Effect of epidermal growth factor on clonogenic growth of primary human tumor cells.

The effect of EGF on the soft agar colony-forming ability of fresh human tumor cells was assessed in 40 specimens obtained from various types of carcinoma including those of the breast, endometrium ovary, and other sites. Cells from four established human tumor cell lines (three breast and one endometrial) were also included in this study. The results showed that addition of EGF at a concentration of 50 ng/ml resulted in a 50% higher cloning efficiency in soft agar in 40% of the samples of fresh human tumors.

The effect of psoralens on hepatic and cutaneous drug metabolizing enzymes and cytochrome P-450.

Psoralens are tricyclic furocoumarins with potent photosensitizing properties in the skin and are now widely used in the treatment of several dermatologic diseases. In this study the effect of 3 different psoralens 8-methoxypsoralen (8-MOP), 4,5',8-trimethylpsoralen (TMP) and isopsoralen on hepatic microsomal drug-metabolizing enzymes and cytochrome P-450 has been assessed in mice and rats. 8-MOP administered orally to CD-1 mice daily for 6 days caused 2-3 fold increases in hepatic aryl hydrocarbon hydroxylase (AHH), ethylmorphine N-demethylase and cytochrome P-450.

Sunscreens: topical and systemic approaches for protection of human skin against harmful effects of solar radiation.

This review deals with topical and systemic approaches for protection of human skin against the harmful effects of solar radiation. Two concerns about the deleterious effects of sun exposure involve: (1) acute effects (e.g.

Molecular aspects of drug photosensitivity with special emphasis on psoralen photosensitization reaction.

Photosensitization reactions involve phototoxic reactions and photoallergic reactions, which are less common. Common drugs and chemicals that photosensitize humans are listed. Phototoxic reactions include the following: 1) direct photosensitization (type I reactions), in which the reactions of the triplet-state sensitizer are directly attributable to a component other than oxygen (e.

Variegate porphyria in New England.

Variegate porphyria (VP) is an autosomal dominant disease characterized in adults by mechanical fragility and blistering of sun-exposed skin or acute visceral and neurological manifestations. The laboratory diagnosis of VP depends on a search for high levels of coproporphyrin and protoporphyrin in the feces. Variegate porphyria has been infrequently diagnosed in the United States.

Pre-clinical evaluation of new antiproliferative agents for the photochemotherapy of psoriasis: angelicin derivatives.

To have, before the clinical evaluation, sufficiently predictive information about the antiproliferative and phototoxic effect of new potential agents for the photochemotherapy of psoriasis some simple tests have been worked out. The antiproliferative activity was evaluated studying the inhibition of DNA synthesis first in Ehrlich ascites tumor cells, and then in mouse skin in vivo, both by topical application and oral administration. The phototoxicity was studied by topical application on guinea-pig skin, and for the most interesting compounds also in man.

Melasma: a clinical, light microscopic, ultrastructural, and immunofluorescence study.

Melasma is an acquired brown hypermelanosis of the face. Although it is thought that melasma is associated with multiple etiologic factors (pregnancy, gastric, racial, and endocrine), one of the primary causes of its exacerbation appears to be exposure to sunlight. Three patterns of melasma are recognized clinically: (1) a centrofacial pattern, (2) a malar pattern, and (3) a mandibular pattern.

Photoreactive water-soluble derivatives of psoralen.

Photobinding to DNA and cross-linking formation in vitro, as well as the skin photosensitizing activity on guinea pigs of two water-soluble derivatives of psoralen (5 and 8-diethylaminopropyloxypsoralen hydrochloride) have been studied. For purposes of comparison, the results have been correlated with those obtained, in the same experimental conditions, with 5- and 8-methoxypsoralen. The water-soluble 8-derivative showed an increased photoaddition to DNA and cross-linking formation, when compared with 8-methoxy-derivative; on the contrary, the water-soluble 5-derivative was less photoreactive than the corresponding 5-methoxy-derivative.

Perceived morbidity, utilisation of health services and factors affecting it in a rural area.

A survey of perceived morbidity was carried out in rural population in eight villages and four wards of Saoner town, covering a total population of 8,876. The nature of illness was assessed by weekly visits to the families. History regarding treatment taken for disease and its source was taken.

Erythropoietic protoporphyria. Photoactivation of the complement system.

The complement system was analysed in 14 asymptomatic patients with erythropoietic protoporphyria. In the majority of the sera studied the levels of complement components C1, C4, C2, and C3 were within the normal range. Upon ultraviolet light (330--460 nm) irradiation of the serum samples in vitro, a marked decrease in total hemolytic activity accompanied by reduction of C1, C4, C2, and C3 levels was observed.

Dermatological and ocular examinations in rabbits chronically photosensitized with methoxsalen.

Four groups of female Dutch-belted rabbits (Oryctulagus cuniculus) were given methoxsalen (12 mg/kg) or placebo by oral intubation and 1 hr later were exposed to UVA for either 2 or 8 hr. This procedure was repeated 5 days each week for 18 mo. A fifth group received no drug and no UVA exposure.

An electron microscopic study of the photochemical cross-linking of DNA in guinea pig epidermis by psoralen derivatives.

Albino guinea pigs were treated with psoralen derivatives plus 320--400 nm ultraviolet radiation, and DNA was extracted from their epidermis. The DNA was assayed for the presence of interstrand cross-links by standard denaturation-renaturation assays and by a new technique, electron microscopy of the DNA under totally denaturing conditions. The latter method allows individual cross-links to be directly observed and counted.

Synthesis and photobiological properties of 4,8-dimethyl-5'-carboxypsoralen: a major metabolite of 4,5',8-trimethylpsoralen.

Recently a major metabolite of 4,5',8-trimethylpsoralen (TMeP) (a photochemotherapeutic agent), was isolated from the urine of mice and human volunteers receiving the drug orally; it was identified as 4,8-dimethyl-5'-carboxypsoralen. The synthesis of this compound has been carried out to obtain a distinct confirmation of the structure of the urinary metabolite and to study its photochemical and photobiological properties. The results obtained showed that this interaction and photoreaction with DNA are very poor; this fact can be correlated with the presence of the ionizable carboxylic group that undergoes a repulsion by the phosphate residues of the macromolecule.

Induction of mixed-function oxidases in mouse liver by psoralens.

8-methoxypsoralen, the most widely used psoralen in photochemotherapy, was shown to induce mixed-function oxidases. Induction of mixed-function oxidases in mouse liver was examined after mice were given a single dose of one of three psoralens. 8-methoxypsoralen clearly induced p-nitroanisole O-demethylase and slightly induced aryl hydrocarbon hydroxylase.

Beta carotene therapy for erythropoietic protoporphyria and other photosensitivity diseases.

We treated with high doses of oral beta carotene (Solatene) (15 to 180 mg/day) 133 patients suffering from erythropoietic protoporphyria (EPP), 27 patients with polymorphous light eruption, six patients with solar urticaria, three patients with hydroa aestivale, one patient with porphyria cutanea tarda, and two patients with actinic reticuloid to relieve the photosensitivity associated with these diseases. Eighty-four percent of the patients with erythropoietic protoporphyria increased by a factor of 3 or more their ability to tolerate sunlight. On the other hand, only nine of the patients with polymorphous light eruption, and one fifth of the patients with all of the other forms of photosensitivity treated showed similar improvement.

Photochemotherapy of vitiligo. Use of orally administered psoralens and a high-intensity long-wave ultraviolet light system.

A new light source that provides high-intensity ultraviolet light (UVA) (300 to 400 nm) to the entire body surface makes orally administered psoralen treatment of vitilligo with an artificial light practical. In the 26 patients studied, the degree of repigmentation with either trioxsalen (TMP) or methoxsalen (8-MOP) and high intensity UVA was at least as great as that with the same oral agents and sunlight. With artificial UVA and similar treatment conditions, the two psoralen derivatives were compared in the treatment of vitiligo; TMP stimulated repigmentation as well as 8-MOP and caused fewer side effects.

Cutaneous effects of pulsed nitrogen gas laser irradiation.

The effects of pulsed nitrogen gas laser emission (337.1 nm wavelength) were studied on human skin. The laser provides high-intensity monochromatic UVA radiation and can elicit delayed erythema in an actual exposure time of about 1 msec (105,000 pulses, each lasting 10 nsec, delivered over 210 sec).