Past, present and future of cyanide antagonism research: From the early remedies to the current therapies.

This paper reviews milestones in antidotal therapies for cyanide (CN) spanning early remedies, current antidotal systems and research towards next generation therapies. CN has been a part of plant defense mechanisms for millions of years. It became industrially important in the nineteenth century with the advent of CN assisted gold mining and the use of CN as a pest control agent. The biochemical basis of CN poisoning was actively studied and key mechanisms were understood as early as 1929. These fundamental studies led to a variety of antidotes, including indirect CN binders that generate methemoglobin, direct CN binders such as hydroxocobalamin, and sulfur donors that convert CN to the less toxic thiocyanate. Research on blood gases at the end of the twentieth century shed new light on the role of nitric oxide (NO) in the body. The discovery of NO's ability to compete with CN for enzymatic binding sites provided a previously missed explanation for the rapid efficacy of NO generating antidotes such as the nitrites. Presently used CN therapies include: methemoglobin/NO generators (e.g., sodium nitrite, amyl nitrite, and dimethyl aminophenol), sulfur donors (e.g., sodium thiosulfate and glutathione), and direct binding agents [(e.g., hydroxocobalamin and dicobalt salt of ethylenediaminetetraacetic acid (dicobalt edetate)]. A strong effort is being made to explore novel antidotal systems and to formulate them for rapid administration at the point of intoxication in mass casualty scenarios. New antidotes, formulations, and delivery systems are enhancing bioavailability and efficacy and hold promise for a new generation of improved CN countermeasures

The environmental and biological risks of extreme low doses of chlorobenzenes

Several environmental chemicals and pesticides have been found to alter neuroendocrine communication and behaviour in exposed biological systems. The aim of this study was to demonstrate the effects of theubiquitous chlorobenzenes on the behaviour elements of Wistar rats. For this reason rats (n=50 in each groups) were treated with a mixture of 0.1 and 1.0 µg/kg each of hexachlorobenzene and 1,2,4-trichlorobenzene via a gastric tube for 30, 60 and 90 days. At the endpoints of the experiment the behavioural elements of rats were detected and tissue samples were taken for chlorobenzene analysis in gas-chromatography. It was found that the anxiety-related behavioural elements were altered and chlorobenzenes were present in different tissues