Background: Previous studies have described apoptosis in the stratum granulosum and in the stratum corneum, but not in the germinative compartment in normal skin. In psoriasis, an increased epidermal apoptosis has been observed in the differentiated compartment, suggesting that apoptosis has a key role in the pathogenesis of psoriasis, as a counteracting factor to the overproduction of cells. Little is known on apoptosis in the germinative compartment. Methods: Apoptosis was studied on biopsies of normal skin, established lesions of psoriasis and PUVA-treated psoriasis using the transferase-mediated uridine nick end labelling method, which detects fragmented DNA, and electron microscopy. Counting of apoptotic cells was restricted to the germinative compartment as defined by Mib1 staining to evaluate the impact of cell loss on cell production and tissue architecture. Results: The apoptotic index was 0.12% in normal epidermis, 0.035% in established psoriasis and 0.31% in regressive psoriasis. Conclusion: These results have three implications: (1) they show the physiological presence of apoptosis in the germinative compartment in normal epidermis; (2) they suggest that induction of apoptosis is involved in the regression of psoriatic hyperplasia after PUVA therapy; (3) the decrease of physiological apoptosis in the psoriatic lesion suggests that this phenomenon could play a role in the induction of psoriatic hyperplasia.

Iron is suspected to be involved in the induction and/or progression of various human tumors. More particularly, iron may be involved in the pathogenesis of Kaposi's sarcoma, a tumor of probable vascular origin. This study was designed to investigate the effect of iron deprivation on Kaposi's sarcoma. The effects of iron chelators and iron deprivation associated with serum withdrawal were investigated on Kaposi's sarcoma-derived spindle cells, on a transformed Kaposi's sarcoma cell line (Kaposi's sarcoma Y-1) and on endothelial cells, which are the probable progenitors of Kaposi's sarcoma cells. Desferrioxamine and deferiprone, two chemically unrelated iron chelators, induced a time- and concentration-dependent inhibition of endothelial and Kaposi's sarcoma cell growth. The inhibition of cell growth was associated with a decrease in Ki-67 and in both stable and total proliferating cell nuclear antigen expression. Inhibition of the progression through the G1-phase of the cell cycle was further evidenced by decreased expression of cyclin D1 and of p34 cyclin-dependent kinase 4. Terminal deoxynucleotidyl transferase-mediated desoxyuridinetriphosphate nick end labeling assay, flow cytometry with annexin-V-fluorescein and morphologic analysis indicated that iron chelation also induced a time- and concentration-dependent apoptosis. This apoptotic effect was prevented by the addition of exogenous iron. Induction of iron deprivation in the culture medium by serum withdrawal led to similar cell cycle effects, which, however, could only be partly reverted by the addition of exogenous iron. In conclusion, these results show that iron deprivation inhibits the growth and induces the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors. This suggests that iron chelators may represent a potential therapeutic approach for the treatment of Kaposi's sarcoma.

Considering the vasospastic hypothesis of Nicolau's syndrome, we acknowledge that this unpredictable and potentially severe outcome has to be recognized early to allow for efficient and harmless treatment.K . E z z e d i n e J . V a d o u

Gal-3 might play a role in melanoma progression and/or inflammation, and warrants further study.

Several triterpenes isolated from Leptadenia hastata latex were tested for their anti-inflammatory activity. Lupeol (1), its acetate (2) and palmitate (3) esters were found to be the main antiinflammatory constituents in the croton oil-induced ear oedema test. Furthermore, lupeol hemisuccinate (4), synthesized from lupeol, exhibited a higher activity than lupeol in the test. These results prove that the triterpenes play a pivotal role in the topical antiinflammatory effect of this latex. In addition, an in vitro model of human skin keratinocytes (epidermal explants) cultured at an air-liquid interface on a de-epidermized human dermis (DED) was used to investigate the effects of lupeol esters on skin repair in vitro. Compared with the control, compounds 2 and 3 improved keratinocyte proliferation at a concentration of 5 microM in the culture medium; however, they remained less active than compounds 1 and 4. In contrast to compound 1, all the lupeol esters (2-4), and particularly compound 4, induced a good differentiation of keratinocytes with a well-formed stratum corneum without parakeratosis. These results substantiate the topical use of Leptadenia hastata latex in traditional medicine and showed that both antiinflammatory activity and the effect on keratinocyte proliferation of compound 1 could be improved by its hemisuccinylation; on the contrary, esterification by acetylation or palmitoylation decreased these activities.