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Botschuijver, S. (author), Roeselers, G. (author), Levin, E. (author), Jonkers, D.M. (author), Welting, O. (author), Heinsbroek, S.E.M. (author), de Weerd, H.H. (author), Boekhout, T. (author), Fornai, M. (author), Masclee, A.A. (author), Schuren, F.H.J. (author), de Jonge, W.J. (author), Seppen, J. (author), van den Wijngaard, R.M. (author)
Background & Aims Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in the activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in the development of IBS. We analyzed intestinal mycobiomes of patients with...
article 2017
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van der Heijden, R.A. (author), Morrison, M.C. (author), Sheedfar, F. (author), Mulder, P. (author), Schreurs, M. (author), Hommelberg, P.P.H. (author), Hofker, M.H. (author), Schalkwijk, C. (author), Kleemann, R. (author), Tietge, U.J.F. (author), Koonen, D.P.Y. (author), Heeringa, P. (author)
Background. Naturally occurring substances from the flavanol and anthocyanin family of polyphenols have been proposed to exert beneficial effects in the course of obesity. We hypothesized that their effects on attenuating obesity-induced dyslipidemia as well as the associated inflammatory sequelae especially have health-promoting potential....
article 2016
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van Dam, A.D. (author), Nahon, K.J. (author), Kooijman, S. (author), van den Berg, S.M. (author), Kanhai, A.A. (author), Kikuchi, T. (author), Heemskerk, M.M. (author), van Harmelen, V. (author), Lombès, M. (author), van den Hoek, A.M. (author), de Winther, M.P. (author), Lutgens, E. (author), Guigas, B. (author), Rensen, P.C. (author), Boon, M.R. (author)
Salsalate improves glucose intolerance and dyslipidemia in type 2 diabetes patients, but the mechanism is still unknown. The aim of the current study was to unravel the molecular mechanisms involved in these beneficial metabolic effects of salsalate by treating mice with salsalate during and after development of high-fat diet-induced obesity. We...
article 2015
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Alić, L. (author), van Vliet, M. (author), Wielopolski, P.A. (author), ten Hagen, T.L.M. (author), van Dijke, C.F. (author), Niessen, W.J. (author), Veenland, J.F. (author)
Experimental evidence supports an association between heterogeneity in tumor perfusion and response to chemotherapy/radiotherapy, disease progression and malignancy. Therefore, changes in tumor perfusion may be used to assess early effects of tumor treatment. However, evaluating changes in tumor perfusion during treatment is complicated by...
article 2013
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Wielinga, P.Y., (author), Harthoorn, L.F., (author), Verschuren, L., (author), Schoemaker, M.H., (author), Jouni, Z.E., (author), van, Tol, E.A.F. (author), Kleemann, R., (author), Kooistra, T. (author)
Scope: This study addresses whether early life arachidonic acid (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism, and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic mice, a humanized model for hyperlipidemia and...
article 2012
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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), TNO Kwaliteit van Leven (author)
The peroxisome proliferator-activated receptor alpha (PPARα) 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 controversial,...
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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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), TNO Kwaliteit van Leven (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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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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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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de Jong, W.H. (author), Arts, J.H.E. (author), de Klerk, A. (author), Schijf, M.A. (author), Ezendam, J. (author), Kuper, C.F. (author), van Loveren, H. (author), TNO Kwaliteit van Leven (author)
There are currently no validated animal models that can identify low molecular weight (LMW) respiratory sensitizers. The Local Lymph Node Assay (LLNA) is a validated animal model developed to detect contact sensitizers using skin exposure, but all LMW respiratory sensitizers tested so far were also positive in this assay. Discrimination between...
article 2009
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Joosen, M.J.A. (author), Jousma, E. (author), van den Boom, T.M. (author), Kuijpers, W.C. (author), Smit, A.B. (author), Lucassen, P.J. (author), van Helden, H.P.M. (author), TNO Defensie en Veiligheid (author)
To date, treatment of organophosphate (OP) poisoning shows several shortcomings, and OP-victims might suffer from lasting cognitive deficits and sleep–wake disturbances. In the present study, long-term effects of soman poisoning on learning ability, memory and neurogenesis were investigated in rats, treated with the anticholinergic atropine and...
article 2009
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Kienhuis, A.S. (author), van de Poll, M.C.G. (author), Wortelboer, H. (author), van Herwijnen, M. (author), Gottschalk, R. (author), de Jong, C.H.C. (author), Boorsma, A. (author), Paules, R.S. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), van Delft, J.H.M. (author), TNO Kwaliteit van Leven (author)
The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these model systems for human risk assessment by direct...
article 2009
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Kersten, S. (author), Lichtenstein, L. (author), Steenbergen, E. (author), Mudde, K. (author), Hendriks, H.F.J. (author), Hesselink, M.K. (author), Schrauwen, P. (author), Müller, M. (author), TNO Kwaliteit van Leven (author)
OBJECTIVE-: Plasma lipoprotein levels are determined by the balance between lipoprotein production and clearance. Recently, angiopoietin-like protein 4 (ANGPTL4) was uncovered as a novel endocrine factor that potently raises plasma triglyceride levels by inhibiting triglyceride clearance. However, very little is known about ANGPTL4 in human....
article 2009
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Noort, D. (author), Fidder, A. (author), Degenhardt-Langelaan, C.E.A.M. (author), Hulst, A.G. (author), TNO Defensie en Veiligheid (author)
The persistence in rats of sulfur mustard adducts to albumin and hemoglobin was studied in vivo after exposure (intravenously; 0.3 mg/kg; approximately 0.1 LD50) of rats to sulfur mustard. The albumin adduct (S-HETE)Cys-Pro-Tyr was detectable up to 7 days after the exposure, while the adduct to the N-terminal valine in hemoglobin was still...
article 2008
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Staal, Y.C.M. (author), Pushparajah, D.S. (author), van Herwijnen, M.H.M. (author), Gottschalk, R.W.H. (author), Maas, L.M. (author), Ioannides, C. (author), van Schooten, F.J. (author), van Delft, J.H.M. (author), TNO Kwaliteit van Leven (author)
Although exposure to polycyclic aromatic hydrocarbons (PAHs) occurs mostly through mixtures, hazard and risk assessment are mostly based on the effects caused by individual compounds. The objective of the current study was to investigate whether interactions between PAHs occur, focusing on gene expression (as measured by cDNA microarrays) and...
article 2008
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Adourian, A. (author), Jennings, E. (author), Balasubramanian, R. (author), Hines, W.M. (author), Damian, D. (author), Plasterer, T.N. (author), Clish, C.B. (author), Stroobant, P. (author), McBurney, R. (author), Verheij, E.R. (author), Bobeldijk, I. (author), van der Greef, J. (author), Lindberg, J. (author), Kenne, K. (author), Andersson, U. (author), Hellmold, H. (author), Nilsson, K. (author), Salter, H. (author), Schuppe-Koistinen, I. (author), TNO Kwaliteit van Leven (author)
High-throughput biomolecular profiling techniques such as transcriptomics, proteomics and metabolomics are increasingly being used in in vivo studies to recognize and characterize effects of xenobiotics on organs and systems. Of particular interest are biomarkers of treatment-related effects which are detectible in easily accessible biological...
article 2008
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Janssen, G.B. (author), Penninks, A.H. (author), Knippels, L.M.J. (author), van Zijverden, M. (author), Spanhaak, S. (author), TNO Kwaliteit van Leven (author)
This paper describes studies performed with ERA-63 a low molecular weight pharmaceutical with intended immunomodulatory effects. Since this compound was also known to have estrogenic activity a non-conventional approach was taken in order to differentiate between estrogenic and non-estrogenic-induced immunomodulatory effects. EE was included not...
article 2008
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van den Hoek, A.M. (author), van Heijningen, C. (author), van der Schröder - Elst, J.P. (author), Ouwens, D.M. (author), Havekes, L.M. (author), Romijn, J.A. (author), Kalsbeek, A. (author), Pijl, H. (author), TNO Kwaliteit van Leven (author)
OBJECTIVE-We recently showed that intracerebroventricular infusion of neuropeptide Y (NPY) hampers inhibition of endogenous glucose production (EGP) by insulin in mice. The down stream mechanisms responsible for these effects of NPY remain to be elucidated. Therefore, the aim of this study was to establish whether intracerebroventricular NPY...
article 2008
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