FIGURE 33-18 The chemical structure of gylcolic acid in .NET

Draw QR Code in .NET FIGURE 33-18 The chemical structure of gylcolic acid

FIGURE 33-18 The chemical structure of gylcolic acid
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effects directly by influencing melanocytes as well as indirectly by modulating melanogenesis Topical retinoids seem to directly affect melanogenesis via tyrosinase, TRP-1, and TRP-2 expression163 165 Furthermore, it is suggested that by inhibiting the detoxi cation of toxic species, retinoic acid enhances the melanocytotoxic effect of depigmenting agents By accelerating the cell turnover of epidermal keratinocytes, topical retinoids promote a decrease in melanosome transfer to the keratinocytes and induce dispersion of keratinocyte pigment granules leading to a uniform distribution of melanin content in the epidermis More rapid epidermal turnover also reduces the cohesiveness of corneocytes and thus induces desquamation that consequently leads to an accelerated loss of melanin in the stratum corneum166 Indirectly, the changes engendered in the stratum corneum may facilitate the penetration of other/additional depigmenting agents into the epidermis and increase their bioavailability, thereby leading to increased depigmentation Tretinoin (Retin-A , Renova , Avita ) in concentrations of 005% to 01% is another agent used to treat PIPA It is frequently employed as an adjuvant in the treatment of pigmentation disorders even though the mechanism of action is not completely understood Part of the effect is based on the stimulation of the cell turnover of epidermal keratinocytes, which promotes a decrease in melanosome transfer and accelerates the loss of melanin via epidermopoiesis Although studies have shown retinoic acid to inhibit the induction of tyrosinase, and subsequently melanogenesis, in mouse melanoma cell cultures,167 animal studies have demonstrated that topical application of retinoic acid can increase melanogenesis168,169 Nevertheless, clinical trials have shown tretinoin to be efficacious for the treatment of melasma170,171 The topical retinoid tazarotene (Avage , Tazorac ) has also been shown to improve irregular hyperpigmentation associated with photoaging172 Adapalene (Differin Gel 01% and 03%) is a potent synthetic retinoid In a randomized trial, adapalene 01% showed the same effect on reduction in MASI as 005% tretinoin, yet the patients treated with adapalene had significantly fewer side effects173 Oral 005% isotretinoin has exhibited clinically important but not statistically significant results in a randomized trial treating Thai patients with melasma174
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The side effects of retinoids, such as dryness, irritation, and scaling, are signs of a damaged skin barrier175 This condition allows for other agents to more readily penetrate into the skin and enhance their efficacy, as is the case with HQ, which often is used in combination with retinoids It is advisable to add a corticosteroid to retinoid therapy to mitigate irritation First proposed by Kligman in 1975, the combination consisting of 01% tretinoin, 5% HQ, and 01% dexamethasone was named the Kligman formula and has been the most widely used combination formula to treat melasma176 There are numerous additional combination treatments in use (see 30 for more information on retinoids)
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Sun protection also plays a role in the treatment of pigmentary disorders UV radiation stimulates the synthesis of melanin and promotes the transfer of pigments from melanocytes to keratinocytes thereby increasing pigmentation The use of a broad-spectrum sunscreen has been shown to improve melasma,174 and should be a part of any skin-lightening regimen (see 29 for a discussion of the different types of sunscreens)
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The process of skin pigmentation is very complex, and more research is necessary to elucidate this integral aspect of skin and cosmetic dermatology Tyrosinase inhibition has so far been the most common approach to treat disorders of pigmentation, but only a small selection of tyrosinase inhibitors have practical applications owing to formulation issues, stability, irritation, and ability to penetrate into the skin Pigmentation disorders are a frustrating problem for many cosmetic patients Manufacturers have responded by making several depigmenting agents available in both prescription and OTC preparations These agents seem to work best when used in combination
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