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Cnubben, N.H.P. (author), Tel, S.L. (author), Hemmes, M.A. (author), Langenkamp-Brand, A. (author), Grossouw, D. (author), Jansen, H.T. (author), de Bie, B.T.H.J. (author)
Background: Worldwide obesity has nearly doubled since 1980 and is a leading risk for global deaths, profoundly affecting morbidity, mortality, health-care costs, and professional and personal quality of life. Treatment of obesity and its consequences include lifestyle intervention, pharmacotherapy, and bariatric surgery. Polyglucosamines have...
article 2016
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van Mierlo, G.J.D. (author), Cnubben, N.H.P. (author), Wouters, D. (author), Wolbink, G.J. (author), Hart, M.H.L. (author), Rispens, T. (author), Ganderup, N.C. (author), Kuper, C.F. (author), Aarden, L. (author), Penninks, A.H. (author)
Immunogenicity is a major issue of concern for monoclonal antibodies used in human diseases and is by default mainly determined in non-human primates (NHP), as target molecules are considered most similar in NHP compared to human. In this manuscript the predictive value of immunogenicity testing in minipigs for human safety is evaluated, as the...
article 2014
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Wopereis, S. (author), Wolvers, D. (author), van Erk, M.J. (author), Gribnau, M. (author), Kremer, S.H.A. (author), van Dorsten, F.A. (author), Boelsma, E. (author), Garczarek, U. (author), Cnubben, N. (author), Frenken, L. (author), van der Logt, P. (author), Hendriks, H.F. (author), Albers, R. (author), van Duynhoven, J. (author), van Ommen, B. (author), Jacobs, D.M. (author)
Background: Resilience or the ability of our body to cope with daily-life challenges has been proposed as a new definition of health, with restoration of homeostasis as target resultant of various physiological stress responses. Challenge models may thus be a sensitive measure to study the body’s health. The objective of this study was to select...
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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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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Wopereis, S. (author), Radonjic, M. (author), Rubingh, C. (author), van Erk, M. (author), Smilde, A. (author), van Duyvenvoorde, W. (author), Cnubben, N. (author), Kooistra, T. (author), van Ommen, B. (author), Kleemann, R. (author)
The prevalence of diabetes mellitus Type 2 could be significantly reduced by early identification of subjects at risk, allowing for better prevention and earlier treatment. Glucose intolerance (GI) is a hallmark of the prediabetic stage. This study aims at identifying 1) prognostic biomarkers predicting the risk of developing GI later in life...
article 2012
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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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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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Rubingh, C.M. (author), van Erk, M.J. (author), Wopereis, S. (author), van Vliet, T. (author), Verheij, E.R. (author), Cnubben, N.H.P. (author), van Ommen, B. (author), van der Greef, J. (author), Hendriks, H.F.J. (author), Smilde, A.K. (author)
Many benefits can be gained if multi-factorial diseases with a high incidence and prevalence are better understood. Sophisticated approaches like multilevel analyses are needed to discover subtle differences between healthy people and people at the onset of disease in these types of studies. Multilevel analysis generates different sub-models for...
article 2011
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van Erk, M.J. (author), Wopereis, S. (author), Rubingh, C. (author), van Vliet, T. (author), Verheij, E. (author), Cnubben, N.H. (author), Pedersen, T.L. (author), Newman, J.W. (author), Smilde, A.K. (author), Greef, J.V.D. (author), Hendriks, H.F. (author), van Ommen, B. (author), TNO Kwaliteit van Leven (author)
Background. Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately describe the complexity of metabolic responses to...
article 2010
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Bakker, G.C.M. (author), van Erk, M.J. (author), Pellis, L. (author), Wopereis, S. (author), Rubingh, C.M. (author), Cnubben, N.H.P. (author), Kooistra, T. (author), van Ommen, B. (author), Hendriks, H.F.J. (author), TNO Kwaliteit van Leven (author)
Background: Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Objective: It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. Design: Dietary products [resveratrol, green tea extract, α-tocopherol,...
article 2010
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TNO Kwaliteit van Leven (author), Kleemann, R. (author), van Erk, M. (author), Verschuren, L. (author), van den Hoek, A.M. (author), Koek, M. (author), Wielinga, P.Y. (author), Jie, A. (author), Pellis, L. (author), Bobeldijk-Pastorova, I. (author), Kelder, T. (author), Toet, K. (author), Wopereis, S. (author), Cnubben, N. (author), Evelo, C. (author), van Ommen, B. (author), Kooistra, T. (author)
BACKGROUND: The sequence of events leading to the development of insulin resistance (IR) as well as the underlying pathophysiological mechanisms are incompletely understood. As reductionist approaches have been largely unsuccessful in providing an understanding of the pathogenesis of IR, there is a need for an integrative, time-resolved approach...
article 2010
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TNO Kwaliteit van Leven (author), Wopereis, S. (author), de Rubingh, C.M. (author), van Erk, M.J. (author), Verheij, E.R. (author), van Vliet, T. (author), Cnubben, N.H. (author), Smilde, A.K. (author), van der Greef, J. (author), van Ommen, B. (author), Hendriks, H.F. (author)
BACKGROUND: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into...
article 2009
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Wortelboer, H.M. (author), Balvers, M.G.J. (author), Usta, M. (author), van Bladeren, P.J. (author), Cnubben, N.H.P. (author), TNO Kwaliteit van Leven (author)
The interactions of three heavy metal-containing compounds, cisplatin (CDDP), arsenic trioxide (As2O3), and mercury dichloride (HgCl2), with the multidrug resistance transporters MRP1 and MRP2 and the involvement of glutathione (GSH)-related processes herein were investigated. In Madin-Darby canine kidney cells stably expressing MRP1 or MRP2,...
article 2008
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Jeurissen, S.M.F. (author), Claassen, F.W. (author), Havlik, J. (author), Bouwmans, E.E. (author), Cnubben, N.H.P. (author), Sudhölter, E.J.R. (author), Rietjens, I.M.C.M. (author), van Beek, T.A. (author), TNO Kwaliteit van Leven (author)
An on-line HPLC screening method for detection of inhibitors of human cytochrome P450 1A2 in extracts was developed. HPLC separation of extracts is connected to a continuous methoxyresorufin-O-demethylation (MROD) assay in which recombinant human P450 1A2 converts methoxyresorufin to its fluorescent metabolite resorufin. The system was tested...
article 2007
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Jeurissen, S.M.F. (author), Punt, A. (author), Boersma, M.G. (author), Bogaards, J.J.P. (author), Fiamegos, Y.C. (author), Schilter, B. (author), van Bladeren, P.J. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)
Human cytochrome P450 enzymes involved in the bioactivation of estragole to its proximate carcinogen 1′-hydroxyestragole were identified and compared to the enzymes of importance for 1′-hydroxylation of the related alkenylbenzenes methyleugenol and safrole. Incubations with Supersomes revealed that all enzymes tested, except P450 2C8, are...
article 2007
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Usta, M. (author), Wortelboer, H.M. (author), Vervoort, J. (author), Boersma, M.G. (author), Rietjens, I.M.C.M. (author), van Bladeren, P.J. (author), Cnubben, N.H.P. (author), TNO Kwaliteit van Leven (author)
Curcumin, an α,β-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional 1H NMR analysis, and their formation in incubations with human...
article 2007
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van Zanden, J.J. (author), van der Woude, H. (author), Vaessen, J. (author), Usta, M. (author), Wortelboer, H.M. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)
The present study characterises the effect of phase II metabolism, especially methylation and glucuronidation, of the model flavonoid quercetin on its capacity to inhibit human MRP1 and MRP2 activity in Sf9 inside-out vesicles. The results obtained reveal that 3′-O-methylation does not affect the MRP inhibitory potential of quercetin. However, 4...
article 2007
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Buscher, B.A.P. (author), Gerritsen, H. (author), van Schöll, I. (author), Cnubben, N.H.P. (author), Brüll, L.P. (author), TNO Kwaliteit van Leven (author)
An LC-MS/MS method has been developed for the quantitative determination of a protein drug (Tenecteplase; MW 58,777 Da) in rat plasma. The protein was digested with trypsin without prior clean-up of the plasma sample, without the use of a label nor internal standard. A limited validation was performed to assess the linearity, the sensitivity and...
article 2007
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Kleemann, R. (author), Verschuren, L. (author), van Erk, M.J. (author), Nikolsky, Y. (author), Cnubben, N.H.P. (author), Verheij, E.R. (author), Smilde, A.K. (author), Hendriks, H.F.J. (author), Zadelaar, A.S.M. (author), Smith, G.J. (author), Kaznacheev, V. (author), Nikolskaya, T. (author), Melnikov, A. (author), Hurt-Camejo, E. (author), van der Greef, J. (author), van Ommen, B. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)
Background: Increased dietary cholesterol intake is associated with atherosclerosis. Atherosclerosis development requires a lipid and an inflammatory component. It is unclear where and how the inflammatory component develops. To assess the role of the liver in the evolution of inflammation, we treated ApoE* 3Leiden mice with cholesterol-free ...
article 2007
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