Searched for: subject%3A%22In%255C-vivo%22
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Suchowerska, A.K. (author), Stokman, G. (author), Palmer, J.T. (author), Coghlan, P.A. (author), Pieterman, E.J. (author), Keijzer, N. (author), Lambert, G. (author), Chemello, K. (author), Jaafar, A.K. (author), Parmar, J. (author), Yan, L. (author), Tong, Y. (author), Mu, L. (author), Princen, H.M.G. (author), Bonnar, J. (author), Evison, B.J. (author)
Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibits the clearance of low-density lipoprotein (LDL) cholesterol (LDL-C) from plasma by directly binding with the LDL receptor (LDLR) and sending the receptor for lysosomal degradation. As the interaction promotes elevated plasma LDL-C levels, and therefore a predisposition to...
article 2022
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Grinberg, M. (author), Stöber, R.M. (author), Edlund, K. (author), Rempel, E. (author), Godoy, P. (author), Reif, R. (author), Widera, A. (author), Madjar, K. (author), Schmidt-Heck, W. (author), Marchan, R. (author), Sachinidis, A. (author), Spitkovsky, D. (author), Hescheler, J. (author), Carmo, H. (author), Arbo, M.D. (author), van de Water, B. (author), Wink, S. (author), Vinken, M. (author), Rogiers, V. (author), Escher, S. (author), Hardy, B. (author), Mitic, D. (author), Myatt, G. (author), Waldmann, T. (author), Mardinoglu, A. (author), Damm, G. (author), Seehofer, D. (author), Nüssler, A. (author), Weiss, T.S. (author), Oberemm, A. (author), Lampen, A. (author), Schaap, M.M. (author), Luijten, M. (author), van Steeg, H. (author), Thasler, W.E. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), Leist, M. (author), Rahnenführer, J. (author), Hengstler, J.G. (author)
Correction to: Arch Toxicol (2014) 88:2261–2287 https://doi.org/10.1007/s00204-014-1400-x.
article 2022
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Rahman, S. (author), Ghiboud, M. (author), Donkers, J.M. (author), van de Steeg, E. (author), van Tol, E.A.F. (author), Hakvoort, T.B.M. (author), de Jonge, W.J. (author)
Over the past years, several preclinical in vitro and ex vivo models have been developed that helped to understand some of the critical aspects of intestinal functions in health and disease such as inflammatory bowel disease (IBD). However, the translation to the human in vivo situation remains problematic. The main reason for this is that these...
article 2021
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Stevens, L.J. (author), Donkers, J.M. (author), Dubbel, J. (author), Vaes, W.H.J. (author), van de Steeg, E. (author), Knibbe, C.A.J. (author), Alwayn, I.P.J. (author), van de Steeg, E. (author)
To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions...
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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van der Veer, C. (author), Hertzberger, R.Y. (author), Bruisten, S.M. (author), Tytgat, H.L.P. (author), Swanenburg, J. (author), de Kat Angelino-Bart, A. (author), Schuren, F. (author), Molenaar, D. (author), Reid, G. (author), de Vries, H. (author), Kort, R. (author)
Background: A vaginal microbiota dominated by lactobacilli (particularly Lactobacillus crispatus) is associated with vaginal health, whereas a vaginal microbiota not dominated by lactobacilli is considered dysbiotic. Here we investigated whether L. crispatus strains isolated from the vaginal tract of women with Lactobacillus-dominated vaginal...
article 2019
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Remington, B. (author), Broekman, H.C.H. (author), Blom, W.M. (author), Capt, A. (author), Crevel, R.W.R. (author), Dimitrov, I. (author), Faeste, C.K. (author), Fernandez-Canton, R. (author), Giavi, S. (author), Houben, G.F. (author), Glenn, K.C. (author), Madsen, C.B. (author), Kruizinga, A.K. (author), Constable, A. (author)
The development and introduction of new dietary protein sources has the potential to improve food supply sustainability. Understanding the potential allergenicity of these new or modified proteins is crucial to ensure protection of public health. Exposure to new proteins may result in de novo sensitization, with or without clinical allergy, or...
article 2018
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Wambaugh, J.F. (author), Hughes, M.F. (author), Ring, C.L. (author), MacMillan, D.K. (author), Ford, J. (author), Fennell, T.R. (author), Black, S.R. (author), Snyder, R.W. (author), Sipes, N.S. (author), Wetmore, B.A. (author), Westerhout, J. (author), Setzer, R.W. (author), Pearce, R.G. (author), Simmons, J.E. (author), Thomas, R.S. (author)
Prioritizing the risk posed by thousands of chemicals potentially present in the environment requires exposure, toxicity, and toxicokinetic (TK) data, which are often unavailable. Relatively high throughput, in vitro TK (HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have been developed to predict TK, but most of the in vivo...
article 2018
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van de Steeg, E. (author), Läppchen, T. (author), Aguilera, B. (author), Jansen, H.T. (author), Muilwijk, D. (author), Vermue, R. (author), van der Hoorn, J.W. (author), Donato, K. (author), Rossin, R. (author), de Visser, P.C. (author), Vlaming, M.L.H. (author)
Antisense oligonucleotides (AONs) are promising candidates for treatment of Duchenne muscular dystrophy (DMD), a severe and progressive disease resulting in premature death. However, more knowledge on the pharmacokinetics of new AON drug candidates is desired for effective application in the clinic. We assessed the feasibility of using...
article 2017
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Strikwold, M. (author), Spenkelink, B. (author), Woutersen, R.A. (author), Rietjens, I.M.C.M. (author), Punt, A. (author)
With our recently developed in vitro physiologically based kinetic (PBK) modelling approach, we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be considered. In the present study, we demonstrated...
article 2017
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Li, M. (author), de Graaf, I.A.M. (author), van de Steeg, E. (author), de Jager, M.H. (author), Groothuis, G.M.M. (author)
Intestinal P-gp and CYP3A4 work coordinately to reduce the intracellular concentration of drugs, and drug-drug interactions (DDIs) based on this interplay are of clinical importance and require pre-clinical investigation. Using precision-cut intestinal slices (PCIS) of human jejunum, ileum and colon, we investigated the P-gp/CYP3A4 interplay and...
article 2017
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Raaphorst, R.M. (author), Savolainen, H. (author), Cantore, M. (author), van de Steeg, E. (author), van Waarde, A. (author), Colabufo, N.A. (author), Elsinga, P.H. (author), Lammertsma, A.A. (author), Windhorst, A.D. (author), Luurtsema, G. (author)
Positron emission tomography (PET) imaging of P-glycoprotein (P-gp) in the blood-brain barrier can be important in neurological diseases where P-gp is affected, such as Alzheimer’s disease. Radiotracers used in the imaging studies are present at very small, nanomolar, concentration, whereas in vitro assays where these tracers are characterized,...
article 2017
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Luijten, M. (author), Olthof, E.D. (author), Hakkert, B.C. (author), Rorije, E. (author), van der Laan, J.-W. (author), Woutersen, R.A. (author), van Benthem, J. (author)
Assessment of genotoxic and carcinogenic potential is considered one of the basic requirements when evaluating possible human health risks associated with exposure to chemicals. Test strategies currently in place focus primarily on identifying genotoxic potential due to the strong association between the accumulation of genetic damage and cancer...
article 2016
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Ripken, D. (author), Hendriks, H.F.J. (author)
This chapter describes the use of the porcine ex vivo intestinal segment model. This includes the advantages and disadvantages of the segment model and a detailed description of the isolation and culture as well as the applications of the porcine ex vivo intestinal segment model in practice. Compared to the Ussing chamber (Chap. 24) the porcine...
bookPart 2015
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Lukovac, S. (author), Roeselers, G. (author)
When it comes to studying the effect of food bioactives on gut health, one of the essential steps that needs to be assessed is characterizing specific effects of the bioactives on the physical barrier of the lumen, the gastrointestinal tissue. In addition to studying the effects on transport function (e.g. by using Ussing chambers or cell...
bookPart 2015
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Westerhout, J. (author), Wortelboer, H. (author), Verhoeckx, K. (author)
The Ussing chamber system is named after the Danish zoologist Hans Ussing, who invented the device in the 1950s to measure the short-circuit current as an indicator of net ion transport taking place across frog skin (Ussing and Zerahn, Acta Physiol Scand 23:110-127, 1951). Ussing chambers are increasingly being used to measure ion transport in...
bookPart 2015
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Higuera, G.A. (author), Fernandes, H. (author), Spitters, T.W.G.M. (author), van de Peppel, J. (author), Aufferman, N. (author), Truckenmueller, R. (author), Stoop, R. (author), van Leeuwen, J.P. (author), de Boer, J. (author), Subramaniam, V. (author), Karperien, M. (author), van Blitterswijk, C. (author), van Boxtel, A. (author), Moroni, L. (author)
Cells and tissues are intrinsically adapted to molecular gradients and use them to maintain or change their activity. The effect of such gradients is particularly important for cell populations that have an intrinsic capacity to differentiate into multiple cell lineages, such as bone marrow derived mesenchymal stromal cells (MSCs). Our results...
article 2015
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Kühnast, S. (author), van der Tuin, S.J.L. (author), van der Hoorn, J.W.A. (author), van Klinken, J.B. (author), Simic, B. (author), Pieterman, E. (author), Havekes, L.M. (author), Landmesser, U. (author), Lüscher, T.F. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author), Jukema, J.W. (author), Princen, H.M.G. (author)
Background The residual risk that remains after statin treatment supports the addition of other LDL-C-lowering agents and has stimulated the search for secondary treatment targets. Epidemiological studies propose HDL-C as a possible candidate. Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from atheroprotective HDL to...
article 2015
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Bosgra, S. (author), Westerhout, J. (author)
In the EU collaborative project ChemScreen an alternative, in vitro assay-based test strategy was developed to screen compounds for reproductive toxicity. A toxicokinetic modeling approach was used to allow quantitative comparison between effective concentrations in the in vitro test battery and observations of developmental toxicity in vivo....
article 2015
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Walczak, A.P. (author), Hendriksen, P.J.M. (author), Woutersen, R.A. (author), van der Zande, M. (author), Undas, A.K. (author), Helsdingen, R. (author), van den Berg, H.H.J. (author), Rietjens, I.M.C.M. (author), Bouwmeester, H. (author)
The likelihood of oral exposure to nanoparticles (NPs) is increasing, and it is necessary to evaluate the oral bioavailability of NPs. In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential. Previously, we assessed the translocation of 50 nm polystyrene NPs of different charges (neutral,...
article 2015
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