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Komninos, D. (author), Ramos, L. (author), van der Heijden, G.W. (author), Morrison, M.C. (author), Kleemann, R. (author), van Herwaarden, A.E. (author), Kiliaan, A.J. (author), Arnoldussen, I.A.C. (author)Obesity can disturb spermatogenesis and subsequently affect male fertility and reproduction. In our study, we aim to elucidate at which cellular level of adult spermatogenesis the detrimental effects of obesity manifest. We induced high fat diet (HFD) obesity in low-density lipoprotein receptor knock-out Leiden (Ldlr−/−.Leiden) mice, and studied...article 2022
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Bodin, J. (author), Kocbach Bølling, A. (author), Wendt, A. (author), Eliasson, L. (author), Becher, R. (author), Kuper, F. (author), Løvik, M. (author), Nygaard, U.C. (author)Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese diabetic (NOD) mice. Here, we hypothesized that...article 2015
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Westerhout, J. (author), van de Steeg, E. (author), Grossouw, D. (author), Zeijdner, E.E. (author), Krul, C.A.M. (author), Verwei, M. (author), Wortelboer, H.M. (author)A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption, however, is often insufficient, especially when...article 2014
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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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Buist, H.E. (author), Schaafsma, G. (author), van de Sandt, J.J.M. (author), TNO Kwaliteit van Leven (author)Quantification of skin absorption is an essential step in reducing the uncertainty of dermal risk assessment. Data from literature indicate that the relative dermal absorption of substances is dependent on dermal loading. Therefore, an internal exposure calculated with absorption data determined at a dermal loading not comparable to the actual...article 2009
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TNO Bouw en Ondergrond (author), Pierik, F.H. (author), Deddens, J.A. (author), Burdorf, A. (author), Keizer-Schrama, S.M.P.F.D.M. (author), Jong, F.H.D. (author), Weber, R.F.A. (author)It is inconclusive whether the feedback mechanisms of the hypothalamus-pituitary-testis (HTP) axis are already established in the first 6 months of life, partly due to the dramatic changes in HPT-axis hormone levels over this period. Moreover, it is unclear whether these hormone levels are aberrant in boys with cryptorchidism or hypospadias, and...article 2009
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van den Hoek, A.M. (author), van Heijningen, C. (author), van der Schröder - Elst, J.P. (author), Ouwens, D.M. (author), Havekes, L.M. (author), Romijn, J.A. (author), Kalsbeek, A. (author), Pijl, H. (author), TNO Kwaliteit van Leven (author)OBJECTIVE-We recently showed that intracerebroventricular infusion of neuropeptide Y (NPY) hampers inhibition of endogenous glucose production (EGP) by insulin in mice. The down stream mechanisms responsible for these effects of NPY remain to be elucidated. Therefore, the aim of this study was to establish whether intracerebroventricular NPY...article 2008
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Ruijssenaars, H.J. (author), Sperling, E.M.G.M. (author), Wiegerinck, P.H.G. (author), Brands, F.T.L. (author), Wery, J. (author), de Bont, J.A.M. (author), TNO Kwaliteit van Leven (author)A steroid 15β-hydroxylating whole-cell solvent tolerant biocatalyst was constructed by expressing the Bacillus megaterium steroid hydroxylase CYP106A2 in the solvent tolerant Pseudomonas putida S12. Testosterone hydroxylation was improved by a factor 16 by co-expressing Fer, a putative Fe-S protein from Bacillus subtilis. In addition, the...article 2007
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Kienhuis, A.S. (author), Wortelboer, H.M. (author), Maas, W.J. (author), van Herwijnen, M. (author), Kleinjans, J.C.S. (author), van Delft, J.H.M. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)A rapid decline of cytochrome P450 (CYP450) enzyme activities remains a drawback of rat hepatocyte-based in vitro cultures. Consequently, judgment of the toxic potential of compounds that need bioactivation by CYP450s may not be adequate using this model. In the present study, an improved hepatocyte-based in vitro system was developed with...article 2007
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Wilkinson, S.C. (author), Maas, W.J.M. (author), Nielsen, J.B. (author), Greaves, L.C. (author), van de Sandt, J.J.M. (author), Williams, F.M. (author), TNO Kwaliteit van Leven TNO Voeding (author)Objectives: To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Methods: Percutaneous penetration of caffeine (log P -0.01), testosterone ...article 2006
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Le Bizec, B. (author), Courant, F. (author), Gaudin, I. (author), Bichon, E. (author), Destrez, B. (author), Schilt, R. (author), Draisci, R. (author), Monteau, F. (author), André, F. (author), TNO Kwaliteit van Leven (author)Boldenone is an androgenic steroid that improves the growth and food conversion in food producing animals. In most countries worldwide, this anabolic steroid is forbidden for meat production. Until recently, the control of its illegal use was based either on 17β-boldenone or 17α-boldenone (its main metabolite in cattle) identification in edible...article 2006
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Parnham, M.J. (author), Bogaards, J.J.P. (author), Schrander, F. (author), Schut, M.W. (author), Orešković, K. (author), Mildner, B. (author), TNO Kwaliteit van Leven (author)PLD-118 is a novel, oral antifungal drug, under development for the treatment of Candida infections. Possible metabolism of PLD-118 by rat, dog and human S9 liver homogenates and inhibition of human cytochrome P450 (CYP) enzymes were investigated. PLD-118 (10 and 100 μm) incubated for 0-60 min with S9 fractions and NADPH was determined by HPLC,...article 2005
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Blankvoort, B.M.G. (author), Rodenburg, R.J.T. (author), Murk, A.J. (author), Koeman, J.H. (author), Schilt, R. (author), Aarts, J.M.M.J.G. (author), TNO Kwaliteit van Leven (author)This paper describes the screening of 22 extracts from 18 different aquatic environmental samples for androgenic activity, including indirect and interactive effects on androgen receptor (AR)-mediated signal transduction, using the AR-LUX bioassay. Four samples, originating from an industrial wastewater treatment plant (WTP) or the river Meuse,...article 2005
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de Brabander, H.F. (author), Poelmans, S. (author), Schilt, R. (author), Stephany, R.W. (author), le Bizec, B. (author), Draisci, R. (author), Sterk, S.S. (author), van Ginkel, L.A. (author), Courtheyn, D. (author), van Hoof, N. (author), Macrì, A. (author), de Wasch, K. (author), TNO Voeding (author)The review summarizes current knowledge on the possible illegal use of the anabolic steroid boldenone. The presence of boldenone and metabolites in different animal species and the possibility of the occurrence of endogenous boldenone and metabolites is assessed, as are the methods of analysis used for detection. Different laboratories in the...article 2004
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Sierksma, A. (author), Sarkola, T. (author), Eriksson, C.J.P. (author), van der Gaag, M.S. (author), Grobbee, D.E. (author), Hendriks, H.F.J. (author), TNO Voeding (author)Background: Moderate alcohol consumption is inversely associated with cardiovascular diseases. Changes in hormone levels might in part help explain the positive health effect. This study was performed to examine the effect of moderate alcohol consumption on plasma dehydroepiandrosterone sulfate (DHEAS), testosterone, and estradiol levels....article 2004
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van de Sandt, J.J.M. (author), van Burgsteden, J.A. (author), Cage, S. (author), Carmichael, P.L. (author), Dick, I. (author), Kenyon, S. (author), Korinth, G. (author), Larese, F. (author), Limasset, J.C. (author), Maas, W.J.M. (author), Montomoli, L. (author), Nielsen, J.B. (author), Payan, J.-P. (author), Robinson, E. (author), Sartorelli, P. (author), Schaller, K.H. (author), Wilkinson, S.C. (author), Williams, F.M. (author), TNO Voeding (author)To obtain better insight into the robustness of in vitro percutaneous absorption methodology, the intra- and inter-laboratory variation in this type of study was investigated in 10 European laboratories. To this purpose, the in vitro absorption of three compounds through human skin (9 laboratories) and rat skin (1 laboratory) was determined. The...article 2004
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Hendriks, H.F.J. (author), Brink, E.J. (author), Meijer, G.W. (author), Princen, H.M.G. (author), Ntanios, F.Y. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)Objective: To evaluate both efficacy and safety in humans of long-term consumption of spreads containing plant sterol esters. Design: Randomized double-blind placebo-controlled parallel trial. Subjects: Hundred and eighty-five healthy volunteers (35-64y). Intervention: Volunteers daily consumed 20g spread enriched with 1.6g plant sterols as...article 2003
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Faassen, F. (author), Kelder, J. (author), Lenders, J. (author), Onderwater, R. (author), Vromans, H. (author)Purpose. The purpose of this work was to study the relevant physicochemical properties for the absorption of steroids. Methods. Various physicochemical properties of steroids were calculated (molecular weight, ClogP, static polar surface area [PSA], etc.). Within this series of steroids, different pharmacological groups were defined. Based on...article 2003
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Versantvoort, C.H.M. (author), Ondrewater, R.C.A. (author), Duizer, E. (author), van de Sandt, J.J.M. (author), Gilde, A.J. (author), Groten, J.P. (author), TNO Voeding (author)Purpose: previous studies have shown that the rat small intestinal cell line IEC-18 provides a size-selective barrier for paracellularly transported hydrophilic macromolecules. In order to determine the utility of IEC-18 cells as an in vitro model to screen the passive paracellular and transcellular components of the intestinal transport of...article 2002
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TNO Voeding (author), Kuilman-Wahls, M.E.M. (author), Vilar, M.S. (author), de Nijs-Tjon, L. (author), Maas, R.F.M. (author), Fink-Gremmels, J. (author)Cyclopiazonic acid and aflatoxin B1 are mycotoxins which can both be produced by the same moulds. Men can be exposed to these mycotoxins directly via ingestion of plant-derived food, as well as, indirectly via consumption of animal products. Although it is well known that aflatoxin B1 is mutagenic, contradictory results exist on the mutagenicity...article 2002
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