Sulfur mustards therapeutics

Casillas, R.P., Kiser, R.C. (2000). Therapeutic approaches to dermatotoxicity by sulfurmustard. I. Modulaton of sulfur mustard-induced cutaneous injury in the mouse ear vesicant model. J. Appl. Toxicol. 20, Suppl. 1 SI45-51. 

Studies of occupational exposures to sulfur mustard indicate an elevated risk of respiratory tract and skin tumors following long-term exposure to acutely toxic concentrations. Overall, several factors are important regarding the assessment of the carcinogenicity of sulfur mustard. Increased cancer incidence in humans appears to be associated only with exposures that caused severe acute effects, and occupational exposures tended to involve repeated exposures and repeated injury of the same tissues. Because the therapeutic use of the sulfur mustard analog nitrogen mustard is associated with an increased incidence of CML, the reports of CML in HD-exposed individuals appear to be relevant to the eareinogenicity of sulfur mustard. 

Sawyer, T.W., Nelson, P., Hill, I., Conley, J.D., Blohm, K., Davidson, C., Sawyer, T.W. (2002). Therapeutic effects of cooling swine skin exposed to sulfur mustard. Mil. Med. 167 ... 

Medical Countermeasures and Other Therapeutic Strategies for Sulfur Mustard Toxicity... 

Calmodulin, poly(ADP-ribose)polymerase and p53 are targets for modulating the effects of sulfur mustard (Rosenthal et al, 2000). It was tested whether calmodulin mediates the mitoehondrial apoptotic pathway induced by SM in human keratinoeytes. Of the three human CaM genes, the predominant form expressed was CaMl. These results indicate that CaM, ealeineurin, and Bad also play a role in SM-induced apoptosis, and may therefore be targets for therapeutic intervention to reduce SM injury (Simbulan-Rosenthal et al, 2006). 

Van Helden, H.P., Kuijpers, W.C., Diemel, R.V. (2004). Asthma like symptoms following intratracheal exposure of guinea pigs to sulfur mustard aerosol therapeutic efficacy of exogenous lung surfactant curosurf and salhutamol. Inhal. Toxicol. 16 537 8. 

Until definitive medical therapeutics for sulfur mustard are fielded, the medical caregivers will have to rely on symptomatic treatments and sound medical judgments. Historically derived treatments, as presented in the Textbook of Military Medicine (Sidell et al., 1997) and the Medical Management of Chemical Casualties Handbook (1999) prepared by the Chemical Casualty Care Division of the U.S. Army Medical Research Institute of Chemical Defense, can also be of assistance. 

A previous report has implicated a role of calpain in mediating the tissue injury caused by the chemical threat agent sulfur mustard. Specifically, tissue homogenates from mouse ear skin exposed to sulfur mustard displayed a marked increase in calpain activity (170% increase 24 h after treatment Powers et al. 2000). These findings underscore the need to identify effective antiproteases with therapeutic use in reducing, or eliminating, tissue injuries. Since excitotoxicity is related directly to calpain activation, it can be surmised that sulfur mustard exposures may be linked to excitotoxicity. 

A. Microarray Analysis of Sulfur Mustard Exposure Reveals Potential Therapeutic Targets Coneirmed by Protein Analysis... 

Dacre JC, Goldman M. Toxicology and pharmacology of the chemical warfare agent sulfur mustard. Am. Soc. Pharmacol. Exp. Therapeut. 1996 48, No. 2. 

Ned D. Heindel (Chair) is H. S. Bunn Chair and Professor of Chemistry at Lehigh University. He joined Lehigh University in 1966. Dr. Heindel s research has focused mainly on the preparation of radiopharmaceuticals and synthesis of useful therapeutic drug candidates. He is working on countermeasures for sulfur mustard vesicant. Dr. Heindel has 11 patents, four of which have been licensed. In 1994 he served as the president of the American Chemical Society. Dr. Heindel earned his B.S. at Lebanon Valley College in 1959 (chemistry and mathematics) and his Ph.D. at the University of Delaware in 1963 (organic chemistry), and he held a postdoctoral fellowship at Princeton University in 1964 (medicinal chemistry). 

Weinberger, B., Laskin, J.D., Sunil, V.R., Sinko, P.J., Heck, D.E., Laskin, D.L. (2011). Sulfur mustard-induced pulmonary injury therapeutic approaches to mitigating toxicity. Pulm Pharmacol Ther., Vol. 24, No. 1, (Feb. 2011), pp. 92-99 ISSN 1094-5539 Wenzel, H.R. and Tschesche, H. (1995). Reversible inhibitors of serine proteinases. In Peptides Synthesis, Structures, and Applications, Ed. B. Gutte, pp. 321-362, Academic Press, ISBN 0123109205, USA... 

Casillas, R.P., Kiser, R.C., 2000. Therapeutic approaches to dermatotoxicity by sulfurmustard. I. Modulation of sulfur mustard-induced cutaneous injury in the mouse ear vesicant model. J. Appl. Toxicol. 20 (Suppl. 1), S145-S151. Coleman, K., 2005. A History of Chemical Warfare. Macmillan, New York, NY. Fitzgerald, G.J., 2008. Chemical warfare and medical response during World War I. Am. J. Public Health 98 (4), 611-625. 

Romano, J.A., Lukey, B.J., Salem, H., 2008. Chemical Warfare Agents Chemistry, Pharmacology, Toxicology, and Therapeutics. CRC Press, Boca Raton, FL. Schlager, J.J., Hart, B.W., 2000. Stress gene activity in HepG2 cells after sulfur mustard exposure. J. Appl. Toxicol. 20 (5), 395-405. 

Poursaleh, Z., Harandi, A.A., Vahedi, E., et al, 2012. Treatment for sulfur mustard lung injuries new therapeutic approaches from acute to chronic phase. Treatment for sulfur mustard lung injuries new therapeutic approaches from acute to chronic phase. Daru J. Pharm. Sd. 20 (1), 20-27. 

Weinberger, B., Laskin, J.D., Sunil, V.R., et al., 2011. Sulfur mustard-induced pulmonary injury therapeutic approaches to mitigating toxicity. Pulm. 

SuMur compounds compounds containing reduced or oxidized sulfur, seldom both (Table). Biochemically important S.a are the sulfur amino adds (see L-C eine, L-Methionine), biotin (thiophane ting) and thiamin (thiazole ting) (see Vitamins), sul-fatides (complex lipids of the nervous system see dy-colipids), and thiol peptides (see Glutathione, Vasopressin, Oxytodn, Insulin). S.c. also include Penicillin (see), and the sulfonamid which are important synthetic therapeutic agents. Hie mustard oil glycosides contain both oxidiz and reduced sulfur. Sulfate esters (see) are excreted by animals. 

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