Histological dermal changes caused by preparation and application procedures in percutaneous dose toxicity studies in dogs,rabbits and rats

We reevaluated histological slides of dorsal skin in control animals from past percutaneous dose toxicity studies using dogs, rabbits and rats to provide background data concerning histological changes related to preparation and application procedures and vehicles or embrocations of every variety. Acanthosis, dermal or perifollicular inflammatory cell infiltration in dogs; hyperkeratosis, acanthosis, dermal inflammatory cell infiltration or hemorrhage in rabbits; and acanthosis, dermal inflammatory cell infiltration, crust or foreign body granuloma in rats were present as procedure-related underlying histological changes in the control animals. Four mechanical acts, (1) rubbing with gauze to remove an administered substance for reapplication, (2) use of a taut bandage to avoid slipping from the application site, (3) peeling a patch off as a preparation procedure for reapplication, and (4) clipping or shaving, were considered to cause injury to the skin. The degree of influence of the various application procedures was found to be as follows: sham, lotion < cream < ointment and tape in dogs; untreated control, sham < lotion < tape and poultice in rabbits; and sham, sodium carboxymethylcellulose < olive oil and lotion < ointment and tape in rats. The degree of ointment influence on rabbits is equivocal.     

Oral pharmacokinetics of acetaminophen to evaluate gastric emptying profiles of Shiba goats

The pharmacokinetics of acetaminophen was investigated following oral dosing to Shiba goats in order to evaluate the properties of gastric emptying. Acetaminophen was intravenously and orally administered at 30 mg/kg body weight to goats using a crossover design with a 3-week washout period. The stability of acetaminophen in rumen juice was also assessed. Acetaminophen concentrations were measured by HPLC. Since acetaminophen was stable in rumen juice for 24 hr, the extremely low bioavailability (16%) was attributed to its hepatic extensive first-pass effect. The mean absorption time and absorption half-life were unexpectedly short (4.93 and 3.35 hr, respectively), indicating its marked absorption from the forestomach, which may have been due to its smaller molecular weight. Therefore, acetaminophen was considered to be unsuitable for evaluating gastric emptying in Shiba goats.     

Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in mice

Loss of imprinting (LOI) of the insulin-like growth factor II gene (IGF2) is an epigenetic alteration that results in a modest increase in IGF2 expression, and it is present in the normal colonic mucosa of about 30% of patients with colorectal cancer. To investigate its role in intestinal tumorigenesis, we created a mouse model of Igf2 LOI by crossing female H19+/- mice with male Apc+/Min mice. Mice with LOI developed twice as many intestinal tumors as did control littermates. Notably, these mice also showed a shift toward a less differentiated normal intestinal epithelium, reflected by an increase in crypt length and increased staining with progenitor cell markers. A similar shift in differentiation was seen in the normal colonic mucosa of humans with LOI. Thus, altered maturation of nonneoplastic tissue may be one mechanism by which epigenetic changes affect cancer risk.     

Effects of Oral Administration of Fucoidan Extracted from Cladosiphon okamuranus on Tumor Growth and Survival Time in a Tumor-Bearing Mouse Model

We evaluated the anti-tumor activities of the oral administration of fucoidan extracted from Cladosiphon okamuranus using a tumor (colon 26)-bearing mouse model. The materials used included low-molecular-weight fucoidan (LMWF: 6.5–40 kDa), intermediate-molecular-weight fucoidan (IMWF: 110–138 kDa) and high-molecular-weight fucoidan (HMWF: 300–330 kDa). The IMWF group showed significantly suppressed tumor growth. The LMWF and HMWF groups showed significantly increased survival times compared with that observed in the control group (mice fed a fucoidan-free diet). The median survival times in the control, LMWF, IMWF and HMWF groups were 23, 46, 40 and 43 days, respectively. It was also found that oral administration of fucoidan increased the population of natural killer cells in the spleen. Furthermore, from the results of the experiment using Myd-88 knockout mice, it was found that these effects are related to gut immunity. These results suggest that fucoidan is a candidate anti-tumor functional food.     

A simple, rapid method for gizzerosine analysis in fish meal by paper electrophoresis

We established a simple, rapid method for gizzerosine analysis in fish meal. Gizzerosine was extracted from fish meal with 0.1?N HCl solution. Samples and standard gizzerosine solutions were absorbed onto a paper disc, which was then set on electrophoresis paper for 18?min, and the paper was dried. Gizzerosine was visualized with Pauly??s reagent, and the intensity of the colored spots was digitized and calculated by image processing method software. We achieved successful separation of gizzerosine from other Pauly??s reagent-positive components in fish meal extracts. The linearity of gizzerosine estimation using this method was within the range 30?C1000?ng (R ²?=?0.99). Gizzerosine was satisfactorily detected and completely separated from histamine and other Pauly??s reagent-positive compounds. This method does not require expensive instruments or tedious pretreatment to eliminate interfering compounds, such as histamine or histidine. It also uses less reagent compared with high-performance liquid chromatography. Moreover, it is a simple, rapid, sensitive, and reproducible method. It is suitable for monitoring gizzerosine in fish meal products that contain as little as 10?ppm gizzerosine.     

Changes in micropores in dry wood with elapsed time in the environment

To investigate the changes in microstructures of wood with elapsed time in the environment, CO₂ adsorption onto dry wood was measured at ice-water temperature (273 K) for samples aged from 0.1 years to over 1000 years. The micropore size distribution was obtained using the Horvath-Kawazoe method. Micropores smaller than 0.6 nm in wood decreased in number with elapsed time in the environment, and a negative correlation was found between cumulative pore volume for pores smaller than 0.6 nm and elapsed time in the environment. Cumulative pore volume in the 1000-year sample was almost half of that in the 0.1- year sample. Micropores smaller than 0.6 nm in wood with a few decades or more of elapsed time increased in number after rewetting and drying. Consequently, microstructures of wood with longer time elapsed in the environment were considered to be more stable, because of longer-term thermal motion and possibly more repeated moisture adsorption and desorption and/or temperature variation in the environment.