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Niks, I.M.W. (author), Veldhuis, G.A. (author), Zwieten, M.H.J. (author), Sluijs, T. (author), Wiezer, N.M. (author), Wortelboer, H.M. (author)This study demonstrates an innovative approach to capture the complexity of individual workplace well-being, improving our understanding of multicausal relationships and feedback loops involved. The literature shows that a high number of interacting factors are related to individual workplace well-being. However, many studies focus on subsets of...article 2022
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Steen, M. (author), Sassen J., (author), Hinkema, M. (author), Wortelboer, H.M. (author)We face enormous challenges, e.g., to transition to sustainable energy, to promote conviviality, to combat economic inequalities. These are wicked problems, which need to be addressed via transdisciplinary approaches. The problem is that we tend to underestimate the difficulties of transdisciplinary innovation. As if putting different people in...conference paper 2021
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Sluijs, T. (author), Lokkers, L. (author), Özsezen, S. (author), Veldhuis, G.A. (author), Wortelboer, H.M. (author)The number of individuals suffering from type 2 diabetes is dramatically increasing worldwide, resulting in an increasing burden on society and rising healthcare costs. With increasing evidence supporting lifestyle intervention programs to reduce type 2 diabetes, and the use of scenario simulations for policy support, there is an opportunity to...article 2021
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Veldhuis, G.A. (author), Sluijs, T. (author), van Zwieten, M.H.J. (author), Bouwman, J. (author), Wiezer, N.M. (author), Wortelboer, H.M. (author)The phenomenon of burnout is a complex issue, which despite major efforts from researchers and organizations remains hard to prevent. The current literature highlights an increasing global prevalence of employees that are dealing with burnout. What has been largely missing is a more systemic, dynamic, and personal perspective on the interactions...article 2020
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Stevens, L.J. (author), van Lipzig, M.M.H. (author), Erpelinck, S.L.A. (author), Pronk, A. (author), van Gorp, J. (author), Wortelboer, H.M. (author), van de Steeg, E. (author)A majority of the preclinical intestinal screening models do not properly reflect the complex physiology of the human intestinal tract, resulting in low translational value to the clinical situation. The often used cell lines such as Caco-2 or HT-29 are not well suited to investigate the different processes that predict oral bioavailability in...article 2019
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Kubbinga, M. (author), Augustijns, P. (author), Garcia, M.A. (author), Heinen, C. (author), Wortelboer, H.M. (author), Verwei, M. (author), Langguth, P. (author)Chitosan is object of pharmaceutical research as a candidate permeability enhancer. However, chitosan was recently shown to reduce the oral bioavailability of acyclovir in humans. The effect of chitosan on two processes determining the oral bioavailability of acyclovir, bioaccessibility and intestinal absorption, was now investigated. Acyclovir...article 2019
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van Groen, B.D. (author), van de Steeg, E. (author), Mooij, M.G. (author), van Lipzig, M.M.H. (author), de Koning, B.A.E. (author), Verdijk, R.M. (author), Wortelboer, H.M. (author), Gaedigk, R. (author), Bi, C. (author), Leeder, S. (author), van Schaik, R.H.N. (author), van Rosmalen, J. (author), Tibboel, D. (author), Vaes, W.H. (author), de Wildt, S.N. (author)Background Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples. Methods Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3,...article 2018
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Vaessen, S.F.C. (author), van Lipzig, M.M.H. (author), Pieters, R.H.H. (author), Krul, C.A.M. (author), Wortelboer, H.M. (author), van de Steeg, E. (author)Intestinal transporter proteins and metabolizing enzymes play a crucial role in the oral absorption of a wide variety of drugs. The aim of the current study was to characterize better available intestinal in vitro models by comparing expression levels of these proteins and enzymes between porcine intestine, human intestine, and Caco-2 cells. We...article 2017
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Wegler, C. (author), Gaugaz, F.Z. (author), Andersson, T.B. (author), Wiśniewski, J.R. (author), Busch, D. (author), Gröer, C. (author), Oswald, S. (author), Norén, A. (author), Weiss, F. (author), Hammer, H.S. (author), Joos, T.O. (author), Poetz, O. (author), Achour, B. (author), Rostami-Hodjegan, A. (author), van de Steeg, E. (author), Wortelboer, H.M. (author), Artursson, P. (author)Many different methods are used for mass-spectrometry-based protein quantification in pharmacokinetics and systems pharmacology. It has not been established to what extent the results from these various methods are comparable. Here, we compared six different mass spectrometry-based proteomics methods by measuring the expression of clinically...article 2017
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Ripken, D. (author), van der Wielen, N. (author), Wortelboer, H.M. (author), Meijerink, J. (author), Witkamp, R.F. (author), Hendriks, H.F.J. (author)Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced...article 2016
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- Wietmarschen, H.A. (author), Wortelboer, H.M. (author), van der Greef, J. (author) article 2016
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Mooij, M.G. (author), van de Steeg, E. (author), van Rosmalen, J. (author), Windster, J.D. (author), de Koning, B.A.E. (author), Vaes, W.H.J. (author), van Groen, B.D. (author), Tibboel, D. (author), Wortelboer, H.M. (author), de Wildt, S.N. (author)Human hepatic membrane-embedded transporter proteins are involved in trafficking endogenous and exogenous substrates. Even though impact of transporters on pharmacokinetics is recognized, little is known on maturation of transporter protein expression levels, especially during early life. We aimed to study the protein expression of 10...article 2016
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van de Steeg, E. (author), Venhorst, J. (author), Jansen, H.T. (author), Nooijen, I.H.G. (author), Degroot, J. (author), Wortelboer, H.M. (author), Vlaming, M.L.H. (author)Human organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3 are important hepatic uptake transporters. Early assessment of OATP1B1/1B3-mediated drug-drug interactions (DDIs) is therefore important for successful drug development. A promising approach for early screening and prediction of DDIs is computational modeling. In this study...article 2015
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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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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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Gozalpour, E. (author), Greupink, R. (author), Wortelboer, H.M. (author), Bilos, A. (author), Schreurs, M. (author), Russel, F.G.M. (author), Koenderink, J.B. (author)Digitalis-like compounds (DLCs) such as digoxin, digitoxin, and ouabain, also known as cardiac glycosides, are among the oldest pharmacological treatments for heart failure. The compounds have a narrow therapeutic window, while at the same time, DLC pharmacokinetics is prone to drug-drug interactions at the transport level. Hepatic transporters...article 2014
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Ripken, D. (author), van der Wielen, N. (author), Wortelboer, H.M. (author), Meijerink, J. (author), Witkamp, R.F. (author), Hendriks, H.F.J. (author)Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are hormones important for satiation and are involved in the process called “ileal brake”. The aim of this study was to investigate the GLP-1- and PYY-stimulating efficacy of rebaudioside A, casein, and sucrose. This was studied using tissue segments collected from various regions of the pig...article 2014
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Reitsma, M. (author), Westerhout, J. (author), Wichers, H.J. (author), Wortelboer, H.M. (author), Verhoeckx, K.C.M. (author)In view of the imminent deficiency of protein sources for human consumption in the near future, new protein sources need to be identified. However, safety issues such as the risk of allergenicity are often a bottleneck, due to the absence of predictive, validated and accepted methods for risk assessment. The current strategy to assess the...article 2014
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Balvers, M.G.J. (author), Wortelboer, H.M. (author), Witkamp, R.F. (author), Verhoeckx, K.C.M. (author)The origin of N-acyl ethanolamides (NAEs) in plasma is not well understood, and it is possible that NAEs are present in plasma in esterified form. To test this hypothesis, a new and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of arachidonoyl ethanolamide, 2...article 2013
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Roeselers, G. (author), Ponomarenko, M. (author), Lukovac, S. (author), Wortelboer, H.M. (author)It is increasingly apparent that the microbial ecosystems in the mammalian gastrointestinal tract play an intricate role in health and disease. There is a growing interest in the development of targeted strategies for modulating health through the modification of these microbiota. Ecologists are faced with the challenge of understanding the...article 2013