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Kentrop, J. (author), Savransky, V. (author), Klaassen, S.D. (author), van Groningen, T. (author), Bohnert, S. (author), Cornelissen, A.S. (author), Cochrane, L. (author), Barry, J. (author), Joosen, M.J.A. (author)Nerve agent exposure is generally treated by an antidote formulation composed of a muscarinic antagonist, atropine sulfate (ATR), and a reactivator of acetylcholinesterase (AChE) such as pralidoxime, obidoxime (OBI), methoxime, trimedoxime or HI-6 and an anticonvulsant. Organophosphates (OPs) irreversibly inhibit AChE, the enzyme responsible for...article 2021
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van Esch, B.C.A.M. (author), van Bilsen, J.H.M. (author), Gros- van Hest, M. (author), Kleinjans, L. (author), Belzer, C. (author), Jeurink, P.V. (author), Garssen, J. (author), Smit, J.J. (author), Pieters, R.H.H. (author), Knippels, L.M. (author)Introduction This 4-center study is part of a project to validate a food allergy murine model for safety testing of hydrolyzed infant formulas. Aim The aim of the current multi-center experiment was to evaluate the residual allergenicity of three partial hydrolyzed whey proteins (pWH) in a multiple-parameter cow’s milk allergy murine model and...article 2020
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Langenberg, J.P. (author), Spruit, W.E.T. (author), Kuijpers, W.C. (author), Mars, R.H. (author), van Helden, H.P.M. (author), van der Schans, G.P. (author), Benschop, H.P. (author), TNO Defensie en Veiligheid (author)ln order to provide a quantitative basis for pretreatment and therapy of intoxications with sulfur mustard the toxicokinetics of this agent as well as its major DNA-adducts are being studied in male hairless guinea pigs for the intravenous, respiratory and percutaneous routes. A highly sensitive method for bioanalysis of the intact agent in...bookPart 2009
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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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Arts, J.H.E. (author), Mommers, C. (author), de Heer, C. (author), TNO Kwaliteit van Leven (author)A literature study was performed to evaluate dose-response relationships and no-effect levels for sensitization and elicitation in skin- and respiratory allergy. With respect to the skin, dose-response relationships and no-effect levels were found for both intradermal and topical induction, as well as for intradermal and topical elicitation of...article 2006
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Lamers, R.J.A.N. (author), van Nesselrooij, J.H.J. (author), Kraus, V.B. (author), Jordan, J.M. (author), Renner, J.B. (author), Dragomir, A.D. (author), Luta, G. (author), van der Greef, J. (author), de Groot, J. (author), TNO Kwaliteit van Leven (author)Objective: Osteoarthritis (OA) is one of the most common diseases among the elderly. The main characteristic is the progressive destruction of articular cartilage. We lack quantitative and sensitive biomarkers for OA to detect changes in the joints in an early stage of the disease. In this study, we investigated whether a urinary metabolite...article 2005
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Smilde, A.K. (author), Jansen, J.J. (author), Hoefsloot, H.C.J. (author), Lamers, R.J.A.N. (author), van der Greef, J. (author), Timmerman, M.E. (author), TNO Kwaliteit van Leven (author)Motivation: Datasets resulting from metabolomics or metabolic profiling experiments are becoming increasingly complex. Such datasets may contain underlying factors, such as time (time-resolved or longitudinal measurements), doses or combinations thereof. Currently used biostatistics methods do not take the structure of such complex datasets into...article 2005
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TNO Defensie en Veiligheid (author), Philippens, I.H.C.H.M. (author), Joosen, M.J.A. (author), Vanwersch, R.A.P. (author)During military operations, soldiers may be exposed to mixtures of chemicals and to physical, emotional and psychological stress factors, which all may influence efficacy of any treatment, including the nerve agent pretreatment regimen. The purpose of this study was therefore to investigate the influence of chronic intermittent, variable,...article 2005
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van Helden, H.P.M. (author), Trap, H.C. (author), Kuijpers, W.C. (author), Oostdijk, J.P. (author), Benschop, H.P. (author), Langenberg, J.P. (author), Prins Maurits Laboratorium TNO (author)The purpose of this pilot study was to indicate, for low-level exposure of conscious guinea pigs and marmoset monkeys to sarin vapour in air, the lowest-observable-adverse-effect level (LOAEL) of sarin for miosis. This is the concentration × time (C·t) value (t = 5 h) of exposure at which miosis becomes significant. The ratio of pupil and iris...article 2004
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van Helden, H.P.M. (author), Kuijpers, W.C. (author), Diemel, R.V. (author)The purpose of the present study was to investigate: (1) the acute effects of sulfur mustard on airway, lung, and surface tension of bronchoalveolar lavage fluid (BALfluid) in guinea pigs following intratracheal (i.t.) exposure to 1LD50 of an aerosolized solution of sulfur mustard in saline, and (2) the therapeutic efficacy of i.t....article 2004
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Bajgar, J. (author), Ševelová, L. (author), Krejčová, G. (author), Fusek, J. (author), Vachek, J. (author), Kassa, J. (author), Herink, J. (author), de Jong, L.P.A. (author), Benschop, H.P. (author)Soman belongs to the most dangerous nerve agents because of the low effectiveness of the presently available antidotes. Soman acts by inhibiting acetylcholinesterase (AChE) both peripherally and centrally, with a subsequent accumulation of neuromediator acetylcholine and other metabolic changes. From the data published in literature it can be...article 2004
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Identification of disease- and nutrient-related metabolic fingerprints in osteoarthritic guinea pigsLamers, R.-J.A.N. (author), de Groot, J. (author), Spies-Faber, E.J. (author), Jellema, R.H. (author), Kraus, V.B. (author), Verzijl, N. (author), te Koppele, J.M. (author), Spijksma, G.K. (author), Vogels, J.T.W.E. (author), van der Greef, J. (author), van Nesselrooij, J.H.J. (author)Osteoarthritis (OA), one of the most common diseases among the elderly, is characterized by the progressive destruction of joint tissues. Its etiology is largely unclear and no effective disease-modifying treatment is currently available. Metabolic fingerprinting provides a novel tool for the identification of biomarkers. A metabolic fingerprint...article 2003
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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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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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TNO Preventie en Gezondheid (author), Maassen, C.B.M. (author), Laman, J.D. (author), van Holten-Neelen, C. (author), Hoogteijling, L. (author), Groenewegen, L. (author), Visser, L. (author), Schellekens, M.M. (author), Boersma, W.J.A. (author), Claassen, E. (author)Oral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we use genetically modified lactobacilli expressing myelin...article 2003
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Cappaert, N.L.M. (author), Klis, S.F.L. (author), Muijser, H. (author), Kulig, B.M. (author), Ravensberg, L.C. (author), Smoorenburg, G.F. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)The present study was designed to compare the ototoxic effects of volatile ethyl benzene in guinea pigs and rats. Rats showed deteriorated auditory thresholds in the mid-frequency range, based on electrocochleography, after 550-ppm ethyl benzene (8 h/day, 5 days). Outer hair cell (OHC) loss was found in the corresponding cochlear regions. In...article 2002
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Huebner, J.L. (author), Hanes, M.A. (author), Beekman, B. (author), TeKoppele, J.M. (author), Kraus, V.B. (author), Gaubius Instituut (author)Objective: To evaluate the interaction of bone and cartilage in knee osteoarthritis (OA) pathogenesis in two guinea-pig strains with appreciable differences in bone metabolism. Design: Two guinea-pig strains were evaluated for their susceptibilities to OA using semi-quantitative histological grading of knee joints and quantification of...article 2002
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van Och, F.M.M. (author), Vandebriel, R.J. (author), Prinsen, M.K. (author), de Jong, W.H. (author), Slob, W. (author), van Loveren, H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)The guinea pig maximization test (GPMT) has been used as a method for the prediction of skin sensitizing potential for over 30 years. Besides hazard identification, risk assessment of sensitizing chemicals requires the assessment of potency. For the determination of potency based on lowest effective dose levels, dose-response studies are...article 2001
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de Groot, D.M.G. (author), Bierman, E.P.B. (author), Bruijnzeel, P.L.B. (author), Carpentier, P. (author), Kulig, B.M. (author), Lallement, G. (author), Melchers, B.P.C. (author), Philippens, I.H.C.H.M. (author), van Huygevoort, A.H.B.M. (author)Poisoning with the potent nerve agent soman produces a cascade of central nervous system (CNS) effects characterized by severe convulsions and eventually death. In animals that survive a soman intoxication, lesions in the amygdala, piriform cortex, hippocampus and thalamus can be observed. In order to examine the mechanisms involved in the...article 2001
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Reichl, F.X. (author), Durner, J. (author), Kunzelmann, K.H. (author), Hickel, R. (author), Spahl, W. (author), Hume, W.R. (author), Moes, G.W.H (author), Kehe, K. (author), Walther, U. (author), Forth, W. (author)The excretion of the dental composite component triethylene glycol dimethacrylate (TEGDMA) in feces and urine in vivo and, using the pendular perfusion technique with segments of jejunum and colon, the biliary and enteric excretion in situ were investigated in anesthetized guinea pigs. In the in situ experiments guinea pigs (n=4) received TEGDMA...article 2001