Topical Acyclothymidine Dinucleosides (aTds) Promote Non-UV-Mediated Endogenous Defense Mechanisms in Guinea Pig Skin  Jaime S. Nugent, Robert Vince, Abbas Raza  Journal of Investigative Dermatology  Volume 135, Issue 6, Pages 1687-1689 (June 2015) DOI: 10.1038/jid.2015.57 Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Acyclothymidine dinucleoside (aTd) topical treatment stimulates natural photoprotective mechanisms. Four treated sites per animal, and nine control sites: a total of nine animals were used. All tested aTd compounds produced the same macroscopic and histological results; a single representative image is shown. (a and b) Digital photographic image of untreated (a) and aTd-treated (b) dorsal area of guinea pig, day 26, showing a visible spot in the treated area. Day 26 was chosen for detailed analysis, as it was determined to be the peak of melanin visibility. (c and d) Fontana–Masson Staining of melanin in the basal layer of the epidermis indicating minimal melanin presence in untreated control site (c) and increased melanin presence in aTd-treated sites (d). (e and f) Thickness measurements were recorded and analyzed using the Mann–Whitney test. The total number of measurements for both control and aTd-treated sites was >1,200. The mean thickness of a control sample was roughly 50% thinner at 22.6 μm (e), whereas the mean thickness of an epidermis treated with aTd was recorded as 41.1 μm (f) (P=<0.001). The standard deviations were 11.9 and 5.3 μm, respectively. Scale marker denotes 50 μm. Journal of Investigative Dermatology 2015 135, 1687-1689DOI: (10.1038/jid.2015.57) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Acyclothymidine dinucleoside (aTd) topical treatment and tyrosinase upregulation. Guinea pig tyrosinase ELISA (Blue Gene, China) data representing increased tyrosinase levels in guinea pigs treated with aTds versus control vehicle. Data were analyzed using the GraphPad InStat software (San Diego, CA), and tyrosinase levels in the aTd-treated and the untreated control samples were compared. The difference between two samples was found to be statistically significant (P=0.0073, unpaired Student’s t-test, 2-tailed n=45). Error bars denote standard deviation. Journal of Investigative Dermatology 2015 135, 1687-1689DOI: (10.1038/jid.2015.57) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions