Pathogenesis of 2,2′-dichlorodiethyl sulfide in hairless guinea pigs

Structural changes in hair follicles and sebaceous glands of hairless mice following exposure to sulfur mustard

“…These degenerative changes were associated with a marked increase in flaky xerotic skin in the wound (unpublished studies). These data are consistent with earlier studies in hairless guinea pig skin showing that SM vapor induces rapid (within 24 hr) follicular necrosis (Snider et al, 1999; Yourick et al, 1993). It has also been reported that hairless guinea pigs, like hairless mice, experience a loss of hair follicles and sebaceous glands 14 days post SM exposure (Benson et al , 2011).…”

Structural changes in hair follicles and sebaceous glands of hairless mice following exposure to sulfur mustard

“…These degenerative changes were associated with a marked increase in flaky xerotic skin in the wound (unpublished studies). These data are consistent with earlier studies in hairless guinea pig skin showing that SM vapor induces rapid (within 24 hr) follicular necrosis (Snider et al, 1999; Yourick et al, 1993). It has also been reported that hairless guinea pigs, like hairless mice, experience a loss of hair follicles and sebaceous glands 14 days post SM exposure (Benson et al , 2011).…”

Time course of lesion development in the hairless guinea‐pig model of sulfur mustard‐induced dermal injury

“…Severe erythema, assessed by Draize score, was present by 6 hours postexposure in both the 6 and 12‐minute exposure groups. This is consistent with erythema reported at 4–8 hours postexposure by Mershon et al 10 and Yourick et al 15 for guinea‐pigs exposed to vapors generated from 10 μL SM for 6 or 8 minutes. Reflectance measurement of erythema in our study (Δ a * ) peaking at 6 hours postexposure and dropping somewhat by 24 hours exposure are also consistent with findings of Snider et al 17 in guinea‐pigs exposed to SM vapor (generated from 10 μL in a vapor cup) for 6 and 12 minutes.…”

“…Due to differences in experimental design, it is difficult to make direct comparisons of histologic changes reported by others in SM‐exposed animals. However, during the first 24 hours postexposure in our study, we identified inflammatory changes (dermatitis, epidermatitis), fluid dysregulatory changes (edema, acantholysis), and degenerative changes (epidermal necrosis, follicular necrosis, and epidermal/dermal blister formation) consistent with early change reported in guinea‐pigs (Table 2) 10,15,17 and man 3 . Apoptosis, mostly observed 6 and 24 hours among the 6‐minute exposure group in our study, was not reported in the above SM studies but was observed in skin biopsy samples of individuals approximately 5 days after being exposed to SM during the Iran–Iraq war 3 .…”

“…SM vapor‐induced skin lesions occurring within 24 hours postexposure have been described previously, 10,15–17 and to the best of our knowledge, only Dachir et al 18 have examined the histological changes for longer periods postexposure. The study reported here is unique in that detailed histological evaluations and effects on pro‐ and active forms of MMPs‐2 and ‐9 are described to 2 weeks postexposure.…”

Life-Cycle-Dependent Toxicities of Mono- and Bifunctional Alkylating Agents in the 3R-Compliant Model Organism C. elegans

“…In previous studies, mustard exposure led to a partial depletion of NAD + levels ex vivo [21], in vivo [22,23], or in vitro [24,25]. In C. elegans, mustards did not cause a substantial change in NAD + levels shortly after CEES and HN2 exposure (Figure 6), although significant NAD + depletion has been observed at later time points (24 h), particularly after exposure to HN2 (Figure 6b): L4 worms showed a dose-dependent effect, which was significant for 2.5 mM and 5 mM HN2 (Figure 6b), concentrations which correspond to 67% and 9% survival (Figure 1b), respectively.…”

Structural changes in hair follicles and sebaceous glands of hairless mice following exposure to sulfur mustard

“…These degenerative changes were associated with a marked increase in flaky xerotic skin in the wound (unpublished studies). These data are consistent with earlier studies in hairless guinea pig skin showing that SM vapor induces rapid (within 24 hr) follicular necrosis (Snider et al, 1999; Yourick et al, 1993). It has also been reported that hairless guinea pigs, like hairless mice, experience a loss of hair follicles and sebaceous glands 14 days post SM exposure (Benson et al , 2011).…”

Time course of lesion development in the hairless guinea‐pig model of sulfur mustard‐induced dermal injury

“…Severe erythema, assessed by Draize score, was present by 6 hours postexposure in both the 6 and 12‐minute exposure groups. This is consistent with erythema reported at 4–8 hours postexposure by Mershon et al 10 and Yourick et al 15 for guinea‐pigs exposed to vapors generated from 10 μL SM for 6 or 8 minutes. Reflectance measurement of erythema in our study (Δ a * ) peaking at 6 hours postexposure and dropping somewhat by 24 hours exposure are also consistent with findings of Snider et al 17 in guinea‐pigs exposed to SM vapor (generated from 10 μL in a vapor cup) for 6 and 12 minutes.…”

“…Due to differences in experimental design, it is difficult to make direct comparisons of histologic changes reported by others in SM‐exposed animals. However, during the first 24 hours postexposure in our study, we identified inflammatory changes (dermatitis, epidermatitis), fluid dysregulatory changes (edema, acantholysis), and degenerative changes (epidermal necrosis, follicular necrosis, and epidermal/dermal blister formation) consistent with early change reported in guinea‐pigs (Table 2) 10,15,17 and man 3 . Apoptosis, mostly observed 6 and 24 hours among the 6‐minute exposure group in our study, was not reported in the above SM studies but was observed in skin biopsy samples of individuals approximately 5 days after being exposed to SM during the Iran–Iraq war 3 .…”

“…SM vapor‐induced skin lesions occurring within 24 hours postexposure have been described previously, 10,15–17 and to the best of our knowledge, only Dachir et al 18 have examined the histological changes for longer periods postexposure. The study reported here is unique in that detailed histological evaluations and effects on pro‐ and active forms of MMPs‐2 and ‐9 are described to 2 weeks postexposure.…”

Life-Cycle-Dependent Toxicities of Mono- and Bifunctional Alkylating Agents in the 3R-Compliant Model Organism C. elegans

“…In previous studies, mustard exposure led to a partial depletion of NAD + levels ex vivo [21], in vivo [22,23], or in vitro [24,25]. In C. elegans, mustards did not cause a substantial change in NAD + levels shortly after CEES and HN2 exposure (Figure 6), although significant NAD + depletion has been observed at later time points (24 h), particularly after exposure to HN2 (Figure 6b): L4 worms showed a dose-dependent effect, which was significant for 2.5 mM and 5 mM HN2 (Figure 6b), concentrations which correspond to 67% and 9% survival (Figure 1b), respectively.…”

Structural changes in hair follicles and sebaceous glands of hairless mice following exposure to sulfur mustard

“…These degenerative changes were associated with a marked increase in flaky xerotic skin in the wound (unpublished studies). These data are consistent with earlier studies in hairless guinea pig skin showing that SM vapor induces rapid (within 24 hr) follicular necrosis (Snider et al, 1999; Yourick et al, 1993). It has also been reported that hairless guinea pigs, like hairless mice, experience a loss of hair follicles and sebaceous glands 14 days post SM exposure (Benson et al , 2011).…”

Time course of lesion development in the hairless guinea‐pig model of sulfur mustard‐induced dermal injury

“…Severe erythema, assessed by Draize score, was present by 6 hours postexposure in both the 6 and 12‐minute exposure groups. This is consistent with erythema reported at 4–8 hours postexposure by Mershon et al 10 and Yourick et al 15 for guinea‐pigs exposed to vapors generated from 10 μL SM for 6 or 8 minutes. Reflectance measurement of erythema in our study (Δ a * ) peaking at 6 hours postexposure and dropping somewhat by 24 hours exposure are also consistent with findings of Snider et al 17 in guinea‐pigs exposed to SM vapor (generated from 10 μL in a vapor cup) for 6 and 12 minutes.…”

“…Due to differences in experimental design, it is difficult to make direct comparisons of histologic changes reported by others in SM‐exposed animals. However, during the first 24 hours postexposure in our study, we identified inflammatory changes (dermatitis, epidermatitis), fluid dysregulatory changes (edema, acantholysis), and degenerative changes (epidermal necrosis, follicular necrosis, and epidermal/dermal blister formation) consistent with early change reported in guinea‐pigs (Table 2) 10,15,17 and man 3 . Apoptosis, mostly observed 6 and 24 hours among the 6‐minute exposure group in our study, was not reported in the above SM studies but was observed in skin biopsy samples of individuals approximately 5 days after being exposed to SM during the Iran–Iraq war 3 .…”

“…SM vapor‐induced skin lesions occurring within 24 hours postexposure have been described previously, 10,15–17 and to the best of our knowledge, only Dachir et al 18 have examined the histological changes for longer periods postexposure. The study reported here is unique in that detailed histological evaluations and effects on pro‐ and active forms of MMPs‐2 and ‐9 are described to 2 weeks postexposure.…”

Life-Cycle-Dependent Toxicities of Mono- and Bifunctional Alkylating Agents in the 3R-Compliant Model Organism C. elegans

“…In previous studies, mustard exposure led to a partial depletion of NAD + levels ex vivo [21], in vivo [22,23], or in vitro [24,25]. In C. elegans, mustards did not cause a substantial change in NAD + levels shortly after CEES and HN2 exposure (Figure 6), although significant NAD + depletion has been observed at later time points (24 h), particularly after exposure to HN2 (Figure 6b): L4 worms showed a dose-dependent effect, which was significant for 2.5 mM and 5 mM HN2 (Figure 6b), concentrations which correspond to 67% and 9% survival (Figure 1b), respectively.…”