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Detection of the mechanism of immunotoxicity of cyclosporine A in murine in vitro and in vivo modelsSchmeits, P.C.J. (author), Schaap, M.M. (author), Luijten, M. (author), van Someren, E. (author), Boorsma, A. (author), van Loveren, H. (author), Peijnenburg, A.A.C.M. (author), Hendriksen, P.J.M. (author)Transcriptomics in combination with in vitro cell systems is a powerful approach to unravel modes of action of toxicants. An important question is to which extent the modes of action as revealed by transcriptomics depend on cell type, species and study type (in vitro or in vivo). To acquire more insight into this, we assessed the transcriptomic...article 2015
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Van der Burg, B. (author), Wedebye, E.B. (author), Dietrich, D.R. (author), Jaworska, J. (author), Mangelsdorf, I. (author), Paune, E. (author), Schwarz, M. (author), Piersma, A.H. (author), Kroese, E.D. (author)There is a great need for rapid testing strategies for reproductive toxicity testing, avoiding animal use.The EU Framework program 7 project ChemScreen aimed to fill this gap in a pragmatic manner prefer-ably using validated existing tools and place them in an innovative alternative testing strategy. In ourapproach we combined knowledge on...article 2015
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Minekus, M. (author)The TNO Gastro–Intestinal Model (TIM) is a multi–compartmental model, designed to realistically simulate conditions in the lumen of the gastro–intestinal tract. TIM is successfully used to study the gastro–intestinal behavior of a wide variety of feed, food and pharmaceutical products. Experiments in TIM are based on a computer simulation of the...bookPart 2015
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Kroese, E.D. (author), Bosgra, S. (author), Buist, H.E. (author), Lewin, G. (author), van der Linden, S.C. (author), Man, H.Y. (author), Piersma, A.H. (author), Rorije, E. (author), Schulpen, S.H.W. (author), Schwarz, M. (author), Uibel, F. (author), van Vugt-Lussenburg, B.M.A. (author), Wolterbeek, A.P.M. (author), van der Burg, B. (author)Previously we showed a battery consisting of CALUX transcriptional activation assays, the ReProGlo assay, and the embryonic stem cell test, and zebrafish embryotoxicity assay as 'apical' tests to correctly predict developmental toxicity for 11 out of 12 compounds, and to explain the one false negative [7]. Here we report on applying this battery...article 2015
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Louisse, J. (author), Bosgra, S. (author), Blaauboer, B.J. (author), Rietjens, I.M.C.M. (author), Verwei, M. (author)The use of laboratory animals for toxicity testing in chemical safety assessment meets increasing ethical, economic and legislative constraints. The development, validation and application of reliable alternatives for in vivo toxicity testing are therefore urgently needed. In order to use toxicity data obtained from in vitro assays for risk...article 2015
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Buist, H.E. (author), Devito, S. (author), Goldbohm, R.A. (author), Stierum, R.H. (author), Venhorst, J. (author), Kroese, E.D. (author)Carbon capture and storage (CCS) technologies are considered vital and economic elements for achieving global CO2 reduction targets, and is currently introduced worldwide (for more information on CCS, consult for example the websites of the International Energy Agency (http://www.iea.org/topics/ccs/) and the Global CCS Institute (http://www...article 2015
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TNO Kwaliteit van Leven (author), Aguirre, M. (author), Eck, A. (author), Koenen, M.E. (author), Savelkoul, P.H.M. (author), Budding, A.E. (author), Venema, K. (author)This study investigated the optimal preservation approach to prepare human feces as inoculum for in vitro fermentations as an alternative to the use of fresh feces. The four treatments studied were: Treatment 1) fresh feces resuspended in dialysate solution + glycerol; Treatment 2) fresh feces resuspended in dialysate solution + glycerol and...article 2015
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Teunis, M.A.T. (author), Spiekstra, S.W. (author), Smits, M. (author), Adriaens, E. (author), Eltze, T. (author), Galbiati, V. (author), Krul, C.A.M. (author), Landsiedel, R. (author), Pieters, R. (author), Reinders, J. (author), Roggen, E. (author), Corsini, E. (author), Gibbs, S. (author)This study describes the international ring trial of the epidermal-equivalent (EE) sensitizer potency assay. This assay does not distinguish a sensitizer from a non-sensitizer, but may classify known skin sensitizers according to their potency. It assesses the chemical concentration resulting in 50% cytotoxicity (EE-EC50) or the 2-fold increase...article 2014
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Aguirre, M. (author), Ramiro-Garcia, J. (author), Koenen, M.E. (author), Venema, K. (author)This study investigated the stability and the activity of the microbiota from a single and a pool of donors in the TNO in vitro model of the colon (TIM-2 system). Our findings demonstrate the suitability of the preparation of a pool of fecal sample to be used for fermentation experiments. Chemicals/CAS: isobutyric acid, 5711-69-3, 79-31-2;...article 2014
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Ashton, R. (author), de Wever, B. (author), Fuchs, H.W. (author), Gaca, M. (author), Hill, E. (author), Krul, C.A.M. (author), Poth, A. (author), Roggen, E.L. (author)Despite changing attitudes towards animal testing and current legislation to protect experimental animals, the rate of animal experiments seems to have changed little in recent years. On May 15–16, 2013, the In Vitro Testing Industrial Platform (IVTIP) held an open meeting to discuss the state of the art in alternative methods, how companies...article 2014
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Kleensang, A. (author), Maertens, A. (author), Rosenberg, M. (author), Fitzpatrick, S. (author), Lamb, J. (author), Auerbach, S. (author), Brennan, R. (author), Crofton, K.M. (author), Gordon, B. (author), Fornace Jr., A.J. (author), Gaido, K. (author), Gerhold, D. (author), Haw, R. (author), Henney, A. (author), Ma’ayan, A. (author), McBride, M. (author), Monti, S. (author), Ochs, M.F. (author), Pandey, A. (author), Sharan, R. (author), Stierum, R. (author), Tugendreich, Z. (author), Willett, C. (author), Wittwehr, C. (author), Xia, J. (author), Patton, G.W. (author), Arvidson, K. (author), Bouhifd, M. (author), Hogberg, H.T. (author), Luechtefeld, T. (author), Smirnova, L. (author), Zhao, L. (author), Adeleye, Y. (author), Kanehisa, M. (author), Carmichael, P. (author), Andersen, M.E. (author), Hartung, T. (author)Despite wide-spread consensus on the need to transform toxicology and risk assessment in order to keep pace with technological and computational changes that have revolutionized the life sciences, there remains much work to be done to achieve the vision of toxicology based on a mechanistic foundation. A workshop was organized to explore one key...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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Ramasamy, U.S. (author), Venema, K. (author), Gruppen, H. (author), Schols, H.A. (author)The aim of this study was to monitor cell wall polysaccharide (CWPs) utilization during fermentation by the human colonic microbiota in the TNO in vitro model of the colon (TIM-2). Chicory root pulp (CRP) and treated (ensiled) CRP (ECRP) containing four times more soluble pectin than CRP, were fermented in the model. After the adaptation phase...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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Minekus, M. (author), Alminger, M. (author), Alvito, P. (author), Ballance, S. (author), Bohn, T. (author), Bourlieu, C. (author), Carrière, F. (author), Boutrou, R. (author), Corredig, M. (author), Dupont, D. (author), Dufour, C. (author), Egger, L. (author), Golding, M. (author), Karakaya, S. (author), Kirkhus, B. (author), Le Feunteun, S. (author), Lesmes, U. (author), MacIerzanka, A. (author), MacKie, A. (author), Marze, S. (author), McClements, D.J. (author), Ménard, O. (author), Recio, I. (author), Santos, C.N. (author), Singh, R.P. (author), Vegarud, G.E. (author), Wickham, M.S.J. (author), Weitschies, W. (author), Brodkorb, A. (author)Simulated gastro-intestinal digestion is widely employed in many fields of food and nutritional sciences, as conducting human trials are often costly, resource intensive, and ethically disputable. As a consequence, in vitro alternatives that determine endpoints such as the bioaccessibility of nutrients and non-nutrients or the digestibility of...article 2014
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Vaessen, S.F. (author), Bruysters, M.W. (author), Vandebriel, R.J. (author), Verkoeijen, S. (author), Bos, R. (author), Krul, C.A.M. (author), Akkermans, A.M. (author)Pertussis vaccines are routinely administered to infants to protect them from whooping cough. Still, an adequate safety test for pertussis toxin (PT), one of the main antigens in these vaccines, is not available. The histamine sensitization test is currently the only assay accepted by regulatory authorities to test for the absence of active PT...article 2014
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Meunier, L. (author), Garthoff, J.A. (author), Schaafsma, A. (author), Krul, L. (author), Schrijver, J. (author), van Goudoever, J.B. (author), Speijers, G. (author), Vandenplas, Y. (author)Locust bean gum (LBG) is a galactomannan polysaccharide used as thickener in infant formulas with the therapeutic aim to treat uncomplicated gastroesophageal reflux (GER). Since its use in young infants below 12. weeks of age is not explicitly covered by the current scientific concept of the derivation of health based guidance values, the...article 2014
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Boon, M.R. (author), Kooijman, S. (author), van Dam, A.D. (author), Pelgrom, L.R. (author), Berbée, J.F.P. (author), Visseren, C.A.R. (author), van Aggele, R.C. (author), van den Hoek, A.M. (author), Sips, H.C.M. (author), Lombès, M. (author), Havekes, L.M. (author), Tamsma, J.T. (author), Guigas, B. (author), Meijer, O.C. (author), Jukema, J.W. (author), Rensen, P.C.N. (author)The endocannabinoid system is an important player in energy metabolism by regulating appetite, lipolysis, and energy expenditure. Chronic blockade of the cannabinoid 1 receptor (CB1R) leads to long-term maintenance of weight loss and reduction of dyslipidemia in experimental and human obesity. The molecular mechanism by which CB1R blockade...article 2014
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van Loo-Bouwman, C.A. (author), Naber, T.H.J. (author), Minekus, M. (author), van Breemen, R.B. (author), Hulshof, P.J.M. (author), Schaafsma, G. (author)Since the food matrix determines β-carotene availability for intestinal absorption, food matrix effects on the bioaccessibility of β-carotene from two diets were investigated in vitro and compared with in vivo data. The "mixed diet" consisted of β-carotene-rich vegetables, and the "oil diet" contained β-carotene-low vegetables with supplemental...article 2014
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- Louisse, J. (author), Bosgra, S. (author), Blaauboer, B.J. (author), Rietjens, Y.M.C.M. (author), Verwei, M. (author) article 2014