Dandruff and Seborrheic Dermatitis: A Head Scratcher 406 assumed to work equivalently. In practice, products containing 2.5 micron platelet ZPT appear to be the most effective.56, 80-81 Despite widespread human use, until recently there has been little known of the antifungal mechanism of action. Ermolayeva and Sanders82 and Chandler and Segel83 showed that ZPT can depolarize membranes and prevent membrane transport, although the ZPT concentrations used ( 100 μM) are much higher than required to inhibit fungal growth. More recently, Yasokawa et al.84 used microarray analysis to show that ZPT induces iron starvation, suggesting the antifungal mechanism is due to iron starvation. Recently, Reeder et al.85 demonstrated a new hypothesis on the mechanism of action of ZPT, namely that ZPT inhibits S.cerevisiae growth through copper influx. The data supporting this conclusion are 1) an increase in cellular copper content, 2) gene expression responses indicative of excess intercellular copper, 3) a requirement for environmental copper for ZPT activity, and 4) the observation that mutant cells more sensitive to copper are likewise more sensitive to ZPT. The molecular mechanism of ZPT-mediated inhibition of S. cerevisiae is copper-mediated loss of function of iron-sulfur proteins. Where possible, parallel studies were performed with the scalp fungus M. globosa where ZPT was also acting through intracellular copper. Selenium sulfide has been approved for over-the-counter use at levels of 0.6% (micronized form) and 1%.60,64,77-78 Shampoos containing selenium sulfide have proven efficacy. 10,86-87 Since selenium sulfide is a particulate, efficacy is dependent on the particle size to optimize coverage. Differences in efficacy may be related to the particle size of the selenium sulfide in the shampoo. Further, selenium sulfide is a complex mixture of multiple isoforms and the relative constitution of formulations affects efficacy. The mechanism of antidandruff activity is presumed to be based on its antifungal activity, but the molecular mechanism of its antifungal action remains unknown. Ketoconazole is an imidazole antimycotic agent and has been
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