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Rijken, D.C. (author), Hoegee-de Nobel, E. (author), Jie, A.F.H. (author), Atsma, D.E. (author), Schalij, M.J. (author), Nieuwenhuizen, W. (author), TNO Kwaliteit van Leven (author)Background: The development of global tests for the fibrinolytic capacity in blood is hampered by the low base-line fibrinolytic activity in blood, by the involvement of both plasmatic components and blood cells in the fibrinolytic system and by the loss of fibrinolytic activity as a result of the action of plasminogen activator inhibitor-1 (PAI...article 2008
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Schutte, M.E. (author), Alink, G.M. (author), Freidig, A.P. (author), Spenkelink, B. (author), Vaessen, J.C.H. (author), van de Sandt, J.J.M. (author), Groten, J.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author), KvL (author)This study investigates whether the previous observation that quercetin increases the transport of PhIP through Caco-2 monolayers in vitro could be confirmed in an in vivo rat model. Co-administration of 1.45 μmol PhIP/kg bw and 30 μmol quercetin/kg bw significantly increased the blood AUC(0-8 h) of PhIP in rats to 131 ± 14% of the AUC(0-8 h)...article 2008
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Vinken, M. (author), Doktorova, T. (author), Ellinger-Ziegelbauer, H. (author), Ahr, H.-J. (author), Lock, E. (author), Carmichael, P. (author), Roggen, E. (author), van Delft, J. (author), Kleinjans, J. (author), Castell, J. (author), Bort, R. (author), Donato, T. (author), Ryan, M. (author), Corvi, R. (author), Keun, H. (author), Ebbels, T. (author), Athersuch, T. (author), Sansone, S.-A. (author), Rocca-Serra, P. (author), Stierum, R. (author), Jennings, P. (author), Pfaller, W. (author), Gmuender, H. (author), Vanhaecke, T. (author), Rogiers, V. (author), TNO Kwaliteit van Leven (author)Recent changes in the European legislation of chemical-related substances have forced the scientific community to speed up the search for alternative methods that could partly or fully replace animal experimentation. The Sixth Framework Program project carcinoGENOMICS was specifically raised to develop omics-based in vitro screens for testing...article 2008
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Dijkstra, S. (author), Kooij, G. (author), Verbeek, R. (author), van der Pol, S.M.A. (author), Amor, S. (author), Geisert Jr., E.E. (author), Dijkstra, C.D. (author), van Noort, J.M. (author), Vries, H.E.D. (author), TNO Kwaliteit van Leven (author)Leukocyte infiltration is a key step in the development of demyelinating lesions in multiple sclerosis (MS), and molecules mediating leukocyte-endothelial interactions represent prime candidates for the development of therapeutic strategies. Here we studied the effects of blocking the integrin-associated tetraspanin CD81 in in vitro and in vivo...article 2008
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Punt, A. (author), Freidig, A.P. (author), Delatour, T. (author), Scholz, G. (author), Boersma, M.G. (author), Schilter, B. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)The present study defines a physiologically based biokinetic (PBBK) model for the alkenylbenzene estragole in rat based on in vitro metabolic parameters determined using relevant tissue fractions, in silico derived partition coefficients, and physiological parameters derived from the literature. The model consists of eight compartments including...article 2008
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Sier, C.F.M. (author), Hawinkels, L.J.A.C. (author), Zijlmans, H.J.M.A.A. (author), Zuidwijk, K. (author), Muller, E.S.M. (author), Ferreira, V. (author), Hanemaaijer, R. (author), Mulder-Stapel, A.A. (author), Kenter, G.G. (author), Verspaget, H.W. (author), Gorter, A. (author), TNO Kwaliteit van Leven (author)Over-expression of matrilysin (MMP-7) is predominantly associated with epithelial (pre)malignant cells. In the present study MMP-7 expression is also found in endothelial cells in various human cancer types. Endothelial MMP-7 was associated with CD34 and/or CD105 expression. These immunohistochemical data were confirmed by RT-PCR on VEGF...article 2008
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Kel, J.M. (author), de Geus, E.D. (author), van Stipdonk, M.J. (author), Drijfhout, J.W. (author), Koning, F. (author), Nagelkerken, L. (author), TNO Kwaliteit van Leven (author)In this study, we investigated the development of T cell responses in mice after administration of a mannosylated ovalbumin peptide (M-OVA323-339). Immunization with M-OVA323-339 in complete adjuvant resulted in enhanced antigen presentation in draining lymph nodes. Monitoring the fate of CFSE-labeled ovalbumin peptide-specific TCR transgenic...article 2008
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Santos, A.F. (author), Zaltsman, A.B. (author), Martin, R.C. (author), Kuzmin, A. (author), Alexandrov, Y. (author), Roquemore, E.P. (author), Jessop, R.A. (author), Erck, M.G.M.V. (author), Verheijen, J.H. (author), TNO Kwaliteit van Leven (author)Angiogenesis is a general term describing formation of new tube-like microvessel sprouts that are the size of capillary blood vessels. Angiogenesis is fundamental in key stages of embryonic development, organ formation, and wound repair and is also involved in the development and progression of a variety of pathological conditions, including...article 2008
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TNO Kwaliteit van Leven (author), Hu, L. (author), van der Hoogt, C.C. (author), Espirito Santo, S.M.S. (author), Out, R. (author), Kypreos, K.E. (author), van Vlijmen, B.J.M. (author), van Berkel, T.J.C. (author), Romijn, J.A. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author)LPL activity plays an important role in preceding the VLDL remnant clearance via the three major apolipoprotein E (apoE)-recognizing receptors: the LDL receptor (LDLr), LDL receptor-related protein (LRP), and VLDL receptor (VLDLr). The aim of this study was to determine whether LPL activity is also important for VLDL remnant clearance...article 2008
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TNO Kwaliteit van Leven (author), Hoogendoorn, R.J.W. (author), Lu, Z.F. (author), Kroeze, R.J. (author), Bank, R.A. (author), Wuisman, P.I. (author), Helder, M.N. (author)Introduction Degenerative disc disease and emerging biological treatment approaches Stem cell sources Integration of ASC-based regenerative medicine and surgery In vitro studies Animal models Cells in disc regeneration in vivo In vivo studies Perspective Conclusions Abstract New regenerative treatment strategies are being developed for...article 2008
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TNO Kwaliteit van Leven (author), Pasman, W.J. (author), Heimerikx, J. (author), Rubingh, C.M. (author), van den Berg, R. (author), O'Shea, M. (author), Gambelli, L. (author), Hendriks, H.F.J. (author), Einerhand, A.W.C. (author), Scott, C. (author), Keizer, H.G. (author), Mennen, L.I. (author)Appetite suppressants may be one strategy in the fight against obesity. This study evaluated whether Korean pine nut free fatty acids (FFA) and triglycerides (TG) work as an appetite suppressant. Korean pine nut FFA were evaluated in STC-1 cell culture for their ability to increase cholecystokinin (CCK-8) secretion vs. several other dietary...article 2008
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TNO Kwaliteit van Leven (author), Madsen, L. (author), Pedersen, L.M. (author), Liaset, B. (author), Ma, T. (author), Petersen, R.K. (author), van den Berg, S. (author), Pan, J. (author), Müller-Decker, K.M. (author), Dülsner, E.D. (author), Kleemann, R. (author), Kooistra, T. (author), Døskeland, S.O. (author), Kristiansen, K. (author)The effect of n-6 polyunsaturated fatty acids (n-6 PUFAs) on adipogenesis and obesity is controversial. Using in vitro cell culture models, we show that n-6 PUFAs was pro-adipogenic under conditions with base-line levels of cAMP, but anti-adipogenic when the levels of cAMP were elevated. The anti-adipogenic action of n-6 PUFAs was dependent on a...article 2008
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Hissink, A.M. (author), Krüse, J. (author), Kulig, B.M. (author), Verwei, M. (author), Muijser, H. (author), Salmon, F. (author), Leenheers, L.H. (author), Owen, D.E. (author), Lammers, J.H.C.M. (author), Freidig, A.P. (author), McKee, R.H. (author), TNO Kwaliteit van Leven (author)As part of a project designed to develop a framework for extrapolating acute central nervous system (CNS) effects of hydrocarbon solvents in animals to humans, experimental studies were conducted in rats and human volunteers in which acute CNS effects were measured and toxicokinetic data were collected. A complex hydrocarbon solvent, white...article 2007
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Gibbs, S. (author), van de Sandt, J.J.M. (author), Merk, H.F. (author), Lockley, D.J. (author), Pendlington, R.U. (author), Pease, C.K. (author), TNO Kwaliteit van Leven (author)In this review, we discuss and compare studies of xenobiotic metabolism in both human skin and 3D human skin reconstructs. In comparison to the liver, the skin is a less studied organ in terms of characterising metabolic capability. While the skin forms the major protective barrier to environmental chemical exposure, it is also a potential...article 2007
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Halter, D. (author), Neumann, S. (author), van Dijk, S.M. (author), Wolthoorn, J. (author), de Mazière, A.M. (author), Vieira, O.V. (author), Mattjus, P. (author), Klumperman, J. (author), van Meer, G. (author), Sprong, H. (author), TNO Kwaliteit van Leven (author)Glycosphingolipids are controlled by the spatial organization of their metabolism and by transport specificity. Using immunoelectron microscopy, we localize to the Golgi stack the glycosyltransferases that produce glucosylceramide (GlcCer), lactosylceramide (LacCer), and GM3. GlcCer is synthesized on the cytosolic side and must translocate...article 2007
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van de Wiele, T.R. (author), Oomen, A.G. (author), Wragg, J. (author), Cave, M. (author), Minekus, M. (author), Hack, A. (author), Cornelis, C. (author), Rompelberg, C.J.M. (author), de Zwart, L.L. (author), Klinck, B. (author), van Wijnen, J. (author), Verstraete, W. (author), Sips, A.J.A.M. (author), TNO Kwaliteit van Leven (author)This paper presents a multi-laboratory comparison study of in vitro models assessing bioaccessibility of soil-bound lead in the human gastrointestinal tract under simulated fasted and fed conditions. Oral bioavailability data from a previous human in vivo study on the same soil served as a reference point. In general, the bioaccessible lead...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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Zafranskaya, M. (author), Oschmann, P. (author), Engel, R. (author), Weishaupt, A. (author), van Noort, J.M. (author), Jomaa, H. (author), Eberl, M. (author), TNO Kwaliteit van Leven (author)Therapy with interferon-β (IFN-β) has well-established clinical effects in multiple sclerosis (MS), albeit the immunomodulatory mechanisms are not fully understood. We assessed the prevalence and functional capacity of CD4+ and CD8+ T cells in healthy donors, and in untreated and IFN-β-treated MS patients, in response to myelin oligodendrocyte...article 2007
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Freidig, A.P. (author), Dekkers, S. (author), Verwei, M. (author), Zvinavashe, E. (author), Bessems, J.G.M. (author), van de Sandt, J.J.M. (author), TNO Kwaliteit van Leven (author)Future EU legislations enforce a fast hazard and risk assessment of thousands of existing chemicals. If conducted by means of present data requirements, this assessment will use a huge number of test animals and will be neither cost nor time effective. The purpose of the current research was to develop methods to increase the acceptability of in...article 2007
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Steenvoorden, M.M.C. (author), Toes, R.E.M. (author), Ronday, H.K. (author), Huizinga, T.W.J. (author), de Groot, J. (author), TNO Kwaliteit van Leven (author)Ligands for the receptor for advanced glycation endproducts (RAGE) are increased in RA synovial fluid (SF), serum and synovium. Since RAGE is present on fibroblast-like synoviocytes (FLS), the present study investigates whether the RAGE ligands HMGB-1 and AGEs are able to stimulate the characteristic, pathological invasive behaviour of these...article 2007