The Experts below are selected from a list of 3183 Experts worldwide ranked by ideXlab platform
Markus Keiser - One of the best experts on this subject based on the ideXlab platform.
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the Ussing Chamber assay to study drug metabolism and transport in the human intestine
Current protocols in pharmacology, 2017Co-Authors: Beatrice Kisser, Eva Mangelsen, Caroline Wingolf, Lars Ivo Partecke, Clausdieter Heidecke, Christer Tannergren, Stefan Oswald, Markus KeiserAbstract:The Ussing Chamber is an old but still powerful technique originally designed to study the vectorial transport of ions through frog skin. This technique is also used to investigate the transport of chemical agents through the intestinal barrier as well as drug metabolism in enterocytes, both of which are key determinants for the bioavailability of orally administered drugs. More contemporary model systems, such as Caco-2 cell monolayers or stably transfected cells, are more limited in their use compared to the Ussing Chamber because of differences in expression rates of transporter proteins and/or metabolizing enzymes. While there are limitations to the Ussing Chamber assay, the use of human intestinal tissue remains the best laboratory test for characterizing the transport and metabolism of compounds following oral administration. Detailed in this unit is a step-by-step protocol for preparing human intestinal tissue, for designing Ussing Chamber experiments, and for analyzing and interpreting the findings. © 2017 by John Wiley & Sons, Inc. Keywords: Ussing Chamber; human intestine; in vitro; Papp-value; transporter protein; metabolizing enzymes
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the Ussing Chamber assay to study drug metabolism and transport in the human intestine
Current protocols in pharmacology, 2017Co-Authors: Beatrice Kisser, Eva Mangelsen, Caroline Wingolf, Lars Ivo Partecke, Clausdieter Heidecke, Christer Tannergren, Stefan Oswald, Markus KeiserAbstract:The Ussing Chamber is an old but still powerful technique originally designed to study the vectorial transport of ions through frog skin. This technique is also used to investigate the transport of chemical agents through the intestinal barrier as well as drug metabolism in enterocytes, both of which are key determinants for the bioavailability of orally administered drugs. More contemporary model systems, such as Caco-2 cell monolayers or stably transfected cells, are more limited in their use compared to the Ussing Chamber because of differences in expression rates of transporter proteins and/or metabolizing enzymes. While there are limitations to the Ussing Chamber assay, the use of human intestinal tissue remains the best laboratory test for characterizing the transport and metabolism of compounds following oral administration. Detailed in this unit is a step-by-step protocol for preparing human intestinal tissue, for designing Ussing Chamber experiments, and for analyzing and interpreting the findings. © 2017 by John Wiley & Sons, Inc.
Cynthia K Larive - One of the best experts on this subject based on the ideXlab platform.
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1h nmr based identification of intestinally absorbed metabolites by Ussing Chamber analysis of the rat cecum
Analytical Chemistry, 2018Co-Authors: Meredith M Dinges, Christian Lytle, Cynthia K LariveAbstract:The large intestine (cecum and colon) is a complex biochemical factory of vital importance to human health. It plays a major role in digestion and absorption by salvaging nutrients from polysaccharides via fermentation initiated by the bacteria that comprise the gut microbiome. We hypothesize that the intestinal epithelium absorbs a limited number of luminal metabolites with bioactive potential while actively excluding those with toxic effects. To explore this concept, we combined 1H NMR detection with Ussing Chamber measurements of absorptive transport by rat cecum. Numerous metabolites transported across the epithelium can be measured simultaneously by 1H NMR, a universal detector of organic compounds, alleviating the need for fluorescent or radiolabeled compounds. Our results demonstrate the utility of this approach to delineate the repertoire of fecal solutes that are selectively absorbed by the cecum and to determine their transport rates.
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1H NMR-Based Identification of Intestinally Absorbed Metabolites by Ussing Chamber Analysis of the Rat Cecum
2018Co-Authors: Meredith M Dinges, Christian Lytle, Cynthia K LariveAbstract:The large intestine (cecum and colon) is a complex biochemical factory of vital importance to human health. It plays a major role in digestion and absorption by salvaging nutrients from polysaccharides via fermentation initiated by the bacteria that comprise the gut microbiome. We hypothesize that the intestinal epithelium absorbs a limited number of luminal metabolites with bioactive potential while actively excluding those with toxic effects. To explore this concept, we combined 1H NMR detection with Ussing Chamber measurements of absorptive transport by rat cecum. Numerous metabolites transported across the epithelium can be measured simultaneously by 1H NMR, a universal detector of organic compounds, alleviating the need for fluorescent or radiolabeled compounds. Our results demonstrate the utility of this approach to delineate the repertoire of fecal solutes that are selectively absorbed by the cecum and to determine their transport rates
Saskia N De Wildt - One of the best experts on this subject based on the ideXlab platform.
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p51 a combined experimental approach to assess intestinal drug absorption in early childhood
Archives of Disease in Childhood, 2019Co-Authors: M Kiss, Johan Nicolai, Jjmw Van Den Heuvel, R Mbasu, Sanne M. B. I. Botden, Fgm Russel, Al Ungell, Saskia N De Wildt, Jan B. KoenderinkAbstract:Background Drug transporters and metabolizing enzymes located in the epithelial lining of the intestine limit or enhance systemic drug exposure. During child development, the abundance and activity of these transporters and enzymes - determining how fast and how much of a drug is being absorbed into the circulation - changes from birth to adolescence. As most drugs given to children are taken by mouth, the aim of this project is to study the abundance and activity of transporters and metabolizing enzymes, involved in the intestinal absorption of drugs. Methods The ex vivo Ussing Chamber with pediatric small intestinal tissue is applied to evaluate intestinal drug absorption and metabolism.1 Transport and metabolism of a selection of drug molecules is assessed across these tissues by sampling the donor and receiver compartment at different intervals and sample analysis by LC-MS/MS. Viability, functionality and integrity of the tissues are monitored using electrophysiological parameters (dP, R, I). Ussing Chamber experiments are combined with a targeted proteomics approach to quantify drug transporter and metabolizing enzyme abundance in these tissues. Results An Using Chamber method has been successfully set up using both adult and pediatric intestinal tissue. To date samples from three children of different ages have been evaluated and show promising results. Tissue from the same patients has been stored for proteomics analysis. Conclusion The Ussing method presents an innovative, feasible approach to study active intestinal transport in children. Further studies are now underway to elucidate age-related variation in intestinal transport and metabolism. Reference Sjoberg A, Lutz M, Tannergren C, Wingolf C, Borde A, Ungell AL:Comprehensive study on regional human intestinal permeability and prediction of fraction absorbed of drugs using the Ussing Chamber technique. Eur J Pharm Sci 2013 Jan 23;48(1–2):166–80. Disclosure(s) The collaboration project is financed by the Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships. Johan Nicolai, Richard Mbasu and Anna-Lena Ungell are employees of UCB Biopharma SPRL.
Christer Tannergren - One of the best experts on this subject based on the ideXlab platform.
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the Ussing Chamber assay to study drug metabolism and transport in the human intestine
Current protocols in pharmacology, 2017Co-Authors: Beatrice Kisser, Eva Mangelsen, Caroline Wingolf, Lars Ivo Partecke, Clausdieter Heidecke, Christer Tannergren, Stefan Oswald, Markus KeiserAbstract:The Ussing Chamber is an old but still powerful technique originally designed to study the vectorial transport of ions through frog skin. This technique is also used to investigate the transport of chemical agents through the intestinal barrier as well as drug metabolism in enterocytes, both of which are key determinants for the bioavailability of orally administered drugs. More contemporary model systems, such as Caco-2 cell monolayers or stably transfected cells, are more limited in their use compared to the Ussing Chamber because of differences in expression rates of transporter proteins and/or metabolizing enzymes. While there are limitations to the Ussing Chamber assay, the use of human intestinal tissue remains the best laboratory test for characterizing the transport and metabolism of compounds following oral administration. Detailed in this unit is a step-by-step protocol for preparing human intestinal tissue, for designing Ussing Chamber experiments, and for analyzing and interpreting the findings. © 2017 by John Wiley & Sons, Inc. Keywords: Ussing Chamber; human intestine; in vitro; Papp-value; transporter protein; metabolizing enzymes
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the Ussing Chamber assay to study drug metabolism and transport in the human intestine
Current protocols in pharmacology, 2017Co-Authors: Beatrice Kisser, Eva Mangelsen, Caroline Wingolf, Lars Ivo Partecke, Clausdieter Heidecke, Christer Tannergren, Stefan Oswald, Markus KeiserAbstract:The Ussing Chamber is an old but still powerful technique originally designed to study the vectorial transport of ions through frog skin. This technique is also used to investigate the transport of chemical agents through the intestinal barrier as well as drug metabolism in enterocytes, both of which are key determinants for the bioavailability of orally administered drugs. More contemporary model systems, such as Caco-2 cell monolayers or stably transfected cells, are more limited in their use compared to the Ussing Chamber because of differences in expression rates of transporter proteins and/or metabolizing enzymes. While there are limitations to the Ussing Chamber assay, the use of human intestinal tissue remains the best laboratory test for characterizing the transport and metabolism of compounds following oral administration. Detailed in this unit is a step-by-step protocol for preparing human intestinal tissue, for designing Ussing Chamber experiments, and for analyzing and interpreting the findings. © 2017 by John Wiley & Sons, Inc.
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comprehensive study on regional human intestinal permeability and prediction of fraction absorbed of drugs using the Ussing Chamber technique
European Journal of Pharmaceutical Sciences, 2013Co-Authors: Asa Sjoberg, Caroline Wingolf, Christer Tannergren, Mareike Lutz, Anders Borde, Annalena UngellAbstract:The purpose of this study was to evaluate the use of human intestinal tissue in Ussing Chamber to predict oral and colonic drug absorption and intestinal metabolism. Data on viability, correlation ...
Caroline Wingolf - One of the best experts on this subject based on the ideXlab platform.
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the Ussing Chamber assay to study drug metabolism and transport in the human intestine
Current protocols in pharmacology, 2017Co-Authors: Beatrice Kisser, Eva Mangelsen, Caroline Wingolf, Lars Ivo Partecke, Clausdieter Heidecke, Christer Tannergren, Stefan Oswald, Markus KeiserAbstract:The Ussing Chamber is an old but still powerful technique originally designed to study the vectorial transport of ions through frog skin. This technique is also used to investigate the transport of chemical agents through the intestinal barrier as well as drug metabolism in enterocytes, both of which are key determinants for the bioavailability of orally administered drugs. More contemporary model systems, such as Caco-2 cell monolayers or stably transfected cells, are more limited in their use compared to the Ussing Chamber because of differences in expression rates of transporter proteins and/or metabolizing enzymes. While there are limitations to the Ussing Chamber assay, the use of human intestinal tissue remains the best laboratory test for characterizing the transport and metabolism of compounds following oral administration. Detailed in this unit is a step-by-step protocol for preparing human intestinal tissue, for designing Ussing Chamber experiments, and for analyzing and interpreting the findings. © 2017 by John Wiley & Sons, Inc. Keywords: Ussing Chamber; human intestine; in vitro; Papp-value; transporter protein; metabolizing enzymes
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the Ussing Chamber assay to study drug metabolism and transport in the human intestine
Current protocols in pharmacology, 2017Co-Authors: Beatrice Kisser, Eva Mangelsen, Caroline Wingolf, Lars Ivo Partecke, Clausdieter Heidecke, Christer Tannergren, Stefan Oswald, Markus KeiserAbstract:The Ussing Chamber is an old but still powerful technique originally designed to study the vectorial transport of ions through frog skin. This technique is also used to investigate the transport of chemical agents through the intestinal barrier as well as drug metabolism in enterocytes, both of which are key determinants for the bioavailability of orally administered drugs. More contemporary model systems, such as Caco-2 cell monolayers or stably transfected cells, are more limited in their use compared to the Ussing Chamber because of differences in expression rates of transporter proteins and/or metabolizing enzymes. While there are limitations to the Ussing Chamber assay, the use of human intestinal tissue remains the best laboratory test for characterizing the transport and metabolism of compounds following oral administration. Detailed in this unit is a step-by-step protocol for preparing human intestinal tissue, for designing Ussing Chamber experiments, and for analyzing and interpreting the findings. © 2017 by John Wiley & Sons, Inc.
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comprehensive study on regional human intestinal permeability and prediction of fraction absorbed of drugs using the Ussing Chamber technique
European Journal of Pharmaceutical Sciences, 2013Co-Authors: Asa Sjoberg, Caroline Wingolf, Christer Tannergren, Mareike Lutz, Anders Borde, Annalena UngellAbstract:The purpose of this study was to evaluate the use of human intestinal tissue in Ussing Chamber to predict oral and colonic drug absorption and intestinal metabolism. Data on viability, correlation ...
