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Onder, S. (author), van Grol, M. (author), Fidder, A. (author), Xiao, G. (author), Noort, D. (author), Yerramalla, U. (author), Tacal, O. (author), Schopfer, L.M. (author), Lockridge, O. (author)Chronic low-dose exposure to organophosphorus pesticides is associated with the risk of neurodegenerative disease. The mechanism of neurotoxicity is independent of acetylcholinesterase inhibition. Adducts on tyrosine, lysine, threonine, and serine can occur after exposure to organophosphorus pesticides, the most stable being adducts on tyrosine....article 2021
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Horn, G. (author), de Koning, M.C. (author), van Grol, M. (author), Thiermann, H. (author), Worek, F. (author)Poisoning by organophosphorus compounds (OP) is characterized by inhibition of the key enzyme acetylcholinesterase (AChE) and potentially fatal outcomes in humans. Insufficient efficacy of the standard therapy with atropine and AChE reactivators (oximes) against certain OP initiated synthesis of novel non-oxime reactivators basing on the common...article 2018
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Kranawetvogl, A. (author), Müller, S. (author), Kubik, S. (author), Spruit, W.E.T. (author), Thiermann, H. (author), Worek, F. (author), Noort, D. (author), Reiter, G. (author)Detoxification mechanisms of the chemical warfare agent cyclosarin (GF) in presence of 6-OxP-CD were investigated in detail in in vitro model systems. Most important finding was the preference of 6-Ox-P-CD to eliminate the more toxic (-)-GF. However, elimination of GF enantiomers was dependent on the 6-OxP-CD:GF ratios showing decreasing...article 2015
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Reinen, J. (author), Nematollahi, L. (author), Fidder, A. (author), Vermeulen, N.P.E. (author), Noort, D. (author), Commandeur, J.N.M. (author)Tri-ortho-cresyl phosphate (ToCP) is a multipurpose organophosphorus compound that is neurotoxic and suspected to be involved in aerotoxic syndrome in humans. It has been reported that not ToCP itself but a metabolite of ToCP, namely, 2-(ortho-cresyl)-4H-1,2,3-benzodioxaphosphoran-2-one (CBDP), may be responsible for this effect as it can...article 2015
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van der Meer, J.A. (author), Trap, H.C. (author), Noort, D. (author), van der Schans, M.J. (author), TNO Defensie en Veiligheid (author)Recently, several methods have been developed to verify exposure to nerve agents. Most of these methods, such as the fluoride reactivation technique and the analysis of inhibited phosphonylated butyrylcholinesterase (BuChE), are based on mass spectrometry. The high specificity of the mass spectrometer might also imply a disadvantage, because the...article 2010
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Noort, D. (author), Fidder, A. (author), van der Schans, M.J. (author), Hulst, A.G. (author), TNO Defensie en Veiligheid (author)We present a generic mass spectrometric method to verify exposure to organophosphates, based on the chemical conversion of the phosphylated peptides obtained after pepsin digestion of human butyrylcholinesterase (HuBuChE) to a common precursor peptide. After exposure of plasma to various organophosphates (nerve agents, pesticides), HuBuChE was...article 2006
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Degenhardt, C.E.A.M. (author), Pleijsier, K. (author), van der Schans, M.J. (author), Langenberg, J.P. (author), Preston, K.E. (author), Solano, M.I. (author), Maggio, V.L. (author), Barr, J.R. (author), Prins Maurits Laboratorium TNO (author)One of the most appropriate biomarkers for the verification of organophosphorus nerve agent exposure is the conjugate of the nerve agent to butyrylcholinesterase (BuChE). The phosphyl moiety of the nerve agent can be released from the BuChE enzyme by incubation with fluoride ions, after which the resulting organophosphonofluoridate can be...article 2004
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Smulders, C.J.G.M. (author), Bueters, T.J.H. (author), Vailati, S. (author), van Kleef, R.G.D.M. (author), Vijvergberg, H.P.M. (author)Chronic and acute exposure to organophosphate (OP) pesticides may lead to persistent neurological and neurobehavioral effects, which cannot be explained by acetylcholinesterase (AChE) inhibition alone. It is suggested that other brain proteins are involved. Effects of commonly used organophosphate pesticides on rat neuronal α4β2 nicotinic...article 2004
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Prins Maurits Laboratorium TNO (author), van der Schans, M.J. (author), Polhuijs, M. (author), van Dijk, C. (author), Degenhardt, C.E.A.M. (author), Pleijsier, K. (author), Langenberg, J.P. (author), Benschop, H.P. (author)The utility was explored of a new approach to detect retrospectively exposure to nerve agents by means of conversion of the inhibitor moiety bound to the active site of the enzyme BuChE in plasma with fluoride ions into a phosphofluoridate which is subsequently analyzed by means of gas chromatography (GC). This quantifies ≥0.01% inhibition of...article 2004
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Mol, H.G.J. (author), van Dam, R.C.J. (author), Steijger, O.M. (author), TNO Voeding (author)A method based on liquid chromatography (LC)-mass spectrometry (MS)/MS was developed for sensitive determination of a number of less gas chromatography (GC)-amenable organophosphorus pesticides (OPs; acephate, methamidophos, monocrotophos, omethoate, oxydemeton-methyl and vamidothion) in cabbage and grapes. For extraction, several solvents were...article 2003
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Fidder, A. (author), Hulst, A.G. (author), Noort, D. (author), de Ruiter, R. (author), van der Schans, M.J. (author), Benschop, H.P. (author), Langenberg, J.P. (author), Prins Maurits Laboratorium TNO (author)In this paper a novel and general procedure is presented for detection of organophosphate-inhibited human butyrylcholinesterase (HuBuChE), which is based on electrospray tandem mass spectrometric analysis of phosphylated nonapeptides obtained after pepsin digestion of the enzyme. The utility of this method is exemplified by the positive analysis...article 2002
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Ingelse, B.A. (author), van Dam, R.C.J. (author), Vreeken, R.J. (author), Mol, H.G.J. (author), Steijger, O.M. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)It was demonstrated that four out of six of the very polar organophosphorus pesticides (OPs), i.e. acephate, methamidophos, monocrotophos, omethoate, oxydemeton-methyl and vamidothion, could not be extracted from water using commonly available SPE cartridges. In addition, GC analysis on all six compounds was found to be troublesome due to their...article 2001
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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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- van Helden, H.P.M. (author), Bueters, T.J.H. (author), Prins Maurits Laboratorium TNO (author) article 1999
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Noort, D. (author), Hulst, A.G. (author), Platenburg, D.H.J.M. (author), Polhuijs, M. (author), Benschop, H.P. (author), Prins Maurits Laboratorium TNO (author)A convenient and rapid micro-anion exchange liquid chromatography (LC) tandem electrospray mass spectrometry (MS) procedure was developed for quantitative analysis in serum of O-isopropyl methylphosphonic acid (IMPA), the hydrolysis product of the nerve agent sarin. The mass spectrometric procedure involves negative or positive ion electrospray...article 1998
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Barak, R. (author), Ordentlich, A. (author), Barak, D. (author), Fischer, M. (author), Benschop, H.P. (author), de Jong, L.P.A. (author), Segall, Y. (author), Velan, B. (author), Shafferman, A. (author)While non-reactivability of cholinesterase from their phosphyl conjugates (aging) is attributed to an unimolecular process involving loss of alkyl group from the phosphyl moiety, no conclusive evidence is available that this is the only reaction path and involvement of other post-inhibitory processes cannot be ruled out, To address this issue,...article 1997
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Degenhardt, C.E.A.M. (author), Kientz, C.E. (author), TNO Prins Maurits Laboratorium (author)The use of large volume injections has been studied for the verification of intact organophosphorus chemical warfare agents in water samples. As the use of ethyl acetate caused severe detection problems new potential solvents were evaluated. With the developed procedure, the nerve agents sarin, tabun, soman, DFP and VX can be determined in...article 1996
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TNO Prins Maurits Laboratorium (author), Langenberg, J.P. (author), de Jong, L.P.A. (author), Benschop, H.P. (author)Several p-nitrophenyl phosphoramidates with the general formula RO(NH2)P(O)OC6H4-p-NO2, in which R = CH2CH3, CH2CH2F, CH2CHF2, CH2CF3, CH2CH2CH2CH3, and CH2CH2Cl, as well as (NH2)2P(O)OC6H4-p-NO2 were administered intravenously to guinea pigs as pretreatment compounds for protection against the lethal effects of 1,2,2-trimethylpropyl...article 1996
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Sänger-van de Griend, C.E. (author), Kientz, C.E. (author), Brinkman, U.A.T. (author)Preliminary work indicates that capillary electrophoresis can be coupled on-line with a gas chromatographic detector such as a flame photometric detector. A test mixture containing low-nanogram amounts of three organophosphorus compounds has successfully been analysed. Chemicals/CAS: methylphosphonic acid, 993-13-5; phosphoric acid, 7664-38-2;...article 1994
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Wolthuis, O.L. (author), Philippens, I.H.C.H.M. (author), Vanwersch, R.A.P. (author), Medisch Biologisch Laboratorium TNO (author), MBL (author)Several earlier studies showed that, in contrast with DFP, repeated injections with soman did not lead to behavioral tolerance in rats. The reason for the difference between the effects of these two organophosphate cholinesterase inhibitors was not clear and a neurophysiological approach was undertaken. Four experiments (A, B, C and D) were...article 1991
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