Despite growing reports on the biological action of nitric oxide (NO) as a function of NO payload, the validity of such work is often questionable due to the manner in which NO is measured and/or the solution composition in which NO is quantified. To highlight the importance of measurement technique for a given sample type, NO produced from a small molecule NO donor (N-diazeniumdiolated l-proline, PROLI/NO) and a NO-releasing xerogel film were quantified in a number of physiological buffers and fluids, cell culture media, and bacterial broth using the Griess assay, a chemiluminescence analyzer, and an amperometric NO sensor. Despite widespread use, the Griess assay proved to be inaccurate for measuring NO in many of the media tested. In contrast, the chemiluminescence analyzer provided superb kinetic information in most buffers, but was impractical for NO analysis in proteinaceous media. The electrochemical NO sensor enabled greater flexibility across the various media with potential for spatial resolution, albeit at lower than expected NO totals versus either the Griess assay or chemiluminescence. The results of this study highlight the importance of measurement strategy for accurate NO analysis and reporting NO-based biological activity.
Non-invasive treatment of injuries and disorders affecting bones and connective tissue is a significant challenge facing the medical community. A treatment route that has recently been proposed is nitric oxide (NO) therapy. Nitric oxide plays several roles in physiology with many conditions lacking adequate levels of NO. As NO is a radical, localized delivery via NO donors is essential to promoting biological activity. Herein, we review current literature related to therapeutic NO delivery in the treatment of bone, skin and tendon repair.
Objective-Bacterial infection of the pin tract represents the most common complication associated with external fixation. This study was designed to evaluate the antibacterial activity of nitric oxide (NO) releasing xerogel films applied to commercially pure titanium pins in a rat model.Methods-Pins were coated with xerogel solution via a dip-coating procedure. Half of the xerogel coated implant pins were modified into NO-donors and served as the NO releasing group while the remaining pins were left unmodified to serve as non-NO releasing xerogel coated controls. Acid etched pins served as uncoated controls. Animal selection was randomized and every rat had one pin from each of the three groups randomly allocated to the 3 rd , 4 th , or 5 th tail vertebrae. Quantification of bacterial infection was performed 48 days post-operatively and the tissue-implant interface was inspected for clinical signs of infection on days 14 and 28 postimplantation.Results-Pin tract bacterial colony counts of the NO releasing group (170K±181K) were significantly lower than both the xerogel coated group (677K±675K) and the control group (1,181K±2,717K) 48 days postoperatively (p<0.05). No significant difference in colony counts were observed between the xerogel coated group and the control group. The NO releasing group Correspondence to: Laurence Dahners. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusion-The application of NO releasing xerogel coatings can inhibit bacterial colonization of external fixation pins both during the initial postsurgical period and up to 48 days postimplantation. NIH Public Access
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