Effects of Ospemifene on Drug Metabolism Mediated by Cytochrome P450 Enzymes in Humans in Vitro and in Vivo

The objective of these investigations was to determine the possible effects of the novel selective estrogen receptor modulator, ospemifene, on cytochrome P450 (CYP)-mediated drug metabolism. Ospemifene underwent testing for possible effects on CYP enzyme activity in human liver microsomes and in isolated human hepatocytes. Based on the results obtained in vitro, three Phase 1 crossover pharmacokinetic studies were conducted in healthy postmenopausal women to assess the in vivo effects of ospemifene on CYP-mediated drug metabolism. Ospemifene and its main metabolites 4-hydroxyospemifene and 4′-hydroxyospemifene weakly inhibited a number of CYPs (CYP2B6, CYP2C9, CYP2C19, CYP2C8, and CYP2D6) in vitro. However, only CYP2C9 activity was inhibited by 4-hydroxyospemifene at clinically relevant concentrations. Induction of CYPs by ospemifene in cultured human hepatocytes was 2.4-fold or less. The in vivo studies showed that ospemifene did not have significant effects on the areas under the plasma concentration-time curves of the tested CYP substrates warfarin (CYP2C9), bupropion (CYP2B6) and omeprazole (CYP2C19), demonstrating that pretreatment with ospemifene did not alter their metabolism. Therefore, the risk that ospemifene will affect the pharmacokinetics of drugs that are substrates for CYP enzymes is low.     

Dynamic analysis of a bistable actuator for digital hydraulics

A fast and small electromagnetic actuator, which requires a small amount of work to switch between two stable positions, for the use in digital hydraulics, is presented. A dynamic study of the bistable actuator as part of a new kind of hydraulic on/off valve is carried out. A prototype is built and measured to verify the analysis. The results show that with careful elaboration the design is feasible. Furthermore, the response times depend on driving frequencies and an optimal current density for minimal energy consumption in cyclic action can be found. A single on/off valve is a critical part of a digital hydraulic system.     

A Dialogue with C. West Churchman

In 1996, the author attended a seminar on ethics given by C. West Churchman at the University of California, Berkeley. During that year, the author also interviewed Churchman several times regarding the future direction of information sciences in general and the information systems research field in particular. This article is a compilation of the seminar and the interviews. It is set in the context of both Churchman's earlier and his current views of a global god, good, kindness, and caring. C. West Churchman holds that global ethics should lead to the study and design of information systems to solve large and difficult problems of the humankind such as poverty, crime and disease. His Global Ethical Management (GEM) of information sciences translates into abandoning the current goals and boundaries of the information sciences fields and changing what constitutes valid research to globally ethical endeavors.     

Visual tests for measuring the picture quality of teleconsultations for medical purposes

Telemedicine provides a new way of delivering medical services. The good quality of the picture is, however, essential for a proper and reliable teleconsultation, especially in the cases when visual information about the patient's physical condition is of great importance as in ophthalmology and dermatology. Therefore real-time telemedical applications need standards for these procedures, e.g. minimum requirements for resolution, as well as contrast and color discrimination. The present study was carried out to test these parameters in a real environment. A panel of different resolution, contrast sensitivity and color discrimination tests was carried out for five test persons via PictureTel videoconference system by ISDN 128 kbit/s line speed and in a normal way. The good color discrimination of the teleconsultation system makes it possible to use the system in the evaluation of different skin lesions and exemas. However, the poor resolution and especially poor contrast sensitivity makes the use of the equipment valueless in the evaluation of diseases where the diagnoses are based on the discrimination of small details, like the biomicroscopical analysis of inflammatory cells in the aqua's humor in cases of intraocular inflammation. The authors are suggesting a simple panel of tests to optimize and standardize these parameters.     

Radio network planning process and methods for WCDMA

This paper describes the system dimensioning and the radio network planning methodology for a third generation wcdma system. The applicability of each method is demonstrated using examples of likely system scenarios. The challenges of modeling the multiservice environment are described and the implications to the system performance simulations are introduced.     

Stability and functionality of freeze-dried probiotic Bifidobacterium cells during storage in juice and milk

We investigated the stability of differently produced (variables being fermentation time, pH during drying, and cryoprotectant) freeze-dried Bifidobacterium animalis subsp. lactis E-2010 (Bb-12) cells in fruit juice and low-fat milk. In addition, the effect of the food matrix on the acid and bile tolerance of the cells was studied. Cells produced in different ways had comparable stability in milk, whereas in juice, sucrose-protected cells survived better than reconstituted skim milk-protected cells. The acid and bile tolerance was better in cells added to milk compared with those in phosphate buffered saline or juice. Despite good culturable stability in milk the acid and bile tolerance of cells decreased during the storage. Apparently, culturable stability data alone do not give an accurate enough prediction of the probiotic functionality in adverse conditions (e.g. survival in acid and bile stress). When choosing a cryoprotectant for a probiotic also the stability in target food applications should be considered.     

Electronic Commerce Internet Strategies and Business Models-A Survey

Today, any doubts about possibilities of significant profits over the Internet are a distant memory. Such has been the proliferation of Internet-based business on the public network. But electronic commerce has turned out to be more difficult to master than previously assumed. For many, ventures have been less lucrative than expected. The problem is that integrating business models with technology is a multifaceted and largely open question (Shaw, et al. 1997). How do businesses of various sizes and industries actually start their Internet activity and how do their business models change over time? More specifically, how do their different Internet strategies play out? This article is the result of a survey of the Internet strategies and business models of 280 companies that sell products and services on the public network. The results show that electronic commerce has penetrated companies of all sizes. Based on this survey it is apparent that while many companies have participated in electronic commerce for years, their business models are still in their infancy stages.     

Detection and decision-support diagnosis of diabetic retinopathy using machine vision

This invited paper considers the results of the IMAGERET project. The goal of the project is to demonstrate how lesions in a retina caused by diabetic retinopathy can be detected from color fundus images by using machine vision methods. The project consists of the following results: an image annotation tool for medical expert annotation, diabetic retinopathy databases, an evaluation framework for development and comparison of methods, image-based and pixel-based methods, and new imaging solutions. The automated diagnosis can be seen in two steps: in the first step, it is decided whether an eye needs further analysis (too many lesions visible) or not (the eye is healthy enough). In the second step, fundus images selected for further analysis are automatically diagnosed. The developed system saves both resources of medical experts and costs in healthcare. It will further offer a tool for the health care providers to improve the quality of the life of diabetes patients. This is important since the number of diabetes patients is increasing, especially rapidly in the developed countries.