Madhukar A. Pathak

Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light.

Abstract Oral administration of a photoactive drug, 8-methoxypsoralen (methoxsalen), followed by exposure to a high-intensity, longwave ultraviolet-light system resulted in complete clearing of generalized psoriasis in 21 patients. In 16 of these cases, a paired comparison showed methoxsalen followed by longwave ultraviolet light to be more effective than conventional ultraviolet light. 8-Methoxypsoralen followed by exposure to longwave ultraviolet light has previously been shown to inhibit epidermal DNA synthesis; this may be its mechanism of action in psoriasis, a disorder characterized by an accelerated cell cycle and rate of DNA synthesis. The term photochemotherapy is used to emphasize the point that the effect on epidermal proliferation and the therapeutic response require the interaction of light and drug. (N Engl J Med 291:1207–1211, 1974)

Photochemotherapy of Skin Diseases

While phototherapy is defined as the application of visible or ultraviolet (UV) radiation to the treatment of disease, in photochemotherapy a chemical sensitizer is administered concurrently and the therapeutic effect depends on photochemical interaction of the chemical and radiation. In the doses used, chemical and radiation alone usually have little or no therapeutic effect. Photochemotherapy utilizing psoralen compounds, including 8-methoxy-psoralen, and long-wave UV radiation is currently used in the treatment of many common skin diseases. Other forms of photochemotherapy not utilizing psoralens have been used in the treatment of certain tumors (see Chapter 23). Topical forms of photochemotherapy have been proposed for treatment of recurrent herpes simplex (see Chapters 19–21).

A fine-structure study of the human epidermal melanosome complex and its acid phosphatase activity

Observations by electron microscopy have revealed that phagocytosing melanophages aggregate melanosomes in special membrane-delimited organelles containing acid-phosphatase activity; their ultrastructure resembles that of lysosomes. Here we report: (a) the presence of a “melanosome complex” associated with acid-phosphatase activity in epidermal keratinocytes; (b) that UV radiation induces larger complexes with more melanosomes. A “melanosome complex”, each an aggregation of one or more melanosomes, surrounded by a membrane and occurring in the keratinocytes, was studied by electron microscopy in biopsies of Caucasians, an Oriental, and a Negro. Modified Gomoris technique was used for the demonstration of acid phosphatase activity. Melanosome complexes in Caucasian and Oriental keratinocytes from unexposed sites usually contain 1–3 melanosomes and some small, about 100-A diameter, less electron dense, particles. In Negro keratinocytes, however, melanosomes usually are singly dispersed. Caucasian subjects biopsied 24 hours after 60-min exposure to sun showed an increase in the size and the quantity of the melanosome complexes. Both in the irradiated and unirradiated biopsies, there are more melanosome complexes in the basal and suprabasal cells than in the upper cells. Electron microscopic study of the biopsies in conjunction with histochemical technique has shown that melanosome complexes exhibit a positive acid phosphatase reaction. Since the melanosome is an entity extrinsic to the keratinocyte, the presence of acid phosphatase activity in melanosome complexes and other observations described in this report appear to have significance in regard to the fate of melanosomes after their discharge from the melanocytes.

Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin

Sunburn, immune suppression, photoaging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photoprotection, are helpful and can be achieved by topical sunscreening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo inmunomodulating properties. Its beneficial photoprotective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photoprotective property of natural extract of PL after topical application or oral ingestion. Twenty‐one healthy volunteers [either untreated or treated with oral psoralens (8‐MOP or 5‐MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD la‐expressing epidermal cells were also performed. PL was found to be photoprotective after topical application as well as oral administration. PL increased UV dose required for IPD (P<0.01), MED (P<0.001) and MPD (P<0.001). After oral administration of PL, MED increased 2.8±0.59 times and MPD increased 2.75±0.5 and 6.8±1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photoprotection of Langherhans cells by oral as well as topical PL. The observed photoprotective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photoprotection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such phototherapies.

Evaluation of Topical Agents That Prevent Sunburn — Superiority of Para-Aminobenzoic Acid and Its Ester in Ethyl Alcohol

SINCE 19221 it has been known that in man sunburn and suntan are caused by the action of only a narrow band within the ultraviolet spectrum (λ 290 to 320 mμ). Various methods have been used to prev...

An extract of Polypodium leucotomos appears to minimize certain photoaging changes in a hairless albino mouse animal model: A pilot study

Chronic ultraviolet B (UVB) exposure of human or murine skin is known to induce cutaneous photoaging and enhanced carcinogenic risk. An extract of Polypodium leucotomos (PL), a tropical fern plant, has been known to exhibit interesting antioxidant and photoprotective properties against acute exposure to ultraviolet radiation. The objective of this preliminary (or pilot) study was to determine the photoprotective role of topically applied Polypodium leucotomos extract in the prevention or amelioration of cutaneous changes of photoaging in hairless mice. PL‐treated mice showed significant reduction of skinfold thickness than those observed in PL‐untreated controls. Additionally, PL‐treated mice showed a significantly lower degree of histologic parameters of photoaging damage, including dermal elastosis, compared with positive control mice. Interestingly, PL treatment also showed reduction in the number of mice showing skin tumors at 8 weeks after the cessation of the UVB exposure protocol. The results of this preliminary study illustrate that PL treatment helped to ameliorate and to partially inhibit some of the histologic damage associated with photoaging of skin and appeared to contribute to a decrease in the prevalence of UVB‐induced skin tumors in mice.

Topical and Systemic Approaches to Protection of Human Skin against Harmful Effects of Solar Radiation

Why is photoprotection of importance to humans? We must be in the light; we cannot be forced to work or live in the dark. The sun is necessary to sustain all life on earth. We are warmed by its rays, and we are able to see with eyes that respond to that portion of the solar spectrum known as visible light. Our skin and blood vessels respond to the electromagnetic spectrum of the sun in the form of sunburn and tanning reactions. Many of our daily rhythms are dependent upon the sunlight. Natural sunlight has always been recognized for, and endowed with, health-giving powers. Yet excessive amounts of this life-supporting radiation can be very damaging to our skin. There are two concerns about the deleterious effects of sun exposure: (1) the acute effects (e.g., sunburn, phototoxicity), and (2) the potential long-term risk of repeated sun exposure, namely, the development of actinic changes (wrinkling, premature aging, irregular thickening and thinning of epidermis, hyper- and hypopigmentation), keratosis, and both nonmelanoma and melanoma skin cancer (1–3).