THERAPEUTIC POTENTIALITIES OF TRIGLYCERIDES 311 albicaus has relatively little of this particular esterase, this may account in part for the ineffectiveness of triacetin formulations in treating superficial candidiasis plus the fact that the yeast is not quite so sensitive to fatty acids as the truly filamentous fungi. The effect of pH on the hydrolysis of triacetin by esterases of various origin is shown in Table 4. In general the esterases have a rather broad TABLE 4.--THE EFFECT OF pH ON THE HYDROLYSIS OF TRIACETIN BY ESTERASES OF DERMATOPHYTES, SERUM AND SKIN • N/10 Acetic Acid Produced in 18 Hr. T. rubrum, T. menta- M. audouini, Serum, ml., pH ml. grophytes, ml. ml. Skin, ml. 35 0.3 0.4 0 4.0 1.0 4.1 0.6 4.5 2.8 1.9 5.0 3.3 •i• 4.6 5.5 3.9 3.8 6.2 6.0 4.4 4.0 11.7 6.5 5.1 5.0 12.2 7,0 7.8 3.8 12.0 7.5 10.8 5.7 12.5 8.0 9.4 4.7 9.1 32 65 80 83 76 56 3.4 3.3 4.5 5.0 0 1.3 2.4 4.0 5.6 7.8 7.4 7.6 7.0 7.0 plateau of maximum activity with rapidly decreasing activity in the region of pH 3.5 to 4.0. Note the eighteen-hour reaction time these esterases seem to have rather low turnover rates, or the conditions for testing were not optimum. Serum esterase is peculiar in that it has a very broad area of activity and maximum activity is at a comparatively low pH. The skin used in these tests was abdominal skin obtained at postmortem examina- tions. It should be pointed out that lipase assays, especially over the pH range, are unsatisfactory generally and all these figures are probably more indicative than quantitative. DISCUSSION It is apparent that the lipases of the dermatophytes, serum and skin can hydrolyze g]ycero] triacetate and that the hydrolyric enzymes are sensitive to a low pH. This property plus some of the properties mentioned earlier make g]ycero] triacetate a suitable source of a prolonged and controlled level of acetic acid whenever it is desired in chemotherapy or for the main- tenance of acidic conditions on the surface of the skin. Another fortunate characteristic is the lack of toxicity or sensitivity to both the glyceride and acetic acid. Apparently lipase may or may not be present upon the surface of normal skin, depending upon factors unknown to us. Recently Nicolaides and Wells (4) cited the sebaceous gland duct and hair-shaft canal as the location

312 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS of lipase in the skin and they presented rather impressive evidence in support of the idea. This might well explain why we obtained erratic results in the search for lipase in skin slices and very consistent positive results in homogenates obtained by disrupting the cells in an electrically driven blender in the latter, the sebaceous glands and canals were dis- rupted and the lipase made more available. We have applied preparations containing triacetin to normal skin sur- faces many times but in only roughly one-third of the instances has there been a decrease in pH detectable with pH papers. The decrease in pH stops in the region of pH 5 and since, in our conditions, normal skin is but slightly above pH 5, the decrease is probably just inside the range of reli- ability of the paper there seems to be no correlation between the original pH and acid formation. We are just now getting information on triacetin hydrolysis and the pH of dermatophyte infected skin. Most of the in- fections are tinea pedis caused by Trichophyton mentagrophytes and Tricho- phyton purpureum. There is no doubt in these infections that the pH of the skin is increased and in even moderately severe infections the pH may be neutral or even alkaline. Also, in these instances triacetin apparently is rapidly hydrolyzed and a pH in the area of 5.0 is obtained we are surprised that here again the pH does not go lower and we can not yet explain why it does not except, and this seems likely, that the skin is heavily buffered about this point. For the sake of convenience, our tests are made within 20-30 minutes after the first application and it might well be that this is not enough time since hydrolysis may be slowing up as the pH enters the lower area. However, after scanning a rather vast literature on the sub- ject we gather that there is no general agreement on the pH of normal skin except that it is generally somewhat below pH 6. Certainly our tests are not to be considered authoritative. Furthermore, if the biogenesis of free fatty acids is inside the sebaceous gland duct and along the hair shaft canal, the pH of the skin surface might well be secondary and variable compared with the pH in openings beneath the surface. We were quite impressed with the comparatively high pH of dermato- phytic skin but have recently learned from data presented by Rothman (5) that this may be common. Certainly this high pH must contribute to the infectious process as it solubilizes the protein in the microenvironment of the infection. Recently Burack and Knight (6) noted that the dermato- phytes in general are very active in deaminating amino acids the ammonia so released might contribute considerably to the high pH of the area. It might well be that the effectiveness of formulations of glycerol triacetate in treating dermatophyte infections is due to two factors: the inhibitory effect of the free acid upon the fungus and the return and maintenance of the area to a normal lower pH. In view of the findings of Bernstein and Herr- mann (7) that the surface of the skin has an elevated pH in certain non-