Abstract Sulfur mustard (HD; 1,1′-thiobis[2-chloroethane]) induces fluid-filled blisters in man but not in conventional laboratory animals. An animal model is needed to emulate both cytotoxic (vesicant) and vascular (irritant) responses of human skin to HD exposures. An acceptable model must permit reproducible comparisons of uniformly graded and dose-related HD control responses with reduced responses that may follow antivesicant treatments. Hairless guinea pigs were evaluated by exposing six or eight dorsal skin sites 12 mm in diameter to similar HD vapor concentrations for graded intervals (1–16 min). HD vapor was delivered under occlusive caps holding 10 μl of HD in filter paper located 5 mm above the skin. Four-minute exposures induced moderate erythema, slight edema, and microblisters in 1 of 39 sites. Eight-minute exposures induced severe erythema, moderate edema, and microblisters in 31 of 40 sites. Gross blistering was not seen after use of vapor cups, but damage to basal cells resembled lesions of vesicant injury in man. The hairless guinea pig model, with graded HD vapor exposures, provides acceptable comparisons of responses. Exposures of both 4- and 8-min durations were used to show the feasibility of using this model to bioassay antivesicant topical protectants. These methods may be useful for measurements of irritant and cytotoxic responses of skin to other toxic vapors.
Previous research has shown the isolated perfused porcine skin flap (IPPSF) to be a novel in vitro experimental model for investigating xenobiotic percutaneous absorption. In this study, the IPPSF was used to biochemically and morphologically assess the dermatotoxicity of 2-chloroethyl methyl sulfide (CEMS), a monofunctional analog of the vesicant, sulfur mustard. IPPSFs were perfused in a recirculating perfusion system and were treated with 97% CEMS (n = 4) or served as controls (n = 4). Additi...
AbstractEuthymic hairless guinea pigs [Crl:IAF(HA)BR] were compared to normal haired guinea pigs [Crl:(HA)BR] to determine whether the hairless guinea pig is a suitable animal model for studying sulfur mustard- (HD) induced vesication of skin. Neat HD was applied to the skin for 30 min and the exposed skin was examined 24 and/or 48 hr postexposure for gross, histopathologic, and ultrastructural lesions. The hairless guinea pig proved to be superior to the haired guinea pig as an animal model; it...
AbstractSix pigs were cutaneously exposed for 1 hr to high doses of sulfur mustard (HD) by both direct droplet contact and indirect vapor. Tissue was harvested for microscopic examination after 72 hr. Three other pigs were cutaneously exposed to HD and lewisite (L) by droplet streak application. Histologically, all test subjects exhibited microvesicle formations of varying intensities. Vapor exposures produced diffuse lesions of lesser severity than lesions induced by direct droplet or droplet s...
Last. Bruno Papirmeister(DA: United States Department of the Army)H-Index: 12
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Abstract Sulfur mustard (SM) (di-2-chloroethyl sulfide), used for chemical warfare in World War I, is a highly reactive radiomimetic alkylating agent. When applied to the skin of rabbits and guinea pigs, it produced vascular leakage, leukocyte infiltration, and slow death of basal epidermal cells. Thirty to sixty minutes after exposure to SM, injury to the superficial microvasculature (beneath the SM application site) was detected by measuring vascular leakage with Evans blue dye and also with h...
AbstractSulfur mustard (SM) is a powerful vesicant in humans whose pathogenic mechanism is not well understood and an agent for which no effective therapy exists. We selected human skin grafted to congenitally athymic nude mice to study SM-induced injury because the injury in various animal models differs from skin injury in humans. Grafts made from full-thickness human neonatal foreskin or from partial-thickness adult facial, mammary, and abdominal skin were exposed to SM in either the liquid o...
The merits of formaldehyde, formaldehyde-glutaraldehyde combinations, and glutaraldehyde in phosphate buffers have been compared as fixatives that will give easy and satisfactory preservation of tissues for routine automated histologic processing and yet keep them suitable for electron microscopical studies after prolonged storage at room temperature. We recommend a combination of 4% commercial formaldehyde and 1% glutaraldehyde in a buffer of 176 mOsm/liter. Tissue sections should not exceed 3 ...
: This study aimed to evaluate the potential adverse effects of the dermal administration of Dillenia indica Linnaeus (D. indica) fruit extract in healthy rodents; the extract was standardized to betulinic acid. In the initial phase, the acute effects were evaluated on the skin application site of a single extract dose. A skin irritation test was performed in male Wistar rats (n = 8/group) receiving the extract (50-150 mg/mL) with betulinic acid (0.5-1.5%, respectively). A photosensitivity test ...
Last. Diane E. Heck(NYMC: New York Medical College)H-Index: 4
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Abstract Nitrogen mustard (NM) is a bifunctional alkylating agent that is highly reactive in the skin causing extensive tissue damage and blistering. In the present studies, a modified cutaneous murine patch model was developed to characterize NM-induced injury and to evaluate the efficacy of an indomethacin pro-drug in mitigating toxicity. NM (20 μmol) or vehicle control was applied onto 6 mm glass microfiber filters affixed to the shaved dorsal skin of CD-1 mice for 6 min. This resulted in abs...
This chapter describes the dermal toxicity events of the alkylating agent, sulfur mustard [bis(2-chloroethyl) sulfide], which ultimately causes detachment of the epidermis from the dermis. Skin exposure to sulfur mustard (SM) starts a series of dermal toxicity events with severity determined in part by mediators of injury that regulate inflammation, immune responses, apoptosis, necrosis, and a number of signaling pathways. This complex series of events involves a host of normal skin responses to...
#1Shlomit Dachir(Israel Institute for Biological Research)H-Index: 19
#2Maayan Cohen(Israel Institute for Biological Research)H-Index: 10
Last. Tamar Kadar(Israel Institute for Biological Research)H-Index: 26
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Sulfur mustard induces severe acute and prolonged damage to the skin and only partially effective treatments are available. We have previously validated the use of hairless guinea pigs as an experimental model for skin lesions. The present study aimed to characterize a model of a deep dermal lesion and to compare it with the previously described superficial lesion. Clinical evaluation of the lesions was conducted using reflectance colorimetry, trans-epidermal water loss and wound area measuremen...
Abstract DNA represents an ideal vaccine platform for HIV and many infectious diseases because of its safety, stability, and ease of manufacture. However, the immunogenicity of DNA vaccines has traditionally been low compared with viral vectors, recombinant protein, and live attenuated vaccines. The immunogenicity of DNA vaccines has been significantly enhanced by delivery with in vivo electroporation. Further improvements now allow electroporation to be performed in the dermis, which could pote...
Sulfur mustard (HD) ranks among the alkylating chemical warfare agents. Skin contact with HD produces an inflammatory response that evolves into separation at the epidermal–dermal junction conducting to blistering and epidermis necrosis. Up to now, current treatment strategies of HD burns have solely consisted in symptomatic management of skin damage. Therapeutic efficacy studies are still being conducted; classically using appropriate animal skin toxicity models. In order to substantiate the us...
Sulfur mustard (SM, bis(2-chloroethyl)sulfide) is a bifunctional alkylating agent that causes dermal inflammation, edema and blistering. To investigate the pathogenesis of SM-induced injury, we used a vapor cup model which provides an occlusive environment in which SM is in constant contact with the skin. The dorsal skin of SKH-1 hairless mice was exposed to saturated SM vapor or air control. Histopathological changes, inflammatory markers and DNA damage were analyzed 1–14 days later. After 1 da...
Exposure to lethal chemical warfare agents (CWAs) is no longer only a military issue due to the terrorist threat. Among the CWAs of concern are the organophosphorus nerve agent O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX) and the vesicant sulfur mustard (SM). Although efficient means of decontamination are available, most of them lose their efficacy when decontamination is delayed after exposure of the bare skin. Alternatively, CWA skin penetration can be prevented by topica...
#1Janet M. Benson(LRRI: Lovelace Respiratory Research Institute)H-Index: 30
#2Brad M. Tibbetts(LRRI: Lovelace Respiratory Research Institute)H-Index: 5
Last. Gary R. Grotendorst(LRRI: Lovelace Respiratory Research Institute)H-Index: 32
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Sulfur mustard (SM), a vessicating agent, has been used in chemical warfare since 1918. The purpose of this study was to quantitate SM vapor deposition, tissue distribution, and excretion following intratracheal inhalation in rats and cutaneous exposure in guinea pigs. 14C-SM vapors for inhalation studies were generated by metering liquid 14C-SM into a heated J tube. Vapors were transported via carrier air supplemented with oxygen and isoflurane to an exposure plenum. Anesthetized rats with tran...
#1Siqi Guo(ODU: Old Dominion University)H-Index: 13
#2Amy Donate(USF: University of South Florida)H-Index: 10
Last. Richard Heller(USF: University of South Florida)H-Index: 57
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Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been sho...
