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Schiffelers, M.J.W.A. (author), Blaauboer, B.J. (author), Bakker, W.E. (author), Beken, S. (author), Hendriksen, C.F.M. (author), Koeter, H. (author), Krul, C.A.M. (author)Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these models must overcome many barriers before being...article 2014
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Holm, L. (author), Liang, W. (author), Thorsell, A. (author), Hilke, S. (author)Background The neuropeptide cholecystokinin (CCK) has been implicated in the neurobiology of anxiety and panic disorders, as well as in dopamine-related behaviours. Anxiety and panic-disorders are twice as common in females compared to males, but studies of females are rare, although increasing in number. Limited studies have found that CCK...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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Beker van Woudenberg, A. (author), Snel, C. (author), Rijkmans, E. (author), de Groot, D. (author), Bouma, M. (author), Hermsen, S. (author), Piersma, A. (author), Menke, A. (author), Wolterbeek, A. (author)To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid (VPA), carbamazepine (CBZ), ethosuximide (ETH)...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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Boon, M.R. (author), Kooijman, S. (author), van Dam, A.D. (author), Pelgrom, L.R. (author), Berbée, J.F.P. (author), Visseren, C.A.R. (author), van Aggele, R.C. (author), van den Hoek, A.M. (author), Sips, H.C.M. (author), Lombès, M. (author), Havekes, L.M. (author), Tamsma, J.T. (author), Guigas, B. (author), Meijer, O.C. (author), Jukema, J.W. (author), Rensen, P.C.N. (author)The endocannabinoid system is an important player in energy metabolism by regulating appetite, lipolysis, and energy expenditure. Chronic blockade of the cannabinoid 1 receptor (CB1R) leads to long-term maintenance of weight loss and reduction of dyslipidemia in experimental and human obesity. The molecular mechanism by which CB1R blockade...article 2014
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Neumann, A. (author), Berends, E.T.M. (author), Nerlich, A. (author), Molhoek, E.M. (author), Gallo, R.L. (author), Meerloo, T. (author), Nizet, V. (author), Naim, H.Y. (author), von Köckritz-Blickwede, M. (author)NETs (neutrophil extracellular traps) have been described as a fundamental innate immune defence mechanism. Duringformation of NETs, the nuclear membrane is disrupted by an asyet unknown mechanism. In the present study we investigated the role of human cathelicidin LL-37 in nuclear membrane disruption and formation of NETs. Immunofluorescence...article 2014
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de Oliveira, J.E. (author), van der Hoeven-Hangoor, E. (author), van de Linde, I.B. (author), Montijn, R.C. (author), van der Vossen, J.M.B.M. (author)The feasibility of establishing probiotic bacteria in the intestine of broiler chickens by in ovo inoculation was investigated, followed by verifying possible subsequent protection against Salmonella Enteriditis infection. In a first study, 7 commercially available probiotics were screened for compatibility with in ovo inoculation. Two of these...article 2014
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Kim, E.S. (author), Cha, Y. (author), Ham, M. (author), Jung, J. (author), Kim, S.G. (author), Hwang, S. (author), Kleemann, R. (author), Moon, A. (author)A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for the expression of CRP and its functional...article 2014
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Belzer, C. (author), Gerber, G.K. (author), Roeselers, G. (author), Delaney, M. (author), DuBois, A. (author), Liu, Q. (author), Belavusava, V. (author), Yeliseyev, V. (author), Houseman, A. (author), Onderdonk, A. (author), Cavanaugh, C. (author), Bry, L. (author)Longitudinal studies of the microbiota are important for discovering changes in microbial communities that affect the host. The complexity of these ecosystems requires rigorous integrated experimental and computational methods to identify temporal signatures that promote physiologic or pathophysiologic responses in vivo. Employing a murine model...article 2014
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Mariman, R. (author), Kremer, S.H.A. (author), Koning, F. (author), Nagelkerken, L. (author)Probiotic bacteria express a wide range of molecular structures that bind to receptors on innate immune cells and mediate health-promoting effects in the host. We have recently demonstrated in a colitis model that favourable effects of the probiotic mixture VSL#3 may in part be due to the suppression of intestinal chemokine expression. To obtain...article 2014
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Saccenti, E. (author), Tenori, L. (author), Verbruggen, P. (author), Timmerman, M.E. (author), Bouwman, J. (author), van der Greef, J. (author), Luchinat, C. (author), Smilde, A.K. (author)Background: Metabolomics has attracted the interest of the medical community for its potential in predicting early derangements from a healthy to a diseased metabolic phenotype. One key issue is the diversity observed in metabolic profiles of different healthy individuals, commonly attributed to the variation of intrinsic (such as (epi)genetic...article 2014
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Kooijman, S. (author), Boon, M.R. (author), Parlevliet, E.T. (author), Geerling, J.J. (author), van de Pol, V. (author), Romijn, J.A. (author), Havekes, L.M. (author), Meurs, I. (author), Rensen, P.C.N. (author)The melanocortin system is an important regulator of energy balance, and melanocortin 4 receptor (MC4R) deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure (EE) is mediated by brown adipose tissue (BAT) activity. Therefore, female APOE∗3...article 2014
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Kühnast, S. (author), van der Hoorn, J.W.A. (author), Pieterman, E.J. (author), van den Hoek, A.M. (author), Sasiela, W.J. (author), Gusarova, V. (author), Peyman, A. (author), Schäfer, H.L. (author), Schwahn, U. (author), Jukema, J.W. (author), Princen, H.M.G. (author)Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a potential novel strategy for treatment of CVD. Alirocumab is a fully human PCSK9 monoclonal antibody in phase 3 clinical development. We evaluated the antiatherogenic potential of alirocumab in APOE∗3Leiden. CETP mice. Mice received a Western-type diet and were treated with...article 2014
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Liang, W. (author), Menke, A.L. (author), Driessen, A. (author), Koek, G.H. (author), Lindeman, J.H. (author), Stoop, R. (author), Havekes, L.M. (author), Kleemann., R. (author), van den Hoek, A.M. (author)Results: The criteria macrovesicular steatosis, microvesicular steatosis, hepatocellular hypertrophy, inflammation and fibrosis were generally applicable to rodent NAFLD. The inter-observer reproducibility (evaluated using the Intraclass Correlation Coefficient) between the ten observers was high for the analysis of macrovesicular steatosis and...article 2014
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Zimmer, B. (author), Pallocca, G. (author), Dreser, N. (author), Foerster, S. (author), Waldmann, T. (author), Westerhout, J. (author), Julien, S. (author), Krause, K.H. (author), van Thriel, C. (author), Hengstler, J.G. (author), Sachinidis, A. (author), Bosgra, S. (author), Leist, M. (author)Developmental toxicity in vitro assays have hitherto been established as stand-alone systems, based on a limited number of toxicants. Within the embryonic stem cell-based novel alternative tests project, we developed a test battery framework that allows inclusion of any developmental toxicity assay and that explores the responses of such test...article 2014
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Gierman, L.M. (author), Kühnast, S. (author), Koudijs, A. (author), Pieterman, E.J. (author), Kloppenburg, M. (author), van Osch, G.J.V.M. (author), Stojanovic-Susulic, V. (author), Huizinga, T.W.J. (author), Princen, H.M.G. (author), Zuurmond. A.M., (author)Objective Hypercholesterolaemia, a risk factor for atherosclerosis (ATH), has been suggested to have a role in the development of osteoarthritis (OA). To test this hypothesis, the effect of cholesterol and different cholesterol-lowering treatments on OA was investigated in a mouse model resembling human lipoprotein metabolism. Methods Female...article 2014
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Baumans, V. (author), van Loo, P.L.P. (author)Housing systems for captive animals have often been designed on the basis of economic and ergonomic considerations, such as equipment, costs, space, workload, ability to observe the animals and to maintain a certain degree of hygiene, with little or no consideration for animal welfare. Environmental refinement can be defined as any modification...article 2013
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Gvaramia, D. (author), Blaauboer, M.E. (author), Hanemaaijer, R. (author), Everts, V. (author)Fibrosis underlies the pathogenesis of numerous diseases and leads to severe damage of vital body organs and, frequently, to death. Better understanding of the mechanisms resulting in fibrosis is essential for developing appropriate treatment solutions and is therefore of upmost importance. Recent evidence suggests a significant antifibrotic...article 2013
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Strikwold, M. (author), Spenkelink, B. (author), Woutersen, R.A. (author), Rietjens, I.M.C.M. (author), Punt, A. (author)In vitro assays are often used for the hazard characterisation of compounds, but their application for quantitative risk assessment purposes is limited. This is because in vitro assays cannot provide a complete in vivo dose-response curve from which a point of departure (PoD) for risk assessment can be derived, like the no observed adverse...article 2013