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Whole Blood Robotic Cholinesterase Assay for Organophosphate Exposure - Testing Soldiers, First Responders, and Civilians in the Field and Laboratory

Authors: Richard K. Gordon; Julian R. Haigh; Gregory E. Garcia; Shawn R. Feaster; Bhupendra P. Doctor; Michael A. Riel; Lee J. Lefkowitz; David E. Lenz; Paul S. Aisen; Wilson Smart; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
 
Abstract: Exposure to organophosphate (OP) chemical warfare agents (CWAs), pesticides, anesthetics, drugs such as cocaine, and a variety of therapeutic drugs including donepezil or rivastigmine for Alzheimer's disease reduces red blood cell acetylcholinesterase (RBC-AChE) or serum butyrylcholinesterase (BChE) activity. The activity of RBC-AChE and BChE can be used as potential biomarkers of suppressed and/or heightened function in the central and peripheral nervous systems. For instance, the toxicity of pesticides is well documented in humans. Therefore, blood cholinesterase (ChE) activity can be exploited as a tool for confirming exposure to these agents and possible treatments. Yet it is the OP CWAs that are some of the most potent and irreversible inhibitors that can produce excessive accumulation of acetylcholine, and a cholinergic crisis in man leading to paralysis and ultimately death. Current assays for measurement of erythrocytebound acetylcholinesterase (RBC-AChE) and serum butyrylcholinesterase (BChE, pseudocholinesterase) require several labor-intensive processing steps, suffer from wide statistical variation, and inter-laboratory comparison is often difficult. Techniques currently used include the Ellman and microEllman microtiter method, radiometric, amperometric, and delta (delta) pH (modified Michel protocol) used by the U.S. Army's Cholinesterase Reference Laboratories (CRL). Such methods determine only the serum BChE or RBC-AChE, and require the use of specific ChE inhibitors or sample processing such as centrifugation.

Limitations: APPROVED FOR PUBLIC RELEASE
Description: Conference paper, 29 Nov-2 Dec 2004
Pages: 9
Report Date: DEC 2004
Report Number: A168234
Keywords relating to this report:
*ANESTHETICS
*BLOOD SERUM
*CHEMICAL WARFARE AGENTS
*CHOLINESTERASE
*DRUGS
*EXPOSURE_PHYSIOLOGY_
*ORGANOPHOSPHATES
ACCUMULATION
ACETYLCHOLINE
ACETYLCHOLINESTERASE
ALZHEIMER DISEASE
ARMY PERSONNEL
BUTYRATES
COCAINE
DEATH
ERYTHROCYTES
HUMANS
INHIBITORS
IRREVERSIBLE PROCESSES
LABORATORIES
NERVOUS SYSTEM
PARALYSIS
PESTICIDES
POTENCY
RESPONSE_BIOLOGY_
STATISTICS
THERAPY
TOXICITY
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