Searched for: subject:"Bile"
(1 - 20 of 57)

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Notenboom, S. (author), Weigand, K.M. (author), Proost, J.H. (author), van Lipzig, M.M.H. (author), van de Steeg, E. (author), van den Broek, P.H.H. (author), Greupink, R. (author), Russel, F.G.M. (author), Groothuis, G.M.M. (author)
Drug-induced liver injury (DILI) is a common reason for drug withdrawal from the market. An important cause of DILI is drug-induced cholestasis. One of the major players involved in drug-induced cholestasis is the bile salt efflux pump (BSEP; ABCB11). Inhibition of BSEP by drugs potentially leads to cholestasis due to increased (toxic)...
article 2018
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van Groen, B.D. (author), van de Steeg, E. (author), Mooij, M.G. (author), van Lipzig, M.M.H. (author), de Koning, B.A.E. (author), Verdijk, R.M. (author), Wortelboer, H.M. (author), Gaedigk, R. (author), Bi, C. (author), Leeder, S. (author), van Schaik, R.H.N. (author), van Rosmalen, J. (author), Tibboel, D. (author), Vaes, W.H. (author), de Wildt, S.N. (author)
Background Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples. Methods Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3,...
article 2018
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Fiamoncini, J. (author), Yiorkas, A.M. (author), Gedrich, K. (author), Rundle, M. (author), Alsters, S.I. (author), Roeselers, G. (author), van den Broek, T.J. (author), Clavel, T. (author), Lagkouvardos, I. (author), Wopereis, S. (author), Frost, G. (author), van Ommen, B. (author), Blakemore, A.I. (author), Daniel, H. (author)
Bile acids (BA) are signaling molecules with a wide range of biological effects, also identified among the most responsive plasma metabolites in the postprandial state. We here describe this response to different dietary challenges and report on key determinants linked to its interindividual variability. Healthy men and women (n = 72, 62 ± 8 yr,...
article 2017
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Kühnast, S. (author), van der Hoorn, J.W.A. (author), Pieterman, E.J. (author), van den Hoek, A.M. (author), Sasiela, W.J. (author), Gusarova, V. (author), Peyman, A. (author), Schäfer, H.L. (author), Schwahn, U. (author), Jukema, J.W. (author), Princen, H.M.G. (author)
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a potential novel strategy for treatment of CVD. Alirocumab is a fully human PCSK9 monoclonal antibody in phase 3 clinical development. We evaluated the antiatherogenic potential of alirocumab in APOE∗3Leiden. CETP mice. Mice received a Western-type diet and were treated with...
article 2014
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Kostewicz, E.S. (author), Abrahamsson, B. (author), Brewster, M. (author), Brouwers, J. (author), Butler, J. (author), Carlert, S. (author), Dickinson, P.A. (author), Dressman, J. (author), Holm, R. (author), Klein, S. (author), Mann, J. (author), McAllister, M. (author), Minekus, M. (author), Muenster, U. (author), Müllertz, A. (author), Verwei, M. (author), Vertzoni, M. (author), Weitschies, W. (author), Augustijns, P. (author)
Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection with in vivo biopharmaceutical performance has...
article 2014
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Gozalpour, E. (author), Greupink, R. (author), Wortelboer, H.M. (author), Bilos, A. (author), Schreurs, M. (author), Russel, F.G.M. (author), Koenderink, J.B. (author)
Digitalis-like compounds (DLCs) such as digoxin, digitoxin, and ouabain, also known as cardiac glycosides, are among the oldest pharmacological treatments for heart failure. The compounds have a narrow therapeutic window, while at the same time, DLC pharmacokinetics is prone to drug-drug interactions at the transport level. Hepatic transporters...
article 2014
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Sugimoto-Kawabata, K. (author), Shimada, H. (author), Sakai, K. (author), Suzuki, K. (author), Kelder, T. (author), Pieterman, E.J. (author), Cohen, L.H. (author), Havekes, L.M. (author), Princen, H.M. (author), van den Hoek, A.M. (author)
Bile acid sequestrants (BASs) are cholesterollowering drugs that also affect hyperglycemia. The mechanism by which BASs exert these and other metabolic effects beyond cholesterol lowering remains poorly understood. The present study aimed to investigate the effects of a BAS, colestilan, on body weight, energy expenditure, and glucose and lipid...
article 2013
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Vrins, C.L. (author), Ottenhoff, R. (author), van den Oever, K. (author), de Waart, D.R. (author), Kruyt, J.K. (author), Zhao, Y. (author), van Berkel, T.J. (author), Havekes, L.M. (author), Aerts, J.M. (author), van Eck, M. (author), Rensen, P.C. (author), Groen, A.K. (author)
Transintestinal cholesterol efflux (TICE) provides an attractive target to increase body cholesterol excretion. At present, the cholesterol donor responsible for direct delivery of plasma cholesterol to the intestine is unknown. In this study, we investigated the role of HDL in TICE. ATP-binding cassette protein A1 deficient (Abca1(-/-)) mice...
article 2012
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Abrahamse, E. (author), Minekus, M. (author), van Aken, G.A. (author), van de Heijning, B. (author), Knol, J. (author), Bartke, N. (author), Oozeer, R. (author), van der Beek, E.M. (author), Ludwig, T. (author)
At least during the first 6 months after birth, the nutrition of infants should ideally consist of human milk which provides 40-60 % of energy from lipids. Beyond energy, human milk also delivers lipids with a specific functionality, such as essential fatty acids (FA), phospholipids, and cholesterol. Healthy development, especially of the...
article 2012
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Treijtel, N. (author), Eijkeren, J.C.H.v. (author), Nijmeijer, S. (author), van der Greef de - Sandt, I.C.J. (author), Freidig, A.P. (author), TNO Kwaliteit van Leven (author)
The metabolism and active transport of ritonavir and saquinavir were studied using sandwich-cultured rat hepatoyctes and rat liver microsomes. For ritonavir four comparable metabolites were observed in the sandwich-culture and in microsomes. For saquinavir eight metabolites were observed in sandwich-culture and 14 different metabolites in...
article 2009
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Bobeldijk, I. (author), Hekman, M. (author), van der Vries de- Weij, J. (author), Coulier, L. (author), Ramaker, R. (author), Kleemann, R. (author), Kooistra, T. (author), Rubingh, C. (author), Freidig, A. (author), Verheij, E. (author), TNO Kwaliteit van Leven (author)
We report a sensitive, generic method for quantitative profiling of bile acids and other endogenous metabolites in small quantities of various biological fluids and tissues. The method is based on a straightforward sample preparation, separation by reversed-phase high performance liquid-chromatography mass spectrometry (HPLC-MS) and electrospray...
article 2008
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van der Hoorn, J.W.A. (author), de Haan, W. (author), Berbée, J.P.P. (author), Havekes, L.M. (author), Jukema, J.W. (author), Rensen, P.C. (author), Princen, H.M.G. (author), TNO Kwaliteit van Leven (author)
Objective - Niacin potently decreases plasma triglycerides and LDL-cholesterol. In addition, niacin is the most potent HDL-cholesterol- increasing drug used in the clinic. In the present study, we aimed at elucidation of the mechanism underlying its HDL-raising effect. Methods and Results - InAPOE*3Leiden transgenic mice expressing the human...
article 2008
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Gautier, T. (author), Tietge, U.J.F. (author), Boverhof, R. (author), Perton, F.G. (author), Le Guern, N. (author), Masson, D. (author), Rensen, P.C.N. (author), Havekes, L.M. (author), Lagrost, L. (author), Kuipers, F. (author), TNO Kwaliteit van Leven (author)
The impact of apolipoprotein C-I (apoC-I) deficiency on hepatic lipid metabolism was addressed in mice in the presence or the absence of cholesteryl ester transfer protein (CETP). In addition to the expected moderate reduction in plasma cholesterol levels, apoCIKO mice showed significant increases in the hepatic content of cholesteryl esters (...
article 2007
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Kitayama, K. (author), Nakai, D. (author), Kono, K. (author), van der Hoop, A.G. (author), Kurata, H. (author), de Wit, E.C. (author), Cohen, L.H. (author), Inaba, T. (author), Kohama, T. (author), TNO Preventie en Gezondheid (author)
1-{7-[(1-(3,5-Diethoxyphenyl)-3-{[(3,5-difluorophenyl)(ethyl)amino]carbo nyl}-4-oxo-1,4-dihydroquinolin-7-yl)oxy]heptyl}-1-methylpiperidinium bromide, R-146224, is a potent, specific ileum apical sodium-dependent bile acid transporter (ASBT) inhibitor; concentrations required for 50% inhibition of [3H]taurocholate uptake in human ASBT-expressing...
article 2006
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Post, S.M. (author), Groenendijk, M. (author), van der Hoogt, C.C. (author), Fievet, C. (author), Luc, G. (author), Hoekstra, M. (author), Princen, H.M.G. (author), Staels, B. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
OBJECTIVE - High-density lipoprotein (HDL) plays a key role in protection against development of atherosclerosis by reducing inflammation, protecting against LDL oxidation, and promoting reverse cholesterol transport from peripheral tissues to the liver for secretion into bile. Cholesterol 7α-hydroxylase (Cyp7a1) catalyzes the rate-limiting step...
article 2006
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Delsing, D.J.M. (author), Post, S.M. (author), Groenendijk, M. (author), Solaas, K. (author), van der Boom, H. (author), van Duyvenvoorde, W. (author), de Wit, E.C.M. (author), Bloks, V.W. (author), Kuipers, F. (author), Havekes, L.M. (author), Princen, H.M.G. (author), TNO Kwaliteit van Leven (author)
The present study was designed to investigate the lipid-lowering properties and mechanisms of action of a new HMG-CoA reductase inhibitor, rosuvastatin, in female ApoE*3-Leiden transgenic mice. Mice received a high fat/cholesterol (HFC) diet containing either rosuvastatin (O [control], 0.00125%, 0.0025%, or 0.005% [w/w]) or 0.05% (w/w)...
article 2005
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Hulzebos, C.V. (author), Voshol, P.J. (author), Wolters, H. (author), Kruit, J.K. (author), Ottenhof, R. (author), Groen, A.K. (author), Stellaard, F. (author), Verkade, H.J. (author), Kuipers, F. (author), TNO Preventie en Gezondheid (author)
Background/Aims: Bile flow consists of bile salt-dependent bile flow (BSDF), generated by canalicular secretion of bile salts, and bile salt-independent flow (BSIF), probably of combined canalicular and ductular origin. Bile salt transport proteins have been identified in cholangiocytes, suggesting a role in control of BSDF and/or in control of...
article 2005
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Minekus, M. (author), Jelier, M. (author), Xiao, J.-Z. (author), Kondo, S. (author), Iwatsuki, K. (author), Kokubo, S. (author), Bos, M. (author), Dunnewind, B. (author), Havenaar, R. (author), TNO Kwaliteit van Leven (author)
The Addition of a compound that lowers the intestinal uptake of fat and cholesterol might be an interesting strategy to reduce the risk of vascular disease. Partially hydrolyzed guar gum (PHGG) has been shown to have this effect in healthy volunteers after intake of a yogurt drink with 3 to 6% PHGG. In the present study a yogurt drink with 3%...
article 2005
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Blanquet, S. (author), Zeijdner, E. (author), Beyssac, E. (author), Meunier, J.-P. (author), Denis, S. (author), Havenaar, R. (author), Alric, M. (author), TNO Voeding (author)
Purpose. The purpose of this study was to demonstrate the potential of a dynamic, multicompartmental in vitro system simulating the human stomach and small intestine (TIM-1) for studying the behavior of oral drug dosage forms under various physiological gastrointestinal conditions. Methods. Two model drug compounds were studied in TIM-1: a...
article 2004
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Post, S.M. (author), Groenendijk, M. (author), Solaas, K. (author), Rensen, P.C.N. (author), Princen, H.M.G. (author), TNO Preventie en Gezondheid (author)
Objective-Cholesterol 7α-hydroxylase (cyp7a1) catalyzes the rate-limiting step in conversion of cholesterol to bile acids. To study the relationship between bile acid biosynthesis and triglyceride metabolism, we cross-bred mice lacking cyp7a1 on a hyperlipidemic APOE*3-Leiden background. Methods and Results-Female mice received a chow or...
article 2004
Searched for: subject:"Bile"
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