molecular techniques. Aerosol-delivered small hairpin osteopontin significantly decreased the expression level of osteopontin and altered the expression of several important metastasis-related proteins in our murine breast cancer model.Conclusion/SignificanceAerosol-delivered small hairpin osteopontin blocked breast cancer metastasis. Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors.

The aim of this study was to determine the immunoreactivity of normal small bronchial, bronchiolar, respiratory bronchiolar, and interalveolar epithelium using antibodies to six mucins: MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC6. The large, gel-forming secreted mucins MUC2, MUC5AC, and MUC5B were widely expressed in the lower respiratory tract. The results of this study demonstrate that these secreted mucins form a gel to cover and protect the mucosal surface in the lower respiratory tract of pigs.