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Pathological mechanisms in acute and long-term HD injuries – Basis for therapeutic strategies

TitlePathological mechanisms in acute and long-term HD injuries – Basis for therapeutic strategies
Publication TypeConference Proceedings
Year of Conference2004
AuthorsKadar T., Amir A., Sahar R., Fishbeine E., Allon N., Dachir S.
Conference NameProceedings of the U.S. Army Medical Defense Bioscience Review
Volume193
Pagination1-36
Conference LocationAberdeen Proving Ground, MD
Abstract

Sulfur mustard (HD) is a potent vesicant known by its ability to cause incapacitation and prolonged injuries to the eyes, skin and respiratory system. Over the last years we have studied diverse histopathological aspects of HD injuries in ocular, dermal and respiratory systems. Our working hypothesis was that the morphological alterations may be useful in diagnostic strategies of HD toxicity and in the development of efficient therapy. An overview of the main findings will be presented. HD induced ocular, respiratory and cutaneous lesions share a common pathological cascade with minor distinctions originating from the unique structural characteristics of each of the tissues. As a general rule, the HD lesions develop in a dose response and time-dependent manner and the epithelium and in particular its basal dividing layer play a major role in the pathogenesis. An asymptomatic latent period is a typical feature in which biochemical events including inflammation are taking place. This is followed by activation of cellular apoptotic and necrotic pathways and basement membrane destruction leading to cell death and microblister formation. Healing is relatively slow and frequently abnormal. Although the morpho-pathology of HD lesions has been studied intensively using in vitro and in vivo models, pathogenesis is still elusive and therapy is only partially effective. As for today, only anti-inflammatory drugs reached the criteria of an applicable efficient post exposure treatment. In recent years we successfully employed the cornea with its rather simple anatomic structure and its transparency as a preferable model for HD research. The transparent tissue enables in vivo simultaneous viewing and ex-vivo visualization of different tissue components such as epithelium, stroma, endothelium, sensory nerves and inflammatory elements. Thus, the damage as well as healing processes can be monitored. Moreover, the well-defined location of epithelial cell types at various stages of differentiation, enables the segregation of HD effects. Our recent findings that partial stem cell deficiency is associated with long-term corneal damage may point towards new therapeutic approaches against HD injuries.

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