title: Adaptation of a dynamic in vitro model with real-time determination  of butyrylcholinesterase activity in the presence of cyclosarin and an  oxime.
abstract: The well-established dynamic in vitro model for the real-time determination of acetylcholinesterase activity was modified for use of human butyrylcholinesterase (BChE) activity. Human plasma as BChE source was layered on a syringe filter and the enzyme reactor was continuously perfused with phosphate buffer, butyrylthiocholine and Ellman’s reagent at pH 7.4 and 37 C which resulted in a stable BChE activity for up to 240 min. Then, the model was applied for investigating the suitability of human BChE in combination with an oxime (HLö 7) to serve as a ‘pseudo-catalytic’ scavenger of the organophosphorus nerve agent cyclosarin. The application of different perfusion protocols demonstrated the ability of BChE-oxime combinations to prevent BChE from irreversible inhibition by cyclosarin even at toxicologically relevant concentrations. In the end, this model seems to be suitable for the investigation of human plasma BChE as an endogenous, ‘pseudo-catalytic’ scavenger of a variety of nerve agents.
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany. franzworek@bundeswehr.org
authors.forename: Franz
authors.initials: F
authors.lastname: Worek
authors.forename: Gabriele
authors.initials: G
authors.lastname: Horn
authors.forename: Timo
authors.initials: T
authors.lastname: Wille
authors.forename: Horst
authors.initials: H
authors.lastname: Thiermann
mesh_terms: D002091:Butyrylcholinesterase / Q000187:drug effects / Q000378:metabolism*; D002092:Butyrylthiocholine / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010477:Perfusion; D011726:Pyridinium Compounds / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D011726:Pyridinium Compounds; C058577:HLo 7; D002092:Butyrylthiocholine; D002091:Butyrylcholinesterase; C053914:cyclohexyl methylphosphonofluoridate