Elephantiasis nostras verrucosa.

Swelling of the leg is a frequent finding in podiatric medicine. Unless the patient draws notice to the condition or the physician is diligent in asking questions and examining the extremity, the condition may be viewed as minor and given little attention. Swelling of the leg can be a clinical sign of certain systemic diseases, lymphatic and venous disorders, or other miscellaneous causes. Dermatologic consequences linked to many of these causes of swelling are well documented. What is not as well chronicled is a dramatic skin alteration associated with chronic lymphedema. This article provides an overview and a case presentation of the unusual and debilitating skin condition related to chronic lymphedema of the lower extremity known as elephantiasis nostras verrucosa.

Murine macrophages produce endothelin-1 after microbial stimulation.

Endothelin-1 (ET-1) was originally characterized as a potent vasoconstrictor secreted by the endothelium and participating in the regulation of vascular tone. Subsequent analysis has revealed ET-1 to be a multifunctional peptide produced by a wide variety of cells and tissues under normal and pathologic conditions. The importance of macrophages as a source of ET-1 during infection and inflammation is supported by clinical observations in humans and in animal models of inflammation. We hypothesize that the production of ET-1 is part of the characteristic macrophage response to infection, and have begun to investigate the ability of various classes of microbes or microbial products to induce macrophage ET-1 production. We report the production of ET-1 by murine macrophages in response to stimulation with both gram-positive and gram-negative bacteria. Stimulation of macrophages with yeast (Candida albicans or Saccharomyces cerevisiae) or the protozoan parasite Leishmania major, elicited no significant release of ET-1. The production of ET-1 in response to lipopolysaccharide (LPS) was dose and time dependent, and required the expression of a functional toll-like receptor 4 (TLR4). Pharmacologic inhibition of the transcription factor, nuclear factor-kappaB (NF-kappaB) suppressed LPS-induced ET-1 production. Our findings complement the growing body of literature implicating a role for macrophage-derived ET-1 in inflammatory pathologies. The production of ET-1 by macrophages during infection and inflammation has the potential to affect tissue perfusion, leukocyte extravasation, and immune cell function.