Structure-permeation relations of met-enkephalin peptide analogues on absorption and secretion mechanisms in Caco-2 monolayers

Due to the low effective permeabilities of peptides at many absorption sites, their structure-permeation relations are of high interest. In this work structure-permeation relations of Met-enkephalin analogues are presented using confluent Caco-2 cells as an in vitro permeation model. Four model peptides (Met-enkephalin, [D-Ala2]Met-enkephalin, [D-Ala2]Met-enkephalinamide, and metkephamid) were tested in terms of permeability, lipophilicity, charge, and molecular size. Permeability coefficients (P(eff)) across Caco-2 cells were low, 3.3 x 10(-8) to 9.5 x 10(-8) cm s-1, and were similar to typical paracellular markers. No correlation of permeability and the log(apparent octanol/buffer partition coefficient) was observed. A 40-fold increase of the permeability of metkephamid in the presence of 10 mM EDTA suggested a significant contribution of paracellular transport. Independent support for this conclusion was obtained by visualizing the pathway of the fluorescein isocyanate isomer I 1-metkephamid by confocal laser scanning microscopy (CLSM). The fluorophore-labeled peptide was observed in the intercallular space only. Metkephamid permeabilities were found to be direction-specific. Permeabilities from basolateral to apical (b-to-a) were significantly higher (ca. 4-fold) than in the opposite (a-to-b) direction. The addition of verapamil equalized the permeabilities in the a-to-b and b-to-a directions, suggesting the involvement of a P-glycoprotein-mediated secretion mechanism. Similar observations were obtained with [D-Ala2]Met-enkephalinamide, but not with Met-enkephalin and [D-Ala2]Met-enkephalin. In contrast to the other analogues, metkephamid and [D-Ala2]Met-enkephalinamide are positively charged at neutral pH, as demonstrated by their isoelectric points (pl = 8.6 for [D-Ala2]Met-enkephalinamide and metkephamid and 5.3 for [D-Ala2]Met-enkephalin and Met-enkephalin). The data is in agreement with the literature showing that most compounds secreted by the P-glycoprotein transporter carry a positive charge.     

Vom freiwilligen Seminar zur Q2-Pflichtveranstaltung

Definition of the problem: Ethical reasoning cannot be enforced. Voluntary understanding is a basic condition for the development of ethical competencies and attitudes. The aim of this survey was to investigate whether the presence of those students who attended our seminars compulsorily would have a negative effect upon the quality of the course. Methods and results: The participants of our small-group seminars in medical ethics were asked to complete a questionnaire on teaching aims, seminar atmosphere, moderation and importance of subjects. One hundred and ninety-two voluntary participants (2001/2) and 293 compulsory participants (2002/3) completed the questionnaire and were statistically compared. There was no significant difference between voluntary and compulsory participants in any of the important items. However, there were considerable differences in some items between male and female participants. Conclusion: We were surprised that there was no difference between the two groups. This leads us to hope that our concept of case-based small-group seminars will prove capable of realising our teaching aims for all students. The difference between male and female participants may have important didactic consequences and will be the subject of further studies.     

针对医疗设备的精确电池备份

本文通过测试测量方案介绍了如何进行医疗设备的精确电池备份。     

Modelling biological processes under anaerobic conditions through integrating titrimetric and off-gas measurements-applied to EBPR systems.

An innovative method for modelling biological processes under anaerobic conditions is presented and discussed. The method is based on titrimetric and off-gas measurements. Titrimetric data is recorded as the addition rate of hydroxyl ions or protons that is required to maintain pH in a bioreactor at a constant level. An off-gas analysis arrangement measures, among other things, the transfer rate of carbon dioxide. The integration of these signals results in a continuous signal which is solely related to the biological reactions. When coupled with a mathematical model of the biological reactions, the signal allows a detailed characterisation of these reactions, which would otherwise be difficult to achieve. Two applications of the method to the enhanced biological phosphorus removal processes are presented and discussed to demonstrate the principle and effectiveness of the method.     

Energy management for commercial servers

Servers: high-end, multiprocessor systems running commercial workloads, have typically included extensive cooling systems and resided in custom-built rooms for high-power delivery. Recently, as transistor density and demand for computing resources have rapidly increased, even these high-end systems face energy-use constraints. Commercial-server energy management now focuses on conserving power in the memory and microprocessor subsystems. Because their workloads are typically structured as multiple application programs, system-wide approaches are more applicable to multiprocessor environments in commercial servers than techniques that primarily apply to single-application environments, such as those based on compiler optimizations.