COSMETIC DERMATOLOGY: PRINCIPLES AND PRACTICE in Visual Studio .NET

Maker QR Code in Visual Studio .NET COSMETIC DERMATOLOGY: PRINCIPLES AND PRACTICE

COSMETIC DERMATOLOGY: PRINCIPLES AND PRACTICE
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Peroxidase/H2O2 & Fe2+/H2O2 mediated pathways
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Tyrosinase mediated pathway
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Tyrosine Mature melanosome
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FIGURE 33-8 Melanin synthesis pathways in a human melanocyte
also shown to prevent UVB-induced darkening of the swine skin In addition, human trials have demonstrated lightening of pigmented spots after application of soybean extract59 A recent study examined the efficacy of a novel soy moisturizer containing nondenaturated STI and BBI on pigmentation, the improvement of skin tone, and additional photoaging characteristics Sixty-five women, aged 30 to 61 with Fitzpatrick phototypes I to III, with moderately severe mottled hyperpigmentation, lentigines, blotchiness, tactile roughness, and dullness were enrolled in the parallel, randomized, double-blind, and vehicle-controlled study The moisturizer and the vehicle, respectively, were administered twice daily for a period of 12 weeks By clinical observation, selfassessment, colorimetry, and digital photography, the researchers could show a significant improvement of mottled pigmentation, blotchiness, dullness, fine lines, overall texture, overall skin tone, and overall appearance, versus the vehicle60 In addition to these depigmentation properties, soy contains isoflavones, which have antioxidant properties and have been found to confer cancer-preventing benefits (see 34)
MELANOCYTE-CYTOTOXIC AGENTS
Azelaic Acid
Azelaic acid (Azelex , Finacea ) (Fig 33-10) is a naturally-occurring saturated dicarboxylic acid that has been shown to be a useful adjunct in the treatment of postinflammatory pigment alteration (PIPA) While several review articles focus on the use of topical azelaic acid in the management of hyperpigmentary skin disorders and the associated proposed mechanism(s) of action of azelaic acid,61,62 how azelaic acid exerts its clinical effect is not fully understood The effect of azelaic acid appears to be attributed to its ability to inhibit the energy production and/or DNA synthesis of hyperactive melanocytes, and partially to its antityrosinase activity63 In addition, as it has been reported that hyperpigmentation and lentigo maligna may be related pathogenetically to reactive oxygen species, the clinical effectiveness of
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azelaic acid is thought to be due in part to its inhibitory action on neutrophil-generated reactive oxygen species, leading to a reduction both in oxidative tissue injury at sites of inflammation and in melanin formation64 Research has demonstrated that in vitro azelaic acid is a scavenger of hydroxyl radicals and inhibits oxyradical toxicity in cell cultures65,66 Further in vitro studies have demonstrated that azelaic acid is a competitive inhibitor of tyrosinase,67 the key enzyme for melanogenesis, and a reversible inhibitor of cytochrome-P450 reductase activity and 5 -reductase in microsomal preparations supplemented with reduced nicotinamide adenine dinucleotide phosphate (NADPH)68 The capacity of azelaic acid to reversibly inhibit the activity of mitochondrial respiratory chain enzymes, such as reduced NADH-dehydrogenase, succinic acid dehydrogenase, and reduced ubiquinone cytochrome-c oxidoreductase,69 and to inhibit the synthesis of DNA,70 responsible for an antiproliferative effect, also appears to be important in hyperpigmentary disorders Azelaic acid has been reported to be even more effective than topical HQ for patients with melasma, without the latter s side effects63,71,72 In a multicenter, randomized trial lasting 24 weeks, azelaic acid 20% cream produced significantly greater decreases in pigmentary intensity than did its vehicle both subjectively and in the chromameter analysis73 Another study demonstrated that the combination of azelaic acid 20% cream and glycolic acid 15% or 20% lotion is as effective as 4% HQ cream in the treatment of hyperpigmentation in darker-skinned patients, with only a slightly higher rate of mild local irritation74 In yet another study, in which hyperpigmented lesions visible only with a UVB camera were evaluated, results showed that azelaic acid is superior to glycolic acid in attenuating the subclinical hyperpigmentation when used over a 3-week period59 In the United States, topical azelaic acid is available by prescription in concentrations of a 15% gel and a 20% cream for the treatment of rosacea and acne, respectively The use for hyperpigmentation is off-label Topically applied azelaic acid is well tolerated, with adverse effects generally limited to mild local cutaneous irritation Azelaic acid is an excellent alternative for patients who cannot tolerate HQ
FIGURE 33-11 The chemical structure of mequinol action is unknown; however, mequinol is a substrate to tyrosinase and acts as a competitive inhibitor of melanogenesis75 Notably, 2% mequinol with 001% tretinoin has been proven to be effective in the treatment of solar lentigines76,77 In a randomized, parallel-grouped, double-masked study with 216 subjects, the effects of 2% mequinol/001% tretinoin were compared with those of 3% HQ in the treatment of solar lentigines With a twice-daily treatment for more than 16 weeks and a follow-up after 24 weeks, a significantly higher proportion of subjects achieved clinical success with 2% mequinol/001% tretinoin compared with 3% HQ78
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