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Wambaugh, J.F. (author), Hughes, M.F. (author), Ring, C.L. (author), MacMillan, D.K. (author), Ford, J. (author), Fennell, T.R. (author), Black, S.R. (author), Snyder, R.W. (author), Sipes, N.S. (author), Wetmore, B.A. (author), Westerhout, J. (author), Setzer, R.W. (author), Pearce, R.G. (author), Simmons, J.E. (author), Thomas, R.S. (author)Prioritizing the risk posed by thousands of chemicals potentially present in the environment requires exposure, toxicity, and toxicokinetic (TK) data, which are often unavailable. Relatively high throughput, in vitro TK (HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have been developed to predict TK, but most of the in vivo...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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Vlaming, M.L. (author), van Duijn, E. (author), Dillingh, M.R. (author), Brands, R. (author), Windhorst, A.D. (author), Hendrikse, N.H. (author), Bosgra, S. (author), Burggraaf, J. (author), de Koning, M.C. (author), Fidder, A. (author), Mocking, J.A. (author), Sandman, H. (author), de Ligt, R.A. (author), Fabriek, B.O. (author), Pasman, W.J. (author), Seinen, W. (author), Alves, T. (author), Carrondo, M. (author), Peixoto, C. (author), Peeters, P.A. (author), Vaes, W.H. (author)Preclinical development of new biological entities (NBEs), such as human protein therapeutics, requires considerable expenditure of time and costs. Poor prediction of pharmacokinetics in humans further reduces net efficiency. In this study, we show for the first time that pharmacokinetic data of NBEs in humans can be successfully obtained early...article 2015
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Garner, C.R. (author), Park, K.B. (author), French, N.S. (author), Earnshaw, C. (author), Schipani, A. (author), Selby, A.M. (author), Byrne, L. (author), Siner, S. (author), Crawley, F.P. (author), Vaes, W.H.J. (author), van Duijn, E. (author), de ligt, R. (author), Varendi, H. (author), Lass, J. (author), Grynkiewicz, G. (author), Maruszak, W. (author), Turner, M.A. (author)Aims The aims of the study were to compare [14C]-paracetamol ([14C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0-2 year old age group. Methods [14C]-PARA concentrations in 10-15 μl...article 2015
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Berbeé, J.F.P. (author), Boon, M.R. (author), Khedoe, P.P.S.J. (author), Bartelt, A. (author), Schlein, C. (author), Worthmann, A. (author), Kooijman, S. (author), Hoeke, G. (author), Mol, I.M. (author), John, C. (author), Jung, C. (author), Vazirpanah, N. (author), Brouwers, L.P.J. (author), Gordts, P.L.S.M. (author), Esko, J.D. (author), Hiemstra, P.S. (author), Havekes, L.M. (author), Scheja, L. (author), Heeren, J. (author), Rensen, P.C.N. (author)Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by b3-adrenergic receptor stimulation protects from atherosclerosis...article 2015
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van Mierlo, G.J.D. (author), Cnubben, N.H.P. (author), Wouters, D. (author), Wolbink, G.J. (author), Hart, M.H.L. (author), Rispens, T. (author), Ganderup, N.C. (author), Kuper, C.F. (author), Aarden, L. (author), Penninks, A.H. (author)Immunogenicity is a major issue of concern for monoclonal antibodies used in human diseases and is by default mainly determined in non-human primates (NHP), as target molecules are considered most similar in NHP compared to human. In this manuscript the predictive value of immunogenicity testing in minipigs for human safety is evaluated, as the...article 2014
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Bosgra, S. (author), van de Steeg, E. (author), Vlaming, M.L. (author), Verhoeckx, K.C. (author), Huisman, M.T. (author), Verwei, M. (author), Wortelboer, H.M. (author)In contrast to primary hepatocytes, estimating carrier-mediated hepatic disposition by using a panel of single transfected cell-lines provides direct information on the contribution of the individual transporters to the net disposition. The most direct way to correct for differences in transporter abundance between cell-lines and tissue is by...article 2014
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Kuper, C.F. (author), Gröllers-Mulderij, M. (author), Maarschalkerweerd, T. (author), Meulendijks, N.M.M. (author), Reus, A. (author), van Acker, F. (author), Zondervan-van den Beuken, E.K. (author), Wouters, M.E.L. (author), Bijlsma, S. (author), Kooter, I.M. (author)We investigated the toxicity of aggregated nanoparticles of cerium oxide (CeO2) using an in vitro 3D human bronchial epithelial model that included a mucociliary apparatus (MucilAir™). CeO2 was dispersed in saline and applied to the apical surface of the model. CeO2 did not induce distinct effects in the model, whereas it did in BEAS-2B and A549...article 2014
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Belzer, C. (author), Gerber, G.K. (author), Roeselers, G. (author), Delaney, M. (author), DuBois, A. (author), Liu, Q. (author), Belavusava, V. (author), Yeliseyev, V. (author), Houseman, A. (author), Onderdonk, A. (author), Cavanaugh, C. (author), Bry, L. (author)Longitudinal studies of the microbiota are important for discovering changes in microbial communities that affect the host. The complexity of these ecosystems requires rigorous integrated experimental and computational methods to identify temporal signatures that promote physiologic or pathophysiologic responses in vivo. Employing a murine model...article 2014
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Tan, R.G. (author), de Wit, J.J.M. (author), van Rossum, W.L. (author)The ability to map building structures at a certain stand-off distance allows intelligence, reconnaissance, and clearance tasks to be performed in a covert way by driving around a building. This will greatly improve security, response time, and reliability of aforementioned tasks. Therefore, through-the-wall radar systems supporting stand-off...conference paper 2012
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Vos, P.A.J.M. (author), de Groot, J. (author), Huisman, A.M. (author), Oostveen, J.C.M. (author), Marijnissen, A.C.A. (author), Bijlsma, J.W.J. (author), van El, B. (author), Zuurmond, A.M. (author), Lafeber, F.P.J.G. (author), TNO Kwaliteit van Leven (author)Objectives: Age-related changes in articular cartilage are likely to play a role in the aetiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced-glycation-endproducts (AGEs). Since, cartilage tissue is not readily available from patients for studying AGE levels, alternative approaches...article 2010
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Mariani, B. (author), Hoskovec, C. (author), Rochat, S. (author), Büla, C. (author), Penders, J. (author), Aminian, K. (author), Laboratory of Movement Analysis and Measurements, Ecole Polytechnique Fédérale de Lausanne, -STI-IBI2-LMAM, Station 11/ELH 137, CH-1015 Lausanne, Switzerland Service of Geriatric Medicine, CHUV and CUTR Sylvana, Epalinges, Switzerland Holst Centre/IMEC, High Tech Campus 31, Eindhoven, Netherlands (author)This study describes the validation of a new wearable system for assessment of 3D spatial parameters of gait. The new method is based on the detection of temporal parameters, coupled to optimized fusion and de-drifted integration of inertial signals. Composed of two wirelesses inertial modules attached on feet, the system provides stride length,...article 2010
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TNO Kwaliteit van Leven (author), Berbé, J.F.P. (author), Coomans, C.P. (author), Westerterp, M. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)Timely sensing of lipopolysaccharide (LPS) is critical for the host to fight invading Gram-negative bacteria. We recently showed that apolipoprotein CI (apoCI) (apoCI1-57) avidly binds to LPS, involving an LPS-binding motif (apoCI48-54), and thereby enhances the LPS-induced inflammatory response. Our current aim was to further elucidate the...article 2010
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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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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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- Hu, L. (author), Bovenschen, N. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Tamsma, J.T. (author), TNO Kwaliteit van Leven (author) article 2007
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Huls, M. (author), Kramers, C. (author), Levtchenko, E.N. (author), Wilmer, M.J.G. (author), Dijkman, H.B.P.M. (author), Kluijtmans, L.A.J. (author), van der Hoorn, J.W.A. (author), Russel, F.G.M. (author), Masereeuw, R. (author), TNO Kwaliteit van Leven (author)The multidrug resistance gene 1 product, P-glycoprotein (P-gp), is expressed in several excretory organs, including the apical membrane of proximal tubules. After inducing acute renal failure, P-gp expression is upregulated and this might be a protective function by pumping out toxicants and harmful products of oxidative stress. We characterized...article 2007
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Tenjarla, S. (author), Romasanta, V. (author), Zeijdner, E. (author), Villa, R. (author), Moro, L. (author), TNO Kwaliteit van Leven (author)5-Aminosalicylate (5-ASA; mesalamine) is the current first-line treatment for mild to moderate ulcerative colitis, a chronic inflammatory condition that most commonly affects the distal part of the colon. MMX™ mesalamine (Lialda™ [US]; Mezavant™ XL [UK and Ireland]; Mezavant™ [elsewhere]; Shire Pharmaceuticals Inc., Wayne, Pa, under license from...article 2007
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Cawello, W. (author), Wolff, H.M. (author), Meuling, W.J.A. (author), Horstmann, R. (author), Braun, M. (author), TNO Kwaliteit van Leven (author)Background and objective: The dopamine agonist rotigotine has been formulated in a silicone-based transdermal system for once-daily administration. The objective of the present study was to characterise the mass balance of rotigotine in humans after administration of a single transdermal patch containing radiolabelled [14C]rotigotine and to...article 2007
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- Basketter, D. (author), Pease, C. (author), Kasting, G. (author), Kimber, I. (author), Casati, S. (author), Cronin, M. (author), Diembeck, W. (author), Gerberick, F. (author), Hadgraft, J. (author), Hartung, T. (author), Marty, J.P. (author), Nikolaidis, E. (author), Patlewicz, G. (author), Roberts, D. (author), Roggen, E. (author), Rovida, C. (author), van de Sandt, J. (author), TNO Kwaliteit van Leven (author) article 2007