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Therapeutic Potential of a Non-Steroidal Bifunctional Anti-Inflammatory and Anti-Cholinergic Agent against Skin Injury Induced by Sulfur Mustard.

Jeffrey D. Laskin, Ph.D. - Wed, 09/03/2014 - 02:00

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Therapeutic Potential of a Non-Steroidal Bifunctional Anti-Inflammatory and Anti-Cholinergic Agent against Skin Injury Induced by Sulfur Mustard.

Toxicol Appl Pharmacol. 2014 Aug 12;

Authors: Chang YC, Wang JD, Hahn RA, Gordon MK, Joseph LB, Heck DE, Heindel ND, Young SC, Sinko PJ, Casillas RP, Laskin JD, Laskin DL, Gerecke DR

Abstract
Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72hr post-SM exposure. After 96hr, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal-epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure.

PMID: 25127551 [PubMed - as supplied by publisher]

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Steven Sotloff beheading video released by ISIS

Homeland Security News - Tue, 09/02/2014 - 16:22

ISIS has released a video that shows the beheading of U.S. journalist Steven Sotloff and says the murder is retaliation for the Obama administration’s continued airstrikes in Iraq. Sotloff is the second American journalist to be killed by ISIS, and his death comes two weeks after James Foley was executed in a similar video. In [...]

This story comes to us via Homeland Security - National Terror Alert. National Terror Alert is America's trusted source for homeland security news and information.

Steven Sotloff beheading video released by ISIS

Categories: Homeland Security News

Missing Libyan Jetliners Raise Fears of Suicide Airliner Attacks on 9/11

Homeland Security News - Tue, 09/02/2014 - 16:17

Islamist militias in Libya took control of nearly a dozen commercial jetliners last month, and western intelligence agencies recently issued a warning that the jets could be used in terrorist attacks across North Africa. Intelligence reports of the stolen jetliners were distributed within the U.S. government over the past two weeks and included a warning that [...]

This story comes to us via Homeland Security - National Terror Alert. National Terror Alert is America's trusted source for homeland security news and information.

Missing Libyan Jetliners Raise Fears of Suicide Airliner Attacks on 9/11

Categories: Homeland Security News