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1.
Pigment Cell Melanoma Res ; 24(1): 136-47, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20979596

ABSTRACT

The relationship between human skin pigmentation and protection from ultraviolet (UV) radiation is an important element underlying differences in skin carcinogenesis rates. The association between UV damage and the risk of skin cancer is clear, yet a strategic balance in exposure to UV needs to be met. Dark skin is protected from UV-induced DNA damage significantly more than light skin owing to the constitutively higher pigmentation, but an as yet unresolved and important question is what photoprotective benefit, if any, is afforded by facultative pigmentation (i.e. a tan induced by UV exposure). To address that and to compare the effects of various wavelengths of UV, we repetitively exposed human skin to suberythemal doses of UVA and/or UVB over 2 weeks after which a challenge dose of UVA and UVB was given. Although visual skin pigmentation (tanning) elicited by different UV exposure protocols was similar, the melanin content and UV-protective effects against DNA damage in UVB-tanned skin (but not in UVA-tanned skin) were significantly higher. UVA-induced tans seem to result from the photooxidation of existing melanin and its precursors with some redistribution of pigment granules, while UVB stimulates melanocytes to up-regulate melanin synthesis and increases pigmentation coverage, effects that are synergistically stimulated in UVA and UVB-exposed skin. Thus, UVA tanning contributes essentially no photoprotection, although all types of UV-induced tanning result in DNA and cellular damage, which can eventually lead to photocarcinogenesis.


Subject(s)
Skin/radiation effects , Sunbathing , Ultraviolet Rays , DNA Damage , Humans , Melanins/metabolism , Protective Agents , Pyrimidine Dimers/metabolism , Skin/metabolism , Skin Pigmentation/radiation effects , Skin, Artificial
2.
J Investig Dermatol Symp Proc ; 14(1): 32-5, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19675550

ABSTRACT

The incidence of skin cancer, including cutaneous melanoma, has risen substantially in recent years, and epidemiological and laboratory studies show that UV radiation is a major causative factor of this increase. UV damage also underlies photoaging of the skin, and these deleterious effects of UV can be, in part, prevented in skin with higher levels of constitutive pigmentation. We review the clinical studies we have made in recent years regarding the rapid and the long-term responses of the pigmentary system in human skin to UV exposure.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 32-35; doi:10.1038/jidsymp.2009.10.


Subject(s)
Skin Pigmentation/radiation effects , Ultraviolet Rays/adverse effects , Cell Count , Dose-Response Relationship, Radiation , Humans , Immunohistochemistry , Melanins/metabolism , Melanocytes/metabolism , Melanocytes/pathology , Melanocytes/radiation effects , Skin/metabolism , Skin/pathology , Skin/radiation effects , Time Factors
3.
J Invest Dermatol ; 129(4): 1002-11, 2009 Apr.
Article in English | MEDLINE | ID: mdl-18946495

ABSTRACT

It is known that UV modulates the expression of paracrine factors that regulate melanocyte function in the skin. We investigated the consequences of repetitive UV exposure of human skin in biopsies of 10 subjects with phototypes 2-3.5 taken 1-4 years later. The expression of melanogenic factors (TYR, MART1, MITF), growth factors/receptors (SCF/KIT, bFGF/FGFR1, ET1/EDNRB, HGF, GM-CSF), adhesion molecules (beta-catenin, E-cadherin, N-cadherin), cell cycle proteins (PCNA, cyclins D1, E2) as well as Bcl-2, DKK1, and DKK3, were analyzed by immunohistochemistry. Most of those markers showed no detectable changes at > or = 1 year after the repetitive UV irradiation. Although increased expression of EDNRB protein was detected in 3 of 10 UV-irradiated subjects, there was no detectable change in the expression of ET1 protein or in EDNRB mRNA levels. In summary, only the expression of TYR, MART1, and/or EDNRB, and only in some subjects, was elevated at > or = 1 year after UV irradiation. Thus the long-term effects of repetitive UV irradiation on human skin did not lead to significant changes in skin morphology and there is considerable subject-to-subject variation in responses. The possibility that changes in the expression and function of EDNRB triggers downstream activation of abnormal melanocyte proliferation and differentiation deserves further investigation.


Subject(s)
Skin/radiation effects , Ultraviolet Rays , Adaptor Proteins, Signal Transducing , Cell Adhesion Molecules/analysis , Chemokines , Humans , Immunohistochemistry , Intercellular Signaling Peptides and Proteins/analysis , Melanins/analysis , Proliferating Cell Nuclear Antigen/analysis , Proto-Oncogene Proteins c-bcl-2/analysis , Receptor, Endothelin B/analysis , Receptors, Growth Factor/analysis , Skin/chemistry , Skin/pathology , Skin Pigmentation/radiation effects
4.
Photochem Photobiol ; 84(3): 539-49, 2008.
Article in English | MEDLINE | ID: mdl-18435612

ABSTRACT

Human skin is repeatedly exposed to UVR that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, as melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin cancer in individuals with darker skin compared to those with fair skin. Skin pigmentation is of great cultural and cosmetic importance, yet the role of melanin in photoprotection is still controversial. This article outlines the major acute and chronic effects of UVR on human skin, the properties of melanin, the regulation of pigmentation and its effect on skin cancer prevention.


Subject(s)
Melanins/physiology , Radiation-Protective Agents , Skin Neoplasms/prevention & control , Skin/radiation effects , Sunburn/prevention & control , Ultraviolet Rays/adverse effects , Humans , Melanins/radiation effects , Skin Neoplasms/etiology , Sunburn/etiology
5.
Drug Discov Today Dis Mech ; 5(2): e189-e199, 2008.
Article in English | MEDLINE | ID: mdl-19578486

ABSTRACT

Rates of skin cancer continue to increase despite the improved use of traditional sunscreens to minimize damage from ultraviolet radiation. The public perception of tanned skin as being healthy and desirable, combined with the rising demand for treatments to repair irregular skin pigmentation and the desire to increase or decrease constitutive skin pigmentation, arouses great interest pharmaceutically as well as cosmeceutically. This review discusses the intrinsic biochemistry of pigmentation, details mechanisms that lead to increased or decreased skin pigmentation, and summarizes established and potential hyper- and hypo-pigmenting agents and their modes of action.

7.
Dermatol Surg ; 33(7): 825-30, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17598848

ABSTRACT

BACKGROUND: Photodynamic therapy (PDT) has been developed into a widely used method to treat actinic keratoses and basal cell carcinoma. OBJECTIVE The objective was to assess the efficacy of PDT in the treatment of actinic cheilitis of the lower lip. METHODS: In this prospective, uncontrolled study at a university dermatology department, 15 patients with actinic cheilitis received two sessions of PDT of the lower lip at an interval of 1 week using methylaminoxopentanoate and red light. Clinical and histopathologic evaluation was performed 3 months after therapy. RESULTS: Complete clinical cure was observed in 47% (7/15) and partial cure in another 47% (7/15) of the patients. By histopathologic analysis, residual disease was found in 62% (8/13). Cosmetic results and patients' satisfaction were good to excellent in most cases. Local pain was sufficiently controlled by local anesthesia. CONCLUSION: PDT can be an effective noninvasive method to treat actinic cheilitis of the lower lip.


Subject(s)
Cheilitis/drug therapy , Photochemotherapy/methods , Adult , Aged , Aged, 80 and over , Aminolevulinic Acid/administration & dosage , Aminolevulinic Acid/analogs & derivatives , Cheilitis/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Satisfaction , Prospective Studies , Treatment Outcome , Wound Healing
8.
Photodermatol Photoimmunol Photomed ; 21(3): 157-65, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15888135

ABSTRACT

The treatment of sclerosing skin diseases [systemic sclerosis, localized scleroderma, lichen sclerosus et atrophicus, sclerodermoid graft-vs.-host disease, scleredema adultorum (Buschke), scleromyxedema and necrobiosis lipoidica] is difficult and remains a great challenge. Numerous treatments, some with potentially hazardous side effects, are currently used with only limited success. The introduction of phototherapy and photochemotherapy for sclerosing skin diseases has considerably enriched the therapeutic panel and proven useful in a number of sclerosing skin diseases especially in localized scleroderma. Two phototherapeutic modalitites are used for the treatment of sclerosing skin diseases, long-wave ultraviolet A and psoralen plus ultraviolet A (PUVA). This article reviews current knowledge about the application of phototherapy and photochemotherapy to various sclerosing skin disorders.


Subject(s)
Photochemotherapy , Skin Diseases/drug therapy , Humans , Sclerosis/drug therapy , Sclerosis/pathology , Skin/pathology , Skin Diseases/pathology
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