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Electronics and FluidicsElectrooptical and Optoelectronic Devices

New Approaches Towards the Elucidation of Epidermal-Dermal Separation in Sulfur Mustard-Exposed Human Skin and Directions For Therapy

Authors: Marijke A. E. Mol; PRINS MAURITS LABORATORIUM TNO RIJSWIJK(NETHERLANDS)
 
Abstract: The first year of the research performed under Award Number DAMD17- 02-02O6 has yielded promising results. with respect to the application of MMP inhibitor BB94 on HD-exposed human skin pieces in order to prevent microvesication. BB94 is effective at a concentration of at least 1 mug/ml and can be added to the culture medium as late as 8 h after exposure to HD, without loosing its inhibiting effect on epidermal-dermal separation. From a therapeutic angle, this time window might allow non-urgent cure of HD casualties. In an adjacent series of experiments, application of proteomic analysis as an unbiased way to study cellular events following HD-exposure has proven to be a valuable approach. 2D-PAGE analysis of the protein profile of cultured HEK that were exposed to 100 muM HD gave clues for the induction of apoptosis by the gradual appearance over 24 h of fragments of the type I keratins K14 and K17, generated by caspase cleavage. It is expected that the identification of several other new spots that appeared in the protein pattern of HD-exposed HEK might shed more light on the mechanistic toxicology of HD. The results obtained in this study so far, suggest a dual treatment of HD-exposed skin: application of a MMP- inhibitor to prevent microvesication together with the use of a caspase- inhibitor to reduce epidermal cell damage.

Description: Annual rept. 16 Dec 2001-16 Dec 2002
Pages: 19
Report Date: JAN 2003
Contract Number: DAMD17-02-1-0206
Report Number: A583714

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Keywords relating to this report:
*MUSTARD AGENTS
*SKIN(ANATOMY)
*SKIN_ANATOMY_
*SULFUR
EPIDERMIS
EXPOSURE_PHYSIOLOGY_
HUMANS
THERAPY
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