TY - JOUR A1 - Bringmann, Gerhard A1 - Hartung, Thomas A1 - Goebel, Lothar A1 - Schupp, Olaf A1 - Ewers, Christian L. J. A1 - Schoener, Bernd A1 - Zagst, Rainer A1 - Peters, Karl A1 - Von Schnering, Hans Georg A1 - Burschka, Christian T1 - Novel concepts in directed biaryl synthesis, IX: Synthesis and structure of benzonaphthopyranones, useful bridged model precursors for stereoselective biaryl syntheses N2 - A practicable two-step procedure for the preparation of a series of lactone-type bridged biaryls 7 as favorable substrates for subsequent atropisomer-selective ring-opening reactions is described. Due to the efficiency of the coupling step, which tolerates even a telt·butyl group next to the biaryl axis and avoids problems of regioselectivity, a variety of differently substituted representatives is prepared. These cover a broad range of steric hindrance and thus molecular distortion. The structures are investigated mainly by NMR spectroscopy and X-ray diffraction, showing the lactones 7 to be helically distorted, depending on the size of the residues R. KW - Chemie Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-46635 ER - TY - JOUR A1 - Alepee, Natalie A1 - Bahinski, Anthony A1 - Daneshian, Mardas A1 - De Weyer, Bart A1 - Fritsche, Ellen A1 - Goldberg, Alan A1 - Hansmann, Jan A1 - Hartung, Thomas A1 - Haycock, John A1 - Hogberg, Helena T. A1 - Hoelting, Lisa A1 - Kelm, Jens M. A1 - Kadereit, Suzanne A1 - McVey, Emily A1 - Landsiedel, Robert A1 - Leist, Marcel A1 - Lübberstedt, Marc A1 - Noor, Fozia A1 - Pellevoisin, Christian A1 - Petersohn, Dirk A1 - Pfannenbecker, Uwe A1 - Reisinger, Kerstin A1 - Ramirez, Tzutzuy A1 - Rothen-Rutishauser, Barbara A1 - Schäfer-Korting, Monika A1 - Zeilinger, Katrin A1 - Zurich, Marie-Gabriele T1 - State-of-the-Art of 3D Cultures (Organs-on-a-Chip) in Safety Testing and Pathophysiology JF - ALTEX - Alternatives to Animal Experimentation N2 - Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs liver, lung, skin, brain are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing. KW - 3D models KW - organotypic KW - organ-on-a-chip KW - multicellular tumor spheroids KW - primary human hepatocytes KW - embryonic stem cell KW - reconstructed human epidermis KW - in-vitro models KW - full thickness skin KW - necrosis-factor-alpha KW - metabolic flux analysis KW - long-term KW - human liver cells Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117826 VL - 31 IS - 4 ER - TY - JOUR A1 - Gordon, Sarah A1 - Daneshian, Mardas A1 - Bouwstra, Joke A1 - Caloni, Francesca A1 - Constant, Samuel A1 - Davies, Donna E. A1 - Dandekar, Gudrun A1 - Guzman, Carlos A. A1 - Fabian, Eric A1 - Haltner, Eleonore A1 - Hartung, Thomas A1 - Hasiwa, Nina A1 - Hayden, Patrick A1 - Kandarova, Helena A1 - Khare, Sangeeta A1 - Krug, Harald F. A1 - Kneuer, Carsten A1 - Leist, Marcel A1 - Lian, Guoping A1 - Marx, Uwe A1 - Metzger, Marco A1 - Ott, Katharina A1 - Prieto, Pilar A1 - Roberts, Michael S. A1 - Roggen, Erwin L. A1 - Tralau, Tewes A1 - van den Braak, Claudia A1 - Walles, Heike A1 - Lehr, Claus-Michael T1 - Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology JF - ALTEX: Alternatives to Animal Experimentation N2 - Models of the outer epithelia of the human body namely the skin, the intestine and the lung have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report. KW - on-a-chip KW - asthmatic bronchial epithelium KW - vesicle-based barrier KW - pulmonary drug-delivery KW - epithelial cell culture KW - cytotoxicity KW - transport studies KW - permeability KW - in vitro models KW - air-liquid interface KW - respiratory syncytial virus KW - reconstructed human epidermis KW - artificial membrane-permeability KW - embryonic stem cells Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144275 VL - 32 IS - 4 ER -