Evaluation of Euthymic Hairless Guinea Pigs (Crl:IAF(HA)BR) as an Animal Model for Vesicant Injury

Marlow, Denver; Mershon, Millard M.; Mitcheltree, Larry W.; Petrali, John P.; Jaax, Gerald P.

doi:10.21236/ada209293

Cited by 9 publications

(9 citation statements)

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“…Skin from the hairless guinea pig has been used to evaluate the pathogenesis of the HD lesion and the efficacy of potential therapeutic compounds (1)(2)(3)(4)(5).…”

Section: Dtic Fup!3 Opi: Dtic-tidmentioning

confidence: 99%

Effect of Sulfur Mustard on Mast Cells in Hairless Guinea Pig Skin

Graham

Bryant

Braue

1994

Journal of Toxicology: Cutaneous and Ocular Toxicology

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The skin of 24 anesthetized hairless guinea pigs was exposed to saturated sulfur mustard (bis-2-chloroethyl sulfide; HD) for 5 and 7 minutes using 14-mm diameter vapor cups. Animals were euthanatized 24 hours after exposure and skin specimens taken for morphometric evaluation of granulated mast cells with an image analysis system (IAS).Tissue specimens were processed in paraffin, sectioned at 5Mm and stained with Unna's stain for mast cells. The number of granulated mast cells and the area occupied by mast cell granules was determined. There were significantly fewer mast cells (p < 0.05) in either HD exposure group than in sham-exposed animals, with significantly fewer mast cells in the 7-minute than the 5-minute HD group.There were also significantly smaller areas occupied by granules in either HD exposure group than in sham-exposed animals. HD-induced lesions in the hairless guinea pig have shown signs of an inflammatory response, and with their granules of vasoactive histamine, mast cells might be expected to play a role in HD-induced injury. Changes in mast cells exposed to low sulfur mustard levels, as detected by an IAS, may serve as an early mafker for cutaneous damage, which might not be as easily determiied with routine light microscopy.

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“…Skin from the hairless guinea pig has been used to evaluate the pathogenesis of the HD lesion and the efficacy of potential therapeutic compounds (1)(2)(3)(4)(5).…”

Section: Dtic Fup!3 Opi: Dtic-tidmentioning

confidence: 99%

Effect of Sulfur Mustard on Mast Cells in Hairless Guinea Pig Skin

Graham

Bryant

Braue

1994

Journal of Toxicology: Cutaneous and Ocular Toxicology

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“…Guinea pigs (hairless and with hair), mice, rabbits and swine are species recognized as the primary models for dermatological and burn research. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] Hairless guinea pigs were the species of choice for vesicant research at USAMRICD. [23][24][25][26][27][28][29] However, the source of hairless guinea pigs was interrupted in 1993 by an outbreak of Listeria monocytogenes at the breeding facility of the commercial supplier.…”

Section: Introductionmentioning

confidence: 99%

“…22,[31][32][33][34][35] Common skin characteristics include: sparse-hair coat; thick epidermis with distinct rete ridges and corresponding dermal papillae; a relatively high concentration of elastic fibers in the dermis; hair follicles with similar vascularity; similar collagenous tissue framework and adipose chambers in the subcutis; comparable enzyme patterns in the epidermis with similar apocrine glands; analogous epidermal tissue turnover time and keratinous protein character; and similar composition of the lipid film of the skin surface. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] There are also differences from human skin in swine skin: the vascularity of the cutaneous glands and subepidermal plexus is poor; eccrine glands are absent in the common integument; extensive fat is deposited below the subcutis; a positive alkaline phosphatase reaction occurring in the basal stratum of the epidermis; a negative or slightly positive reaction for hydrolytic enzymes (particularly S154 F. M. REID ET AL. alkaline phosphatase) occurring in the capillaries of the subepidermal vascular plexus; strong enzyme reactions occurring in active connective tissue cells of the dermis; more dramatic seasonal shedding of hair; and apocrine skin glands are not involved in thermoregulation.…”

Section: Introductionmentioning

confidence: 99%

“…alkaline phosphatase) occurring in the capillaries of the subepidermal vascular plexus; strong enzyme reactions occurring in active connective tissue cells of the dermis; more dramatic seasonal shedding of hair; and apocrine skin glands are not involved in thermoregulation. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] The pig is the model of choice for percutaneous HD exposures because it has limited hair cover, fixed skin similar to that of humans and exhibits microvesication (i.e. epidermal-dermal separation).…”

Section: Introductionmentioning

confidence: 99%

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Sulfur mustard-induced skin burns in weanling swine evaluated clinically and histopathologically†

et al. 2001

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“…Even though the exposure time-dependent response of cutaneous exposure to SM vapor in humans more closely parallels those of the haired and hairless guinea pig with respect to dermal-epidermal separation, weanling pig skin shares many more similarities to human skin and has the potential to be a useful model for antivesicant research. This model should prove valuable in 1) efficacy testing of pretreatments, treatments and topical skin protectants; 2) wound healing studies; 3) evaluationlof skinlwound decontamination systems; and 4) basic vesicant research.HE CYTOTOXIC effects of the alkylating agent sulfur T mustard [bis(2-chloroethyl)sulfide; SM] on skin have been widely described for a number of species (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) and in vitro human skin equivalent models (20,21). There is no definitive animal model for vesicant injury that mimics the blister/vesicle formation seen in human skin following exposure to this lipophilic chemical warfare agent.…”

mentioning

confidence: 99%

Assessment of cutaneous sulfur mustard injury in the weanling pig

Graham

Martin

Zallnick

et al. 1999

Skin Research and Technology

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Background/aims: The euthymic hairless guinea pig was the animal model of choice at this laboratory for vesicant injury research. The supply of these animals, however, was interrupted in 1993 by an outbreak of Lisferia monocyfogenes at the commercial supplier's breeding facility, thereby forcing a search for alternative animal models. This report describes the development of a weanling pig model for use in evaluating the severity of skin lesions induced by sulfur mustard [bis(2‐chloroethyl)sulfide; SM] using a variety of bioengineering techniques. These methods include reflectance colorimetry (erythema response), high frequency ultrasound imaging (edema response) and a modified dermal torque meter procedure to test for Nikolsky's sign (damage at the dermal‐epidermal junction). The time course and exposure time‐dependence of SM‐induced lesions for these parameters were characterized in this model and compared with previous results in the haired and hairless guinea pig. Methods: Six male Yorkshire Cross pigs (7–10 kg) were used in this study. The hair on the dorsal surface of each animal was shaved the afternoon prior to SM exposure. Twenty‐four dorsal skin sites on each pig were exposed to saturated SM vapor (1.4 mg/l) using 14‐mm diameter vapor cups for 0 (control), 5, 10, 15, 20, or 25 min, with four sites per exposure level. Control and exposure sites were rotated to prevent site‐specific biases. Lesions were evaluated for erythema (reflectance colorimeter) at 4, 6, 12, 24 and 48 h post‐exposure, and for edema (high frequency ultrasound) at 6, 12, 24, and 48 h post‐exposure. Evaluations for Nikolsky's sign and histopathology were conducted at 48 h post‐exposure. Results: Maximum erythema responses occurred at 24 h postexposure for all SM exposure times (5, 10, 15, 20 and 25 min). The overall maximum response occurred with a 15‐min SM vapor exposure at 24 h post‐exposure. Exposures longer than 15 min did not induce significantly greater erythema at any of the time points examined. The earliest time point at which significant edema was noted was at 12 h for the 15‐ and 25‐min SM vapor groups. Maximum edema occurred at 48 h following a 15‐min exposure. No significant increase in edema was noted at any observation time point with exposures longer than 15 min. All sites showed a weakening of the dermal‐epidermal junction (positive Nikolsky's sign) 48 h after a 15‐min or longer SM vapor challenge. The histologic severity of the lesions did not significantly worsen as the vapor exposure was increased beyond 15 min. (Following a 15‐min SM exposure, incidences of epidermal necrosis, pustular epidermitis, microblisters and vascular damage had reached 100%, with maximum mean severity scores.) The weanling pig is more resistant to the effects of SM vapor than either the haired or hairless guinea pig, showing a delayed response and requiring a longer exposure time to generate the same (quantitative and qualitative) response in erythema, Nikolsky's sign and microblister formation. SM vapor‐induced edema formation in the wean...

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Evaluation of Euthymic Hairless Guinea Pigs (Crl:IAF(HA)BR) as an Animal Model for Vesicant Injury

Cited by 9 publications

References 1 publication

Effect of Sulfur Mustard on Mast Cells in Hairless Guinea Pig Skin

Effect of Sulfur Mustard on Mast Cells in Hairless Guinea Pig Skin

Sulfur mustard-induced skin burns in weanling swine evaluated clinically and histopathologically†

Assessment of cutaneous sulfur mustard injury in the weanling pig

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