Accession Number : ADA463834


Title :   The Mustard Consortium's Elucidation of the Pathophysiology of Sulfur Mustard and Antidote Development


Descriptive Note : Final rept. 15 Aug 2003-31 Aug 2006


Corporate Author : MICHIGAN UNIV ANN ARBOR


Personal Author(s) : Ward, Peter A ; Smith, Milton G ; Crawford, Keith ; Stone, William ; Das, Salil ; Sciuto, Alfred ; Anderson, Dana


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a463834.pdf


Report Date : Sep 2006


Pagination or Media Count : 36


Abstract : The Mustards Consortium has utilized both in vivo and in vitro models simultaneously to continue to elucidate mustard gas pathophysiology. In previous work done by the MC it was found that CEES, the mustard analogue, induced oxidative stress and was its primary mechanism of action. Consequently, NAC (N-acetyl cystiene) was found to be protective as a prophylaxis and treatment. A combination of a water and fat soluble antioxidant encapsulated in a liposome (STIMAL) was found to have the best ameliorative effect against CEES. We have initiated development of next generation STIMAL, in order to optimize its ameliorative effect. The mechanism of action of the antioxidants is suspected to be primarily by their effect on redox regulated pathways. In an effort to elucidate the mechanism of action of the antioxidants and the pathophysiology of mustards, profiles are being developed for: gene expression and antioxidant levels, as well as biochemical pathways. The first known histological comparison between CEES and sulfur mustard was carried out. Two new rat lung models were developed for the administration of sulfur mustards in preparation for efficacy testing of STIMAL against sulfur mustards. Pulmonary fibrosis was demonstrated in both guinea pig and rat lung models.


Descriptors :   *ANTIDOTES , *MUSTARD AGENTS , *PATHOPHYSIOLOGY , STRESSES , RATS , WATER , CYTOPLASM , SOLUBILITY , ANTIOXIDANTS , FIBROSIS , SULFUR COMPOUNDS , GUINEA PIGS , HISTOLOGY , PREVENTIVE MEDICINE , CONSORTIUMS , IN VIVO ANALYSIS , FATS , GENES , LUNG , IN VITRO ANALYSIS , GASES


Subject Categories : Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE