Psoralen Derivatives with Enhanced Potency.

Psoralen is a furocoumarin natural product that intercalates within DNA and forms covalent adducts when activated by ultraviolet radiation. It is well known that this property contributes to psoralen's clinical efficacy in several disease contexts, which include vitiligo, psoriasis, graft-versus-host disease and cutaneous T-cell lymphoma. Given the therapeutic relevance of psoralen and its derivatives, we attempted to synthesize psoralens with even greater potency.

UVA and UVB-Induced 8-Methoxypsoralen Photoadducts and a Novel Method for their Detection by Surface-Enhanced Laser Desorption Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF MS).

UVA-activated psoralens are used to treat hyperproliferative skin conditions due to their ability to form DNA photoadducts, which impair cellular processes and may lead to cell death. Although UVA (320-400 nm) is more commonly used clinically, studies have shown that UVB (280-320 nm) activation of psoralen can also be effective. However, there has been no characterization of UVB-induced adduct formation in DNA alone.

Effect of topical tretinoin, chemical peeling and dermabrasion on p53 expression in facial skin.

The tumour suppressor protein p53 is a phosphoprotein that is activated by DNA damage. It is involved in the decision whether the cells should stop replication and proceed to repair their DNA, or to die by apoptosis. In the present study, we evaluate the effect of some treatment modalities on the expression of p53 in facial skin.

Expression of p53 in normal sun-exposed and protected skin (type IV-V) in different decades of age.

The checkpoint protein p53, which is activated by DNA damage, is involved in the decision whether the cells should stop replication and proceed to repair their DNA or die by apoptosis. We evaluate the expression of p53 and the number of apoptotic cells in normal sun-exposed (face) and protected (abdomen) skin in Egyptians between 6 and 77 years of age. The degree of p53 expression in facial skin significantly increases from a score of 1.

UV doses of young adults.

Since 1986, people have been informed that they get about 80% of their lifetime ultraviolet (UV) dose by the age of 18. This belief originated from the mathematical conclusion that diligent use of sunscreens (sun protection factor 15 or higher) during the first 18 years of life would reduce the lifetime incidence of nonmelanoma skin cancers by 78%. These data were misconstrued to mean that individuals also got about 80% of their lifetime dose of UV by the age of 18 (linear relationship).

Photochemotherapy of vascular cells with 8-methoxypsoralen and visible light: differential effects on endothelial and smooth muscle cells.

Background: The long-term efficacy of percutaneous transluminal coronary angioplasty is limited by the restenosis which occurs in approximately 40% of patients, usually within 6 months of the procedure.

Purpose: The present study was designed to evaluate the effects of 8-methoxypsoralen (8-MOP) activated with visible light on the properties of bovine aortic smooth muscle cells (SMC) and endothelial cells (EC) in vitro.

Methods: Cells were seeded in polystyrene wells, allowed to attach over a 24-h period, incubated with 1, 20, or 50 microg/ml 8-MOP and then exposed to 12 J/cm2 visible light (447 nm).

Intrinsic aging vs. photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin.

Cutaneous aging is a complex biological phenomenon affecting the different constituents of the skin. To compare the effects of intrinsic and extrinsic aging processes, a total of 83 biopsies were collected from sun-exposed and protected skin of healthy volunteers representing decades from the 1st to the 9th (6-84 years of age). Routine histopathology coupled with computer-assisted image analysis was used to assess epidermal changes.

The role of PUVA in the treatment of psoriasis. Photobiology issues related to skin cancer incidence.

Photochemotherapy with methoxsalen (8-methoxypsoralen) and long wavelength ultraviolet (UV) radiation (referred to as 'PUVA' for psoralen plus UVA) is commonly used to treat psoriasis and vitiligo. These vastly different diseases respond to the therapy by different mechanisms even though the immediate effects of the therapy--the photomodification of cellular biomolecules--is the same for each. Because psoriasis is not cured by PUVA, patients receive many treatments over their lifetime and have a significantly increased risk for the development of skin cancers (primarily squamous cell carcinomas).

UVA-340 as energy source, mimicking natural sunlight, activates the transcription factor AP-1 in cultured fibroblasts: evidence for involvement of protein kinase-C.

Ultraviolet radiation (UVR) is known to affect a variety of cellular functions, including gene expression. A number of signaling pathways have been suggested to mediate these effects, including the participation of activator protein-1 (AP-1), activator protein-2 (AP-2) and nuclear factor-kappa B (NF-kappa B). The divergent results from previous studies could be explained, at least in part, by the source of UVR with different spectral characteristics as well as the type of cells employed as targets.

Ultraviolet-filtering properties of commonly used tissue cell culture plasticware.

Background: Fluorescent sunlamps are a common source of ultraviolet radiation (UVR) for photobiology research. However, these lamps emit a significant amount of biologically "irrelevant" wavelengths that, if not removed, can drastically skew results and perhaps lead to mistaken conclusions regarding human photobiology. The use of a cellulose triacetate sheet (Kodacel) to filter the shorter ultraviolet wavelengths has become the accepted standard in photobiology.

Keratinocyte apoptosis induced by ultraviolet B radiation and CD95 ligation -- differential protection through epidermal growth factor receptor activation and Bcl-x(L) expression.

Previous work has shown that activation of the epidermal growth factor receptor by endogenous or exogenous signals markedly enhances survival of cultured keratinocytes upon cellular stress such as passaging. This is due, in part, to epidermal-growth-factor-receptor-dependent expression of Bcl-x(L), an antiapoptotic Bcl-2 homolog. In this study we tested whether epidermal-growth-factor-receptor-dependent signal transduction and attendant Bcl-x(L) expression affected survival of human keratinocytes upon exposure to a frequently encountered apoptotic stimulus, radiation with ultraviolet B.

The nitroxide Tempol affords protection against ultraviolet radiation in a transgenic murine fibroblast culture model of cutaneous photoaging.

The generation of reactive oxygen species is among the various mechanisms by which ultraviolet radiation damages skin. Tempol, a superoxide dismutase analogue which readily penetrates cell membranes when administered exogenously, has been shown to provide protection against some forms of oxygen-dependent damage. In this study, we measured the ability of Tempol to protect against ultraviolet A- and ultraviolet B-induced damage, using a previously described transgenic mouse model of cutaneous photoaging.

Stimulation of melanogenesis by DNA oligonucleotides: effect of size, sequence and 5' phosphorylation.

It has been shown that the small DNA fragment thymidine dinucleotide, (pTpT) induces photoprotective responses in cultured cells and intact skin. These responses include increased melanogenesis, enhanced DNA repair, and induction of TNF-alpha, and are accomplished, at least in part, through the induction and activation of the p53 tumor suppressor and transcription factor. Here it is reported that other, but not all, larger oligonucleotides induce the pigmentation response even more efficiently than pTpT.

Common fluorescent sunlamps are an inappropriate substitute for sunlight.

Fluorescent sunlamps are commonly employed as convenient sources in photobiology experiments. The ability of Kodacel to filter photobiologically irrelevant UVC wavelengths has been described. Yet there still remains a major unaddressed issue--the over representation of UVB in the output.

Photodermatology: progress, problems and prospects.

Photodermatology is a sub-specialty of photobiology. As such it includes all aspects of photobiology related to the skin ranging from sun exposure and its consequences (both short term and long term) to the therapeutic effects derived from exposure to natural or artificial radiation. In this review the terms photodermatology and photomedicine are used in a somewhat interchangeable fashion, although the former is really a portion of the latter.

Sunscreens, skin photobiology, and skin cancer: the need for UVA protection and evaluation of efficacy.

Sunscreens are ultraviolet radiation (UVR)-absorbing chemicals that attenuate the amount and nature of UVR reaching viable cells in the skin. They are selected and tested for their ability to prevent erythema. No sunscreen prevents photodamage, as it has been demonstrated that suberythemal doses of UVR cause a variety of molecular changes (including DNA damage) in these cells.

Psoriasis, PUVA, and skin cancer--molecular epidemiology: the curious question of T-->A transversions.

Photochemotherapy with 8-methoxypsoralen and long wavelength ultraviolet radiation (PUVA) is commonly used to treat psoriasis and vitiligo. These vastly different diseases respond to the therapy by different mechanisms even though the immediate effects of the therapy - photoadduct formation - is the same for both. Because psoriasis is not cured by PUVA, patients receive many treatments over their lifetime and develop a significant risk for the development of skin cancers (primarily squamous cell carcinomas).

Psoralen photobiology and photochemotherapy: 50 years of science and medicine.

In 1998 it is appropriate to commemorate the 50th anniversary of el Mofty's use of purified 8-methoxypsoralen (8-MOP) in the treatment of vitiligo (el Mofty AM. A preliminary clinical report on the treatment of leukoderma with Ammi majus linn. J R Egypt Med Assn 1948,31:651 65.

A review of sunscreen safety and efficacy.

The use of sunscreen products has been advocated by many health care practitioners as a means to reduce skin damage produced by ultraviolet radiation (UVR) from sunlight. There is a need to better understand the efficacy and safety of sunscreen products given this ongoing campaign encouraging their use. The approach used to establish sunscreen efficacy, sun protection factor (SPF), is a useful assessment of primarily UVB (290-320 nm) filters.