Elma D. Baron

Topical application of green and white tea extracts provides protection from solar-simulated ultraviolet light in human skin

Background:u2002 Tea polyphenols have been found to exert beneficial effects on the skin via their antioxidant properties.

Non-Sunscreen Photoprotection: Antioxidants Add Value to a Sunscreen

The association between ultraviolet radiation (UVR) exposure and both skin cancer and photo-aging is well documented. In addition to the conventional organic-chemical and physical-mineral type sunscreens, other non-sunscreen protective strategies have been developed. These include topically applied botanical extracts and other antioxidants as well as topical DNA repair enzymes. Standard terms of photoprotection such as sun protection factor (SPF) do not accurately reflect the photoprotection benefits of these materials. For example, in spite of minimal SPF, tea extract containing polyphenols such as (-)-epigallocatechin-3-gallate (EGCG) has been shown to protect against UV-induced DNA damage and immune suppression, in part through its ability to reduce oxidative stress and inhibit NF-kB. The addition of botanical antioxidants and vitamins C and E to a broad-spectrum sunscreen may further decrease UV-induced damage compared with sunscreen alone. These agents have been shown to enhance protection against UV-induced epidermal thickening, overexpression of MMP-1and MMP-9, and depletion of CD1a(+) Langerhans cells. Non-sunscreen materials such as botanical extracts, antioxidants, and DNA repair enzymes can contribute value when applied topically to human skin in vivo.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 56-59; doi:10.1038/jidsymp.2009.14.

Phototherapy for cutaneous T-cell lymphoma

ABSTRACT:u2002 Phototherapy has been utilized for decades in the treatment of various dermatologic conditions, including cutaneous T‐cell lymphoma (CTCL). Currently, a number of light sources are available, and selection of the specific modality is based on a number of factors, the most important of which is disease stage. The efficacy of broadband ultraviolet B (UVB) is limited to the patch stage, while psoralen and ultraviolet A (PUVA) is capable of clearing plaques and, sometimes, early tumors. Narrowband UVB is also effective for early stages and has practical advantages over PUVA, but more studies are needed to more fully evaluate its role in CTCL. Long‐wave ultraviolet A (UVA1) has likewise shown efficacy, supported by findings of apoptosis induction in UVA1‐treated cells. Long‐term remissions have been reported for PUVA, but in the majority of cases, maintenance therapy was necessary. Although beneficial as monotherapy for early stages of the disease, phototherapy is also a useful adjunct to other modalities such as interferons, retinoids and electron beam therapy. Studies are ongoing to refine protocols for combination therapy, with the goal of improving efficacy, while minimizing adverse effects.

Photodynamic Therapy with Pc 4 Induces Apoptosis of Candida albicans

The high prevalence of drug resistance necessitates the development of novel antifungal agents against infections caused by opportunistic fungal pathogens, such as Candida albicans. Elucidation of apoptosis in yeast‐like fungi may provide a basis for future therapies. In mammalian cells, photodynamic therapy (PDT) has been demonstrated to generate reactive oxygen species, leading to immediate oxidative modifications of biological molecules and resulting in apoptotic cell death. In this report, we assess the in vitro cytotoxicity and mechanism of PDT, using the photosensitizer Pc 4, in planktonic C. albicans. Confocal image analysis confirmed that Pc 4 localizes to cytosolic organelles, including mitochondria. A colony formation assay showed that 1.0u2003μm Pc 4 followed by light at 2.0u2003Ju2003cm−2 reduced cell survival by 4 logs. XTT (2,3‐bis[2‐methoxy‐4‐nitro‐5‐sulfophenyl]‐2H‐tetrazolium‐5‐carboxyanilide) assay revealed that Pc 4‐PDT impaired fungal metabolic activity, which was confirmed using the FUN‐1 (2‐chloro‐4‐[2,3‐dihydro‐3‐methyl‐(benzo‐1,3‐thiazol‐2‐yl)‐methylidene]‐1‐phenylquinolinium iodide) fluorescence probe. Furthermore, we observed changes in nuclear morphology characteristic of apoptosis, which were substantiated by increased externalization of phosphatidylserine and DNA fragmentation following Pc 4‐PDT. These data indicate that Pc 4‐PDT can induce apoptosis in C. albicans. Therefore, a better understanding of the process will be helpful, as PDT may become a useful treatment option for candidiasis.

Photodynamic therapy in dermatology: current concepts in the treatment of skin cancer.

Photodynamic therapy is a treatment modality that is developing rapidly and increasing in utilization within various medical specialties, including dermatology. This technique requires the presence of a photosensitizer, light energy and molecular oxygen to selectively destroy pathologic cells. A thorough understanding of photobiology and tissue optics is necessary to correctly and effectively utilize photodynamic therapy in dermatology. Photodynamic therapy has been approved by the US Food and Drug Administration to treat actinic keratoses. In Europe, photodynamic therapy is currently being used in the treatment of actinic keratoses and basal cell carcinoma. Other off-label uses of photodynamic therapy have included cutaneous lesions of Bowen’s disease, psoriasis, cutaneous T-cell lymphoma and acne. Most recently, photodynamic therapy has been employed in photorejuvenation. The advantages of photodynamic therapy include the capacity for noninvasive targeted therapy via topical application of the drug and local irradiation of involved areas, as well as the ability to generate excellent cosmetic results with minimal discomfort. This review summarizes the fundamentals of photodynamic therapy and its role in the treatment of cutaneous disorders, particularly skin malignancies.

Review of extracorporeal photopheresis in early‐stage (IA, IB, and IIA) cutaneous T‐cell lymphoma

Background: Extracorporeal photopheresis (ECP) has been used for nearly 20 years for the treatment of cutaneous T‐cell lymphoma (CTCL). A substantial body of literature reports that this form of photoimmunotherapy improves or stabilizes the course of disease in a subset of patients across all stages. However, current clinical approach usually reserves ECP for patients who do not respond to other treatments or for patients with late‐stage disease or Sézary syndrome (SS).

Role of photodynamic therapy in psoriasis: a brief review.

Background and purpose: Photodynamic therapy (PDT) is a light treatment modality which involves either systemic or local application of a photosensitizing compound, which preferentially deposits in the target cells, and is then followed by selective illumination of the lesion with visible light. The purpose of this study was to review the literature to examine the success, side effects, and different protocols used thus far to treat psoriasis using PDT.

Apoptosis mechanisms related to the increased sensitivity of Jurkat T-cells vs A431 epidermoid cells to photodynamic therapy with the phthalocyanine Pc 4.

To examine the clinical applicability of Pc 4, a promising second‐generation photosensitizer, for the photodynamic treatment of lymphocyte‐mediated skin diseases, we studied the A431 and Jurkat cell lines, commonly used as surrogates for human keratinocyte‐derived carcinomas and lymphocytes, respectively. As revealed by ethyl acetate extraction and absorption spectrophotometry, uptake of Pc 4 into the two cell lines was linear with Pc 4 concentration and similar on a per cell basis but greater in Jurkat cells on a per mass basis. Flow cytometry showed that uptake was linear at low doses; variations in the dose–response for uptake measured by fluorescence supported differential aggregation of Pc 4 in the two cell types. As detected by confocal microscopy, Pc 4 localized to mitochondria and endoplasmic reticulum in both cell lines. Jurkat cells were much more sensitive to the lethal effects of phthalocyanine photodynamic therapy (Pc 4‐PDT) than were A431 cells, as measured by a tetrazolium dye reduction assay, and more readily underwent morphological apoptosis. In a search for molecular factors to explain the greater photosensitivity of Jurkat cells, the fate of important Bcl‐2 family members was monitored. Jurkat cells were more sensitive to the induction of immediate photodamage to Bcl‐2, but the difference was insufficient to account fully for their greater sensitivity. The antiapoptotic protein Mcl‐1 was extensively cleaved in a dose‐ and caspase‐dependent manner in Jurkat, but not in A431, cells exposed to Pc 4‐PDT. Thus, the greater killing by Pc 4‐PDT in Jurkat compared with A431 cells correlated with greater Bcl‐2 photodamage and more strongly to the more extensive Mcl‐1 degradation. Pc 4‐PDT may offer therapeutic advantages in targeting inflammatory cells over normal keratinocytes in the treatment of T‐cell‐mediated skin diseases, such as cutaneous lymphomas, dermatitis, lichenoid tissue reactions and psoriasis, and it will be instructive to evaluate the role of Bcl‐2 family proteins, especially Mcl‐1, in the therapeutic response.

Monitoring Pc 4 photodynamic therapy in clinical trials of cutaneous T-cell lymphoma using noninvasive spectroscopy

Silicon phthalocyanine Pc 4 photodynamic therapy (Pc 4-PDT) has emerged as a potentially effective treatment for cutaneous T-cell lymphoma (CTCL). Noninvasive reflectance and fluorescence spectroscopy before, during, and after PDT may provide useful dose metrics and enable therapy to be tailored to individual lesions. We present the design and implementation of a portable bedside spectroscopy system for initial clinical trials of Pc 4-PDT of CTCL. Reflectance and fluorescence spectra were obtained from an early stage CTCL patient throughout the course of the PDT treatment. Preliminary patient data show a significant effect of Pc 4 on the tissue absorption, modest Pc 4 photobleaching, and heterogeneity of Pc 4 within and between the lesions.

Sunscreens and immune protection

Sunscreens are chemical agents formulated primarily for the purpose of preventing solar ultraviolet (UV) radiation-induced erythema. These products have been commercially available since the 1920s, and while they are distributed worldwide, eight countries account for 70% of consumption, namely the U.S.A., Canada, France, Germany, Japan, Italy, Spain and the U.K. In most parts of the world sunscreens are classified as cosmetic products, except in the U.S.A., Canada and Australia, where they are regulated as drugs. The active ingredients are UV filters, which are either organic ( chemical sunscreens) or inorganic ( physical sunscreens). Organic filters (e.g. aminobenzoic acid, salicylates, cinnamates, benzophenones, avobenzone) are generally aromatic compounds that absorb UV radiation through delocalization of their electrons, while inorganic filters (e.g. titanium dioxide, zinc oxide) attenuate UV radiation by reflection and scattering, owing to their large particle size (150– 300 nm). In the early 1990s, both titanium dioxide and zinc oxide were formulated as microfine preparations, with particle sizes ranging from 30 to 150 nm, enabling them to exert their sunscreen effect predominantly by absorbing UV radiation, similar to an organic sunscreen. Sunscreen formulations undergo a series of tests to evaluate their safety, photostability, substantivity and efficacy in preventing erythema, as denoted by the sun protection factor (SPF; Table 1). The SPF is equal to the dose of UV radiation that induces minimal perceptible erythema with defined borders in an area of skin on which sunscreen at a dose of 2Æ0 mg cm has been applied, divided by the dose that induces the same degree of erythema in unprotected skin. This value is internationally accepted and is currently the standard employed by the U.S. Food and Drug Administration (FDA) to classify the level of protection (from minimal to high) a sunscreen product affords (Table 2). However, it is well established that solar UV radiation exerts effects other than erythema, such as DNA damage, immune suppression, and consequently carcinogenesis. These events, particularly immune suppression, have been shown to occur at suberythemogenic UV doses. Thus, the SPF does not necessarily reflect the immune protection factor (IPF; Table 1) that the sunscreen product affords. Unfortunately, the mechanism behind UV-induced immune suppression remains unclear. In humans, this phenomenon has been observed to correlate with sensitivity to sunburn. This does not, however, mean that immune suppression occurs exclusively among light-skinned individuals with a low threshold for erythema. A dose–response study for UV immune suppression in darker-skinned individuals showed that the shape of their erythemal response curve was more predictive of susceptibility to photoimmunosuppression than skin pigmentation. The absence of a definitive action spectrum for immune suppression, as well as existing controversies pertaining to the chromophore(s) responsible for this effect, are limitations that must be recognized when interpreting data derived from experiments on the immune-protective effects of sunscreens. Moreover, the ideal method for IPF determination has not been described in the literature. In most experiments, IPF is calculated using either one of two variables: the ID50 or minimum immunosuppressive dose (MISD; Table 1). The ID50 is defined as the dose of UV radiation that corresponds to 50% immunosuppression, or the UV radiation dose that results in an immune response that is 50% that of unirradiated controls. The MISD refers to the lowest dose of UV radiation resulting in an immune response that is significantly different (P < 0Æ05) from that of unirradiated controls. In a recent review that Correspondence: Seth R.Stevens. E-mail: srs@po.cwru.edu British Journal of Dermatology 2002; 146: 933–937.