Accession Number : ADA305800

Title :   Mechanisms of Cutaneous Vesication.

Descriptive Note : Final rept. 17 Jul 92-30 Nov 95,

Corporate Author : NORTH CAROLINA STATE UNIV AT RALEIGH

Personal Author(s) : Monteiro-Riviere, Nancy A. ; Zhang, Jason Z. ; Inman, Alfred O. ; Riviere, Jim E.

PDF Url : ADA305800

Report Date : 16 DEC 1995

Pagination or Media Count : 162

Abstract : This project investigated the mechanism of bis (2-chioroethyl) sulfide SULFUR MUSTARD, HD induced cutaneous vesication using the isolated perfused porcine skin flap (IPPSF) and in vitro cell cultures. Treatment of IPPSFs with 5.0 mg/ml of HD results in a characteristic increase in vascular resistance, decrease in glucose utilization, and the formation of gross and microblisters. The first study demonstrated that the vascular changes associated with HD vesication are accompanied by increases in the efflux of prostaglandins PGE2 and PGF2a. Additionally, studies were designed to evaluate the protective effects of sodium thiosulfate, cysteine, niacinamide and indomethacin. Treatments with niacinamide and indomethacin resulted in an inhibition of the vascular response and microvesicles were partially prevented with indomethacin. These data suggested that none of these agents alone would be successful antivesicant and different mechanisms are involved in the production of dark basal cells, microvesicles, and the vascular response. Unfortunately, blocking of the cellular toxicity as evidenced by dark basal cell formation did not prevent vesication, suggesting that other mechanisms must be operative and that there is a multistep, biochemical process that leads to the blister. The flux of HD through the skin was investigated to determine if metabolites are formed due to epidermal metabolism. These experiments showed that little, if any HD, appears in the venous perfusate and that epidermal metabolism of HD does occur to a significant degree in the IPPSF. Assessment of extracellular and intravascular space using radiolabeled inulin and albumin infusions, respectively, demonstrated that HD primarily produced an increase in intravascular space.

Descriptors :   *TOXICITY, *IN VITRO ANALYSIS, *MUSTARD AGENTS, *SULFUR, *CELLS(BIOLOGY), *SKIN(ANATOMY), *CULTURES(BIOLOGY), *VESICANTS, *SUBCUTANEOUS TISSUE, PRODUCTION, BIOCHEMISTRY, ISOLATION, RESPONSE, PROTECTION, FLAPS(CONTROL SURFACES), RESPONSE(BIOLOGY), INHIBITION, IMMUNITY, UTILIZATION, CARDIOVASCULAR SYSTEM, SULFIDES, CYSTEINE, METABOLITES, ALBUMINS, GLUCOSE, LABELED SUBSTANCES, RADIOACTIVE ISOTOPES, RESISTANCE(BIOLOGY), SWINE, SKIN DISEASES, ANALGESICS, VITAMIN B COMPLEX, INFUSIONS, SODIUM COMPOUNDS, INULIN, THIOSULFATES.

Subject Categories : Anatomy and Physiology
      Toxicology
      Chemical, Biological and Radiological Warfare

Distribution Statement : APPROVED FOR PUBLIC RELEASE