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Sweeney, R.E. (author), Langenberg, J.P. (author), Maxwell, D.M. (author), TNO Defensie en Veiligheid (author)A physiologically based pharmacokinetic (PB/PK) model has been developed in advanced computer simulation language (ACSL) to describe blood and tissue concentration-time profiles of the C(±)P(-) stereoisomers of soman after inhalation, subcutaneous and intravenous exposures at low (0.8-1.0 × LD50), medium (2-3 × LD50) and high (6 × LD50) levels...article 2006
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van der Schans, M.J. (author), Lander, B.J. (author), van der Wiel, H. (author), Langenberg, J.P. (author), Benschop, H.P. (author), Prins Maurits Laboratorium TNO (author)In continuation of our investigations on the toxicokinetics of the volatile nerve agents C(±)P(±)-soman and (±)-sarin, we now report on the toxicokinetics of the rather nonvolatile agent (±)-VX. A validated method was developed to determine blood levels of (±)-VX by means of achiral gas chromatography at blood levels ≥10 pg/ml. The ratio of the...article 2003
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- Spruit, W.E.T. (author), Trap, H.C. (author), Langenberg, J.P. (author), Benschop, H.P. (author) article 2001
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Izeboud, C.A. (author), Vermeulen, R.M. (author), Zwart, A. (author), Vos, H.P. (author), van Miert, A.S.J.P.A.M. (author), Witkamp, R.F. (author)Previous research has shown that β-adrenoceptor (β-AR) agonists have potent anti-inflammatory capabilities, e.g. represented by suppression of release of the proinflammatory cytokines. Aim of this research was to determine whether the effects of β-agonists on LPS-induced TNFα and IL-10 release are influenced by their different stereochemistry....article 2000
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van der Werf, M.J. (author), Boot, A.M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Rhodococcus euythropolis DCL14 assimilates all stereoisomers of carveol and dihydrocarveol as sole source of carbon and energy. Induction experiments with carveol- or dihydrocarveol-grown cells showed high oxygen consumption rates with these two compounds and with carvone and dihydrocarvone. (Dihydro)carveol-grown cells of R. erythropolis DCL14...article 2000
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van der Werf, M.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)A Baeyer-Villiger mono-oxygenase (BVMO), catalysing the NADPH- and oxygen-dependent oxidation of the monocyclic monoterpene ketones 1-hydroxy-2-oxolimonene, dihydrocarvone and menthone, was purified to homogeneity from Rhodococcus erythropolis DCL14. Monocyclic monoterpene ketone mono-oxygenase (MMKMO) is a monomeric enzyme of molecular mass 60...article 2000
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Spruit, W.E.T. (author), Langenberg, J.P. (author), Trap, H.C. (author), van der Wiel, H.J. (author), Helmich, R.B. (author), van Helden, H.P.M. (author), Benschop, H.P. (author)We report the first toxicokinetic studies of (±)-sarin. The toxicokinetics of the stereoisomers of this nerve agent were studied in anesthetized, atropinized, and restrained guinea pigs after intravenous bolus administration of a dose corresponding to 0.8 LD50 and after nose-only exposure to vapor concentrations yielding 0.4 and 0.8 LCt50 in an...article 2000
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Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author), van der Werf, M.J. (author), Keijzer, P.M. (author), van der Schaft, P.H. (author)Xanthobacter sp. C20 was isolated from sediment of the river Rhine using cyclohexane as sole source of carbon and energy. Xanthobacter sp. C20 converted both enantiomers of limonene quantitatively into limonene-8,9-epoxide, a not previously described bioconversion product of limonene. With (4R)-limonene, (4R,8R)-limonene-8,9-epoxide was formed...article 2000
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Bär, A. (author), Leeman, W.R. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Previous investigations have demonstrated that L-sorbose induces hemolysis of dog erythrocytes. This effect is probably the consequence of an ATP depletion of the red blood cells subsequent to inhibition of hexokinase, and thus the glycolytic pathway, by sorbose 1-phosphate. In the present study, the susceptibility of dog erythrocytes to D...article 1999
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Hulshof, K.F.A.M. (author), Erp van - Baart, M.A. (author), Anttolainen, M. (author), Becker, W. (author), Church, S.M. (author), Couet, C. (author), Hermann-Kunz, E. (author), Kesteloot, H. (author), Leth, T. (author), Martins, I. (author), Moreiras, O. (author), Moschandreas, J. (author), Pizzoferrato, L. (author), Rimestad, A.H. (author), Thorgeirsdottir, H. (author), van Amelsvoort, J.M.M. (author), Aro, A. (author), Kafatos, A.G. (author), Lanzmann-Petithory, D. (author), van Poppel, G. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Objective: To assess the intake of trans fatty acids (TFA) and other fatty acids in 14 Western European countries. Design and subjects: A maximum of 100 foods per country were sampled and centrally analysed. Each country calculated the intake of individual trans and other fatty acids, clusters of fatty acids and total fat in adults and/or the...article 1999
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Ordentlich, A. (author), Barak, D. (author), Kronman, C. (author), Benschop, H.P. (author), de Jong, L.P.A. (author), Ariel, N. (author), Barak, R. (author), Segall, Y. (author), Velan, B. (author), Shafferman, A. (author)The stereoselectivity of the phosphonylation reaction and the effects of adduct configuration on the aging process were examined for human acetylcholinesterase (HuAChE) and its selected active center mutants, using the four stereomers of 1,2,2-trimethylpropyl methylphosphonofluoridate (soman). The reactivity of wild type HuAChE toward the P(S)...article 1999
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van den Nieuwendijk, A.M.C.H. (author), Benningshof, J.C.J. (author), Wegmann, V. (author), Bank, R.A. (author), te Koppele, J.M. (author), Brussee, J. (author), van der Gen, A. (author), TNO Preventie en Gezondheid (author)A new synthetic route to reduced collagen crosslinks (LNL and HLNL) is described in this report. It enables an enantioselective synthesis of LNL. HLNL was obtained as a mixture of two diastereoisomers. This method also provides the possibility to introduce radio-labels during the synthesis.article 1999
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Prins Maurits Laboratorium TNO (author), Langenberg, J.P. (author), Spruit, W.E.T. (author), van der Wiel, H.J. (author), Trap, H.C. (author), Helmich, R.B. (author), Bergers, W.W.A. (author), van Helden, H.P.M. (author), Benschop, H.P. (author)The toxicokinetics of the four stereoisomers of the nerve agent C(±)P(±)-soman were studied in anesthetized, atropinized guinea pigs for nose-only exposure to soman vapor. During exposure the respiratory minute volume (RMV) and respiratory frequency (RF) were monitored. Blood samples were taken for chiral gas chromatographic analysis of the...article 1998
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Benschop, H.P. (author), Trap, H.C. (author), Spruit, H.E.T. (author), van der Wiel, H.J. (author), Langenberg, J.P. (author), de Jong, L.P.A. (author), Prins Maurits Laboratorium TNO (author)In order to initiate a quantitative basis for the toxicology of low level exposure to nerve agents, the toxicokinetics of soman stereoisomers during nose-only exposure for 5 h to 20 ppb (160 μg/m3) of C(±)P(±)- soman in air were studied in restrained, anesthetized, and atropinized guinea pigs. The concentrations of the toxic C(±)P(-)-soman...article 1998
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Centraal Instituut voor Voedingsonderzoek TNO (author), van Iersel, M.L.P.S. (author), van Lipzig, M.M.H. (author), Rietjens, I.M.C.M. (author), Vervoort, J. (author), van Bladeren, P.J. (author)Using 1H NMR two diastereoisomers of the ethacrynic acid glutathione conjugate (EASG) as well as ethacrynic acid (EA) could be distinguished and quantified individually. Chemically prepared EASG consists of equal amounts of both diastereoisomers. GSTP1-1 stereospecifically catalyzes formation of one of the diastereoisomers (A). The GSTP1-1...article 1998
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Ridley, R.G. (author), Matile, H. (author), Jaquet, C. (author), Dorn, A. (author), Hofheinz, W. (author), Leupin, W. (author), Masciadri, R. (author), Theil, F.P. (author), Richter, W.F. (author), Girometta, M.A. (author), Guenzi, A. (author), Urwyler, H. (author), Gocke, E. (author), Potthast, J.M. (author), Csato, M. (author), Thomas, A. (author), Peters, W. (author), TNO Preventie en Gezondheid (author)The S,S enantiomer of the bisquinoline trans-N1,N2-bis(7- chloroquinolin-4-yl)cyclohexane-1,2-diamine, Ro 47-7737, is significantly more potent against chloroquine-resistant Plasmodium falciparum than the R,R enantiomer and the previously described racemate. Both the enantiomers and the racemate are more potent inhibitors of heme polymerization...article 1997
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Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author), Evers, R. (author), Cnubben, N.H.P. (author), Wijnholds, J. (author), van Deemter, L. (author), van Bladeren, P.J. (author), Borst, P. (author)The human multidrug resistance protein MRP1 mediates transport of organic substrates conjugated to glutathione, glucuronide, or sulfate. The naturally occurring prostaglandins A1 and A2 can form two diastereomeric glutathione S-conjugates, and it has been speculated that these might be substrates for MRP1. Here we present evidence that polarized...article 1997
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Groen, K. (author), Breimer, D.D. (author), Jansen, E.J. (author), van Bezooijen, C.F.A. (author), Gaubius Instituut TNO (author)The influence of aging on the metabolism of antipyrine (AP) and hexobarbital enantiomers (R-HB and S-HB) with and without phenobarbital (PB) induction was investigated in a longitudinal study in rats aged 6, 12, 24 and 30 months. The metabolic clearances of AP (Cl(m AP)), R-HB (Cl(m R-HB)) and S-HB (Cl(m S-HB)) were used as indicators for P450...article 1994
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Instituut CIVO-Toxicologie en Voeding TNO (author), Boyd, D.R. (author), Sharma, N.D. (author), Agarwal, R. (author), McMordie, R.A.S. (author), Bessems, J.G.M. (author), van Ommen, B. (author), van Bladeren, P.J. (author)Both 1,2-dihydronaphthalene and 1,2-dihydroanthracene were hydroxylated at the benzylic (1-) or the allylic (2-) position by rat liver microsomes and purified cytochrome P-450 enzymes to yield "arene hydrates". Two other classes of metabolites were formed, the dehydrogenation products naphthalene and anthracene, and trans-1,2-dihydroxy-1,2,3,4...article 1993
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Instituut CIVO-Toxicologie en Voeding TNO (author), van Ommen, B. (author), Ploemen, J.H.T.M. (author), Bogaards, J.J.P. (author), Monks, T.J. (author), Gau, S.S. (author), van Bladeren, P.J. (author)The irreversible inhibition of the rat glutathione S-transferase (GST) isoenzyme 1-1 by a series of halogenated 1,4-benzoquinones and their GSH conjugates was studied quantitatively by analysing the time course of enzyme inactivation. With increasing numbers of chlorine substituents, the rate of inhibition greatly increased. Incorporation of a...article 1991
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