The tissue photosensitizer protoporphyrin IX (PpIX) is an immediate precursor of heme in the biosynthetic pathway for heme. In certain types of cells and tissues, the rate of synthesis of PpIX is determined by the rate of synthesis of 5-aminolevulinic acid (ALA), which in turn is regulated via a feedback control mechanism governed by the concentration of free heme. The presence of exogenous ALA bypasses the feedback control, and thus may induce the intracellular accumulation of photosensitizing concentrations of PpIX. However, this occurs only in certain types of cells and tissues. The resulting tissue-specific photosensitization provides a basis for using ALA-induced PpIX for photodynamic therapy. The topical application of ALA to certain malignant and non-malignant lesions of the skin can induce a clinically useful degree of lesion-specific photosensitization. Superficial basal cell carcinomas showed a complete response rate of approximately 79% following a single exposure to light. Recent preclinical studies in experimental animals and human volunteers indicate that ALA can induce a localized tissue-specific photosensitization if administered by intradermal injection. A generalized but still quite tissue-specific photosensitization may be induced if ALA is administered by either subcutaneous or intraperitoneal injection or by mouth. This opens the possibility of using ALA-induced PpIX to treat tumors that are too thick or that lie too deep to be accessible to either topical or locally injected ALA.

Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy.

Chemical Diversity in the Sialic Acids and Related α-Keto Acids: An Evolutionary Perspective

Oxidative stress in the pathogenesis of skin disease.

Oxygen free radicals and metallothionein

Biomedical Diagnostics. Edited by Tuan Vo-Dinh Edited by Tuan VoDinh. CRC Press 20142014. Pages 311–356. Print ISBN: 978-1-42008514-3. eBook ISBN:. Bjorn Kemper is a senior researcher at the Biomedical Technology Center of the Srirang Manohar is an associate professor of biomedical photonic imaging. This volume discusses biomedical photonics, spectroscopy and microscopy, the basic physical principles underlying the technology and its applications.

https://www.spiedigitallibrary.org/journals/journal-of-biomedical-optics/volume-9/issue-5/0000/Book-Review-Biomedical-Photonics-Handbook/10.1117/1.1776177.pdf

Biomedical Photonics Handbook

Products of lipid peroxidation (malonaldehyde, Schiff-bases) were detected in human skin. These products were increased after UV-light exposition, on chronically sun-exposed areas as well as with advancing age. Malonaldehyde cross linked epidermal glucose-6-phosphate-dehydrogenase and diminished their activity.

Stable lipid peroxidation products in human skin: detection, ultraviolet light-induced increase, pathogenic importance.

Treatment of human peripheral blood mononuclear cells with UVB light, the photosensitizing system 8-methoxypsoralen plus UVA light (PUVA), or hematoporphyrin derivative plus visible light leads to an inhibition of their stimulatory capacity in an allogeneic mixed leukocyte reaction despite unaltered expression of HLA-DR antigens when tested immediately after irradiation. However, HLA-DR positive cells disappear among mononuclear cells in the interval between 4 and 8 h after treatment with either UVB, PUVA, hematoporphyrin derivative and light, or heating to 45 degrees C. The expression of HLA-DQ, but not HLA-A,B,C, antigens, was similarly affected by these treatments. The significance of these results is discussed.

Inhibition of HLA-DR antigen expression and of the allogeneic mixed leukocyte reaction by photochemical treatment.

The influence of combined photochemical treatment with a haematoporphyrin derivative and visible light on antigen-presenting cells was evaluated. Treatment of murine skin grafts with this procedure prolonged their subsequent survival on allogeneic recipients. The haematoporphyrin derivative and light decreased the ATPase activity of epidermal Langerhans cells in murine skin. When stimulator cells in a human allogeneic mixed leucocyte reaction were treated with the haemaioporphyrin derivative and light, they lost their stimulatory capacity. It is proposed that the haemaioporphyrin derivative and visible lighl interfere, on analogy with ultraviolet radiation, with the function of antigen-presenting cells.

The influence of haematoporphyrin derivative and visible light on murine skin graft survival, epidermal Langerhans cells and stimulation of the allogeneic mixed leucocyte reaction.

Treatment of acne vulgaris with visible light

Recently, high-dose UVA-1 therapy (340–400 nm) was introduced as an effective treatment of severe exacerbated atopic dermatitis. Since the target of this type of radiation in the skin is not known we investigated using the mouse model whether surface markers of the antigen-presenting function of epidermal Langerhans cells are affected by UVA-1 radiation. Even repeated high doses of UVA-1 radiation (up to 50 J/cm2) had no detectable effect on surface ATPase activity and Ia antigen expression on Langerhans cells. Also, the contact allergen oxazolone was presented normally in skin treated with UVA-1 radiation. In contrast, if the mice were injected 1 h before irradiation with 8-methoxypsoralen a dramatic reduction in ATPase activity and Ia antigen expression on Langerhans cells was observed and the induction of contact sensitivity was suppressed (PUVA effect). These results show that epidermal Langerhans cells are not impaired either in structure or function and that these cells probably do not represent the primary target of UVA-1 radiation in the skin. No side effects resulting from a diminished Langerhans cell function should result from high-dose UVA-1 therapy.

Hans Meffert

Papers

Stable lipid peroxidation products in human skin: detection, ultraviolet light-induced increase, pathogenic importance.

Inhibition of HLA-DR antigen expression and of the allogeneic mixed leukocyte reaction by photochemical treatment.

The influence of haematoporphyrin derivative and visible light on murine skin graft survival, epidermal Langerhans cells and stimulation of the allogeneic mixed leucocyte reaction.

Treatment of acne vulgaris with visible light

Studies on the effects of a high dose UVA-1 radiation therapy on surface markers and function of epidermal Langerhans cells