Involvement of Multidrug Resistance-Associated Protein 1 in Intestinal Toxicity of Methotrexate

金沢大学医薬保健研究域薬学系Purpose: Methotrexate (MTX) causes dose-limiting gastrointestinal toxicity due to exposure of intestinal tissues, and is a substrate of the multidrug resistance-associated protein (MRP) 1. Here we examine the involvement of MRP1, which is reported to be highly expressed in the proliferative crypt compartment of the small intestine, in the gastrointestinal toxicity of MTX. Methods: MTX was intraperitonealy administered to mrp1 gene knockout (mrp1(-/-)) and wild-type (mrp1(+/+)) mice. Body weight, food and water intake were monitored, intestinal histological studies and pharmacokinetics of MTX were examined. Results: mrp1(-/-) mice more severely decreased body weight, food and water intake than mrp1(+/+) mice. Almost complete loss of villi throughout the small intestine in mrp1(-/-) mice was observed, whereas the damage was only partial in mrp1(+/+) mice. Plasma concentration and biliary excretion profiles of MTX were similar in mrp1(-/-) and mrp1(+/+) mice, though accumulation of MTX in immature proliferative cells isolated from mrp1(-/-) mice was much higher compared to mrp1(+/+) mice. Immunostaining revealed localization of Mrp1 in plasma membrane of the intestinal crypt compartment in mrp1(+/+) mice, but not in mrp1(-/-) mice. Conclusion: Mrp1 determines the exposure of proliferative cells in the small intestine to MTX, followed by gastrointestinal toxicity. © 2009 Springer Science+Business Media, LLC

P-Glycoprotein (Abcb1) is involved in absorptive drug transport in skin

金沢大学医薬保健研究域薬学系 金沢大学医薬保健研究域医学系The purpose of the present study was to investigate the role of P-glycoprotein (P-gp) in drug disposition in skin. The distribution of P-gp substrates (rhodamine 123 and itraconazole) to the skin after administration from the epidermal side was lower in P-gp gene knockout (mdr1a/1b-/-) mice than that in wild-type mice. Coadministration of propranolol, a P-gp inhibitor, decreased the distribution of itraconazole to the skin in wild-type mice, but not in mdr1a/1b-/- mice. These results suggest that P-gp contributes to the influx (from the epidermal side) of its substrates into skin, although P-gp is generally involved in efflux of drugs from various tissues. This finding was supported by the lower vectorial transport of rhodamine 123 from the epidermal to the hypodermal side in mdr1a/1b-/- mice in Ussing-type chamber experiments and by the immunohistochemical localization of P-gp throughout the dermal layer. Distribution of itraconazole after intravenous administration, on the other hand, was higher in mdr1a/1b-/- mice than that in wild-type mice, suggesting that P-gp transports this drug from the skin to the circulation. The present findings are the first to demonstrate involvement of P-gp in dermal drug disposition. © 2008

MAGIC and H.E.S.S. detect VHE gamma rays from the blazar OT081 for the first time: a deep multiwavelength study

https://pos.sissa.it/395/815/pdfPublished versio

Spatial variations of tritium concentrations in groundwater collected in the southern coastal region of Fukushima, Japan, after the nuclear accident

Abstract Spatial variations in tritium concentrations in groundwater were identified in the southern part of the coastal region in Fukushima Prefecture, Japan. Higher tritium concentrations were measured at wells near the Fukushima Daiichi Nuclear Power Station (F1NPS). Mean tritium concentrations in precipitation in the 5 weeks after the F1NPS accident were estimated to be 433 and 139 TU at a distance of 25 and 50 km, respectively, from the F1NPS. The elevations of tritium concentrations in groundwater were calculated using a simple mixing model of the precipitation and groundwater. By assuming that these precipitation was mixed into groundwater with a background tritium concentration in a hypothetical well, concentrations of 13 and 7 TU at distances of 25 and 50 km from the F1NPS, respectively, were obtained. The calculated concentrations are consistent with those measured at the studied wells. Therefore, the spatial variation in tritium concentrations in groundwater was probably caused by precipitation with high tritium concentrations as a result of the F1NPS accident. However, the highest estimated tritium concentrations in precipitation for the study site were much lower than the WHO limits for drinking water, and the concentrations decreased to almost background level at the wells by mixing with groundwater

Easy Aligned Telescope for CubeSat

Recently there is high demand on earth observation with Cubesat. Usually the researcher only uses general COTS on board camera with Cubesat on its purpose. However, if the researcher needs more resolution or different wavelength, it needs custom designed telescope for it, but telescope needs high accurate optics components and its aligned accuracy. Creating a specially designed optical telescope not only costs enormously, but also takes time from design to manufacture. Furthermore, if the processing accuracy in optical processing and the accuracy in the degree of adjustment in the assembly adjustment stage are ensured, higher-precision design, processing, and assembly adjustment are required. When using Cubesat, considering how to shorten the time from kick-off to launch, and considering the short lifetime due to low orbit, it is important to build a system that can acquire fast, cheap, but high-definition images. In this study, we aimed to achieve higher resolution even with a limited optical element configuration by combining the optical design of the reflection system and the refraction system. Furthermore, by simplifying the assembling adjustment process as much as possible, a low cost and quick manufacturing was sought

Purely organic electroluminescent material realizing 100% conversion from electricity to light.

効率100％で電気を光に変換する有機EL材料の高性能化に成功. 京都大学プレスリリース. 2015-10-21.Efficient organic light-emitting diodes have been developed using emitters containing rare metals, such as platinum and iridium complexes. However, there is an urgent need to develop emitters composed of more abundant materials. Here we show a thermally activated delayed fluorescence material for organic light-emitting diodes, which realizes both approximately 100% photoluminescence quantum yield and approximately 100% up-conversion of the triplet to singlet excited state. The material contains electron-donating diphenylaminocarbazole and electron-accepting triphenyltriazine moieties. The typical trade-off between effective emission and triplet-to-singlet up-conversion is overcome by fine-tuning the highest occupied molecular orbital and lowest unoccupied molecular orbital distributions. The nearly zero singlet-triplet energy gap, smaller than the thermal energy at room temperature, results in an organic light-emitting diode with external quantum efficiency of 29.6%. An external quantum efficiency of 41.5% is obtained when using an out-coupling sheet. The external quantum efficiency is 30.7% even at a high luminance of 3, 000 cd m(-2)