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Study expands frontier, with caveats.

Nitric oxide (NO) is an unassuming, simple diatomic lipophilic gaseous molecule which in fact is anything but, involved in almost every biological process and serving as possibly the most important signaling molecule in the human system.

From antimicrobial action to vasodilation to the dichotomous role as a pro- and anti-inflammatory agent, it is no surprise that there is a frantic race to develop means to translate our massive fund of knowledge on this biomolecule to the bedside. As an NO enthusiast, scientist, and participant in this rat race, it is, no question, exciting to see an NO-related technology evaluated in a clinical trial.

There are some inherent flaws with this delivery system and study protocol.

First, we are not presented with any pharmacokinetics with respect to concentration of NO generation, duration, permeation, etc. This is extremely important as how much NO is produced, where it is produced, and for how long it is produced are key to its activity in vivo. Depending on the answers to these questions, the biological impact can range for cytoregulatory to cytotoxicity.

Second, the reduction of nitrite by an acid results in a rapid burst of NO formation with limited potential for sustained delivery. The concentrations used are exceedingly high (6 gm/100 mL nitrite; 9 gm/100 mL citric acid), likely generating a massive bolus of NO that could possibly be toxic to eukaryotic cells (not discussed).

Third, the lack of citric acid alone as a control is extremely concerning, as we often use acidic agents as keratolytics to destroy verruca, not to mention to instigate an immune response through injury to aid in lesion resolution. Could citric acid alone be responsible for these successful results? It's possible.

However, even with these flaws, I commend the authors/investigators for pushing the frontiers of NO biomedical applications. I believe all NO researchers will agree, we are all on the same team, hoping to translate the awesome power of NO to the bedside. Pointing the spotlight on NO, especially in a high level journal such as JAMA Dermatology, only furthers the case and fuels further investigation. Kudos.

Dr. Adam Friedman is associate professor of dermatology and director of translational research at George Washington University in Washington. He had no relevant financial conflicts to disclose, but is a member of the Dermatology News Editorial Advisory Board.

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Title Annotation:VIEW ON THE NEWS
Author:Friedman, Adam
Publication:Dermatology News
Article Type:Report
Date:Jun 1, 2015
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