Sulfur mustards treatment

Mechlorethamine (nitrogen mustard Mustargen), a derivative of the war gas sulfur mustard, is considered to be the first modern anticancer drug. In the early 1940s it was discovered to be effective in the treatment of human lymphomas. 

Wils et al. (25,26) previously reported an entirely different approach to TDG analysis. TDG in urine was converted back to sulfur mustard by treatment with concentrated HC1. The sample treatment is less straightforward than the methods described above, but analysis as sulfur mustard is facile. Urine, plus 2H8-TDG as internal standard, was cleaned up by elution through two C18 cartridges. Concentrated HC1 was added and the sample stirred and heated at 120 °C. Nitrogen was blown over the solution and sulfur mustard isolated from the headspace by adsorption onto Tenax-TA. The method was used to detect TDG in urine from casualties of CW attacks (see below). A disadvantage of this method is that it may convert metabolites other than TDG to sulfur mustard. This is supported by the detection of relatively high levels of analytes in urine from control subjects. Vycudilik (27) used a similar procedure, but recovered the mustard by steam distillation and extraction. 

Figure 8. GC/MS/MS/MRM chromatograms showing the detection of f5-lyase metabolites in urine from two casualties of sulfur mustard poisoning (Cl, 220ng/ml and C4, 5ng/ml), their absence in urine from an unexposed subject, and the internal standard (is). Samples Cl and C4 were from two Iranian subjects undergoing treatment in Ghent in 1984, collected 10 days after the exposure...

The ELISA for detection of the DNA adduct was successfully applied to blood samples from two casualties of the Iraq-Iran conflict. These samples were collected 22 and 26 days following the alleged exposure to sulfur mustard (13). Concentrations found in lymphocytes and granulocytes were equivalent to similar levels found in human blood after treatment in vitro with 0.015-0.43 xM sulfur mustard. 

The use of sulfur mustard as a vesicant CW agent implies that proteins of the skin are a primary target. It was found that upon exposure of human callus to [14C]sulfur mustard, a significant part of the radioactivity was covalently bound to keratin (30). Most of the radioactivity (80%) bound to keratin could be removed by treatment with alkali, indicating the presence of adducts to glutamic and/or aspartic acid residues. 

Effects of orally administered sulfur mustard in rats were studied by Sasser et al. (1996a). Repeated gavage administration of sulfur mustard in sesame oil produced epithelial hyperplasia of the forestomach at the highest dose tested but no deaths and no other treatment-related pathological lesions or changes in clinical chemistry or hematological parameters. 

Results of a multigeneration study in rats given sulfur mustard by gavage showed no significant adverse effects on reproductive parameters at any dose level, but revealed dose-related lesions of the squamous epithelium of the forestomach (acanthosis and hyperplasia). It is likely that the fore stomach lesions were a function of the treatment regimen whereby the bolus dose in an oil vehicle (sesame... 

Medical management of nitrogen mustard exposure is similar to that for sulfur mustard and involves prevention of exposure and, where exposure has occurred, decontamination and support therapy. The use of antioxidants in the treatment of nitrogen mustard toxicity is currently under investigation (Hardej and Billack, 2006). 

L., Kadar, T. (2002). Topical dexamycin treatment against sulfur mustard ocular injury. US Army Medical Defense Bioscience Review 221. 

Anderson, D., Byers, S., Vesely, K. (2000). Treatment of sulfur mustard (HD)-induced lung iniury. J. Appl. Toxicol. 20 (Suppl. 1) S129-32. 

Bahru, M., Ricketts, K., Gazaway, M., Lee, R., Sweeney, R., Brozetti, J. (2004). A comhination drug treatment against ocular sulfur mustard injury. J. Toxicol. Cutan. Ocul. Toxicol. 23(1) 65-75. 

Vidan, A., Luria, S., Eisenkraft, A., Hourvitz, A. (2002). Ocular injuries following sulfur mustard exposure clinical characteristics and treatment. Isr. Med. Assoc. J. 4 511-8. 

Dachir, S., Fishheine, E., Meshulam, Y., Sahar, R., Amir, A., Kadar, T. (2002). Potential anti-inflammatory treatments against cutaneous sulfur mustard injury using the mouse ear vesicant model. Hum. Exp. Toxicol. 21 197-203. 

Dachir, S., Cohen, M., Fishhine, E., Sahar, R., Kadar, T. (2008). Beneficial effect of treatment with nonsteroidal antiinflammatory drugs against sulfur mustard skin injury. Proceedings of the U.S. Army Medical Defense Bioscience Review, Hunt Valley, MD, 150 pp. 

Hess, J.F., FitzGerald, P.G. (2007). Treatment of keratin intermediate filaments with sulfur mustard analogs. Biochem. Biophys. Res. Commun. 359 616-21. 

Kiser, R.C., Moore, D.M. et al. (2005). Mouse ear vesicant model (MEVM) evaluation of treatment combinations against topical sulfur mustard challenge. Toxicol. Set. 84 451. 

Schultz, G.S., Mol, M.A.E., Galardy, R.E., Friel, G.E. (2004). Protease inhibitor treatment of sulfur mustard injuries in cultured human skin. Proceedings of the U.S. Army Medical Defense Bioscience Review, Aberdeen Proving Ground, MD. 

Anderson, D.R., Holmes, W.W., Lee, R.B., Dalai, S.J., Hurst, C.G., Maimer, B.I., Newmark, J., Smith, W.J. (2006). Sulfur mustard-induced neutropenia treatment with gran-uloc de colony-stimulating factor. Mil. Med. 171 448-53. 

Ghanei, M., Shohrati, M., Harandi, A.A., Eshraghi, M., Aslani, J., Alaeddini, F., Manzoori, H. (2007). Inhaled corticosteroids and long-acting beta 2-agonists in treatment of patients with chronic bronchiolitis following exposure to sulfur mustard. Inhal. Toxicol. 19 889-94. 

Illig, L., Paul, E., Eyer, P., Weger, N., Bom, W. (1979). Treatment of psoriasis vulgaris with external sulfur mustard gas with particular reference to its potential carcinogenic risk. III. Clinical and experimental studies on the extent of percutaneous and inhalational uptake of sulfur mustard gas. Z Hautkr. 54 941-51. 

Shohrati, M., Davoudi, M., Almasi, M., Sadr, B., Peyman, M. (2007a). Comparative study of Unna s Boot and betamethasone cream in the treatment of sulfur mustard-related pruritus. Cutan. Ocul. Toxicol. 26 303-9. 

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