http://www.cnr.it/ontology/cnr/individuo/prodotto/ID179940
High level benzodiazepine and ammonia clearance by flat membrane bioreactors with porcine liver cells (Articolo in rivista)
- Type
- Label
- High level benzodiazepine and ammonia clearance by flat membrane bioreactors with porcine liver cells (Articolo in rivista) (literal)
- Anno
- 2000-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1016/S0168-1656(00)00233-9 (literal)
- Alternative label
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Augustinus Bader, Loredana De Bartolo, Axel Haverich (literal)
- Pagina inizio
- Pagina fine
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- Rivista
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- Note
- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Leibniz Institute for Biotechnology and Artificial Organs, Di6ision of Thoracic and Cardio. Surgery,
Medizinische Hochschule Hanno6er, Podbielskistr. 380, D-30659 Hanno6er, Germany
National Research Institute for Biotechnology (GBF), Mascheroder Weg 1B, D-38124 Braunschweig, Germany
Research Institute on Membranes and Modelling of Chemical Reactors, IRMERC-CNR, c:o Uni6ersity of Calabria, cubo 17 :C,
Rende (CS), Italy (literal)
- Titolo
- High level benzodiazepine and ammonia clearance by flat membrane bioreactors with porcine liver cells (literal)
- Abstract
- The onset of hepatic encephalopathy is a multifactorial process in which endogenous benzodiazepines and
hyperammonemia play a pivotal role. The treatment of comatose states in liver failure is one of the major functions
of a bioartificial liver. A controlled study demonstrating the capacity of a large scale bioartificial liver to detoxify
benzodiazepines could be a crucial prerequisite to break this circle of events leading to coma. The aim of this study
was therefore to expose the bioreactor to high levels of benzodiazepines and ammonia for evaluation of its detoxifying
capacity. We have developed a novel and unique device reconstructing the plate architecture of the liver. Porcine
hepatocytes were co-cultured with non-parenchymal cells. We investigated benzodiazepine metabolism using diazepam
as model drug. The bioreactor was also loaded with high levels of ammonia and ammonia clearance as well
as urea secretion with ammonia challenge were investigated. Albumin secretion was analysed in parallel as a control
viability and tissue specific secretory parameter. The results clearly show that the velocity of diazepam turnover
increases between day 1 and 2 and stabilises at high levels. Typical diazepam metabolites including temazepam,
N-desmethyl-diazepam and oxazepam were generated. Cell specific functions, including albumin secretion, were
comparable to an in vivo liver. We conclude that the flat membrane bioreactor used as bioartificial liver has the
potential to detoxify diazepam and ammonia at significant amounts. Maintenance of monoxygenase activities in vitro
is one of the strongholds of the bioreactor concept presented in this study. © 2000 Elsevier Science B.V. All rights
reserved. (literal)
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