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ME Myles, C Alack, P Manino, E Reish, S Higaki, K Maruyama, A Mallakin, FA Ragan, JM Hill; Nicotine Applied by Transdermal Patch Induced HSV-1 Ocular Shedding in Latently Infected Rabbits . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4323.
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Purpose: To examine the ability of nicotine, a compound known to be involved in stress-associated immunomodulation, to induce ocular viral shedding in rabbits latently infected with HSV-1 strain McKrae. Methods: New Zealand white rabbits latently infected with HSV-1 were randomly divided into two groups. One group received nicotine by transdermal patch (21 mg/d) for 20 days, the other served as a control. Reactivation data were obtained by detection of infectious virus in tear film collected by daily ocular swabs. The concentration of nicotine (mg/ml) in the serum was determined at 0, 1, 4, 8, 15, and 24 hrs after patch replacement. Results: Rabbits receiving nicotine exhibited a significantly (p=0.00001) higher rate of HSV-1 ocular shedding than controls. Compilation of data from three separate experiments demonstrated that 16.5% (258/1560) of the swabs taken from rabbits treated with nicotine were positive for virus, compared to only 8.3% (53/639) of swabs taken from controls. Peak serum levels of nicotine were obtained 8 hours after patch replacement and exhibited a broad range of values (.233 mg/ml - 6.21 mg/ml). Conclusion: These results show that systemic exposure to nicotine significantly increases reactivation. Further studies are needed to test the effects of nicotine dependency and nicotine withdrawal on herpesvirus reactivation.
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