[Practical training of pharmacokinetics with an web-based simulation application].

A computer simulation application on pharmacokinetics, which we developed using a software, named "Stella®", has been successfully used for the virtual training of pharmacokinetics at multiple medical schools. The training course using Stella® has encouraged the medical students to optimize drug administration for individual patients on the computers. Importantly, the virtual training is free of any concern on human and animal ethics. The simulation application has been freely provided for medical schools without any restrictions and charge. For many years, it has been under constant version-upgrade in response to updates of the operating systems (OS) of personal computers or the software. Very recently, major updates of the OS and the software, and the emergence of tablet- and smartphones-type computers have been prompting us to perform a major revision of the simulation application. Here, we introduce the new version of the "web-based" simulation application that is available through any device including personal computers, tablets, and smartphones irrespective of the OSs (Microsoft Windows and Macintosh, Android, and iOS), without any extra charge unless the modification is required. We believe that the new-version of web-based simulation application will be useful not only for medical, nursing and pharmacy students, but also for medical workers who need to simulate drug pharmacokinetics on the computers before they administer drugs to the patients.

Anti-atherosclerotic effects of tamoxifen in cholesterol-fed ovariectomized rabbits.

It has been indicated that the anti-estrogen agent, tamoxifen, developed for the treatment of breast cancer, may act on the vascular system as an estrogen agonist. However, to our knowledge few reports suggest that tamoxifen exerts anti-atherogenic actions. In the present study, we evaluated the anti-atherosclerotic effects of tamoxifen in ovariectomized cholesterol-fed rabbits. Ovariectomized rabbits were fed a 1% cholesterol diet and divided into 4 groups: control group (C, n=5); estrogen treatment (E, n=6); low-dose tamoxifen treatment (0.5 mg/kg) (LT, n=6); and high-dose tamoxifen (1.0 mg/kg) (HT, n=7). After 6 weeks, both Oil red O-positive areas on the intimal surfaces of aortae and the ratios of intimal to medial areas (I/M ratios) measured from cross-sections of aortae were significantly lower in groups E, LT and HT compared with group C. Although there were no significant differences in serum NOx (NO2 and NO3) levels among the 4 groups, NOx levels were slightly higher in groups E, LT and HT than group C. Acetylcholine (ACh) was administered to all animals, and the responses of ear arteriole diameters were compared among the 4 groups. While ear arteriole diameters were significantly decreased in group C, no significant changes were observed in groups E, LT or HT following ACh administration. Ratios of ear arteriole diameters after to before ACh administration were significantly greater in groups E, LT and HT compared to group C. These findings suggest that tamoxifen exerts anti-atherosclerotic effects, and that these effects are attributed to the maintenance of vascular endothelial function.

Effects of osthole on postmenopausal osteoporosis using ovariectomized rats; comparison to the effects of estradiol.

The purpose of this study was to examine effects of osthole on postmenopausal osteoporosis using ovariectomized (OVX) rats. All of the rats were divided into sham and OVX groups. At 2 weeks post-operation, the sham-operated rats received solvent vehicle (97% corn oil and 3% ethanol, 1.0 ml/kg, subcutaneously); the OVX rats were divided into three groups which were treated with solvent vehicle (same the sham rats, 1.0 ml/kg, subcutaneously), 17beta-estradiol (30 microg/kg, subcutaneously) or osthole (9.0 mg/kg, orally) 5 d/week for 4 weeks, respectively. In OVX rats, the increases of body weight, spleen and thymus weight were significantly decreased and the atrophy of uterus was preserved by 17beta-estradiol treatment, but not by osthole. Treatment with either 17beta-estradiol or osthole significantly protected cancellous bone loss owing to estrogen deficiency and significantly increased the maximal load in the femoral neck of OVX rats. In addition, the increases of serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) levels caused by ovariectomy were all significantly suppressed by 17beta-estradiol. However, only urinary DPD was significantly reduced by osthole and no change was found in serum OC. Our results demonstrate that osthole may be just as effective as 17beta-estradiol in suppressing bone loss due to ovariectomy but osthole perhaps does not work through the estrogen pathway.