The CD1-haired mouse and the SKH-hairless mouse are two animal models that have been used to evaluate sulfur mustard (HD) exposure and protection in our laboratory. In a recent study we observed that a substance P inhibitor protected the haired mouse ear against an HD solution, but the same drug was not successful in protecting the hairless mouse against HD vapor. This experiment prompted us to compare HD exposures between these models. We determined the 14C content in the skin after exposures to HD containing 14C-HD. Rate curves were generated for applications of (1) HD in methylene chloride to the haired mouse ear; (2) HD in methylene chloride to the hairless mouse dorsal skin; and (3) saturated HD vapor to the hairless mouse dorsal skin for 6 min. The curves showed a reduction in 14C disintegrations per min in animals euthanized 0 to 2 h postexposure. The largest percentage of decrease of 14C content in skin occurred within 30 min of HD challenge for all exposures. An 8-mm skin-punch biopsy and a 14-mm...
#1Thomas P. Logan(United States Army Medical Research Institute of Chemical Defense)H-Index: 2
#1Thomas P. Logan(United States Army Medical Research Institute of Chemical Defense)H-Index: 6
Last. Rodolfo Bongiovanni(United States Army Medical Research Institute of Chemical Defense)H-Index: 2
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ABSTRACTThe hairless guinea pig (HGP) is used by our laboratory to model the human cutaneous response to sulfur mustard (HD), bis(2-chloroethylsulfide), exposure. We determined the HD content in the skin of HGP after a 7-min exposure to vapors saturated with a mixture of HD and l4C-HD. Concentration/time (CT) values in the range of 2 μg/cm2/min were determined by counting skin 14C disintegrations per min (dpm) in animals euthanized immediately after exposure. These values are similar to human pe...
The mouse ear inflammation model was used to establish simple endpoints of skin injury following cutaneous exposure to sulfur mustard (bis(2- chloroethyl)sulfide, HD). Mouse ear edema and histopathologic response to a single topical application of 5 muL of 8, 16, 32, 64, or 128 mg/mL HD in dichloromethane was evaluated at 12, 18, and 24 h postexposure. Edema response was determined from weighed 8 mm diameter skin punch biopsies taken from the center of exposed and control ears. Key light microsc...
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 o...
#1Bruno Papirmeister(DA: United States Department of the Army)H-Index: 12
Last. Henry Louis Meier(DA: United States Department of the Army)H-Index: 11
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AbstractThe human skin graft/nude mouse model was used to study sulfur mustard (SM) -induced pathology of skin at the ultrastructural level. The electron microscope confirms and extends the histopathology previously noted under light microscopy. SM caused extensive injury to the basal keratinocytes, the severity of which was dependent on both time and dose. Ultrastructurally visible damage took several hours to develop. The following sequence of morphological changes was observed: (a) Extensive ...
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...
Hope everyone had an enjoyable and relaxing holiday. In this issue of the newsletter, we have included the mission statement and goals of the ISS that was developed with input from the past ISS presidents and the ISS Executive Committee. Please carefully review the goals and send me your comments. The goals will be continually revised and reprioritized as needed in the future. We plan to develop committees to address each of these goals. This is your chance to volunteer for specific committee an...
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...