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• W1982583749 abstract "Primary hepatocytes represent a well-accepted in vitro cell culture system for studies of drug metabolism, enzyme induction, transplantation, viral hepatitis, and hepatocyte regeneration. Recently, a multicentric research program has been initiated to optimize and standardize new in vitro systems with hepatocytes. In this article, we discuss five of these in vitro systems: hepatocytes in suspension, perifusion culture systems, liver slices, co-culture systems of hepatocytes with intestinal bacteria, and 96-well plate bioreactors. From a technical point of view, freshly isolated or cryopreserved hepatocytes in suspension represent a readily available and easy-to-handle in vitro system that can be used to characterize the metabolism of test substances. Hepatocytes in suspension correctly predict interspecies differences in drug metabolism, which is demonstrated with pantoprazole and propafenone. A limitation of the hepatocyte suspensions is the length of the incubation period, which should not exceed 4hr. This incubation period is sufficiently long to determine the metabolic stability and to allow identification of the main metabolites of a test substance, but may be too short to allow generation of some minor, particularly phase II metabolites, that contribute less than 3% to total metabolism. To achieve longer incubation periods, hepatocyte culture systems or bioreactors are used. In this research program, two bioreactor systems have been optimized: the perifusion culture system and 96-well plate bioreactors. The perifusion culture system consists of collagen-coated slides allowing the continuous superfusion of a hepatocyte monolayer with culture medium as well as establishment of a constant atmosphere of 13% oxygen, 82% nitrogen, and 5% CO2. This system is stable for at least 2 weeks and guarantees a remarkable sensitivity to enzyme induction, even if weak inducers are tested. A particular advantage of this systemis that the same bioreactor can be perfused with different concentrations of a test substance in a sequential manner. The 96-well plate bioreactor runs 96 modules in parallel for pharmacokinetic testing under aerobic culture conditions. This system combines the advantages of a three-dimensional culture system in collagen gel, controlled oxygen supply, and constant culture medium conditions, with the possibility of high throughput and automatization. A newly developed co-culture system of hepatocytes with intestinal bacteria offers the possibility to study the metabolic interaction between liver and intestinal microflora. It consists of two chambers separated by a permeable polycarbonate membrane, where hepatocytes are cultured under aerobic and intestinal bacteria in anaerobic conditions. Test substances are added to the aerobic side to allow their initial metabolism by the hepatocytes, followed by the metabolism by intestinal bacteria at the anaerobic side. Precision-cut slices represent an alternative to isolated hepatocytes and have been used fo the investigation of hepatic metabolism, hepatotoxicity, and enzyme induction. A specific advantage of liver slices is the possibility to study toxic effects on hepatocytes that are mediated or modified by nonparenchymal cells (e.g., by cytokine release from Kupffer cells) because the physiological liver microarchitecture is maintained in cultured slices. For all these in vitro systems, a prevalidation has been performed using standard assays for phase I and II enzymes. Representative results with test substances and recommendations for application of these in vitro systems, as well as standard operation procedures are given." @default.
• W1982583749 created "2016-06-24" @default.
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• W1982583749 date "2003-01-01" @default.
• W1982583749 modified "2023-10-06" @default.
• W1982583749 title "New Hepatocyte In Vitro Systems for Drug Metabolism: Metabolic Capacity and Recommendations for Application in Basic Research and Drug Development, Standard Operation Procedures" @default.
• W1982583749 cites W100421642 @default.
• W1982583749 cites W113982714 @default.
• W1982583749 cites W1465738810 @default.
• W1982583749 cites W1490154674 @default.
• W1982583749 cites W1536923222 @default.
• W1982583749 cites W1633747844 @default.
• W1982583749 cites W1669026407 @default.
• W1982583749 cites W1812719615 @default.
• W1982583749 cites W18695919 @default.
• W1982583749 cites W1964170811 @default.
• W1982583749 cites W1966321578 @default.
• W1982583749 cites W1970009464 @default.
• W1982583749 cites W1970054537 @default.
• W1982583749 cites W1972179251 @default.
• W1982583749 cites W1975273361 @default.
• W1982583749 cites W1977404096 @default.
• W1982583749 cites W1983365935 @default.
• W1982583749 cites W1987252526 @default.
• W1982583749 cites W1990348225 @default.
• W1982583749 cites W1990498836 @default.
• W1982583749 cites W1990771351 @default.
• W1982583749 cites W1995913886 @default.
• W1982583749 cites W1996334061 @default.
• W1982583749 cites W1999012118 @default.
• W1982583749 cites W2001511546 @default.
• W1982583749 cites W2001569101 @default.
• W1982583749 cites W2003672755 @default.
• W1982583749 cites W2005356916 @default.
• W1982583749 cites W2005358947 @default.
• W1982583749 cites W2011233017 @default.
• W1982583749 cites W2013906085 @default.
• W1982583749 cites W2014884144 @default.
• W1982583749 cites W2014902441 @default.
• W1982583749 cites W2018278633 @default.
• W1982583749 cites W2018969311 @default.
• W1982583749 cites W2022900528 @default.
• W1982583749 cites W2023430796 @default.
• W1982583749 cites W2025424238 @default.
• W1982583749 cites W2026032930 @default.
• W1982583749 cites W2028706407 @default.
• W1982583749 cites W2031073731 @default.
• W1982583749 cites W2032712232 @default.
• W1982583749 cites W2035054866 @default.
• W1982583749 cites W2037914995 @default.
• W1982583749 cites W2038673852 @default.
• W1982583749 cites W2039248750 @default.
• W1982583749 cites W2040162622 @default.
• W1982583749 cites W2044695596 @default.
• W1982583749 cites W2047121384 @default.
• W1982583749 cites W2047759690 @default.
• W1982583749 cites W2051608380 @default.
• W1982583749 cites W2052428509 @default.
• W1982583749 cites W2053077754 @default.
• W1982583749 cites W2053465821 @default.
• W1982583749 cites W2053886810 @default.
• W1982583749 cites W2066439022 @default.
• W1982583749 cites W2069071894 @default.
• W1982583749 cites W2070065330 @default.
• W1982583749 cites W2071566492 @default.
• W1982583749 cites W2072482644 @default.
• W1982583749 cites W2075284857 @default.
• W1982583749 cites W2076156119 @default.
• W1982583749 cites W2076352568 @default.
• W1982583749 cites W2076719315 @default.
• W1982583749 cites W2079943481 @default.
• W1982583749 cites W2080482503 @default.
• W1982583749 cites W2083395260 @default.
• W1982583749 cites W2086632136 @default.
• W1982583749 cites W2087267562 @default.
• W1982583749 cites W2089231631 @default.
• W1982583749 cites W2089520258 @default.
• W1982583749 cites W2092308274 @default.
• W1982583749 cites W2099867777 @default.
• W1982583749 cites W2100288900 @default.
• W1982583749 cites W2100305360 @default.

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