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Kleinnijenhuis, A.J. (author), Staal, Y.C.M. (author), Duistermaat, E. (author), Engel, R. (author), Woutersen, R.A. (author)Formaldehyde (FA) is suspected of being associated with the development of leukemia. An inhalation experiment with FA was performed in rats to study whether FA can enter the blood and could thus cause systemic toxicity in remote tissues such as the bone marrow. Therefore, a sophisticated analytical method was developed to detect blood...article 2013
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Radonjic, M. (author), Cappaert, N.L.M. (author), de Vries, E.F.J. (author), de Esch, C.E.F. (author), Kuper, F.C. (author), van Waarde, A. (author), Dierckx, R.A.J.O. (author), Wadman, W.J. (author), Wolterbeek, A.P.M. (author), Stierum, R.H. (author), de Groot, D.M.G. (author)Maternal exposure to the neurotoxin methylmercury (MeHg) has been shown to have adverse effects on neural development of the offspring in man. Little is known about the underlying mechanisms by which MeHg affects the developing brain. To explore the neurodevelopmental defects and the underlying mechanism associated with MeHg exposure, the...article 2013
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van Mierlo, G.J.D. (author), Cnubben, N.H.P. (author), Kuper, C.F. (author), Wolthoorn, J. (author), van Meeteren-Kreikamp, A.P. (author), Nagtegaal, M.M. (author), Doornbos, R. (author), Ganderup, N.-C. (author), Penninks, A.H. (author)The use of recombinant human proteins for the treatment of several diseases has increased considerably during the last decades. A major safety and efficacy issue of biopharmaceuticals is their potential immunogenicity. To prevent immunogenicity, biotechnology-derived proteins are engineered to be as human-like as possible. Immunogenicity is...article 2013
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van Esch, B.C.A.M. (author), van Bilsen, J.H.M. (author), Jeurink, P.V. (author), Garssen, J. (author), Penninks, A.H. (author), Smit, J.J. (author), Pieters, R.H.H. (author), Knippels, L.M.J. (author)This study describes two phases of a multi-phase project aiming to validate a mouse model for cow's milk allergy to assess the potential allergenicity of hydrolysed cow's milk based infant formulas (claim support EC-directive 2006/141/E). The transferability and the discriminatory power of this model was evaluated in 4 research centers. Mice...article 2013
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Destexhe, E. (author), Prinsen, M.K. (author), van Schöll, I. (author), Kuper, C.F. (author), Garçon, N. (author), Veenstra, S. (author), Segal, L. (author)Introduction: Inflammatory reactions are one of the potential safety concerns that are evaluated in the framework of vaccine safety testing. In nonclinical studies, the assessment of the inflammation relies notably on the measurement of biomarkers. C-reactive protein (CRP) is an acute-phase plasma protein of hepatic origin that could be used for...article 2013
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Radonjic, M. (author), Wielinga, P.Y. (author), Wopereis, S. (author), Kelder, T. (author), Goelela, V.S. (author), Verschuren, L. (author), Toet, K. (author), van Duyvenvoorde, W. (author), van der Werff van der Vat, B. (author), Stroeve, J.H.M. (author), Cnubben, N. (author), Kooistra, T. (author), van Ommen, B. (author), Kleemann, R. (author)Excess caloric intake leads to metabolic overload and is associated with development of type 2 diabetes (T2DM). Current disease management concentrates on risk factors of the disease such as blood glucose, however with limited success. We hypothesize that normalizing blood glucose levels by itself is insufficient to reduce the development of...article 2013
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Wei, H. (author), Pasman, W. (author), Rubingh, C. (author), Wopereis, S. (author), Tienstra, M. (author), Schroen, J. (author), Wang, M. (author), Verheij, E. (author), van der Greef, J. (author)The prevalence of type 2 diabetes continuously increases globally. A personalized strategy applied in the pre-diabetic stage is vital for diabetic prevention and management. The personalized diagnosis of Chinese Medicine (CM) may help to stratify the diabetics. Metabolomics is regarded as a potential platform to provide biomarkers for disease...article 2012
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Buist, H.E. (author), de Wit-Bos, L. (author), Bouwman, T. (author), Vaes, W.H.J. (author)Quantitative Property Property Relationships (QPPRs) for human and rat blood:air partition coefficients (PBAs) have been derived, based on vapour pressure (Log(VP)), the octanol:water partition coefficient (Log(K_OW)) and molecular weight (MW), using partial least squares multilinear modelling. These parameters are all included in the standard...article 2012
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Buscher, B.A.P. (author), Jägfeldt, H. (author), Sandman, H. (author), Brust-van Schaik, R. (author), van Schaik, F. (author), Brüll, L.P. (author)A bioanalytical method for the quantitative determination of budesonide and fluticasone in human sputum was developed. Sputolysin ® Reagent was added to the sputum samples. After incubation (37°C; 60-70min under shaking) and automated solid phase extraction the extracts were analysed using LC-MS/MS. Budesonide and fluticasone showed good...article 2012
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Kuper, C.F. (author), Ernst, H. (author), van Oostrum, L.C.M. (author), Rittinghausen, S. (author), Penninks, A.H. (author), Ganderup, N.-C. (author), Wolterbeek, A.P.M. (author)Histopathological examination of the nasal passages requires a standardized approach for recording lesion distribution patterns. Nasal diagrams provide guidance to map the lesions. Information on lesions exists for rodents, dogs, and monkeys, which all have been used in inhalation studies. Recently, minipigs have garnered interest as an...article 2012
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Krishnan, S. (author), Vogels, J.T.W.E. (author), Coulier, L. (author), Bas, R.C. (author), Hendriks, M.W.B. (author), Hankemeier, T. (author), Thissen, U. (author)Setting appropriate bin sizes to aggregate hyphenated high-resolution mass spectrometry data, belonging to similar mass over charge (m/. z) channels, is vital to metabolite quantification and further identification. In a high-resolution mass spectrometer when mass accuracy (ppm) varies as a function of molecular mass, which usually is the case...article 2012
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Beker-van Woudenberg, A.C.R.L. (author), Gröllers-Mulderij, M. (author), Snel, C. (author), Jeurissen, N. (author), Stierum, R. (author), Wolterbeek, A. (author)Reproductive toxicity testing according to the present guidelines requires a high number of animals. Therefore, the development of alternative in vitro methods is urgently required. The aim of the present study was to investigate the applicability domain of the bovine oocyte in vitro maturation assay (bIVM) to study female reproductive...article 2012
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Reus, A.A. (author), van Meeuwen, R.N.C. (author), de Vogel, N. (author), Maas, W.J.M. (author), Krul, C.A.M. (author)Photosafety testing is of concern for the evaluation of personal care products and pharmaceuticals. Current regulatory guidance state that photosafety should be evaluated for compounds that absorb radiation between 290 and 700 nm with relevant exposure in the skin or eyes. However, oversensitivity and the occurrence of 'pseudo-effects' with...article 2011
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Coulier, L. (author), Gerritsen, H. (author), van Kampen, J.J.A. (author), Reedijk, M.L. (author), Luider, T.M. (author), Osterhaus, A.D.M.E. (author), Gruters, R.A. (author), Brüll, L. (author)Nucleoside reverse transcriptase inhibitors (NRTIs) are a key class of drugs for the treatment of HIV infection. NRTIs are intracellularly phosphorylated to their active triphosphate metabolites and compete with endogenous deoxynucleotides (dNTP) for substrate binding. It is therefore important to analyze the intracellular concentrations of...article 2011
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Coulier, L. (author), Bas, R. (author), Hekman, M. (author), van der Werff, B.J.C. (author), Burgering, M. (author), Thissen, U. (author)An ion-pair LC-ESI-MS method was developed capable of analyzing various reported umami or umami-enhancing compounds, including glutamic acid and 5'-ribonucleotides. The method was validated using tomato and potato samples and showed overall good analytical performance with respect to selectivity, detection limit, linearity, and repeatability....article 2011
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Zuurmond, A.M. (author), Koudijs, A. (author), van El, B. (author), Doornbos, R.P. (author), van Manen-Vernooij, B.C.T. (author), Bastiaans, J.H.M.W. (author), Penninks, A.H. (author), van Bilsen, J.H.M. (author), Cnubben, N.H.P. (author), de Groot, J. (author)Pharmacokinetic properties and safety profile of a drug are likely influenced by the disease state of a patient. In this study, we investigated the influence of arthritic processes on pharmacokinetics and immunotoxicity of interleukin-1 receptor antagonist (Anakinra) in the rat adjuvant arthritis model. Anakinra dose-dependently suppressed joint...article 2011
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van Ginneken, V.J.T. (author), Verheij, E. (author), Hekman, M. (author), van der Greef, J. (author), Feskens, E.J.M. (author), Poelmann, R.E. (author)We investigated with LC-MS techniques, measuring approximately 109 lipid compounds, in mouse brain and liver tissue after 48 hours of starvation and a High-Fat Diet if brain and liver lipid composition changed. We measured Cholesterolesters (ChE), Lysophosphatidyl-cholines (LPC), Phosphatidylcholine (PC), Sphingomyelin (SPM) and Triacylglycerols...bookPart 2011
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Rosenling, T. (author), Stoop, M.P. (author), Smolinska, A. (author), Muilwijk, B. (author), Coulier, L. (author), Shi, S. (author), Dane, A. (author), Christin, C. (author), Suits, F. (author), Horvatovich, P.L. (author), Wijmenga, S.S. (author), Buydens, L.M.C. (author), Vreeken, R. (author), Hankemeier, T. (author), van Gool, A.J. (author), Luider, T.M. (author), Bischoff, R. (author)BACKGROUND: Because cerebrospinal fluid (CSF) is in close contact with diseased areas in neurological disorders, it is an important source of material in the search for molecular biomarkers. However, sample handling for CSF collected from patients in a clinical setting might not always be adequate for use in proteomics and metabolomics studies....article 2011
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Koek, M.M. (author), Jellema, R.H. (author), van der Greef, J. (author), Tas, A.C. (author), Hankemeier, T. (author)Metabolomics involves the unbiased quantitative and qualitative analysis of the complete set of metabolites present in cells, body fluids and tissues (the metabolome). By analyzing differences between metabolomes using biostatistics (multivariate data analysis; pattern recognition), metabolites relevant to a specific phenotypic characteristic...article 2011
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Kuper, C.F. (author), Radonjic, M. (author), van Triel, J. (author), Stierum, R. (author), de Groot, R.J. (author), Arts, J.H.E. (author)Oxazolone (OXA) is a potent contact allergen in man, and it is used as a model Th1-allergen to test (Q)SAR's and screening assays for allergenic potential of chemicals. However, it elevates serum IgE levels and Thelper2 cytokines at relatively low doses in test animals, suggesting that it has also respiratory allergenic potential. The lack of...article 2011