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Low Dose Betaine Supplementation Leads to Immediate and Long Term Lowering of Plasma Homocysteine in Healthy Men and Women

Olthof, M.R. (author), van Vliet, T. (author), Boelsma, E. (author), Verhoef, P. (author)

High plasma homocysteine is a risk for cardiovascular disease and can be lowered through supplementation with 6 g/d of betaine. However, dietary intake of betaine is ∼0.5-2 g/d. Therefore, we investigated whether betaine supplementation in the range of dietary intake lowers plasma homocysteine concentrations in healthy adults. Four groups of 19...

article 2003

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Long-term, low-level exposure of guinea pigs and marmosets to sarin vapor in air: Lowest observable effect level

van Helden, H.P.M. (author), Trap, H.C. (author), Oostdijk, J.P. (author), Kuijpers, W.C. (author), Langenberg, J.P. (author), Benschop, H.P. (author), Prins Maurits Laboratorium TNO (author)

Realistic scenarios for low-level exposure to nerve agents will often involve exposures over several hours to extremely low doses of agent. In order to expose animals to the lowest controllable concentrations of agent and to increase exposure times until a lowest observable effect level (LOEL) becomes measurable, a validated system was developed...

article 2003

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Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: The Netherlands cohort study on diet and cancer

van Engeland, M. (author), Weijenberg, M.P. (author), Roemen, G.M.J.M. (author), Brink, M. (author), de Bruïne, A.P. (author), Goldbohm, R.A. (author), van den Brandt, P.A. (author), Baylin, S.B. (author), de Goeij, A.F.P.M. (author), Herman, J.G. (author)

Sporadic colorectal cancer (CRC) is characterized by genetic and epigenetic changes such as regional DNA hypermethylation and global DNA hypomethylation. Epidemiological and animal studies suggest that aherrant DNA methylation is associated with low dietary folate intake, which is aggravated by high alcohol intake. The relationship between...

article 2003

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Interplay between MRP Inhibition and Metabolism of MRP Inhibitors: The Case of Curcumin

Wortelboer, H.M. (author), Usta, M. (author), van der Velde, A.E. (author), Boersma, M.G. (author), Spenkelink, B. (author), van Zanden, J.J. (author), Rietjens, I.M.C.M. (author), van Bladeren, P.J. (author), Cnubben, N.H.P. (author)

The multidrug resistance proteins MRP1 and MRP2 are efflux transporters with broad substrate specificity, including glutathione, glucuronide, and sulfate conjugates. In the present study, the interaction of the dietary polyphenol curcumin with MRP1 and MRP2 and the interplay between curcumin-dependent MRP inhibition and its glutathione-dependent...

article 2003

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Approaches to induce and elicit respiratory allergy: Impact of route and intensity of exposure

Arts, J.H.E. (author), Kuper, C.F. (author), TNO Voeding (author)

Although a number of test protocols have been developed to predict respiratory allergenic potential, none of these are widely applied or fully accepted. However, given the serious health problems caused by respiratory allergy and the ever-increasing stream of new chemicals into workplaces, early identification of chemical respiratory allergens...

article 2003

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Selective effects of carbamate pesticides on rat neuronal nicotinic acetylcholine receptors and rat brain acetylcholinesterase

Prins Maurits Laboratorium TNO (author), Smulders, C.J.G.M. (author), Bueters, T.J.H. (author), van Kleef, R.G.D.M. (author), Vijverberg, H.P.M. (author)

Effects of commonly used carbamate pesticides on rat neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes have been investigated using the two-electrode voltage clamp technique. The potencies of these effects have been compared to the potencies of the carbamates to inhibit rat brain acetylcholinesterase. The potency...

article 2003

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Decrease of hemostatic cardiovascular risk factors by aggressive vs. conventional atorvastatin treatment in patients with Type 2 diabetes mellitus.

van de Ree, M.A. (author), de Maat, M.P. (author), Kluft, C. (author), Meinders, A.E. (author), Princen, H.M. (author), Huisman, M.V. (author), Gaubius Instituut TNO (author)

BACKGROUND: Patients with Type 2 diabetes mellitus have increased levels of hemostatic risk variables for cardiovascular disease, such as fibrinogen, von Willebrand factor (VWF), factor (F)VIIa, d-dimer and plasminogen activator inhibitor-1 (PAI-1). OBJECTIVES: To evaluate the effect of aggressive vs. standard dose atorvastatin on hemostatic...

article 2003

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Stabilization versus inhibition of TAFIa by competitive inhibitors in vitro

Gaubius Instituut TNO (author), Walker, J.B. (author), Hughes, B. (author), James, I. (author), Haddock, P. (author), Kluft, C. (author), Bajzar, L. (author)

Two competitive inhibitors of TAFIa (activated thrombin-activable fibrinolysis inhibitor), 2-guanidinoethyl-mercaptosuccinic acid and potato tuber carboxypeptidase inhibitor, variably affect fibrinolysis of clotted human plasma. Depending on their concentration, the inhibitors shortened, prolonged, or had no effect on lysis in vitro. The...

article 2003

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Particle size-dependent total mass deposition in lungs determines inhalation toxicity of cadmium chloride aerosols in rats: Application of a multiple path dosimetry model

Cassee, F.R. (author), Muijser, H. (author), Duistermaat, E. (author), Freijer, J.J. (author), Geerse, E.K.B. (author), Marijnissen, J.C.M. (author), Arts, J.H.E. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

The relative importance of the three particulate matter (PM) size fractions in ambient air, i.e. coarse (2.5-10 μm), fine (0.1-2.5 μm) and ultrafine (< 0.1 μm) fractions, on the induction of adverse health effects is still unknown. Moreover, there is no straightforward relationship between ambient concentration levels, exposure (external dose)...

article 2002

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Evaluation of the sensory irritation test (alarie test) for the assessment of respiratory tract irritation

Bos, P.M.J. (author), Busschers, M. (author), Arts, J.H.E. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Within the framework of risk assessment of existing substances in the EC the irritating properties on the respiratory tract should be considered. Since no standardized test is available it was studied whether the Alarie test could be used for this purpose, as proposed by the Technical Guidance Document for new and existing substances. The...

article 2002

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The range of minimum provoking doses in hazelnut-allergic patients as determined by double-blind, placebo-controlled food challenges

Wensing, M. (author), Penninks, A.H. (author), Hefle, S.L. (author), Akkerdaas, J.H. (author), van Ree, R. (author), Koppelman, S.J. (author), Bruijnzeel-Koomen, C.A.F.M. (author), Knulst, A.C. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Background: The risk for allergic reactions depends on the sensitivity of individuals and the quantities of offending food ingested. The sensitivity varies among allergic individuals, as does the threshold dose of a food allergen capable of inducing an allergic reaction. Objective: This study aimed at determining the distribution of minimum...

article 2002

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Inhibition of zaleplon metabolism by cimetidine in the human liver: In vitro studies with subcellular fractions and precision-cut liver slices

Renwick, A.B. (author), Ball, S.E. (author), Tredger, J.M. (author), Price, R.J. (author), Walters, D.G. (author), Kao, J. (author), Scatina, J.A. (author), Lake, B.G. (author), TNO Voeding (author)

The effect of cimetidine on the metabolism of zaleplon (ZAL) in human liver subcellular fractions and precision-cut liver slices was investigated. 2. ZAL was metabolized to a number of products including 5-oxo-ZAL (M2), which is known to be formed by aldehyde oxidase, N-desethyl-ZAL (DZAL), which is known to be formed by CYP3A forms, and N...

article 2002

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Comparative in vitro-in vivo percutaneous penetration of the fungicide ortho-phenylphenol

Cnubben, N.H.P. (author), Elliott, G.R. (author), Hakkert, B.C. (author), Meuling, W.J.A. (author), van de Sandt, J.J.M. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)

The validity of in vitro and in vivo methods for the prediction of percutaneous penetration in humans was assessed using the fungicide ortho-phenylphenol (OPP) (log Po/w 3.28, MW 170.8, solubility in water 0.7 g/L). In vivo studies were performed in rats and human volunteers, applying the test compound to the dorsal skin and the volar aspect of...

article 2002

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Selenium supplementation and selenium status of dairy cows fed diets based on grass, grass silage or maize silage

Gierus, M. (author), Schwarz, F.J. (author), Kirchgessner, M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

In three separate trial series (TS) the effect of diet composition on selenium (Se) status of dairy cows were investigated. Diets were formulated based mainly on grass (TS1), grass silage (TS2) or maize silage (TS3) with different levels of Se supplementation. Each TS comprised a total of 30 dairy cows and contained one treatment group without...

article 2002

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Statistically designed experiments in a tiered approach to screen mixtures of Fusarium mycotoxins for possible interactions

Tajima, O. (author), Schoen, E.D. (author), Feron, V.J. (author), Groten, J.P. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

This paper presents a test strategy to detect interactive effects between several mycotoxins using a DNA synthesis inhibition assay in L929 cells. The joint action of the Fusarium mycotoxins T-2 toxin (T2), deoxynivalenol (DON), nivalenol (NIV), zearalenone (ZEA) and fumonisin (FB1) was studied in a tiered approach. In the first stage, the...

article 2002

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Hazard characterisation of chemicals in food and diet: Dose response, mechanisms and extrapolation issues

Dybing, E. (author), Doe, J. (author), Groten, J. (author), Kleiner, J. (author), O'Brien, J. (author), Renwick, A.G. (author), Schlatter, J. (author), Steinberg, P. (author), Tritscher, A. (author), Walker, R. (author), Younes, M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Hazard characterisation of low molecular weight chemicals in food and diet generally use a no-observed-adverse-effect level (NOAEL) or a benchmark dose as the starting point. For hazards that are considered not to have thresholds for their mode of action, low-dose extrapolation and other modelling approaches may be applied. The default position...

article 2002

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Toxicity of terpenes to spores and mycelium of Penicillium digitatum

Wolken, W.A.M. (author), Tramper, J. (author), van der Werf, M.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Spores, although often considered metabolically inert, catalyze a variety of reactions. The use of spores instead of mycelium for bioconversions has several advantages. In this paper, we describe the difference in susceptibility of mycelium and spores against toxic substrates and products. A higher resistance of spores toward the toxic effects...

article 2002

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An in vitro model for detecting skin irritants: Methyl green-pyronine staining of human skin explant cultures

Jacobs, J.J.L. (author), Lehé, C. (author), Cammans, K.D.A. (author), Das, P.K. (author), Elliott, G.R. (author)

We evaluated the potential of human organotypic skin explant cultures (hOSECs) for screening skin irritants. Test chemicals were applied to the epidermis of the skin explants which were incubated for 4, 24 or 48 h in tissue culture medium. A decrease in epidermal RNA staining, visualised in frozen sections using a modified methyl-green pyronine ...

article 2002

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Lack of effect of doxycycline on disease activity and joint damage in patients with rheumatoid arthritis. A double blind, placebo controlled trial

van der Laan, W. (author), Molenaar, E. (author), Ronday, K. (author), Verheijen, J. (author), Breedveld, F. (author), Greenwald, R. (author), Dijkmans, B. (author), Tekoppele, J. (author), Gaubius instituut TNO (author)

Objective. To investigate the effects of doxycycline on disease activity and joint destruction in patients with rheumatoid arthritis (RA). Methods. A 36 week double blind, placebo controlled crossover trial was conducted. Patients (n = 66) received 50 mg doxycycline or placebo twice a day during 12, 24, or 36 weeks. Patient assessments were...

article 2001

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Impact of apolipoprotein(a) on in vitro angiogenesis

Schulter, V. (author), Koolwijk, P. (author), Peters, E. (author), Frank, S. (author), Hrzenjak, A. (author), Graier, W.F. (author), van Hinsbergh, V.W.M. (author), Kostner, G.M. (author), Gaubius Instituut TNO (author)

Angiostatin, which consists of the kringle I-IV domains of plasminogen and which is secreted into urine, is an efficient inhibitor of angiogenesis and tumor growth. Because N-terminal apolipoprotein(a) [apo(a)] fragments, which also contain several types of kringle IV domains, are found in urine as well, we evaluated the potential angiostatic...

article 2001