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Biomedical subjects

Thomas Zielinski

Publications and source records attributed to Thomas Zielinski.

4 recordsLinked to original sources

A simultaneous assessment of CYP3A4 metabolism and induction in the DPX-2 cell line.

The DPX-2 cell line, a derivative of HepG2 cells, harbors human PXR and a luciferase-linked CYP3A4 promoter. These cells were used in a panel of cell-based assays for a parallel assessment of CYP3A4 induction, metabolism, and inhibition at the cellular level. CYP3A4 induction in the DPX-2 cell line by various agents was monitored in 96-well plates by a luciferase-based transcriptional activation assay. Of the prototypical CYP3A4 inducers examined, all exhibited elevated luciferase activity in DPX-2 cells. CYP3A4 enzyme activity in noninduced and rifampicin-induced DPX-2 cells was also assessed using Vivid fluorogenic substrates. Significantly elevated CYP3A4 activity levels (2.8-fold +/- 0.2-fold above DMSO-treated cells) were found in DPX-2 cells after 48 hours of exposure to rifampicin, but were undetectable in parental HepG2 cells. Rifampicin-induced activity levels were found to be suitable for assessing the inhibitory potential of new chemical entities in downstream CYP3A4 inhibition assays. The elevated CYP3A4 activity was inhibited 85% by 10 microM ketoconazole. In addition, a cytotoxicity assay to correct for possible toxic effects of compounds at the cellular level was applied. The comparative data obtained with a combination of the above assays suggests that the application of several independent in vitro technologies used in DPX-2 cells is the best possible strategy for the assessment of the complex phenomena of CYP3A4 induction and inhibition.

Carcinoma, Hepatocellular↗

Star-shaped azo-based dipolar chromophores: design, synthesis, matrix compatibility, and electro-optic activity.

Three new azo-benzene-based push-pull chromophores with dendritic architecture were synthesized as active materials for electro-optic applications. These chromophores were synthesized in six or seven synthetic steps with an overall yield of around 80% per step and high purity. UV-vis spectroscopy showed significant influence of the transient dipole moment on the observed r(33) values. The chromophores were stable to photochemical oxidation in ambient light and air. The electrical poling conditions were optimized for each chromophore as the T(g) of the composite material varied significantly. The highest EO coefficient achieved was 22-25 pm/V at 1550 nm wavelength. STEM analysis of the blends enabled the correlation of the activity of these large chromophores with the blend morphology. An amorphous polycarbonate host effectively disperses the chromophores in 2-20 nm aggregates in the active materials. However, macrophase separation into 200-500 nm aggregates was observed in a methacrylate host matrix.

Journal Article↗

Web-based, virtual course units as a didactic concept for medical teaching.

The objective was to develop a web-based, virtual series of lectures for evidence-based, standardized knowledge transfer independent of location and time with possibilities for interactive participation and a concluding web-based online examination. Within the framework of a research project, specific Intranet and Internet capable course modules were developed together with a concluding examination. The concept of integrating digital and analogue course units supported by sound was based on FlashCam (Nexus Concepts), Flash MX (Macromedia), HTML and JavaScript. A Web server/SGI Indigo Unix server was used as a platform by the course provider. A variety of independent formats (swf, avi, mpeg, DivX, etc.) were integrated in the individual swf modules. An online examination was developed to monitor the learning effect. The examination papers are automatically forwarded by email after completion. The results are also returned to the user automatically after they have been processed by a key program and an evaluation program. The system requirements for the user PC have deliberately been kept low (Internet Explorer 5.0, Flash-Player 6, 56 kbit/s modem, 200 MHz PC). Navigation is intuitive. Users were provided with a technical online introduction and a FAQ list. Eighty-two students of dentistry in their 3rd to 5th years of study completed a questionnaire to assess the course content and the user friendliness (SPSS V11) with grades 1 to 6 (1 = 'excellent' and 6 = 'unsatisfactory'). The course units can be viewed under the URL: http://giga.rrze.uni-erlangen.de/movies/MKG/trailer and URL: http://giga.rrze.uni-erlangen.de/movies/MKG/demo/index. Some 89% of the students gave grades 1 (excellent) and 2 (good) for accessibility independent of time and 83% for access independent of location. Grades 1 and 2 were allocated for an objectivization of the knowledge transfer by 67% of the students and for the use of video sequences for demonstrating surgical techniques by 91% of the students. The course units were used as an optional method of studying by 87% of the students; 76% of the students made use of this facility from home; 83% of the students used Internet Explorer as a browser; 60% used online streaming and 35% downloading as the preferred method for data transfer. The course units contribute to an evidence-based objectivization of multimedia knowledge transfer independent of time and location. Online examinations permit automatic monitoring and evaluation of the learning effect. The modular structure permits easy updating of course contents. Hyperlinks with literature sources facilitate study.

Computer-Assisted Instruction↗