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Bosgra, S. (author), Westerhout, J. (author)In the EU collaborative project ChemScreen an alternative, in vitro assay-based test strategy was developed to screen compounds for reproductive toxicity. A toxicokinetic modeling approach was used to allow quantitative comparison between effective concentrations in the in vitro test battery and observations of developmental toxicity in vivo....article 2015
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van de Steeg, E. (author), Venhorst, J. (author), Jansen, H.T. (author), Nooijen, I.H.G. (author), Degroot, J. (author), Wortelboer, H.M. (author), Vlaming, M.L.H. (author)Human organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3 are important hepatic uptake transporters. Early assessment of OATP1B1/1B3-mediated drug-drug interactions (DDIs) is therefore important for successful drug development. A promising approach for early screening and prediction of DDIs is computational modeling. In this study...article 2015
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Jantos, R. (author), Schuhmacher, M. (author), Veldstra, J.L. (author), Bosker, W.M. (author), Klöpping-Ketelaars, I. (author), Touliou, K. (author), Sardi, G.M. (author), Brookhuis, K.A. (author), Ramaekers, J.G. (author), Mattern, R. (author), Skopp, G. (author)For forensic toxicological investigations only whole blood, but no serum is often available. Pharmacokinetic data are helpful for interpreting the results, but most of these studies indicate serum or plasma concentrations. In order to obtain reliable conversion factors which also take intersubject variability into account, the blood/serum ratios...article 2011
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End, C. (author), Bikker, F.J. (author), Renner, M. (author), Bergmann, G. (author), Lyer, S. (author), Blaich, S. (author), Hudler, M. (author), Helmke, B. (author), Gassler, N. (author), Autschbach, F. (author), Ligtenberg, A.J.M. (author), Benner, A. (author), Holmskov, U. (author), Schirmacher, P. (author), Nieuw Amerongen, A.V. (author), Rosenstiel, P. (author), Sina, C. (author), Franke, A. (author), Hafner, M. (author), Kioschis, P. (author), Schreiber, S. (author), Poustka, A. (author), Mollenhauer, J. (author)Deleted in malignant brain tumors 1 (DMBT1) is a secreted glycoprotein displaying a broad bacterial-binding spectrum. Recent functional and genetic studies linked DMBT1 to the suppression of LPS-induced TLR4-mediated NF-kappaB activation and to the pathogenesis of Crohn's disease. Here, we aimed at unraveling the molecular basis of its function...article 2009
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Noort, D. (author), van Zuylen, A. (author), Fidder, A. (author), van Ommen, B. (author), Hulst, A.G. (author), TNO Defensie en Veiligheid (author)Biomonitoring of exposure to the insecticide permethrin is usually performed by analysis of its urinary metabolites 3-phenoxybenzoic acid (3-PBA) or cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Cl2CA). We are engaged in the development of a methodology to assess the cumulative internal dose of exposure to...article 2008
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Damsten, M.C. (author), Commandeur, J.N.M. (author), Fidder, A. (author), Hulst, A.G. (author), Touw, D. (author), Noort, D. (author), Vermeulen, N.P.E. (author), TNO Defensie en Veiligheid (author)Covalent binding of reactive electrophilic intermediates to proteins is considered to play an important role in the processes leading to adverse drug reactions and idiosyncratic drug reactions. Consequently, both for the discovery and the development of new drugs, there is a great interest in sensitive methodologies that enable the detection of...article 2007
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Peeters, K.A.B.M. (author), Nordlee, J.A. (author), Penninks, A.H. (author), Chen, L. (author), Goodman, R.E. (author), Bruijnzeel-Koomen, C.A.F.M. (author), Hefle, S.L. (author), Taylor, S.L. (author), Knulst, A.C. (author), TNO Kwaliteit van Leven (author)Background: Reports of lupine allergy are increasing as its use in food products increases. Lupine allergy might be the consequence of cross-reactivity after sensitization to peanut or other legumes or de novo sensitization. Lupine allergens have not been completely characterized. Objectives: We sought to identify allergens associated with...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
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TNO Kwaliteit van Leven (author), Westerterp, M. (author), Berbée, J.F.P. (author), Delsing, D.J.M. (author), Jong, M.C. (author), Gijbels, M.J.J. (author), Dahlmans, V.E.H. (author), Offerman, E.H. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1+/+ mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In...article 2007
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TNO Kwaliteit van Leven (author), van der Horst, M.A. (author), Arents, J.C. (author), Kort, R. (author), Hellingwerf, K.J. (author)The bacterial photoreceptor protein photoactive yellow protein (PYP) covalently binds the chromophore 4-hydroxy coumaric acid, tuning (spectral) characteristics of this cofactor. Here, we study this binding and tuning using a combination of pointmutations and chromophore analogs. In all photosensor proteins studied to date the covalent linkage...article 2007
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Pant, N. (author), Hultberg, A. (author), Zhao, Y. (author), Svensson, L. (author), Pan-Hammarström, Q. (author), Johansen, K. (author), Pouwels, P.H. (author), Ruggeri, F.M. (author), Hermans, P. (author), Frenken, L. (author), Borén, T. (author), Marcotte, H. (author), Hammarström, L. (author), TNO Preventie en Gezondheid (author)Background. Rotavirus-induced diarrhea poses a worldwide medical problem in causing substantial morbidity and mortality among children in developing countries. We therefore developed a system for passive immunotherapy in which recombinant lactobacilli constitutively express neutralizing variable domain of llama heavy-chain (VHH) antibody...article 2006
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Valstar, D.L. (author), Schijf, M.A. (author), Arts, J.H.E. (author), Kuper, C.F. (author), Nijkamp, F.P. (author), Storm, G. (author), Bloksma, N. (author), Henricks, P.A.J. (author), TNO Kwaliteit van Leven (author)Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter these inhaled compounds and were previously shown to affect TMA-induced asthma-like symptoms in the Brown Norway rat (Valstar et al., Toxicol. Appl....article 2006
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de Jong, R.J. (author), Verwei, M. (author), West, C.E. (author), van Vliet, T. (author), Siebelink, E. (author), van den Berg, H. (author), Castenmiller, J.J.M. (author), TNO Kwaliteit van Leven (author)Objective: The aim of this study was to investigate whether milk fortified with folic acid enhances the folate status of humans and whether the presence of folate-binding proteins (FBP) in pasteurised milk affects the bioavailability of folic acid from fortified milk. In untreated and pasteurised milk, folate occurs bound to FBP, while FBP is ...article 2005
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Berbée, J.F.P. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)An increasing body of evidence demonstrates a close interplay between lipoprotein metabolism and sepsis. Sepsis results in an increase of plasma triglycerides within VLDL as a consequence of an enhanced hepatic VLDL production and/or inhibited peripheral and hepatic VLDL clearance. In contrast, sepsis decreases plasma cholesterol within LDL and...article 2005
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Joosten, V. (author), Roelofs, M.S. (author), van den Dries, N. (author), Goosen, T. (author), Verrips, C.T. (author), van den Hondel, C.A.M.J.J. (author), Lokman, B.C. (author), TNO Kwaliteit van Leven (author)The Arthromyces ramosus peroxidase gene (arp) was genetically fused to either the 5′- or 3′-terminal ends of the gene encoding llama variable heavy chain antibody fragment VHH R9, resulting in the fusion expression cassettes ARP-R9 or R9-ARP. Aspergillus awamori transformants were obtained which produced up to 30 mg l-1 fusion protein in the...article 2005
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Verwei, M. (author), van den Berg, H. (author), Havenaar, R. (author), Groten, J.P. (author), TNO Defensie en Veiligheid TNO Kwaliteit van Leven (author)Background: Milk products are a potential matrix for fortification with synthetic folic acid or natural 5-methyltetrahydrofolate (5-CH 3-H4folate) to enhance the daily folate intake. In milk, folate occurs bound to folatebinding proteins (FBP). Our previous studies with an in vitro gastrointestinal model showed that 70% of the initial FBP...article 2005
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Wortelboer, H.M. (author), Usta, M. (author), van Zanden, J.J. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), Cnubben, N.H.P. (author), TNO Kwaliteit van Leven (author)To study the possible interplay between glutathione metabolism of and MRP inhibition by thiol reactive compounds, the interactions of a series of α,β-unsaturated carbonyl compounds with multidrug resistance proteins 1 and 2 (MRP1/ABCC1 and MRP2/ABCC2) were studied. α,β-Unsaturated carbonyl compounds react with glutathione, and therefore either...article 2005
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- Coecke, S. (author), Blaauboer, B.J. (author), Elaut, G. (author), Freeman, S. (author), Freidig, A. (author), Gensmantel, N. (author), Hoet, P. (author), Kapoulas, V.M. (author), Ladstetter, B. (author), Langley, G. (author), Leahy, D. (author), Mannens, G. (author), Meneguz, A. (author), Monshouwer, M. (author), Nemery, B. (author), Pelkonen, O. (author), Pfaller, W. (author), Prieto, P. (author), Proctor, N. (author), Rogiers, V. (author), Rostami-Hodjegan, A. (author), Sabbioni, E. (author), Steiling, W. (author), van de Sandt, J.J.M. (author), TNO Kwaliteit van Leven (author) article 2005
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TNO Kwaliteit van Leven (author), Verschuur, M. (author), Jong, M.de (author), Felida, L. (author), Maat, M.P.M.de (author), Vos, H.L. (author)An elevated plasma fibrinogen level is an independent risk factor for cardiovascular disease. Therefore, an understanding of the regulation of fibrinogen expression is important. Inflammation and genetic variation of the fibrinogen beta gene regulate plasma fibrinogen levels, and there are indications that inflammation and genetic variation...article 2005
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TNO Preventie en Gezondheid (author), Lindahl, U. (author), Li, J.P. (author), Kusche-Gullberg, M. (author), Salmivirta, M. (author), Alaranta, S. (author), Veromaa, T. (author), Emeis, J. (author), Roberts, I. (author), Taylor, C. (author), Oreste, P. (author), Zoppetti, G. (author), Naggi, A. (author), Torri, G. (author), Casu, B. (author)Heparin remains a major drug in prevention of thromboembolic disease. Concerns related to its animal source have prompted search for heparin analogues. The anticoagulant activity of heparin depends on a specific pentasaccharide sequence that binds antithrombin. We report the generation of a product with antithrombin-binding, anticoagulant, and...article 2005