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Dose-dependent prebiotic effect of lactulose in a computer-controlled in vitro model of the human large intestine

Bothe, M.K. (author), Maathuis, A.J.H. (author), Bellmann, S. (author), van der Vossen, J.M.B.M. (author), Berressem, D. (author), Koehler, A. (author), Schwejda-Guettes, S. (author), Gaigg, B. (author), Kuchinka-Koch, A. (author), Stover, J.F. (author)

Lactulose, a disaccharide of galactose and fructose, used as a laxative or ammonia-lowering drug and as a functional food ingredient, enhances growth of Bifidobacterium and Lactobacillus at clinically relevant dosages. The prebiotic effect of subclinical dosages of Lactulose, however, remains to be elucidated. This study analyses changes in the...

article 2017

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Feasibility of a 3D human airway epithelial model to study respiratory absorption

Reus, A.A. (author), Maas, W.J.M. (author), Jansen, H.T. (author), Constant, S. (author), Staal, Y.C.M. (author), van Triel, J.J. (author), Kuper, C.F. (author)

The respiratory route is an important portal for human exposure to a large variety of substances. Consequently, there is an urgent need for realistic in vitro strategies for evaluation of the absorption of airborne substances with regard to safety and efficacy assessment. The present study investigated feasibility of a 3D human airway epithelial...

article 2014

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Pre-processing liquid chromatography/high-resolution mass spectrometry data: Extracting pure mass spectra by deconvolution from the invariance of isotopic distribution

Krishnan, S. (author), Verheij, E.E.R. (author), Bas, R.C. (author), Hendriks, M.W.B. (author), Hankemeier, T. (author), Thissen, U. (author), Coulier, L. (author)

RATIONALE Mass spectra obtained by deconvolution of liquid chromatography/high-resolution mass spectrometry (LC/HRMS) data can be impaired by non-informative mass-over-charge (m/z) channels. This impairment of mass spectra can have significant negative influence on further post-processing, like quantification and identification. METHODS A metric...

article 2013

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The OSIRIS Weight of Evidence approach: ITS mutagenicity and ITS carcinogenicity.

Buist, H. (author), Aldenberg, T. (author), Batke, M. (author), Escher, S. (author), Kühne, R. (author), Marquart, H. (author), Pauné, E. (author), Rorije, E. (author), Schüürmann, G. (author), Kroese, D.E. (author)

Risk assessment of chemicals usually implies data evaluation of in vivo tests in rodents to conclude on 31 their hazards. The FP7 European project OSIRIS has developed integrated testing strategies (ITS) for rel- 32 evant toxicological endpoints to avoid unnecessary animal testing and thus to reduce time and costs. This 33 paper describes the...

article 2013

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Developmental immunotoxicity of ethanol in an extended one-generation reproductive toxicity study

Tonk, E.C.M. (author), de Groot, D.M.G. (author), Wolterbeek, A.P.M. (author), Penninks, A.H. (author), Waalkens-Berendsen, I.D.H. (author), Piersma, A.H. (author), van Loveren, H. (author)

The susceptibility of developing immune system to chemical disruption warrants the assessment of immune parameters in reproductive and developmental testing protocols. In this study, a wide range of immune endpoints was included in an extended one-generation reproduction toxicity study (EOGRTS) design to determine the relative sensitivity of...

article 2013

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Metabolite profiling of small cerebrospinal fluid sample volumes with gas chromatography-mass spectrometry: Application to a rat model of multiple sclerosis

Coulier, L. (author), Muilwijk, B. (author), Bijlsma, S. (author), Noga, M. (author), Tienstra, M. (author), Attali, A. (author), van Aken, H. (author), Suidgeest, E. (author), Tuinstra, T. (author), Luider, T.M. (author), Hankemeier, T. (author), Bobeldijk, I. (author)

Analysis of metabolites in biofluids by gas chromatography-mass spectrometry (GC-MS) after oximation and silylation is a key method in metabolomics. The GC-MS method was modified by a modified vial design and sample work-up procedure in order to make the method applicable to small volumes of cerebrospinal fluid (CSF), i. e. 10 μL, with similar...

article 2013

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The determination of exogenous formaldehyde in blood of rats during and after inhalation exposure

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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Delay and impairment in brain development and function in rat offspring after maternal exposure to methylmercury

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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The Göttingen minipig® as an alternative non-rodent species for immunogenicity testing: A demonstrator study using the IL-1 receptor antagonist anakinra

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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Management of Undescended Testis: A Decision Analysis

van den Akker-van Marle, M.E. (author), Kamphuis, M. (author), van Gameren-Oosterom, H.B.M. (author), Pierik, F.H. (author), Kievit, J. (author)

Background. Undescended testis (UDT) or cryptorchidism is the most common genital anomaly seen in boys and can be treated surgically by orchidopexy. The age at which orchidopexy should be performed is controversial for both congenital and acquired UDT. Methods. A decision analysis is performed in which all available knowledge is combined to...

article 2013

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Interlaboratory evaluation of a cow's milk allergy mouse model to assess the allergenicity of hydrolysed cow's milk based infant formulas

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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Evaluation of C-reactive protein as an inflammatory biomarker in rabbits for vaccine nonclinical safety studies

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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Predicting blood:air partition coefficients using basic physicochemical properties

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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Potentially increased sensitivity of pregnant and lactating female rats to immunotoxic agents

Menke, A. (author), Wolterbeek, A. (author), Snel, C. (author), Bruijntjes, J. (author), Groot, D.D. (author), Oostrum, L.V. (author), Waalkens, I. (author), Kuper, C.F. (author)

Characteristic susceptibility to environmental and pharmaceutical exposure may occur during periods in life of marked histophysiological changes of the immune system. Perinatal development is such a period; pregnancy followed by lactation is potentially another one. Here, we explored the influence of pregnancy and lactation on the model...

article 2012

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The determination of budesonide and fluticasone in human sputum samples collected from COPD patients using LC-MS/MS

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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Nasal passages of Göttingen minipigs from the neonatal period to young adult

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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Plasma metabolomics and proteomics profiling after a postprandial challenge reveal subtle diet effects on human metabolic status

Pellis, L. (author), van Erk, M.J. (author), van Ommen, B. (author), Bakker, G.C.M. (author), Hendriks, H.F.J. (author), Cnubben, N.H.P. (author), Kleemann, R. (author), van Someren, E.P. (author), Bobeldijk, I. (author), Rubingh, C.M. (author), Wopereis, S. (author)

We introduce the metabolomics and proteomics based Postprandial Challenge Test (PCT) to quantify the postprandial response of multiple metabolic processes in humans in a standardized manner. The PCT comprised consumption of a standardized 500 ml dairy shake containing respectively 59, 30 and 12 energy percent lipids, carbohydrates and protein....

article 2012

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Instrument and process independent binning and baseline correction methods for liquid chromatography-high resolution-mass spectrometry deconvolution

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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Di-n-octyltin dichloride (DOTC) induced developmental immunotoxicity in male rats after juvenile exposure

Tonk, E.C. (author), Verhoef, A. (author), de la Fonteyne, L.J. (author), Waalkens-Berendsen, I.D. (author), Wolterbeek, A.P.M. (author), van Loveren, H. (author), Piersma, A.H. (author)

article 2011

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Comprehensive analysis of the intracellular metabolism of antiretroviral nucleosides and nucleotides using liquid chromatography-tandem mass spectrometry and method improvement by using ultra performance liquid chromatography

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