Sulfur mustard [bis(2‐chloroethyl)sulfide, SM] is a chemical warfare agent that penetrates the skin rapidly and causes extensive blistering. Using the mouse ear vesicant model (MEVM), we evaluated the effect of topically applied anti‐inflammatory agents (octyl homovanillamide and heptyl isovanillamide) on ear edema formation and gene expression following SM exposure. Relative ear weight and real‐time reverse transcriptase polymerase chain reaction of GM‐CSF, IL‐1β, and IL‐6 were used to evaluate the effects of octyl homovanillamide and heptyl isovanillamide. Both vanilloids significantly reduced SM‐induced edema. At the single dose and number of animals/group tested, octyl homovanillamide produced a trend of reduced mRNA levels; however, the reduction was not significant for GM‐CSF, IL‐1β, or IL‐6. Heptyl isovanillamide significantly reduced (p ≤ 0.05) GM‐CSF, IL‐1β, and IL‐6 mRNA levels. These results show that octyl homovanillamide and heptyl isovanillamide reduce skin edema and heptyl isovanillamide si...
Abstract Sulfur mustard [bis(2-chloroethyl)sulfide; SM] is a chemical warfare agent that produces edema and blister formation with a severe inflammatory reaction. The mouse ear vesicant model for SM injury has been used to evaluate pharmacological agents for countering SM dermal injury. The vanilloid olvanil reduces SM-induced edema and mRNA expression of cytokines and chemokines, suggesting that blocking the inflammatory effects of neuropeptides, such as substance P (SP), may provide protection...
The mouse ear vesicant model (MEVM) is a screening tool used to identify protective compounds against acute sulfur mustard (SM)‐induced skin injury. It provides endpoints of edema and histopathology 24 h following a topical SM exposure to assess protection against inflammation and tissue damage. To further evaluate successful compounds, the MEVM was modified for use as a 7‐day model. Dose response studies were conducted with SM to select an optimal challenge dose for the new model. Due to severi...
Last. Robert P. Casillas(United States Army Medical Research Institute of Chemical Defense)H-Index: 20
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Cutaneous exposure to sulfur mustard [bis(2-chloroethyl) sulfide (SM)] produces a delayed inflammatory skin response that is followed by severe dermal injury. Assessment of anti-inflammatory therapies against SM-induced skin injury has mainly relied on qualitative histopathological evaluation. The goal of this study was to identify proinflammatory biomarkers in the hairless mouse vesicant model that could be used as additional indicators of SM-induced skin injury for evaluating anti-inflammatory...
Cutaneous exposure to sulfur mustard [bis(2-chloroethyl) sulfide; SM] produces a delayed inflammatory skin response and severe tissue injury. Pig skin has organ similarities to human skin that is characterized by the content and types of epidermal lipids, the density of hair follicles and presence of sweat glands, which together afford penetration of topically applied compounds, complex inflammatory responses, and subsequent wound healing. The goal of this study was to identify in vivo proinflam...
#1Karen M. Ricketts(United States Army Medical Research Institute of Chemical Defense)H-Index: 6
#2C. T. Santai(United States Army Medical Research Institute of Chemical Defense)H-Index: 1
Last. Robert P. Casillas(United States Army Medical Research Institute of Chemical Defense)H-Index: 20
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Assessment of anti-inflammatory therapies against sulfur-mustard (bis(2-chloroethyl)sulfide, HD)-induced skin injury has mainly relied on qualitative histopathological evaluation. Development of quantifiable inflammatory biomarkers using fast and reliable molecular methods is needed for screening anti-inflammatory drugs against HD injury. In this study, we used two different HD exposure models to determine the in vivo cutaneous response of the inflammatory cytokines interleukin-6 (IL-6), IL-lα, ...
#1Michael C. Babin(United States Army Medical Research Institute of Chemical Defense)H-Index: 12
#2Karen M. Ricketts(United States Army Medical Research Institute of Chemical Defense)H-Index: 6
Last. Robert P. Casillas(United States Army Medical Research Institute of Chemical Defense)H-Index: 20
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The mouse ear vesicant model (MEVM) provides a quantitative edema response as well as histopathological and biochemical endpoints as measurements of inflammation and tissue damage following exposure to the chemical warfare agent sulfur mustard (HD). In the MEVM, several topically applied anti-inflammatory agents provided a significant degree of protection against HD-induced edema and dermal-epidermal separation. This study evaluated the protective effects of three of these pharmacological compou...
Last. James A. Blank(Battelle Memorial Institute)H-Index: 6
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The mouse ear edema model is recognized for its usefulness in studying skin responses and damage following exposure to chemical irritants, and for evaluating pharmacological agents against chemically induced skin injury. We recently modified the mouse ear edema model for use with sulfur mustard (HD) and used this model to study the protective effect of 33 topically applied compounds comprising five pharmaceutical strategies (anti-inflammatories, protease inhibitors, scavengers/chelators, poly(AD...
#2John P. Petrali(United States Army Medical Research Institute of Chemical Defense)H-Index: 17
Last. Robert P. Casillas(United States Army Medical Research Institute of Chemical Defense)H-Index: 20
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Abstract : Cutaneous exposure to sulfur mustard (bis(2-chloroethyl) sulfide, HD), a chemical warfare agent, produces a delayed inflammatory skin response and severe tissue injury. Despite defined roles of inflammatory cytokines produced or released in response to skin-damaging chemicals, in vivo cytokine responses associated with HD-induced skin pathogenesis are not well understood. Additionally, there is little information on the in vivo temporal sequence of gene expression of cytokines postexp...
Upon stimulation, cutaneous sensory nerves release neuropeptides such as substance P (SP), which modulate responses in the skin by activating a number of target cells via neurokinin receptors. We have demonstrated that SP preferentially binds to the NK-1R on human dermal microvascular cells, resulting in increased intracellular Ca2+ and induction of ICAM-1 and VCAM-1 expression. In the current studies, we identify specific elements in the regulatory regions of ICAM-1 and VCAM-1 genes as necessar...
Last. Brennie E. Hackley(DA: United States Department of the Army)H-Index: 12
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N-methyl-2,2′-dichlorodiethylamine (HN2)is a topical chemotherapeutic agent used as therapy for cutaneous T-cell lymphomas (CTCL). Di(2-chloroethyl)sulfide (SM), and less often HN2, have been used as chemical weapons, with the skin being a principle target. The mechanisms by which these chemicals pr
#1S.C. Pant(DRDE: Defence Research and Development Establishment)H-Index: 21
#2Vinay Lomash(DRDE: Defence Research and Development Establishment)H-Index: 12
Sulphur mustard (SM), chemically, bis (2-chloroethyl) sulphide is a bifunctional alkylating agent that causes cutaneous blisters in human or animals. It was first used in the World War I. Since then, there have been 11 conflicts where SM allegedely had caused mass distruction. Additionally, discarded weapons and stockpiles periodically come to surface during agricultural or fishing activities leading to serious injury. Concerns for threat to modern societies by the serious effects of SM, agreeme...
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...
Sulfur mustard (SM)–induced dermatotoxicity can be prevented by an immediate use of decontamination agents. However, practically due to the time lapse between decontamination and exposure, there is always a possibility of wound formation. In view of this, a hydrophilic decontamination formulation of CC-2 (DRDE/WH-03) was fortified with Aloe vera gel and betaine (DRDE/WH-01) for improving its wound healing ability. Swiss albino mice were exposed to SM percutaneously (5 mg/kg) once, and after 24 h...
#1Vinay Lomash(DRDE: Defence Research and Development Establishment)H-Index: 12
#2S.E. Jadhav(DRDE: Defence Research and Development Establishment)H-Index: 7
Last. S.C. Pant(DRDE: Defence Research and Development Establishment)H-Index: 21
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Sulphur mustard (SM) is a bifunctional alkylating agent that causes cutaneous blisters in human and animals. Remedies to SM-induced dermatotoxicity are still in experimental stage. Due to inevitable requirement of a wound-healing formulation against SM-induced skin lesions, efficacy of formulations including povidone iodine, Aloe vera gel, betaine or framycetin sulphate was evaluated in present study. SM was applied percutaneously (5 mg/kg) once on back region of Swiss albino mice; and after 24 ...
Severe cutaneous injuries continue to result from exposure to sulfur mustard [bis(2-chloroethyl)sulfide; HD] and thermal burns. Microarray analysis was utilized in this study to evaluate transcriptional changes in porcine skin assessing the underlying repair mechanisms of HD and thermal injury involved in wound healing. Four ventral abdominal sites on each of 4 weanling swine were exposed to 400 μL undiluted HD or a heated brass rod (70°C) for 8 minutes and 45–60 seconds, respectively. At 7 days...
Publisher Summary This chapter deals with the cutaneous actions of sulfur mustard (SM) and discusses the basic mechanism of action and mediators involved. While stable in lipophilic solvents, SM has a half life of only 24 min at room temperature in aqueous physiological solutions, since it rapidly reacts with water to form thiodiglycol and HCl. This rapid activation of SM in an aqueous environment also allows it to react with small molecules of biological interest, as well as proteins, carbohydr...
In military and civilian environments, serious cutaneous damage can result from thermal burns or exposure to the blistering agent sulfur mustard [bis (2-chloroethyl) sulfide; HD]. Similar therapies have historically been used to treat cutaneous thermal and HD injuries; however, the underlying molecular mechanisms of tissue damage and wound healing may differ between the types of burns. Using microarray analysis, this study assessed the transcriptional responses to cutaneous HD and thermal injury...
Bis-(2-chloroethyl) sulfide (sulfur mustard; SM) is a potent alkylating agent. Three treatment compounds have been shown to limit SM damage in the mouse ear vesicant model: dimercaprol, octyl homovanillamide, and indomethacin. Microarrays were used to determine gene expression profiles of biopsies taken from mouse ears after exposure to SM in the presence or absence of treatment compounds. Mouse ears were topically exposed to SM alone or were pretreated for 15 min with a treatment compound and t...
The chemical warfare agent sulfur mustard [bis-(2-chloroethyl)-sulfide; SM] produces a delayed inflammatory response followed by blister formation in skin of exposed individuals. Studies are underway evaluating the efficacy of pharmacological compounds to protect against SM skin injury. Microarray analysis provides the opportunity to identify multiple transcriptional biomarkers associated with SM exposure. This study examined SM-induced changes in gene expression in skin from mice cutaneously ex...
