Exposure of human and murine melanocytes in vitro to the diacylglycerol (DAG) 1-oleoyl-2-acetyl-sn-glycerol (OAG) markedly increases melanin production within 24 h. To determine whether OAG can increase melanin production in vivo, increasing concentrations of OAG (10-60 mg/ml) in propylene glycol were applied daily for 5 d to shaved guinea pigs. Dose-dependent increased pigmentation was visible first on days 17-22 and persisted for 10-14 weeks. Peak epidermal melanin content in OAG-treated sites was more than twice that of untreated or vehicle-treated sites, as assessed by computerized image analysis of Fontana-Masson stained biopsy cross sections. In another experiment to assess the mechanism of DAG-mediated pigmentation, guinea pigs received twice daily separate applications of OAG, dipalmitoylglycerol (diC16), dioctanoylglycerol (diC8), each 50 mg/ml, 20 microliters/application, and propylene glycol vehicle alone for 5 d. Increased pigmentation was visible after 10 d in the OAG and diC8 sites but not in diC16 or vehicle sites. These results correlate with the reported ability of these compounds to activate protein kinase C in vitro. In a final experiment, guinea pigs received OAG 25 mg/ml three times daily to one test site, and once daily ultraviolet B (70 mJ/cm2, equivalent to 0.6 minimal erythemal dose) radiation to another for 10 d. The OAG and ultraviolet B test sites developed comparable pigmentation by both clinical and histologic criteria. Our data demonstrate that topically applied DAGs can produce a long-lasting increase in epidermal pigmentation, presumably through protein kinase C activation, which clinically and histologically closely resembles ultraviolet-induced tanning.
We conclude that the long-pulsed tunable dye laser can be employed successfully to treat superficial lesions of ALHE, particularly in cosmetically sensitive areas.
Although angiosarcoma is the most frequent tumor arising in the clinical setting of chronic lymphedema, as in Stewart-Treves syndrome, Kaposi's sarcoma has also been reported in this setting, although rarely. We describe two women who developed Kaposi's sarcoma in the lymphedematous arm many years after surgery for breast cancer. Case 1 is a 92-year-old and Case 2 is an 81-year-old; they underwent left total mastectomy and axillary node dissection for infiltrating breast carcinoma in 1981 and 1982 respectively. At that time, neither patient received further treatment. Except for persistent lymphedema, both women did well until over fourteen years later when each noted the development of several purple asymptomatic plaques on the edematous arm. In both, the clinical diagnosis at the time of biopsy was angiosarcoma. However, histologic findings in both cases were typical for Kaposi's sarcoma. In addition, a nested polymerase chain reaction (PCR) for the detection of a 233bp segment of KSHV/HHV8 was performed on DNA extracted from the paraffin-embedded specimens and both cases were positive for this sequence. Histologic sections of both cases were also tested for KSHV by in situ hybridization and demonstrated a positive signal in the lesional cells in each case.
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