Organophosphorus (OP) compounds are organic derivatives of phosphorus that have largely been used as pesticides and nerve agents. Tetraethylpyrophosphate was synthesized in 1854 as the first OP cholinesterase inhibitor. During 1934–1944, Gerhard Schrader, a German chemist at I. G. Farben industries and his coworkers synthesized about 2,000 OP compounds, including parathion as a pesticide and ta...

Current oxime therapies do not readily cross the blood-brain barrier to reactivate organophosphorus nerve agent-inhibited cholinesterase (ChE) within the CNS. We investigated the ability of monoisonitrosoacetone (MINA), a tertiary oxime, to reactivate ChE inhibited by the nerve agent sarin (GB), cyclosarin (GF), or VX, in peripheral tissues and brain of guinea pigs and determined whether reacti...

Acetylcholinesterase (AChE) inhibitors, including PB, produce acute destructive changes at the neuromuscular junction, the site of connection between nerve cells and muscle fibers, at which nerve cells signal muscles to contract. Because studies of the neuromuscular junction require microscopic inspection of muscle tissue and tests of electrical and chemical properties of the neuromuscular junc...

This study compared the ability of nine oximes (HI-6, HLö7, MMB-4, TMB-4, carboxime, ICD585, ICD692, ICD3805, and 2-PAM) to reactivate in vivo cholinesterase (ChE) in blood, brain, and peripheral tissues in guinea pigs intoxicated by one of four organophosphorus nerve agents. Two bis-pyridinium compounds without an oxime group, SAD128 and ICD4157, served as non-oxime controls. Animals were inje...

With regard to detection of exposure to anticholinesterase, the presently used methods have the disadvantage that they cannot detect either low-level exposures with certainty or the structure of the agent and the extent of poisoning. In principle, organophosphate-inhibited butyrylcholinesterase in human plasma is the most persistent and abundant source for biomonitoring of exposure to organopho...

This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD(50) dose of sarin (42 microg/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholineste...

Prolidases hydrolyze Xaa-Pro dipeptides and can also cleave the P-F and P-O bonds found in organophosphorus (OP) compounds, including the nerve agents soman and sarin. Ph1prol (PH0974) has previously been isolated and characterized from Pyrococcus horikoshii and was shown to have higher catalytic activity over a broader pH range, higher affinity for metal, and increased thermostability compared...

Organophosphorus nerve agents such as sarin (GB) and VX irreversibly inhibit acetylcholinesterase, causing a buildup of acetylcholine (ACh) in synapses and neuromuscular junctions, which leads to excess bronchial secretions, convulsions, seizures, coma, and death. Understanding the unique toxic characteristics of different nerve agents is vital in the effort to develop broad spectrum medical co...

In the present issue of Critical Care, an article by Okumura and colleagues has been published on the problem of secondary contamination following chemical agent release [1]. The authors' draw on first-hand experience [2–5] of the secondary contamination experienced during the Tokyo sarin release in 1995. This experience is important, both for the care of contaminated patients and for the safet...

We report the use of carbon nanotubes as a sensor for chemical nerve agents. Thin-film transistors constructed from random networks of single-walled carbon nanotubes were used to detect dimethyl methylphosphonate ~DMMP!, a simulant for the nerve agent sarin. These sensors are reversible and capable of detecting DMMP at sub-ppb concentration levels, and they are intrinsically selective against i...