The αvβ6 integrin plays a role in compromised epidermal wound healing

The alphavbeta6 integrin is an exclusively epithelial integrin that is highly expressed during fetal development. In adult tissue, alphavbeta6 integrin is expressed during inflammation, carcinogenesis, and in wound healing. We previously reported that alphavbeta6 integrin is highly expressed in poorly healing human wounds and its over-expression is associated with chronic wounds in a mouse model. The objective of this study was to investigate the role of alphavbeta6 integrin in compromised wound healing induced by hydrocortisone treatment or aging by using young and old mice deficient in or overexpressing the beta6 integrin subunit in the epidermis. Untreated aged beta6 integrin-deficient (beta6-/-) animals showed a significant delay in wound healing when compared to their age-matched controls or younger beta6-/- mice. The most significant delay was observed at the stages where granulation tissue deposition was occurring. Hydrocortisone treatment significantly delayed wound healing in wild-type and beta6 integrin-deficient mice in comparison with the untreated controls. However, hydrocortisone treatment in beta6 integrin overexpressing animals did not cause a significant delay in wound healing. The results of this study suggest that alphavbeta6 integrin plays an important role in wound healing in animals compromised by either age or stress mimicked by hydrocortisone.     

Reproducibility of Two Four-Point Clinical Severity Scores for Lateral Canthal Lines (Crow''s Feet)

BACKGROUND: Several clinical scoring systems have been used to evaluate the efficacy of botulinum toxin A in the treatment of hyperkinetic wrinkles. So far very few have been investigated for their reproducibility. OBJECTIVE: The aim of this study was to investigate the reproducibility of two clinical four-point scales for lateral canthal lines (crow's feet), at rest and at maximum smile. MATERIAL AND METHODS: Based on standardized photographs, a consensus atlas depicting the different severity grades [from 0 (none) to 3 (severe)] was developed. After training based on the atlas, 49 photographs at rest and 48 at maximum smile were graded by the same group of investigators on 2 consecutive days (n=9 on Day 1; n=8 on Day 2). The scores were compared for reproducibility using kappa statistics. RESULTS: Overall, reproducibility was good for both scales. Interobserver reproducibility showed an agreement of 0.6 at rest and 0.58 at maximum smile (unweighted kappa). Intraobserver reproducibility showed an agreement between 0.47 and 0.86 at rest and between 0.62 and 0.81 at maximum smile (unweighted kappa). Using weighted kappa analysis, the agreement ranged between 0.63 and 0.91 at rest and between 0.71 and 0.85 at maximum smile. CONCLUSION: The clinical scales using scores of 0 to 3 for crow's feet, both at rest and at maximum smile, show a good inter- and intraobserver reproducibility. The use of these scores in clinical trials can be recommended.     

Lecithin vesicles for topical delivery of diclofenac.

Skin penetration of topically applied diclofenac is important for the treatment of rheumatic diseases and actinic keratoses. We have studied the permeation of diclofenac across human cadaver epidermis in-vitro from four lecithin vesicle formulations and a few marketed semi-solid preparations. The lecithin vesicle formulations were prepared by dissolving the lipid contents (lecithin and sodium cholate) in a 1:1 mixture of methanol-chloroform, evaporating the solvents under vacuum, and hydrating the lipid layer with the drug solution in water or 10% ethanol. The vesicles were sonicated for 5 min to reduce the vesicle size and their size and Zeta potential were characterized. The cumulative amount and maximum flux of diclofenac was 69.7+/-40.3 micrograms and 4.77+/-3.16 micrograms/hcm(2) from lecithin vesicles containing sodium cholate and 10% ethanol, and is the highest of all formulations studied. The cumulative amount and mean maximum flux obtained from other formulations were in the range of 2.46+/-1.98-29.9+/-10.1 micrograms and 0.53+/-0.46-3.61+/-0.86 micrograms/hcm(2). Based on the results, lecithin vesicles of diclofenac appear to be advantageous for the topical delivery of diclofenac.