Synopsis Topically applied water, occlusion and topically applied glycerol were used to investigate and characterize some of the changes which occur in the hydrated stratum corneum. The effects of these treatments were monitored using non-invasive techniques under controlled conditions. The Servomed Evaporimeter was used to determine natural water flux from the skin surface before and after treatment. The performance of the Evaporimeter in this type of study had previously been improved by attaching a paper baffle to the detector. This eliminated the variance in output caused by atmospheric movement. Experiments were carried out at temperatures below the threshold of thermal sweating and emotional sweating was minimized. Skin surface topography was characterized by means of a new type of profilometer. The instrument's design allowed a diamond stylus to traverse the living skin surface without significantly altering its structure. Changes in skin surface roughness were further elucidated using scanning electron microscopy and macrophotography. In vivo penetration of glycerol was assessed by chemical analysis of stratum corneum layers of treated skin. Samples were obtained by sequential stripping of the stratum corneum using adhesive tape. Topically applied water produced only a transient benefit because of rapid evaporation. More prolonged hydration was achieved by suppressing transepidermal water loss with polyethylene film. This occlusive hyperhydration was characterized by a significant reduction in profile roughness and by a smoother macroscopic appearance. Glycerol achieved the same effects by reducing the magnitude of the natural water flux from the skin surface and by reducing the rate of evaporation of water from applied aqueous glycerol solution or cosmetic product. Both effects were seen as the result of lowered water activity in the proximity of glycerol. Smoothing effects of glycerol on the skin surface, and improved appearance, persisted for at least 24 h. This persistence was explained by evidence for diffusion of glycerol into the stratum corneum where it formed a reservoir. Hydration of the skin is known to affect its barrier function and thereby exert a profound effect on penetration of both lipophilic and hydrophilic molecules. Clinically, this effect may be achieved using liberal applications of occlusive petroleum jelly and ointments. The results presented in this paper suggest that the use of humectants could achieve useful hydration using cosmetically acceptable materials.

[Chemical reaction: See text] Depurination is an important degradation pathway for antisense phosphorothioate oligonucleotides under conditions of thermal stress. We present evidence showing that depurinated oligonucleotides react with cytosine-containing sequences giving products containing a 6-(2-deoxy-beta-D-erythro-pentofuranosyl)-3-(2-oxopropyl)imidazo[1,2-c]pyrimidin-5(6H)-one residue. Further, we demonstrate that the same product is formed upon treatment of 2'-deoxycytidine with 4-oxo-2-pentenal, the latter being an expected byproduct of serial elimination reactions at apurinic sites. In addition to being important for synthetic oligonucleotides, apurinic site formation in cellular DNA is a common occurrence. Because repair of these sites can result in the production of 4-oxo-2-pentenal, it is interesting to speculate whether 6-(2-deoxy-beta-D-erythro-pentofuranosyl)-3-(2-oxopropyl)imidazo[1,2-c]pyrimidin-5(6H)-one residues can form in vivo.

No abstract

Using a hypomitotic agent, triamcinolone acetonide, and a hypermitotic agent, retinyl propionate, we investigated the relationship between epidermal mitotic activity and stratum corneum renewal time of topically treated skin as determined by the dansyl chloride staining technique. Treatment with the base cream resulted in a reduction in renewal time compared with an untreated control site. The predicted increase in renewal time with the hypomitotic agent and reduction with the hypermitotic agent was only observed when daily treatment was commenced 2 weeks prior to and continued after dansyl chloride staining and not when treatment was started after staining. These results indicate that in order to use cell renewal methods to demonstrate changes in mitotic activity brought about by topical treatments, it is necessary to pre-treat the skin with the test material to establish full epidermal equilibrium at the changed mitotic state before labelling with dansyl chloride. Meaningful claims for effects on cell renewal of specific cosmetic ingredients should only be made after comparison with a base cream treated site, both having been allowed to equilibrate, rather than on the basis of comparison with untreated skin.

Nucleic acids U 0700 Formation of Modified Cytosine Residues in the Presence of Depurinated DNA. -(RENTEL, C.; WANG, X.; BATT, M.; KURATA, C.; OLIVER, J.; GAUS, H.; KROTZ, A. H.; MCARDLE, J. V.; CAPALDI*, D. C.; J. Org. Chem. 70 (2005) 20, 7841-7845; ISIS Pharm., Inc., Carlsbad, CA 92008, USA; Eng.) -Lindner 52-185