title: Efficacy and physiological effects of human butyrylcholinesterase as a post-exposure therapy against percutaneous poisoning by VX in the guinea-pig.
abstract: The physiological effects of human plasma-derived butyrylcholinesterase (huBuChE) administration and its modulation of the effects of percutaneous VX challenge are poorly understood. Percutaneously administered nerve agents are more slowly absorbed than inhaled agents; consequently, signs of poisoning occur later, with a longer duration. Telemetry was used to monitor heart rate, EEG, temperature and activity in guinea-pigs. Treatment with huBuChE at 30 or 120 min following percutaneous VX challenge ( approximately 2.5 x LD(50)) provided 100% protection from lethality. When huBuChE administration was delayed until the onset of observable signs of poisoning only 1 out of 6 animals survived to the end of the experiment at 7 days. This study adds to the body of evidence demonstrating the efficacy of huBuChE in animals by describing the successful therapeutic use of a protein bioscavenger as a post-exposure treatment against dermal exposure to VX up to 2h post-exposure. This study simultaneously used telemetric methods to show that the efficacy of huBuChE is linked to the prevention of detrimental physiological changes observed in control VX-treated animals. Post-exposure therapy is a promising additional indication for the concept of use of this material, and one that has particular relevance in a civilian exposure scenario.
authors.affiliation: Biomedical Sciences Department, Dstl Porton Down, Salisbury, Wiltshire SP4 0JQ, UK. hmumford@dstl.gov.uk
authors.forename: Helen
authors.initials: H
authors.lastname: Mumford
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Price
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Cerasoli
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Teschner
authors.forename: Hartmut
authors.initials: H
authors.lastname: Ehrlich
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Schwarz
authors.forename: David E
authors.initials: DE
authors.lastname: Lenz
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D002091:Butyrylcholinesterase / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D002619:Chemical Warfare Agents / Q000506:poisoning*; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000506:poisoning*; D013997:Time Factors
chemical_list: D000931:Antidotes; D002091:Butyrylcholinesterase; D002619:Chemical Warfare Agents; D009946:Organothiophosphorus Compounds; C009680:VX-agent