60 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS the corneocyte model was used to analyze a variety of effects on normal skin. Regarding corneocyte size, there are substantial regional variations within different body sites, with relatively small cells on the head and on the peripheral parts of the extremities, and much larger cells on the central parts of the body such as the trunk (13,14). Another biological constant is the increasing size of corneocytes with age. This holds true for almost every body site investigated (13, 15), including the corneocytes of nail- plates (16). Another finding was the surprisingly thin dimension of single corneocytes, much less than 1 •m, with fairly constant characteristics for various body sites (17,18). The corneocyte count, expressed in cells/cm 2 skin surface, is another way to characterize human skin conditions. The numbers vary more than the corneocyte surface area, but still give fairly constant figures (9,11, 19-25). Glabrous skin yields 40,000-80,000 cells/cm2 the scalp, much more (26). It is often used to define scaly conditions, such as dandruff (26,27) or the ameliorating effects of antidandruff shampoos (27,28). Some use this model for advertising ("corneocyte countdown"). We, like others, feel that there is a good correlation between cell size, cell numbers, and turnover. If the epider- mopoiesis is increased (faster turnover of epidermis or stratum corneum), the cell numbers go up and the cell surface areas go down. This holds true for various condi- tions. On normal human skin, one will find high cell counts but small cells in body sites with a fairly high turnover (e.g., the scalp), and low counts but large cells in areas with a much slower turnover (e.g., the back) (9, 13, 14,21,29,30). Consequently, this exfoliative cytology model was used to confirm the inverse relation +10' -1 AREA of CORNEOCYTES -20- ß ßMOTRETINID O.5Y• ß ßMOTRETINID 0.25ø4 I TREAT MENT J /• /•GEL BASE •) '• • • •. • WEEKS Figure 7. Experiment II: Changes in corneocyte areas following treatment with motretinid 0.5% and 0.25 % and the gel base.

CYTOLOGY OF STRATUM CORNEUM 61 Table III Corneocyte Counts in Trial I (mean and standard deviation) Weeks 0 1 2 3 4 6 Isotretinoin 1.5% m 53,981 81,429 56,344 80,5 12 sd 15,017 43,106 14,138 17,664 Tretinoin 0.05% m 34,733 48,336 72,987 74,820 sd 15,951 22,737 18,382 25,639 Ethanol + m 45,104 45,490 26,291 45,104 propyleneglycol aa sd 29,087 26,430 8,514 22,156 Motretinid 0.5% m 39,557 62,278 60,445 64,931 sd 18,205 29,639 27,035 13,335 Gel base m 34,009 39,074 33,382 24,313 sd 15,506 23,358 15,550 13,368 83 455 1 845 76.521 14 617 33.648 12.192 74 241 8.890 30 488 15,799 46,4O2 15,799 36,569 14,465 38,716 16,974 45,156 29,427 65,900 34,099 between cell numbers and cell size: Skin was treated topically to enhance (stripping with cellophane tape (2,24,25)) topical application of an irritating concentration of reti- noids (2,3) or to reduce epidermopoiesis (glucocorticosteroids on normal skin or on contact dermatitis (2,9)). As expected, the corneocytes followed this pattern. Another type of experiment involved the systemic treatment of patients with isotre- tinoin, a drug known to cause exfoliation of the skin. Again, as postulated, corneocytes became much smaller, and the cell counts went up (12). Several other questions were asked in this model. One was concerned with seasonal variation of human stratum corneum during the year. Indeed, it was possible to charac- terize the fluctuation between warm and cold seasons for both parameters, cell counts and cell size, in four groups of subjects, young and old females and young and old males (10). It is not surprising that the dry skin condition (chapping or dry skin, dry skin in the winter time, dry skin in the aged, dry skin from inappropriate exposure to water and soap or detergents) is measurable in the corneocyte assay (15,31,32). Tretinoin (vitamin-A acid) is a popular and effective peeling agent to remove stratum corneum cells and even comedones from follicular infundibula. Commercial concentrations range between 0.1% and 0.025%. Isotretinoin (13-cis retinoic acid) is a powerful oral anti- acne drug. We (33) have looked into sebum suppression after its topical application in humans, while others used the hairless rat (34). There was no substantial sebum reduc- tion. However, there is clinical improvement of comedonal and inflammatory acne (33), hence our ongoing interest to study the effects on the stratum corneum by the exfoliative cytology model. Motretinid is a somewhat forgotten retinoid. It is marketed in Switzerland and France. Very few clinical studies attest to its efficacy, and we know of only one experimental study, in which the size and shape of corneocytes were investi- gated following motretinid application.* We wish to point out that, at least in the concentrations used in this study, motretinid was tolerated better than tretinoin or isotretinoin but led to measurable effects in the exfoliative cytology model. It seems appropriate to further explore the usefulness of this or other retinoids where exfoliation from topical treatment is intended. * R. Marks, A.D. Pearse, D. Black, and S. Hill, Techniques for assessment of the activity of topically applied retinoids (1986, unpublished personal communication).