Long-wave ultraviolet radiation (UVA1) and visible light : Therapeutic and adverse effects in human skin

Detta är en avhandling från Stockholm : Karolinska Institutet, Department of Medicine

Sammanfattning: We studied the effects of repetitive low-dose UVA1 radiation and visible light in normal sunshielded skin, using immunohistochemical staining for p53, p21WAF-1, bcl-2, Ki67 and cyclin A. An increased expression of Ki67 after UVA1 and visible light were observed as a sign of increased proliferation. By comparison to untreated skin, increased expression of p53 protein, but not p21WAF-1, in epidermis after UVA1 and only slightly increased expression after visible light were seen. These results suggested that suberythemal doses of UVA1 - and even visible light - may cause DNA damage. Single p53 positive cells from UVA1 irradiated, earlier sun-shielded, skin were therefore microdissected and thereafter PCR-amplified with p53 sequence analysis. This showed three mutations, all GgT transversion. One of the mutations was found in codon 231 of exon 7 and the other two in the intron. The average mutation was I per 8700 bases or 1 per 12 cells, correlating well with the earlier findings of ultraviolet A signature mutations in normal sunexposed human skin. The wavelength at which the dye laser operates is in the visible range commonly used in treating port-wine stains (PWS). The treatment result depends on the wavelength, pulse duration and fluence of the laser system. Twenty-two patients with PWS were treated with flashlamp-pulsed dye laser (FPDL) using wavelengths 585 and 600 nm There was significantly less lightening with 600 run than with 585 nm when equal fluences were used. When 1.5 and 2 times the 585 nm fluence were applied with 600 nm, the lightening was equal to that of 585 nm. We compared the FPDL at 0.45 msec pulse duration and spot size 5 mm with an argonpumped dye laser with a robotized scanning laser handpiece (Hexascan) at 70-190 msec pulse duration and spot size I mm. Both were tuned to 585 nm. Thirty patients with PWS were treated on test areas with both laser systems. Twelve weeks later the degree of lightening was evaluated and biopsies were taken. The skin sections were immunohistochemically stained with CD34 to count the vessels. The clinical result showed a significant better lightening using the flashlamp-pulsed dye laser. The histological result showed significantly fewer vessels of diameter larger than 20 pin in treated PWS than in untreated, but no difference between the two laser types. However, there was a tendency towards more small vessels (diameter < 10 µm ) after one treatment with the FPDL compared to untreated. Mycosis fungoides (NU) is a cutaneous T-cell lymphoma commonly treated with psoralen and ultraviolet A (PUVA). In photodynamic therapy (PDT) porphyrin-based photosensitizers are used which absorb light energy resulting in cellular damage. We used the prodrug 5aminolevulinic acid topically on MF lesions. Thereafter we exposed the lesions to red visible light. Skin biopsies were taken before treatment, after clinical improvement and after clinical remission. The expression of CD3, CD4, CD7, CD8, CD1a CD34, CD68, CD71, Ki67, bcl-2, p53 was studied inummohistochemically. There was complete clinical clearance in 7 of 9 plaque lesions but not of two tumour lesions. The biopsies confirmed a regress of the infiltrate after treatment. In the sparse remaining infiltrate a few CD4+ and CD8+ cells were found, most showing normal bcl-2. There were also fewer proliferating cells, illustrated by decrease of Ki67 and CD71. PDT has good clinical and histological effects in treating local plaque MF lesions.

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