Further studies of the efficacy of military, commercial and novel skin decontaminants against the chemical warfare agents sulphur Mustard, Soman and VX.

BACKGROUND/AIMS: Following an incident involving toxic chemicals, deployment of countermeasures before the arrival of specialised services at the scene may provide a "therapeutic" window in which to mitigate skin absorption. METHODS: Five potential candidates (itaconic acid, N,N'-methylenebisacrylamide, 2-trifluoromethylacrylic acid, fuller's earth and Fast-Act®) previously found effective against a simulant (methyl salicylate) were evaluated against a 10 µL droplet of 14C-sulphur mustard (HD), soman (GD) or VX applied to the surface of porcine skin mounted on static skin diffusion cells. RESULTS: All the decontaminants applied to the skin 5 min post exposure achieved a marked reduction in the amount of 14C contaminant remaining within the skin at 24 h. Itaconic acid significantly (p < .05) reduced the amount of 14C-HD, GD and VX remaining in the skin at 24 h. Additionally, 2-trifluoromethylacrylic acid significantly reduced the amount of 14C-HD, whilst fuller's earth significantly reduced the amounts of 14C-HD and VX recovered within the skin at 24 h. CONCLUSION: All of the products evaluated in this study performed well in reducing the dermal absorption of all the chemical warfare agents tested.

Preliminary evaluation of military, commercial and novel skin decontamination products against a chemical warfare agent simulant (methyl salicylate).

Rapid decontamination is vital to alleviate adverse health effects following dermal exposure to hazardous materials. There is an abundance of materials and products which can be utilised to remove hazardous materials from the skin. In this study, a total of 15 products were evaluated, 10 of which were commercial or military products and five were novel (molecular imprinted) polymers. The efficacies of these products were evaluated against a 10 µl droplet of (14)C-methyl salicylate applied to the surface of porcine skin mounted on static diffusion cells. The current UK military decontaminant (Fuller's earth) performed well, retaining 83% of the dose over 24 h and served as a benchmark to compare with the other test products. The five most effective test products were Fuller's earth (the current UK military decontaminant), Fast-Act® and three novel polymers [based on itaconic acid, 2-trifluoromethylacrylic acid and N,N-methylenebis(acrylamide)]. Five products (medical moist-free wipes, 5% FloraFree™ solution, normal baby wipes, baby wipes for sensitive skin and Diphotérine™) enhanced the dermal absorption of (14)C-methyl salicylate. Further work is required to establish the performance of the most effective products identified in this study against chemical warfare agents.

Comparative analysis of showering protocols for mass-casualty decontamination.

A well-established provision for mass-casualty decontamination that incorporates the use of mobile showering units has been developed in the UK. The effectiveness of such decontamination procedures will be critical in minimizing or preventing the contamination of emergency responders and hospital infrastructure. The purpose of this study was to evaluate three empirical strategies designed to optimize existing decontamination procedures: (1) instructions in the form of a pictorial aid prior to decontamination; (2) provision of a washcloth within the showering facility; and (3) an extended showering period. The study was a three-factor, between-participants (or "independent") design with 90 volunteers. The three factors each had two levels: use of washcloths (washcloth/no washcloth), washing instructions (instructions/no instructions), and shower cycle duration (three minutes/six minutes). The effectiveness of these strategies was quantified by whole-body fluorescence imaging following application of a red fluorophore to multiple, discrete areas of the skin. All five showering procedures were relatively effective in removing the fluorophore "contaminant", but the use of a cloth (in the absence of instructions) led to a significant ( appox. 20%) improvement in the effectiveness of decontamination over the standard protocol (p <0.05). Current mass-casualty decontamination effectiveness, especially in children, can be optimized by the provision of a washcloth. This simple but effective approach indicates the value of performing controlled volunteer trials for optimizing existing decontamination procedures.

Role of mitochondria in drug-induced cholestatic injury.

Mitochondria have multiple functions in eukaryotic cells and are organized into dynamic tubular networks that continuously undergo changes through coordinated fusion and fission and migration through the cytosol. Mitochondria integrate cell-signaling networks, especially those involving the intracellular messenger Ca(2+), into the regulation of metabolic pathways. Recently, it has become clear that mitochondria are central to the three main cell death pathways, namely necrosis, apoptosis, and autophagic cell death. This article discusses the role of mitochondria in drug-induced cholestatic injury to the liver. The role of mitochondria in the cellular adaptation against the toxic effects of bile acids is discussed also.

Involvement of mitochondria in acetaminophen-induced apoptosis and hepatic injury: roles of cytochrome c, Bax, Bid, and caspases.

The role of apoptosis in acetaminophen (AAP)-induced hepatic injury was investigated. Six hours after AAP administration to BALB/c mice, a significant loss of hepatic mitochondrial cytochrome c was observed that was similar in extent to the loss observed after in vivo activation of CD95 by antibody treatment. AAP-induced loss of mitochondrial cytochrome c coincided with the appearance in the cytosol of a fragment corresponding to truncated Bid (tBid). At the same time, tBid became detectable in the mitochondrial fraction, and concomitantly, Bax was found translocated to mitochondria. However, AAP failed to activate the execution caspases 3 and 7 as evidenced by a lack of procaspase processing and the absence of an increase in caspase-3-like activity. In contrast, the administration of the pan-inhibitor of caspases, benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone (but not its analogue benzyloxycarbonyl-Phe-Ala-fluoromethylketone) prevented the development of liver injury by AAP and the appearance of apoptotic parenchymal cells. This correlated with the inhibition of the processing of Bid to tBid. The caspase inhibitor failed to prevent both the redistribution of Bax to the mitochondria and the loss of cytochrome c. In conclusion, apoptosis is an important causal event in the initiation of the hepatic injury inflicted by AAP. However, as suggested by the lack of activation of the main execution caspases, apoptosis is not properly executed and degenerates into necrosis.