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Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice

van der Hoorn, J.W.A. (author), de Haan, W. (author), Berbée, J.P.P. (author), Havekes, L.M. (author), Jukema, J.W. (author), Rensen, P.C. (author), Princen, H.M.G. (author), TNO Kwaliteit van Leven (author)

Objective - Niacin potently decreases plasma triglycerides and LDL-cholesterol. In addition, niacin is the most potent HDL-cholesterol- increasing drug used in the clinic. In the present study, we aimed at elucidation of the mechanism underlying its HDL-raising effect. Methods and Results - InAPOE*3Leiden transgenic mice expressing the human...

article 2008

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Efficacy of caffeine and modafinil in counteracting sleep deprivation in the marmoset monkey

TNO Defensie en Veiligheid (author), van Vliet, S.A.M. (author), Jongsma, M.J. (author), Vanwersch, R.A.P. (author), Olivier, B. (author), Philippens, I.H.C.H.M. (author)

article 2008

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The respiratory local lymph node assay as a tool to study respiratory sensitizers

Arts, J.H.E. (author), de Jong, W.H. (author), van Triel, J.J. (author), Schijf, M.A. (author), de Klerk, A. (author), van Loveren, H. (author), Kuper, C.F. (author), TNO Kwaliteit van Leven (author)

The local lymph node assay (LLNA) is used to test the potential of low molecular weight (LMW) compounds to induce sensitization via the skin. In the present study, a respiratory LLNA was developed. Male BALB/c mice were exposed head/nose-only during three consecutive days for 45, 90, 180, or 360 min/day to various LMW allergens. Ear application ...

article 2008

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Angiogenesis: An improved in vitro biological system and automated image-based workflow to aid identification and characterization of angiogenesis and angiogenic modulators

Santos, A.F. (author), Zaltsman, A.B. (author), Martin, R.C. (author), Kuzmin, A. (author), Alexandrov, Y. (author), Roquemore, E.P. (author), Jessop, R.A. (author), Erck, M.G.M.V. (author), Verheijen, J.H. (author), TNO Kwaliteit van Leven (author)

Angiogenesis is a general term describing formation of new tube-like microvessel sprouts that are the size of capillary blood vessels. Angiogenesis is fundamental in key stages of embryonic development, organ formation, and wound repair and is also involved in the development and progression of a variety of pathological conditions, including...

article 2008

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Exposure of human cartilage tissue to low concentrations of blood for a short period of time leads to prolonged cartilage damage: An in vitro study

Jansen, N.W.D. (author), Roosendaal, G. (author), Bijlsma, J.W.J. (author), de Groot, J. (author), Lafeber, F.P.J.G. (author), TNO Kwaliteit van Leven (author)

Objective. Joint bleeding, or hemarthrosis, leads in time to severe joint damage. This study was carried out to test the in vitro thresholds of exposure time and concentration that lead to irreversible joint damage, to add to the discussion on the usefulness of aspiration of the joint after a hemorrhage. Methods. Explants of healthy human...

article 2007

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Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents. III. PBPK modeling of white spirit constituents as a tool for integrating animal and human test data

Hissink, A.M. (author), Krüse, J. (author), Kulig, B.M. (author), Verwei, M. (author), Muijser, H. (author), Salmon, F. (author), Leenheers, L.H. (author), Owen, D.E. (author), Lammers, J.H.C.M. (author), Freidig, A.P. (author), McKee, R.H. (author), TNO Kwaliteit van Leven (author)

As part of a project designed to develop a framework for extrapolating acute central nervous system (CNS) effects of hydrocarbon solvents in animals to humans, experimental studies were conducted in rats and human volunteers in which acute CNS effects were measured and toxicokinetic data were collected. A complex hydrocarbon solvent, white...

article 2007

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One-generation reproductive toxicity study of DHA-rich oil in rats

Blum, R. (author), Kiy, T. (author), Waalkens-Berendsen, I. (author), Wong, A.W. (author), Roberts, A. (author), TNO Kwaliteit van Leven (author)

Polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are natural constituents of the human diet. DHA-algal oil is produced through the use of the marine protist, Ulkenia sp. The reproductive toxicity of DHA-algal oil was assessed in a one-generation study. Rats were provided diets containing DHA-algal oil at concentrations of 1.5,...

article 2007

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Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion

Smeets, P.A.M. (author), Vidarsdottir, S. (author), de Graaf, C. (author), Stafleu, A. (author), van Osch, M.J.P. (author), Viergever, M.A. (author), Pijl, H. (author), van der Grond, J. (author), TNO Kwaliteit van Leven (author)

We previously showed that hypothalamic neuronal activity, as measured by the blood oxygen level-dependent (BOLD) functional MRI signal, declines in response to oral glucose intake. To further explore the mechanism driving changes in hypothalamic neuronal activity in response to an oral glucose load, we here compare hypothalamic BOLD signal...

article 2007

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Effect of fortified spread on homocysteine concentration in apparently healthy volunteers

van Vliet, T. (author), Jacobs, R.G.J.M. (author), de Deckere, E. (author), van den Berg, H. (author), de Bree, A. (author), van der Put, N.M.J. (author), TNO Kwaliteit van Leven (author)

Objective: To determine the effect of folic acid, vitamin B6 and B12 fortified spreads on the blood concentrations of these vitamins and homocysteine. Design and setting: A 6-week randomized, double-blinded, placebo-controlled, parallel trial carried out in a clinical research center. Subjects: One hundred and fifty healthy volunteers (50% males...

article 2007

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Sensitivity of 1H NMR analysis of rat urine in relation to toxicometabonomics. Part I: Dose-dependent toxic fffects of Bromobenzene and paracetamol

Schoonen, W.G.E.J. (author), Kloks, C.P.A.M. (author), Ploemen, J.P.H.T.M. (author), Horbach, G.J. (author), Smit, M.J. (author), Zandberg, P. (author), Mellema, J.R. (author), van Zuylen, C.T. (author), Tas, A.C. (author), van Nesselrooij, J.H.J. (author), Vogels, J.T.W.E. (author), TNO Kwaliteit van Leven (author)

1H nuclear magnetic resonance (NMR) spectroscopy of rat urine in combination with pattern recognition analysis was evaluated for early noninvasive detection of toxicity of investigational chemical entities. Bromobenzene (B) and paracetamol (P) were administered at five single oral dosages between 2 and 500 mg/kg and between 6 and 1800 mg/kg,...

article 2007

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Mouse models for atherosclerosis and pharmaceutical modifiers

Zadelaar, A.S.M. (author), Kleemann, R. (author), Verschuren, L. (author), de Vries-van der Weij, J. (author), van der Hoorn, J. (author), Princen, H.M. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)

Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically and will develop lesions comparable to those in...

article 2007

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Does skin prick test reactivity to purified allergens correlate with clinical severity of peanut allergy?

Peeters, K.A.B.M. (author), Koppelman, S.J. (author), van Hoffen, E. (author), van der Tas, C.W.H. (author), den Hartog Jager, C.F. (author), Penninks, A.H. (author), Hefle, S.L. (author), Bruijnzeel-Koomen, C.A.F.M. (author), Knol, E.F. (author), Knulst, A.C. (author), TNO Kwaliteit van Leven (author)

Background: Recognition of specific peanut allergens or the diversity of IgE binding to peanut allergens may play a role in the elicitation of severe allergic reactions. Objective: To investigate whether sensitization to individual allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 is correlated with clinical severity. Methods: The reactivity of...

article 2007

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Statistical validation of megavariate effects in ASCA

Vis, D.J. (author), Westerhuis, J.A. (author), Smilde, A.K. (author), van der Greef, J. (author), TNO Kwaliteit van Leven (author)

Background: Innovative extensions of (M) ANOVA gain common ground for the analysis of designed metabolomics experiments. ASCA is such a multivariate analysis method; it has successfully estimated effects in megavariate metabolomics data from biological experiments. However, rigorous statistical validation of megavariate effects is still...

article 2007

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Tolerization of an established αb-crystallin-reactive T-cell response by intravenous antigen

Verbeek, R. (author), van der Mark, K. (author), Wawrousek, E.F. (author), Plomp, A.C. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven (author)

Tolerance induction to prevent activation of a naïve T-cell repertoire has been well documented in rodents and can be readily achieved by intravenous, oral or intranasal administration of antigen in the absence of adjuvants. In autoimmune diseases such as multiple sclerosis (MS) the presence of an established memory/effector T-cell repertoire...

article 2007

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TAFI and pancreatic carboxypeptidase B modulate in vitro capillary tube formation by human microvascular endothelial cells

TNO Kwaliteit van Leven (author), Guimarães, A.H.C. (author), Laurens, N. (author), Weijers, E.M. (author), Koolwijk, P. (author), van Hinsbergh, V.W.M. (author), Rijken, D.C. (author)

OBJECTIVE - Besides having a key role in fibrinolysis, the plasminogen system has been implicated in cell migration and angiogenesis. A common mechanism is the binding of plasminogen to carboxy-terminal lysine residues in partially degraded fibrin or on cellular surfaces. Here we examined the involvement of thrombin activatable fibrinolysis...

article 2007

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ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT

TNO Kwaliteit van Leven (author), Ceconi, C. (author), Fox, K.M. (author), Remme, W.J. (author), Simoons, M.L. (author), Bertrand, M. (author), Parrinello, G. (author), Kluft, C. (author), Blann, A. (author), Cokkinos, D. (author), Ferrari, R. (author)

Objectives: EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease [EUROPA] demonstrates reduction in cardiovascular mortality and myocardial infarction for a possible vascular and antiatherosclerotic effect of angiotensin-converting enzyme (ACE) inhibition with perindopril. Our objective was to study...

article 2007

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Chronic PYY3-36 treatment promotes fat oxidation and ameliorates insulin resistance in C57BL6 mice

Gaubius Instituut TNO (author), van den Hoek, A.M. (author), Heijboer, A.C. (author), Voshol, P.J. (author), Havekes, L.M. (author), Romijn, J.A. (author), Corssmit, E.P.M. (author), Pijl, H. (author)

PYY3-36 is a gut-derived hormone acting on hypothalamic nuclei to inhibit food intake. We recently showed that PYY3-36 acutely reinforces insulin action on glucose disposal in mice. We aimed to evaluate effects of PYY3-36 on energy metabolism and the impact of chronic PYY3-36 treatment on insulin sensitivity. Mice received a single injection of...

article 2007

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Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies

Wilkinson, S.C. (author), Maas, W.J.M. (author), Nielsen, J.B. (author), Greaves, L.C. (author), van de Sandt, J.J.M. (author), Williams, F.M. (author), TNO Kwaliteit van Leven TNO Voeding (author)

Objectives: To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Methods: Percutaneous penetration of caffeine (log P -0.01), testosterone ...

article 2006

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Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways

Verhoeckx, K.C.M. (author), Korthout, H.A.A.J. (author), van Meeteren-Kreikamp, A.P. (author), Ehlert, K.A. (author), Wang, M. (author), van der Greef, J. (author), Rodenburg, R.J.T. (author), Witkamp, R.F. (author), TNO Kwaliteit van Leven (author)

There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Δ9-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa extracts and its main non-psychoactive constituent Δ9...

article 2006

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Within-animal variation as an indication of the minimal magnitude of the critical effect size for continuous toxicological parameters applicable in the benchmark dose approach

Dekkers, S. (author), Telman, J. (author), Rennen, M.A.J. (author), Appel, M.J. (author), de Heer, C. (author), TNO Industrie en Techniek TNO Kwaliteit van Leven (author)

In this study, the within-animal variation in routinely studied continuous toxicological parameters was estimated from temporal fluctuations in individual healthy nonexposed animals. Assuming that these fluctuations are nonadverse, this within-animal variation may be indicative of the minimal magnitude of the critical effect size (CES). The CES...

article 2006