Cyclosarin-An Organophosphate Nerve Agent

Organophosphorus compounds ascribed to as nerve agents (sarin, soman, tabun, cyclosarin) are highly toxic, and are considered to be the most dangerous chemical compounds. All apparently share a common mechanism of cholinesterase inhibition and can cause similar sv.m .ot oms. The standard therapy, in the case of organophosphorus poisoning, has the prophylactic use of reversibly acting AChE inhibitors and antidotal administration of AChE reactivators-oximes. Unfortunately, none of these oximes can be regarded as a broad spectrum antidote, ie, effective against all nerve agents. While the presently available oximes (pralidoxime, ohidoxime) are not considered to be sufficiently effective against nerve agents, especially in the case of soman poisoning, the H oximes (HI-6, HLo7) appear to,be very promising antidotes against nerve agents because these are able to protect the experimental animals from toxic effects and improve survival of animals poisoned with supralethal doses. A lot of research has been pursued on the treatment of sarin, soman, and tabun, but cyclosarin was not considered for such a study for a long time. Recently, attention of researchers has also turned to cyclosarin because of its potential use as a chemical warfare agent. Cyclosarin is highly toxic organophosphorus compound which is resistant to conventional oxime therapy. This paper reviews the latest positionof cyclosarin in standpoint of medical treatment by various reactivators considering the ability of various oximes, HI-6, HS-6, BI-6, and KO33 of their reactivation potency

H2S biosynthesis and catabolism: new insights from molecular studies

Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissue