Acral lesions of vitiligo: why are they resistant to photochemotherapy?

BACKGROUND: Acral lesions of vitiligo are usually resistant to conventional lines of treatment as well as surgical interventions. OBJECTIVE: To clarify causes underlying resistance of acral lesions to pigmentation in vitiligo by studying some of the factors associated with mechanisms of repigmentation following photochemotherapy. METHODS: The study included twenty patients with active vitiligo. Skin biopsies were taken from lesional and perilesional skin of areas expected to respond (trunk and proximal limb) and skin of acral areas, before and after PUVA therapy. Sections were stained with H and E, Melan-A, MHCII, CD1a, SCF and c-kit protein. RESULTS: Before treatment acral areas showed significantly lower hair follicle density, melanocyte density, Langerhans cell (LC) density, epidermal MHCII expression, lesional SCF expression and perilesional c-kit expression. Following treatment with PUVA in both non-responsive acral and repigmenting non-acral lesions identical immunohistochemical changes in the form of significant decrease in LC density, epidermal MHC-II and SCF expression were observed. CONCLUSION: The surprisingly similar histochemical changes in response to PUVA in acral and non-acral lesions did not manifest with clinical repigmentation except in non-acral ones. Factors such as inherent lower melanocyte density, lower melanocyte stem cell reservoirs and/or lower baseline epidermal stem cell factor may be considered as possible play makers in this respect.

Prevention of skin tumors induced by 7,12-dimethylbenz(a)anthracene in mice by black seed oil.

The effect of topical application of black seed oil on 7,12-dimethylbenz(a)anthracene (DMBA)-induced skin tumors in BALB/c mice was investigated. Topical application of chemically extracted oil (C.O.) and naturally extracted oil (N.O.) highly prevented the appearance of skin tumors in experimental animals. Skin tumors (papillomas and carcinomas) were initiated by application of 300 mu g DMBA (on days 1,8) followed by applying 0.5 mg croton oil, biweekly until the end of the experiment (25 weeks). The application of N.O. completely prevented the appearance of skin tumors in mice of group 3 versus a tumor incidence of 78.9% in animals of group 1 (carcinogenic control) (cc). Painting the skin of mice with C.O. (group 2) significantly reduced the tumor incidence to 14.2%. Moreover, a significant decrease was observed in number of mice bearing tumors, and number of tumors per mouse in group 2. Multiplicity was also decreased but insignificantly in the same group. The treatment with C.O. and N.O. insignificantly increased the rate of mice survival as compared to that of animals of group 1.

The use of toads (Bufo regularis) in a new biological assay for screening chemicals or drugs which induce leukaemia in man.

Injection of Egyptian toads Bufo regularis, with adriamycin subcutaneously in the dorsal lymph sac at a dose level of 0.1 mg/toad, once every 3 weeks for 3 months induced pronounced alterations in the blood cells. These alterations were more or less similar to the criteria reported in human leukaemia. These changes were all comparable to those observed after the treatment of the experimental animals with the chemical carcinogen 7,12-dimethylbenz(a)anthracene. It is speculated that toads (Bufo regularis) can be used as biological test animals for screening chemicals or drugs which induce leukaemia in man.

Pathological-changes of the blood-cells in griseofulvin treated toads.

Griseofulvin is a valuable oral antifungal drug, used extensively in the treatment of superficial fungal infections of man and animals. Electron microscopical studies of peripheral blood of toads force-fed with griseofulvin revealed pronounced alterations of the blood cells more or less similar to the criteria of monocytic leukaemia and were all comparable to those observed after the administration of the carcinogenic chemical 7,12 dimethylbenz(a)anthracene.

Inhibition of mammary-gland tumorigenesis in the rat by caraway seeds and dried leaves of watercress.

The effect of consumption of caraway seeds and dried leaves of watercress on 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced mammary gland tumorigenesis in female Sprague-Dawley rats was determined. At 6 weeks of age, animals were fed a basal (control) diet and experimental diets containing caraway or watercress (20%). Animals were maintained on their diets till termination of the experiment (25 weeks after DMBA). At 8 weeks of age, all rats were given DMBA 10 mg, one dose, p.o. in oily formulation). Neither caraway nor watercress affected the body weight or the rate of growth of animals. By week 25 after DMBA, 77% of the control rats developed mammary tumors, with a mean of 2.27 tumors per rat. Caraway decreased significantly (P<0.05) the percentage of rats with tumors (42.8% protection) and the mean number of tumors per rat (50.6% protection) and increased significantly (P<0.05) the mean latency period of tumor appearance. Watercress, though decreased the percentage of rats with tumors (28.5% protection) and the mean number of tumors per rat (31.7% protection), this decrease was significant (P < 0.05) during some week intervals only. The increase in the mean latency period of tumor appearance by watercress was not significant. The results of this study suggest that caraway and watercress possess chemopreventive effects against DMBA-induced mammary gland tumorigenesis in rats.

Induction of breast and lung neoplastic lesions in mice by alpha-ecdysone.

Alpha ecdysone is naturally present in the leaves of some plants, including the carcinogenic plant bracken fern (Pteris aquilina). Feeding mice with alpha-ecdysone at a dose level of 3 ppm/25 g body weight, 2 times per week for 22 months induced a significant increase in the body weight of the animals. Breast and lung tumors developed in the experimental mice. Other pathological changes such as fibrocystic disease of the breast and bronchocentric granulomas appeared in these animals. The results of this study proved that alpha-ecdysone may be one of the active carcinogens in bracken fern plant which was responsible for induction of tumors in different animals investigated by previous authors.

Induction of breast neoplasia and lung granulomas in mice by an antifungal drug (griseofulvin).

Infiltrating duct carcinomas were induced in the mammary glands of 7 out of 60 experimental female mice force-fed with the antifungal drug griseofulvin, at a daily dose lever of 0.3 mg/30g body weight, for 12 months. The first mammary gland tumor appeared 8 months after the initiation of feeding. Other pathological changes such as bronchocentric granulomas appeared in some male and female treated animals (16.5%).