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Tonk, E.C.M. (author), de Groot, D.M.G. (author), Penninks, A.H. (author), Waalkens - Berendsen, I.D.H. (author), Wolterbeek, A.P.M. (author), Slob, W. (author), Piersma, A.H. (author), van Loveren, H. (author), TNO Kwaliteit van Leven (author)Current developmental and reproductive toxicity protocols include only a limited set of parameters for effects on the developing immune system. In this study, a wide range of immunological parameters were included in a pre- and postnatal developmental toxicity study. Dose-response data were compared to determine the relative sensitivity of...article 2010
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Savolainen, K. (author), Pylkkänen, L. (author), Norppa, H. (author), Falck, G. (author), Lindberg, H. (author), Tuomi, T. (author), Vippola, M. (author), Alenius, H. (author), Hämeri, K. (author), Koivisto, J. (author), Brouwer, D. (author), Mark, D. (author), Bard, D. (author), Berges, M. (author), Jankowska, E. (author), Posniak, M. (author), Farmer, P. (author), Singh, R. (author), Krombach, F. (author), Bihari, P. (author), Kasper, G. (author), Seipenbusch, M. (author), TNO Kwaliteit van Leven (author)The significance of engineered nanomaterials (ENM) and nanotechnologies grows rapidly. Nanotechnology applications may have a positive marked impact on many aspects of on human every day life, for example by providing means for the production of clean energy and pure drinking water. Hundreds of consumer nano-based products are already on the...article 2010
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Bsibsi, M. (author), Bajramovic, J.J. (author), Vogt, M.H. (author), van Duijvenvoorden, E. (author), Baghat, A. (author), Persoon-Deen, C. (author), Tielen, F. (author), Verbeek, R. (author), Huitinga, I. (author), Ryffel, B. (author), Kros, A. (author), Gerritsen, W.H. (author), Amor, S. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven (author)TLR3 recognizes dsRNAs and is considered of key importance to antiviral host-defense responses. TLR3 also triggers neuroprotective responses in astrocytes and controls the growth of axons and neuronal progenitor cells, suggesting additional roles for TLR3-mediated signaling in the CNS. This prompted us to search for alternative, CNS-borne...article 2010
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Louisse, J. (author), Bai, Y. (author), Verwei, M. (author), van de Sandt, J.J.M. (author), Blaauboer, B.J. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)Embryotoxicity of glycol ethers is caused by their alkoxyacetic acid metabolites, but the mechanism underlying the embryotoxicity of these acid metabolites is so far not known. The present study investigates a possible mechanism underlying the embryotoxicity of glycol ether alkoxyacetic acid metabolites using the methoxyacetic acid (MAA)...article 2010
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Eefting, D. (author), Seghers, L. (author), Grimbergen, J.M. (author), de Vries, M.R. (author), de Boer, H.C. (author), Lardenoye, J.W.H.P. (author), Jukema, J.W. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)Aims Matrix metalloproteinases (MMP) and plasminogen activator (PA)/plasmin-mediated proteolysis, especially at the cell surface, play important roles in matrix degeneration and smooth muscle cell migration, which largely contributes to vein graft failure. In this study, a novel hybrid protein was designed to inhibit both protease systems...article 2010
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Intema, F. (author), Sniekers, Y.H. (author), Weinans, H. (author), Vianen, M.E. (author), Yocum, S.A. (author), Zuurmond, A.-M.M. (author), de Groot, J. (author), Lafeber, F.P. (author), Mastbergen, S.C. (author), TNO Kwaliteit van Leven (author)In osteoarthritis (OA), cartilage degradation is accompanied by subchondral bone changes. The pathogenesis and physiology of bone changes in OA are still unclear. The changes in subchondral bone architecture and cartilage damage were compared in differently induced experimental models of OA. Experimental OA was induced bilaterally by anterior...article 2010
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Vink, S.R. (author), Mikkers, J. (author), Bouwman, T. (author), Marquart, H. (author), Kroese, E.D. (author), TNO Kwaliteit van Leven (author)REACH requests the exploration of alternative strategies for hazard identification before resorting to (in vivo) testing. Here, we combined read-across as non-testing strategy with a tiered exposure assessment for the risk characterisation of 1-methoxypropan-2-ol (PGME) as a representative for phase-in substances to be registered under REACH....article 2010
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de Vries-van der Weij, J. (author), Toet, K. (author), Zadelaar, A.S.M. (author), Wielinga, P.Y. (author), Kleemann, R. (author), Rensen, P.C.N. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)Objective: Inflammation plays an important role in all stages of atherosclerosis, but little is known about the therapeutic effects of quenching inflammation in already existing atherosclerotic lesions. Putative beneficial effects of salicylate, an inhibitor of NF-κB activation, were studied in mice with established lesions. Methods: ApoE*3...article 2010
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de Leeuw van Weenen, J.E. (author), Parlevliet, E.T. (author), Maechler, P. (author), Havekes, L.M. (author), Romijn, J.A. (author), Ouwens, D.M. (author), Pijl, H. (author), Guigas, B. (author), TNO Kwaliteit van Leven (author)Treatment with the dopamine receptor D2 (DRD2) agonist bromocriptine improves metabolic features in obese patients with type 2 diabetes by a still unknown mechanism. In the present study, we investigated the acute effect of bromocriptine and its underlying mechanism(s) on insulin secretion both in vivo and in vitro. For this purpose, C57Bl6/J...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), Berbé, J.F.P. (author), Coomans, C.P. (author), Westerterp, M. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)Timely sensing of lipopolysaccharide (LPS) is critical for the host to fight invading Gram-negative bacteria. We recently showed that apolipoprotein CI (apoCI) (apoCI1-57) avidly binds to LPS, involving an LPS-binding motif (apoCI48-54), and thereby enhances the LPS-induced inflammatory response. Our current aim was to further elucidate the...article 2010
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TNO Kwaliteit van Leven (author), Caesar, R. (author), Manieri, M. (author), Kelder, T. (author), Boekschoten, M. (author), Evelo, C. (author), Müller, M. (author), Kooistra, T. (author), Cinti, S. (author), Kleemann, R. (author), Drevon, C.A. (author)Depot-dependent differences in adipose tissue physiology may reflect specialized functions and local interactions between adipocytes and surrounding tissues. We combined time-resolved microarray analyses of mesenteric- (MWAT), subcutaneous- (SWAT) and epididymal adipose tissue (EWAT) during high-fat feeding of male transgenic ApoE3Leiden mice...article 2010
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TNO Kwaliteit van Leven (author), Bijland, S. (author), Pieterman, E.J. (author), Maas, A.C.E. (author), van der Hoorn, J.W.A. (author), van Erk, M.J. (author), van Klinken, J.B. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Princen, H.M.G. (author), Rensen, P.C.N. (author)The peroxisome proliferator-activated receptor alpha (PPARalpha) activator fenofibrate efficiently decreases plasma triglycerides (TG), which is generally attributed to enhanced very low density lipoprotein (VLDL)-TG clearance and decreased VLDL-TG production. However, because data on the effect of fenofibrate on VLDL production are...article 2010
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Eefting, D. (author), Bot, I. (author), de Vries, M.R. (author), Schepers, A. (author), van Bockel, J.H. (author), van Berkel, T.J.C. (author), Biessen, E.A.L. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)Objective: Inflammatory responses to vascular injury are key events in vein graft disease and accelerated atherosclerosis, which may result in bypass failure. The monocyte chemoattractant protein-1 (MCP-1)/CC-chemokine receptor (CCR)-2 pathway is hypothesized to play a central role. A murine model for vein graft disease was used to study the...article 2009
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Voshol, P.J. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author), Romijn, J.A. (author), Havekes, L.M. (author), TNO Kwaliteit van Leven (author)The obesity epidemic is associated with an increased incidence of type 2 diabetes, cardiovascular morbidity and various types of cancer. A better insight into the molecular mechanisms that underlie adipogenesis and obesity may result in novel therapeutic handles to fight obesity and these associated diseases. Adipogenesis is determined by the...article 2009
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de Haan, W. (author), de Vries-van der Weij, J. (author), Mol, I.M. (author), Hoekstra, M. (author), Romijn, J.A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Princen, H.M.G. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)Pregnane X receptor (PXR) agonism has been shown to affect multiple steps in both the synthesis and catabolism of HDL, but its integrated effect on HDL metabolism in vivo remains unclear. The aim of this study was to evaluate the net effect of PXR agonism on HDL metabolism in ApoE*3-Leiden (E3L) and E3L.CETP mice, well-established models for...article 2009
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Oranje, A.P. (author), Verbeek, R. (author), Verzaal, P. (author), Haspels, I. (author), Prens, E. (author), Nagelkerken, L. (author), TNO Kwaliteit van Leven (author)Background: Wet-wrap treatment (WWT) with diluted topical steroids is widely used in atopic dermatitis (AD). Mice with transgenic overexpression of human apolipoprotein C1 (APOC1) in the liver and the skin are not only characterized by hyperlipidaemia and raised IgE levels, but also by pruritic dermatitis and a disturbed skin barrier function,...article 2009
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Treijtel, N. (author), Eijkeren, J.C.H.v. (author), Nijmeijer, S. (author), van der Greef de - Sandt, I.C.J. (author), Freidig, A.P. (author), TNO Kwaliteit van Leven (author)The metabolism and active transport of ritonavir and saquinavir were studied using sandwich-cultured rat hepatoyctes and rat liver microsomes. For ritonavir four comparable metabolites were observed in the sandwich-culture and in microsomes. For saquinavir eight metabolites were observed in sandwich-culture and 14 different metabolites in...article 2009
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Stone, O.A. (author), Richer, C. (author), Emanueli, C. (author), van Weel, V. (author), Quax, P.H.A. (author), Katare, R. (author), Kraenkel, N. (author), Campagnolo, P. (author), Barcelos, L.S. (author), Siragusa, M. (author), Sala-Newby, G.B. (author), Baldessari, D. (author), Mione, M. (author), Vincent, M.P. (author), Benest, A.V. (author), Al Haj Zen, A. (author), Gonzalez, J. (author), Bates, D.O. (author), Alhenc-Gelas, F. (author), Madeddu, P. (author), TNO Kwaliteit van Leven (author)OBJECTIVE : Human Tissue Kallikrein (hKLK1) overexpression promotes an enduring neovascularization of ischemic tissue, yet the cellular mechanisms of hKLK1-induced arteriogenesis remain unknown. Furthermore, no previous study has compared the angiogenic potency of hKLK1, with its loss of function polymorphic variant, rs5515 (R53H), which...article 2009
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Parlevliet, E.T. (author), Schröder-van der Elst, J.P. (author), Corssmit, E.P.M. (author), Picha, K. (author), O'Neil, K. (author), Stojanovic-Susulic, V. (author), Ort, T. (author), Havekes, L.M. (author), Romijn, J.A. (author), Pijl, H. (author), TNO Kwaliteit van Leven (author)CNTO736 is a glucagon-like peptide (GLP) 1 receptor agonist that incorporates a GLP-1 peptide analog linked to the Mimeti-body platform. We evaluate the potential of acute and chronic CNTO736 treatment on insulin sensitivity and very low-density lipoprotein (VLDL) metabolism. For acute studies, diet-induced insulin-resistant C57BL76 mice...article 2009