Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Diagnosticsrecently, a large portion of the biomedical samples obtainedfrom casualties of suspected exposure to sulfurmustard have come from the Iran-Iraq war in the 1980s.Many victims of that conflict who exhibited clinicalsigns consistent with exposure to sulfur mustardwere transported to hospitals in Europe for medicaltreatment. Prior to 1995 laboratory analysis of thesespecimens used methods to measure unmetabolizedsulfur mustard or thiodiglycol (TDG), a hydrolysisproduct of sulfur mustard. Fortunately, some of theblood components and urine specimens were frozenand reanalyzed years later, after newer analytical methodswere developed. Recently reported methods ofanalysis generally indicate greater levels of sensitivitythan previous methods or target other biomarkers ofsulfur mustard exposure. In addition to samples from2.5(placebo, predose control)2.01.560% Inhibition by Hup-A(reversibly inhibited AChE)40% AChE activity remaining54% AChE activity recovered46% AChE Inhibition1.0placebo, no Hup-AHup-A treated, precolumnHup-A postcolumn0.50.0control, no GDGD (1μM, 10 min)00.5 h1 h2 h3 h4 h1. Precolumn1. treatment2. Postcolumn recovery (h)Fig. 22-5. Effects of soman (GD) on acetylcholinesterase (AChE) activity in whole blood from human volunteers who weregiven an increasing dose of huperzine A (Hup A). Blood was drawn 1.5 hours after the final 200-μg dose (blue bar, left ofdashed line). The red bars represent red blood cell AChE from volunteers prior to receiving a placebo, while the blue barsrepresent AChE from an individual receiving the 200-µg Hup A dose. In the first part, after soman treatment, no AChE activityis observed by the Walter Reed Army Institute of Research assay in either the placebo- or drug-treated volunteers (redbars, close to 0 U/mL). However, after the spin column removal of free Hup A and soman, and a 4-hour period to allow forcomplete dissociation, the Hup-A–inhibited AChE is restored to the level that was initially inhibited by the drug (green barwith arrow, about 60% inhibition by the drug before the column versus 54% returned AChE activity after the column). Errorbars represent the mean plus or minus the standard error of the mean. Note the increased inhibition and sequestering ofAChE by Hup A compared to pyridostigmine bromide (see Fig. 22-4).AChE: acetylcholinesteraseHup A: huperzine A707