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Bhattacharya, C. (author), Sandinge, A.S. (author), Bragg, R.A. (author), Heijer, M. (author), Yan, J. (author), Andersson, L.C. (author), Jurva, U. (author), Pelay-Gimeno, M. (author), Vaes, W.H.J. (author), de Ligt, R.A.F. (author), Gränfors, M. (author), Amilon, C. (author), Lindstedt, E.L. (author), Menakuru, S.R. (author), Garkaviy, P. (author), Weidolf, L. (author), Gopaul, V.S. (author)This study evaluated the mass balance and disposition of AZD4831, a novel myeloperoxidase inhibitor, in six healthy participants using a 14C-labeled microtracer coupled with analysis by accelerator mass spectrometry (AMS). A single oral dose of 10 mg 14C-AZD4831 (14.8 kBq) was administered as a solution, and 14C levels were quantified by AMS in...article 2023
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de Ligt, R. (author), van Duijn, E. (author), Grossouw, D. (author), Bosgra, S. (author), Burggraaf, J. (author), Windhorst, A. (author), Peeters, P.A.M. (author), van der Luijt, G.A. (author), Alexander-White, C. (author), Vaes, W.H.J. (author)A clinical pharmacokinetic study was performed in 12 healthy women to evaluate systemic exposure to aluminum following topical application of a representative antiperspirant formulation under real-life use conditions. A simple roll-on formulation containing an extremely rare isotope of aluminum (26 Al) chlorohydrate (ACH) was prepared to...article 2018
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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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Turner, M.A. (author), Mooij, M.G. (author), Vaes, W.H.J. (author), Windhorst, A.D. (author), Hendrikse, N.H. (author), Knibbe, C.A.J. (author), Körgvee, L.T. (author), Maruszak, W. (author), Grynkiewicz, G. (author), Garner, R.C. (author), Tibbocl, D. (author), Park, B.K. (author), de Wildt, S.N. (author)Important information gaps remain on the efficacy and safety of drugs in children. Pediatric drug development encounters several ethical, practical, and scientifîc chaflenges One barrier to the evaluation of medicines for children is a lack of Innovative methodologies that have been adapted to the needs of chiIdren This article presents our...article 2015
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Läppchen, T. (author), Vlaming, M.L.H. (author), Custers, E. (author), Lub, J. (author), Sio, C.F. (author), DeGroot, J. (author), Steinbach, O.C. (author)In recent years, [ 18F]gefitinib PET has successfully been employed for a number of applications ranging from oncology to in vivo studies of drug transporter proteins. We here report a reliable, automated procedure for routine synthesis of this radiotracer on an Eckert and Ziegler modular system. The 3-step radiosynthesis followed by preparative...article 2012
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Gaining Insight into Microbial Physiology in the Large Intestine: A Special Role for Stable Isotopesde Graaf, A.A. (author), Venema, K. (author), TNO Kwaliteit van Leven (author)The importance of the human large intestine for nutrition, health, and disease, is becoming increasingly realized. There are numerous indications of a distinct role for the gut in such important issues as immune disorders and obesity-linked diseases. Research on this long-neglected organ, which is colonized by a myriad of bacteria, is a rapidly...conference paper 2008
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Hueber-Becker, F. (author), Nohynek, G.J. (author), Dufour, E.K. (author), Meuling, W.J.A. (author), de Bie, A.T.H.J. (author), Toutain, H. (author), Bolt, H.M. (author), TNO Kwaliteit van Leven (author)We monitored the exposure of hairdressers to oxidative hair dyes for 6 working days under controlled conditions. Eighteen professional hairdressers (3/day) coloured hairdresser's training heads bearing natural human hair (hair length: approximately 30 cm) for 6 h/working day with a dark-shade oxidative hair dye containing 2% [14C]-para...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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Buist, H.E. (author), van de Sandt, J.J.M. (author), van Burgsteden, J.A. (author), de Heer, C. (author), TNO Kwaliteit van Leven (author)The dermal route of exposure is important in worker exposure to biocidal products. Many biocidal active substances which are used on a daily basis may decrease the barrier function of the skin to a larger extent than current risk assessment practice addresses, due to possible skin effects of repeated exposure. The influence of repeated and...article 2005
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Nohynek, G.J. (author), Skare, J.A. (author), Meuling, W.J.A. (author), Hein, D.W. (author), de Bie, A.T.H.J. (author), Toutain, H. (author), TNO Voeding (author)In the organism of mammals, important detoxification pathways of arylamines are catalysed by N-acetyltransferase 2 (NAT2). A recent case-control epidemiology study suggested that human NAT2 slow acetylators exposed to oxidative hair dyes may be at greater risk to develop bladder cancer. We therefore profiled urinary [14C]-metabolites and NAT2...article 2004
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Klaasse, E. (author), de Ligt, R.A.F. (author), Roerink, S.F. (author), Lorenzen, A. (author), Milligan, G. (author), Leurs, R. (author), IJzerman, A.P. (author), TNO Voeding (author)We studied fusion proteins between the human adenosine A1 receptor and different 351Cys-mutated Gi1 α-subunits (A1-Giα) with respect to two important concepts in receptor pharmacology, i.e. allosteric modulation and constitutive activity/inverse agonism. The aim of our study was twofold. We first analysed whether such fusion products are still...article 2004
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van Ommen, B. (author), de Bie, A.T.H.J. (author), Bär, A. (author), TNO Voeding (author)The absorption, disposition, metabolism, and excretion of uniformly 14C-labeled α-cyclodextrin (14C-α-CD) was examined in four separate experiments with Wistar rats. In Experiment 1, 14C-α-CD (25μCi, 50mg/kg bw) was administered intravenously to four male and four female conventional rats. In Experiment 2, 14C-α-CD (25μCi, 200mg/kg bw) was given...article 2004
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TNO Preventie en Gezondheid (author), Rensen, P.C.N. (author), van Leeuwen, S.H. (author), Sliedregt, L.A.J.M. (author), van Berkel, T.J.C. (author), Biessen, E.A.L. (author)A novel glycolipid has been prepared that contains a cluster glycoside with an unusually high affinity for the asialoglycoprotein receptor (ASGPr) and a bile acid moiety that mediates stable incorporation into lipidic particles. The glycolipid spontaneously associated with low-density lipoproteins (LDL) and high-density lipoproteins (HDL) within...article 2004
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Tryfonidou, M.A. (author), Stevenhagen, J.J. (author), van den Bemd, G.J.C.M. (author), Oosterlaken-Dijksterhuis, M.A. (author), Deluca, H.F. (author), Mol, J.A. (author), van den Brom, W.E. (author), van Leeuwen, J.P.T.M. (author), Hazewinkel, H.A.W. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Hormonal regulation of calcium (Ca) absorption was investigated in a cholecalciferol (vitamin D3)supplemented group (hVitD) vs. a control group (cVitD) of growing Great Danes (100 vs. 12.5 μg vitamin D3/kg diet). Although Ca intakes did not differ, fractional Ca absorption was significantly lower in the hVitD group than in the cVitD group. There...article 2002
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te Loo, D.M.W.M. (author), Monnens, L.A.H. (author), van der Velden, T.J.A.M. (author), Vermeer, M.A. (author), Preyers, F. (author), Demacker, P.N.M. (author), van den Heuvel, L.P.W.J. (author), van Hinsbergh, V.W.M. (author), Gaubius instituut TNO (author)The hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children. The role of a verocytotoxin (VT)-producing Escherichia coli has been strongly implicated in the epidemic form of HUS. Although direct toxicity of VT on glomerular endothelial cells has been demonstrated, it remained still unclear how the VT is...article 2000
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Noort, D. (author), Fidder, A. (author), Hulst, A.G. (author), de Jong, L.P.A. (author), Benschop, H.P. (author), Department of Chemical Toxicology, TNO Prins Maurits Laboratory, PO Box 45, 2280 AA Rijswijk, Netherlands Department of Analysis of Toxic and Explosive Substances, TNO Prins Maurits Laboratory, PO Box 45, 2280 AA Rijswijk, Netherlands (author)Experiments were carried out to develop a standard operating procedure for analysis of sulfur mustard adducts to the N-terminal valine in haemoglobin and to explore adduct formation with albumin and keratin. In the first approach, gas chromatography-negative chemical ionization/mass spectrometry (GC-NCI/MS) of the thiohydantoin sample subsequent...article 2000
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Fidder, A. (author), Noort, D. (author), Hulst, A.G. (author), de Jong, L.P.A. (author), Benschop, H.P. (author), Prins Maurits Laboratorium TNO (author)The development of a procedure for retrospective detection and quantitation of exposure to the arsenical dichloro(2-chlorovinyl)arsine (lewisite; L1) has been initiated. Upon incubation of human blood with [14C]L1 (20 nM-0.2 mM) in vitro, more than 90% of the total radioactivity was found in the erythrocytes and 25-50% of the radioactivity...article 2000
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de Beer, F. (author), Hendriks, W.L. (author), van Vark, L.C. (author), Kamerling, S.W.A. (author), van Dijk, K.W. (author), Hofker, M.H. (author), Smelt, A.H.M. (author), Havekes, L.M. (author), Gaubius instituut TNO (author)The binding of β-VLDL to heparan sulfate proteoglycans (HSPG) has been reported to be stimulated by both apoE and lipoprotein lipase (LPL). In the present study we investigated the effect of the isoform and the amount of apoE per particle, as well as the role of LPL on the binding of β-VLDL to HSPG. Therefore, we isolated β-VLDL from transgenic...article 1999
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Effects of cadmium chloride on the paracellular barrier function of intestinal epithelial cell linesDuizer, E. (author), Gilde, A.J. (author), Versantvoort, C.H.M. (author), Groten, J.P. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)In the present study we characterized the functional and structural disruption of the paracellular barrier of intestinal epithelium in vitro in relation to cytotoxicity after apical Cd2+ exposure. For that purpose filter-grown Caco-2 and IEC-18 cells were apically exposed to 5 to 100 μM CdCl2 for 4 or 14 h. It was found that the effects of Cd2+...article 1999
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Chaillou, S. (author), Pouwels, P.H. (author), Postma, P.W. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)We have identified and characterized the D-xylose transport system of Lactobacillus pentosus. Uptake of D-xylose was not driven by the proton motive force generated by malolactic fermentation and required D-xylose metabolism. The kinetics of D-xylose transport were indicative of a low- affinity facilitated-diffusion system with an apparent K(m)...article 1999