SummaryHistidine-containing natural dipeptides, such as L-carnosine, were reported to be effective against different oxygenderived free radicals, and also lipoperoxyl radicals. However, L-carnosine appeared to be uneffective in vivo, due to the presence of ubiquitous specific or semi-specific hydrolytic enzymes. Therefore, a series of peptidomimetics were synthesized in order to confer resistance to enzymatic hydrolysis. Some structural modifications were also done in an attempt to improve the antioxidant power of the molecule, for example, in relation to binding of ferrous ions. The following methods were used for the evaluation of peptidomimetics:-The resistance to enzymatic deactivation was determined using either a purified specific enzyme or a multienzymatic system.-The free radical scavenging potential was measured by different in vitro methods involving different free radical species and biological targets.-Deactivation of lipid hydroperoxides was monitored by HPLC and protection of membrane phospholipids and proteins was demonstrated.-The effectiveness of peptidomimetics in vivo was evaluated. It was shown that decarboxylation of L-carnosine results in an important improvement of the resistance towards hydrolytic enzymes. In vitro experiments have demonstrated, for a series of peptidomimetics, free radical scavenging and lipid hydroperoxide deactivating properties similar to or even better than the natural peptide (depending on the experimental design). In addition, the two peptidomimetics fl-alanylhistamine and L-prolylhistamine proved to be far superior in inhibiting the lipid hydroperoxide-mediated cross-linking of a representative protein. Finally, /3-alanylhistamine was able to protect skin enzymes from UV-induced degradation in vivo.

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A new experimental design, more reliable for in vitro testing of active ingredients' effect on ultraviolet (UV)-induced melanogenesis has been carried out. It uses a bicompartmental coculture system where cell communication between keratinocytes and melanocytes can take place. Thus, this experimental situation enables to monitor the effect of biological agents released by both cell types on melanogenesis and the interference of tested compounds with this 'paracrine linkage'. Experiments with UVB-irradiated cocultures show the importance of cell communication in the melanogenic response. In this model, the endogenous mediator, nitric oxide (NO), increased melanin production. Different compounds were tested in the coculture system, and comparison with data obtained from irradiated monocultures of melanocytes enables to distinguish a specific effect on cell communication. In addition, this more close-to-reality experimental model proved to provide a valuable first approach for the assessment of the 'bioavailability' of the tested substances. Finally, the effect of an innovative photoprotective agent capable of 'boosting' UV-induced melanogenic cell communication is presented.

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While the beneficial effects of topical EGF on wound healing have been repeatedly reported, there are few reports about the effects of EFG on inflammatory skin diseases, including acne. Recently, it was reported that topical application of recombinant human EGF (rhEGF) improved the clinical severity of mild to moderate acne. In order to clarify the effects of EGF on acne, it was investigated whether EGF signaling can affect the Propionibacterium acneinduced cytokine expression in human keratinocytes. After infecting the cultured human keratinocytes with live P. acnes, increased expressions of proinflammatory cytokines (IL-1a, IL-8, and TNF-a) were detected, which was prevented by rhEGF co-treatment. Further investigation about the underlying mechanism of EGF on the cytokine expressions, toll-like receptor activation was measured. Increased expression of TLR-2 was observed after P. acnes treatment, and rhEGF treatment dose-dependently decreased the TLR-2 expression. These results were also observed in positive control (nicotinamide) treated cells. These results suggest that possible involvement of EGF in P. acnes induced inflammatory responses is, at least in part, through modulating TLR-2 signaling and topical application of rhEGF might be beneficial to relive the inflammatory symptoms in acne. 440Topical application of anti-cancer drug Bortezomib stimulates proliferation of follicular cells and induces expression of hair keratins via GATA-3 transcription factor