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relating to the bile ducts or the gallbladder

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〈U〉排泄,排泄作用 / 〈U〉〈C〉排泄物,分泌物

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1. 急性胆管炎 acute cholangitis
2. 胆道閉鎖症 biliary atresia
3. Chapter 11A：腎臓での水排泄 chapter 11a renal hydrogen excretion
4. 総胆管損傷の修復 repair of common bile duct injuries
5. 悪性膵胆管閉塞に対する内視鏡下ステント留置術 endoscopic stenting for malignant pancreaticobiliary obstruction

English Journal

Toxicity and intracellular accumulation of bile acids in sandwich-cultured rat hepatocytes: Role of glycine conjugates.

Chatterjee S1, Bijsmans IT2, van Mil SW3, Augustijns P4, Annaert P5.Author information 1KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, O&N2, Herestraat 49 - Bus 921, 3000 Leuven, Belgium. Electronic address: Sagnik.Chatterjee@pharm.kuleuven.be.2Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: i.bijsmans@umcutrecht.nl.3Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: s.w.c.vanmil@umcutrecht.nl.4KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, O&N2, Herestraat 49 - Bus 921, 3000 Leuven, Belgium. Electronic address: Patrick.Augustijns@pharm.kuleuven.be.5KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, O&N2, Herestraat 49 - Bus 921, 3000 Leuven, Belgium. Electronic address: Pieter.Annaert@pharm.kuleuven.be.AbstractExcessive intrahepatic accumulation of bile acids (BAs) is a key mechanism underlying cholestasis. The aim of this study was to quantitatively explore the relationship between cytotoxicity of BAs and their intracellular accumulation in sandwich-cultured rat hepatocytes (SCRH). Following exposure of SCRH (on day-1 after seeding) to various BAs for 24h, glycine-conjugated BAs were most potent in exerting toxicity. Moreover, unconjugated BAs showed significantly higher toxicity in day-1 compared to day-3 SCRH. When day-1/-3 SCRH were exposed (0.5-4h) to 5-100μM (C)DCA, intracellular levels of unconjugated (C)DCA were similar, while intracellular levels of glycine conjugates were up to 4-fold lower in day-3 compared to day-1 SCRH. Sinusoidal efflux was by far the predominant efflux pathway of conjugated BAs both in day-1 and day-3 SCRH, while canalicular BA efflux showed substantial interbatch variability. After 4h exposure to (C)DCA, intracellular glycine conjugate levels were at least 10-fold higher than taurine conjugate levels. Taken together, reduced BA conjugate formation in day-3 SCRH results in lower intracellular glycine conjugate concentrations, explaining decreased toxicity of (C)DCA in day-3 versus day-1 SCRH. Our data provide for the first time a direct link between BA toxicity and glycine conjugate exposure in SCRH.
Toxicology in vitro : an international journal published in association with BIBRA.Toxicol In Vitro.2014 Mar;28(2):218-30. doi: 10.1016/j.tiv.2013.10.020. Epub 2013 Nov 7.
Excessive intrahepatic accumulation of bile acids (BAs) is a key mechanism underlying cholestasis. The aim of this study was to quantitatively explore the relationship between cytotoxicity of BAs and their intracellular accumulation in sandwich-cultured rat hepatocytes (SCRH). Following exposure of
PMID 24211540

ABCG5/ABCG8 in cholesterol excretion and atherosclerosis.

Yu XH1, Qian K2, Jiang N2, Zheng XL3, Cayabyab FS4, Tang CK5.Author information 1Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.2The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.3Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada.4Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.5Life Science Research Center, University of South China, Hengyang, Hunan 421001, China; Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China. Electronic address: tangchaoke@qq.com.AbstractCholesterol is essential for the growth and function of all mammalian cells, but abnormally increased blood cholesterol is a major risk factor for atherosclerotic cardiovascular disease. ATP-binding cassette (ABC) transporters G5 (ABCG5) and G8 (ABCG8) form an obligate heterodimer that limits intestinal absorption and facilitates biliary secretion of cholesterol and phytosterols. Consistent with their function, ABCG5 and ABCG8 are located on the apical membrane of enterocytes and hepatocytes. Liver X receptor is the major positive regulator of ABCG5 and ABCG8 expression. Mutations in either of the two genes cause sitosterolemia, a condition in which cholesterol and plant sterols accumulate in the circulation leading to premature cardiovascular disease. Overexpression of ABCG5 and ABCG8 in mice retards diet-induced atherosclerosis because of reduced circulating and hepatic cholesterol. In the current review, we summarize recent developments and propose a future framework that provides new perspectives on the regulation of cholesterol metabolism and treatment of atherosclerotic cardiovascular disease.
Clinica chimica acta; international journal of clinical chemistry.Clin Chim Acta.2014 Jan 20;428:82-8. doi: 10.1016/j.cca.2013.11.010. Epub 2013 Nov 16.
Cholesterol is essential for the growth and function of all mammalian cells, but abnormally increased blood cholesterol is a major risk factor for atherosclerotic cardiovascular disease. ATP-binding cassette (ABC) transporters G5 (ABCG5) and G8 (ABCG8) form an obligate heterodimer that limits intest
PMID 24252657

Spheroid culture for enhanced differentiation of human embryonic stem cells to hepatocyte-like cells.

Subramanian K, Owens DJ, Raju R, Firpo M, O'Brien TD, Verfaillie CM, Hu WS.Author information 1 Department of Chemical Engineering and Materials Science, University of Minnesota , Minneapolis, Minnesota.AbstractStem cell-derived hepatocyte-like cells hold great potential for the treatment of liver disease and for drug toxicity screening. The success of these applications hinges on the generation of differentiated cells with high liver specific activities. Many protocols have been developed to guide human embryonic stem cells (hESCs) to differentiate to the hepatic lineage. Here we report cultivation of hESCs as three-dimensional aggregates that enhances their differentiation to hepatocyte-like cells. Differentiation was first carried out in monolayer culture for 20 days. Subsequently cells were allowed to self-aggregate into spheroids. Significantly higher expression of liver-specific transcripts and proteins, including Albumin, phosphoenolpyruvate carboxykinase, and asialoglycoprotein receptor 1 was observed. The differentiated phenotype was sustained for more than 2 weeks in the three-dimensional spheroid culture system, significantly longer than in monolayer culture. Cells in spheroids exhibit morphological and ultrastructural characteristics of primary hepatocytes by scanning and transmission electron microscopy in addition to mature functions, such as biliary excretion of metabolic products and cytochrome P450 activities. This three-dimensional spheroid culture system may be appropriate for generating high quality, functional hepatocyte-like cells from ESCs.
Stem cells and development.Stem Cells Dev.2014 Jan 15;23(2):124-31. doi: 10.1089/scd.2013.0097. Epub 2013 Oct 22.
Stem cell-derived hepatocyte-like cells hold great potential for the treatment of liver disease and for drug toxicity screening. The success of these applications hinges on the generation of differentiated cells with high liver specific activities. Many protocols have been developed to guide human e
PMID 24020366