ORGANOPHOSPHORUS COMPOUNDS are one of the important insecticides and pesticides that have been used in chemical warfare as nerve agents. They are a major global clinical problem, with thousands of deaths occurring every year. ORGANOPHOSPHORUS COMPOUNDS inhibit acetylcholinesterase activity cause to the accumulation of acetylcholine at many synapses in the brain and different parts of neuromuscular junctions. In the cases of intoxication to organophosphours poisons four clinical syndromes have been described; cholinergic crisis, intermediate syndrome, delayed neuropathy and chronic organophosphate inducted neuropsychiatric disorder. Whichever stages has special signs and symptoms. The determination of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity in whole blood and plasma, is a rapid, convenient and benefit screening method of poisoning due to ORGANOPHOSPHORUS COMPOUNDS but without high sensitivity and specificity, also assess their degradation products in plasma and urine will be feasible but is expensive and is limited to specialized laboratories. The conventional and standard management of poisoned patients include supportive care, detoxification and treatment with antidote atropine sulfate alone or with an oxime. Some of other drugs have been suggested for treatment, e.g. glycopyrrolate, sodium bicarbonate and magnesium sulfate which may in some cases necessary. But still there are many unanswered questions and controversies in the management of ORGANOPHOSPHORUS poisoning. Patients with moderate to severe intoxication who receive first aid and emergency medical treatment may survive. However, the presence of either a cardiac arrhythmia or respiratory failure is associated with a poor prognosis. Finally, to reduce mortality rate, early diagnosis, precise monitoring and selection appropriate treatments are useful. This article presents a review of poisoning with ORGANOPHOSPHORUS COMPOUNDS.

ORGANOPHOSPHORUS (OP) COMPOUNDS are cholinesterase inhibitors widely used as pesticides in agriculture and nerve agents in battlefields. Exposure to these COMPOUNDS leads to accumulation of acetylcholine at cholinergic synapses and overstimulation of muscarinic and nicotinic receptors by inhibiting the enzyme acetylcholinesterase. Seizure activity is one of the major manifestations of OP poisoning that is produced as a result of hyperstimulation of brain muscarinic receptors and subsequent recruitment of other neurotransmitter systems. Disruption of the excitatory/inhibitory balance can lead to OP-induced seizure activity and subsequent brain damages.Gamma -aminobutyric acid (GABA), the main inhibitory neurotransmitter in mammalian central nervous system, is synthesized from glutamate by glutamic acid decarboxylase and modulates neuronal excitability. After release, GABA binds to two different types of receptors: ionotrpic (GABAA and GABAC) and metabotropic (GABAB) receptors.Drugs that enhance GABAA-mediated inhibition are effective in treatment of OP-induced seizures. There is discrepancy in the literatures regarding changes on brain GABAergic system during OP intoxication.This review discusses the mechanism and toxic effects of OP COMPOUNDS, brain GABAergic system, and how it changes following exposure to OP COMPOUNDS.

ORGANOPHOSPHORUS COMPOUNDS have been used as pesticides and as chemical warfare nerve agents. The mechanism of toxicity of ORGANOPHOSPHORUS COMPOUNDS is the inhibition of acetyl cholinesterase, which results in accumulation of acetylcholine and the continued stimulation of acetylcholine receptors. Therefore, they are also called ant cholinesterase agents. Organophosphrus pesticides have largely been used worldwide, and poisoning by these agents, particularly in developing countries, is a serious health problem. ORGANOPHOSPHORUS nerve agents were used by Iraqi army against Iranian combatants and even civilian population in 1983-1988. They were also used for chemical terrorism in Japan in 1994-1995. Their use is still a constant threat to the population. Therefore, medical and health professionals should be aware and learn more about the toxicology and proper management of ORGANOPHOSPHORUS poisoning. Determination of acetyl cholinesterase and butyrylcholinesterase activity in blood remains a mainstay for the fast initial screening of ORGANOPHOSPHORUS COMPOUNDS but lacks sensitivity and specificity. Quantitative analysis of ORGANOPHOSPHORUS COMPOUNDS and their degradation products in plasma and urine by mass spectrometric methods may prove exposure but is expensive and is limited to specialized laboratories. However, history of exposure to organophosphorous COMPOUNDS and clinical manifestations of a cholinergic syndrome are sufficient for management of the affected patients. The standard management of poisoning with organophosphorous COMPOUNDS consists of decontamination, and injection of atropine sulfate with an oxime. Recent advances on treatment of ORGANOPHOSPHORUS pesticides poisoning revealed that blood alkalinization with sodium bicarbonate and also magnesium sulfate as adjunctive therapies are promising. Patients who receive prompt proper treatment usually recover from acute toxicity but may suffer from neurologic complications.

Objective: ORGANOPHOSPHORUS hydrolase (OPH) is a homodimeric enzyme that can hydrolyze phosphoester bonds and reduce the toxicity of ORGANOPHOSPHORUS COMPOUNDS. This makes OPH a suitable element for the biodegradation of these COMPOUNDS.Methods: We successfully cloned the OPH gene from Pseudomonas diminuta, after optimization for Pichia pastoris, into a yeast expression vector (pPICZaB). After transformation and induction of recombinant yeasts, the expressed enzyme was investigated for its biochemical and kinetical parameters.Results: The enzyme was purified 7.49-fold to a specific activity of 0.421×103 U/mg protein from the supernatant with a yield of 33%. The purified enzyme was able to degrade organophosphates. It had an optimal activity and stability up to 50oC, and a pH range of 7.0-10.0. The enzyme had a Km of 45.96 mM and a Vmax of 11.23 mM/min (421 mM/min/mg) for paraoxon as a substrate. This enzyme was sensitive to divalent cations and inactivated by denaturing COMPOUNDS such as SDS. The molecular mass of the purified enzyme as estimated by SDS–PAGE analysis was approximately 40 kDa. Conclusion: In this study, the purified enzyme effectively hydrolyzed paraoxon, an ORGANOPHOSPHORUS compound. The activity and stability of this enzyme at high temperatures and pH, and low Km in comparision with bacterial isolates could make it an attractive biocatalyst for applied bioremediation and bio sensing.

Detection and identification of chemical warfare agents and their precursors/reaction products in various environmental matrices are important tasks which are considered in chemical weapons convention (CWC). 2-[(2-chloroethyl) (alkyl) amino] ethyl alkyl methylphosphonates I and N-alkyl bis (2-(alkoxy-methylphosphoryloxy)amines II are covered under schedule 2.B.4 of CWC and have structures closely related to the nerve and blister agents. In fact, they are products of the reactions between these two different CWC scheduled COMPOUNDS: nerve agents and nitrogen mustards. Ion fragmentations during mass spectrometry studies of these chemicals were investigated using electron ionization mass spectrometry. Structures of fragments were confirmed using EI-MS analysis of the deuterated analogs. Density functional theory was also used to show preferred fragmentation pathways. Mass spectrometric studies revealed some fragmentation pathways, such as, McLafferty-type and hydrogen rearrangements and elimination of chlorine, chloromethylene radical, alkene and HCl.

In this research sampling of Azolla was done in the southwest (Siahkeshim), center (Hendekhaleh) and east (Sheijan) of the Anzali Lagoon for two seasons (Summer and Autumn 2001). Extraction of ORGANOPHOSPHORUS and organochlorine COMPOUNDS in Azolla were done by mixture of methylene chloride- acetone solvents. Separation and identification of COMPOUNDS in extracted samples were done by GC- NPD, ion trap and quadrupole GC/MS Sequentially. The most important pollutant identified in Azolla was Fenitrothion pesticide. Selected Ion Monitoring (SIM) technique was also used for further confirmation of Fenitrothion and the quantitative analysis was done by GC-NPD. The highest concentration of Fenitrothion in Azolla on wet weight basis was 591 ng/g in the southwest region and the lowest concentration 341 ng/g in the east region of Lagoon in Summer.