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Gibbs, S. (author), van de Sandt, J.J.M. (author), Merk, H.F. (author), Lockley, D.J. (author), Pendlington, R.U. (author), Pease, C.K. (author), TNO Kwaliteit van Leven (author)In this review, we discuss and compare studies of xenobiotic metabolism in both human skin and 3D human skin reconstructs. In comparison to the liver, the skin is a less studied organ in terms of characterising metabolic capability. While the skin forms the major protective barrier to environmental chemical exposure, it is also a potential...article 2007
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Zuiderwijk-Sick, E.A. (author), van der Putten, C. (author), Bsibsi, M. (author), Deuzing, I.P. (author), de Boer, W. (author), Persoon-Deen, C. (author), Kondova, I. (author), Boven, L.A. (author), van Noort, J.M. (author), 't Hart, B.A. (author), Amor, S. (author), Bajramovic, J.J. (author), TNO Defensie en Veiligheid TNO Kwaliteit van Leven (author)Activated microglia are found in a variety of neuroinflammatory disorders where they have attributed roles as effector as well as antigen-presenting cells (APC). Critical determinants for the multifaceted role of microglia are the differentiation potential of microglia and their mode of activation. In this study, we have investigated the effects...article 2007
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Pires, N.M.M. (author), Eefting, D. (author), de Vries, M.R. (author), Quax, P.H.A. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)Background: Drug-eluting stents (DES) have been introduced successfully in clinical practice to prevent post angioplasty restenosis. Nevertheless, concerns about the safety of DES still exist. Objective: To investigate the vascular pathology and transcriptional responses to sirolimus and paclitaxel in a murine model for restenosis on underlying...article 2007
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Hendriksen, P.J.M. (author), Freidig, A.P. (author), Jonker, D. (author), Thissen, U. (author), Bogaards, J.J.P. (author), Mumtaz, M.M. (author), Groten, J.P. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)The present research aimed to study the interaction of three chemicals, methyl mercury, benzene and trichloroethylene, on mRNA expression alterations in rat liver and kidney measured by microarray analysis. These compounds were selected based on presumed different modes of action. The chemicals were administered daily for 14 days at the Lowest...article 2007
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Meijer, M.J. (author), Mieremet-Ooms, M.A.C. (author), van Duijn, W. (author), van der Zon, A.M. (author), Hanemaaijer, R. (author), Verheijen, J.H. (author), van Hogezand, R.A. (author), Lamers, C.B.H.W. (author), Verspaget, H.W. (author), TNO Kwaliteit van Leven (author)Background: Previous studies have shown an upregulation of matrix metalloproteinases (MMPs) in intestinal tissue of patients with inflammatory bowel disease (IBD) and significant clinical improvement after administration of the anti-TNF-α antibody infliximab. The aims of our study were to determine expression and secretion of MMP-1, -2, -3, -9,...article 2007
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TNO Kwaliteit van Leven (author), Pires, N.M.M. (author), Pols, T.W.H. (author), de Vries, M.R. (author), Tiel, C.M.van (author), Bonta, P.I. (author), Vos, M. (author), Arkenbout, E.K. (author), Pannekoek, H. (author), Jukema, J.W. (author), Quax, P.H.A. (author), de Vries, C.J.M. (author)BACKGROUND - Restenosis is a common complication after percutaneous coronary interventions and is characterized by excessive proliferation of vascular smooth muscle cells (SMCs). We have shown that the nuclear receptor Nur77 protects against SMC-rich lesion formation, and it has been demonstrated that 6-mercaptopurine (6-MP) enhances Nur77...article 2007
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Pieterse, B. (author), Jellema, R.H. (author), van der Werf, M.J. (author), TNO Kwaliteit van Leven (author)Messenger RNA levels change on a minutes scale due to both degradation and de novo transcription. Consequently, alterations in the transcript profiles that are not representative for the condition of interest are easily introduced during sample harvesting and work-up. In order to avoid these unwanted changes we have validated a - 45°C methanol...article 2006
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Lopatinskaya, L. (author), Zwemmer, J. (author), Uitdehaag, B. (author), Lucas, K. (author), Polman, C. (author), Nagelkerken, L. (author), TNO Kwaliteit van Leven (author)TNF-α, IL-12p35, IL-12p40, IL-4, IL-10, TGF-β1, CCR3, CXCR3, CCR5, Fas and FasL mRNA levels in PBMC of 25 multiple sclerosis (MS) patients were quantified at baseline by real-time PCR according to a post-hoc study design. The baseline values of the different markers were analysed with respect to their correlation with the increase in disability...article 2006
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Mandelin, J. (author), Hukkanen, M. (author), Li, T.F. (author), Korhonen, M. (author), Liljeström, M. (author), Sillat, T. (author), Hanemaaijer, R. (author), Salo, J. (author), Santavirta, S. (author), Konttinen, Y.T. (author), TNO Kwaliteit van Leven (author)Healthy bone is a rigid yet living tissue that undergoes continuous remodeling. Osteoclasts resorb bone in the remodeling cycle. They secrete H+-ions and proteinases to dissolve bone mineral and degrade organic bone matrix, respectively. One of the main collagenolytic proteinase in osteoclasts is cathepsin K, a member of papain family cysteine...article 2006
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Schepers, A. (author), de Vries, M.R. (author), van Leuven, C.J. (author), Grimbergen, J.M. (author), Holers, V.M. (author), Daha, M.R. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)BACKGROUND - Venous bypass grafts may fail because of development of intimal hyperplasia and accelerated atherosclerosis. Inflammation plays a major role in these processes. Complement is an important part of the immune system and participates in the regulation of inflammation. The exact role of complement in the process of accelerated...article 2006
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Duivenvoorden, I. (author), Voshol, P.J. (author), Rensen, P.C.N. (author), van Duyvenvoorde, W. (author), Romijn, J.A. (author), Emeis, J.J. (author), Havekes, L.M. (author), Nieuwenhuizen, W.F. (author), TNO Kwaliteit van Leven (author)Background: The prevalence of dyslipidemia and obesity resulting from excess energy intake and physical inactivity is increasing. The liver plays a pivotal role in systemic lipid homeostasis. Effective, natural dietary interventions that lower plasma lipids and promote liver health are needed. Objective: Our goal was to determine the effect of...article 2006
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Post, S.M. (author), Groenendijk, M. (author), van der Hoogt, C.C. (author), Fievet, C. (author), Luc, G. (author), Hoekstra, M. (author), Princen, H.M.G. (author), Staels, B. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)OBJECTIVE - High-density lipoprotein (HDL) plays a key role in protection against development of atherosclerosis by reducing inflammation, protecting against LDL oxidation, and promoting reverse cholesterol transport from peripheral tissues to the liver for secretion into bile. Cholesterol 7α-hydroxylase (Cyp7a1) catalyzes the rate-limiting step...article 2006
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TNO Kwaliteit van Leven (author), Steenvoorden, M.M.C. (author), Huizinga, T.W.J. (author), Verzijl, N. (author), Bank, R.A. (author), Ronday, H.K. (author), Luning, H.A.F. (author), Lafeber, F.P.J.G. (author), Toes, R.E.M. (author), de Groot, J. (author)Objective. The major risk factor for osteoarthritis (OA) is aging, but the mechanisms underlying this risk are only partly understood. Age-related accumulation of advanced glycation end products (AGEs) could be one of these mechanisms. We undertook this study to investigate the role of the receptor for AGEs (RAGE) in mediating the cellular...article 2006
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Brinckmann, J. (author), Kim, S. (author), Wu, J. (author), Reinhardt, D.P. (author), Batmunkh, C. (author), Metzen, E. (author), Notbohm, H. (author), Bank, R.A. (author), Krieg, T. (author), Hunzelmann, N. (author), TNO Kwaliteit van Leven (author)The major pathological processes of systemic scleroderma (SSc) comprise inflammation and microvascular damage in the early or acute progressive stage as well as tissue fibrosis and hypoxia in the chronic end stage. Fibrosis seems to be a general phenomenon characterized by an increase of hydroxylysine aldehyde derived collagen cross-links which...article 2005
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Hulzebos, C.V. (author), Voshol, P.J. (author), Wolters, H. (author), Kruit, J.K. (author), Ottenhof, R. (author), Groen, A.K. (author), Stellaard, F. (author), Verkade, H.J. (author), Kuipers, F. (author), TNO Preventie en Gezondheid (author)Background/Aims: Bile flow consists of bile salt-dependent bile flow (BSDF), generated by canalicular secretion of bile salts, and bile salt-independent flow (BSIF), probably of combined canalicular and ductular origin. Bile salt transport proteins have been identified in cholangiocytes, suggesting a role in control of BSDF and/or in control of...article 2005
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Zuurmond, A.M. (author), Slot van der-Verhoeven, A.J. (author), van Dura, E.A. (author), de Groot, J. (author), Bank, R.A. (author), TNO Kwaliteit van Leven (author)Collagen deposits in fibrotic lesions often display elevated levels of hydroxyallysine (pyridinoline) cross-links. The relation between the occurrence of pyridinoline cross-links and the irreversibility of fibrosis suggests that these cross-links contribute to the aberrant accumulation of collagen. Based on its inhibitory effect on lysyl...article 2005
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Heijboer, A.C. (author), van den Hoek, A.M. (author), Pijl, H. (author), Voshol, P.J. (author), Havekes, L.M. (author), Romijn, J.A. (author), Corssmit, E.P.M. (author), TNO Kwaliteit van Leven (author)Aims/hypothesis: The present study was conducted to evaluate the effects of central administration of melanotan II (MTII), a melanocortin-3/4 receptor agonist, on hepatic and whole-body insulin sensitivity, independent of food intake and body weight. Methods: Over a period of 24 h, 225 ng of MTII was injected in three aliquots into the left...article 2005
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Witkamp, R.F. (author), TNO Kwaliteit van Leven (author)This review discusses some of the recent developments in genomics and its current and future relevance for veterinary pharmacology and toxicology. With the rapid progress made in this field several new approaches in pharmacological and toxicological research have developed and drug discovery and drug development strategies have changed...article 2005
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Monraats, P.S. (author), Pires, N.M.M. (author), Schepers, A. (author), Agema, W.R.P. (author), Boesten, L.S.M. (author), de Vries, M.R. (author), Zwinderman, A.H. (author), de Maat, M.P.M. (author), Doevendans, P.A.F.M. (author), de Winter, R.J. (author), Tio, R.A. (author), Waltenberger, J. (author), 't Hart, L.M. (author), Frants, R.R. (author), Quax, P.H.A. (author), van Vlijmen, B.J.M. (author), Havekes, L.M. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNFα, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER)...article 2005
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Joosten, V. (author), Gouka, R.J. (author), van den Hondel, C.A.M.J.J. (author), Verrips, C.T. (author), Lokman, B.C. (author), TNO Kwaliteit van Leven TNO Voeding (author)We report the expression and production of llama variable heavy-chain antibody fragments (VHHs) by Aspergillus awamori. Fragments encoding VHHs were cloned in a suitable Aspergillus expression vector and transformants secreting VHH fragments were analysed for integrated gene copy-numbers, mRNA levels and protein production. Functional V HHs were...article 2005