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Emulsifying agents in aqueous solution lead to dehydration of the horny layer of the epidermis and damage to the barrier. This is only partly true if emulsifying agents are constituents of emulsions. Water-in-oil (W/O) emulsions cause an improvement in the hydration of the horny layer and barrier function. In the case of an additional effect of wash solutions, a partial or complete abolition of the drying out and barrier-damaging effect of the wash solution results. Oil-in-water (O/W) emulsions without glycerol have no effect on the moisture of the horny layer or indeed increase it, but they lead to considerable damage to the barrier and irritation. In wash tests, they do not induce any protective effect. With micro-emulsions this is still more the case and, moreover, they can also lead to exsiccation. As a result of the addition of glycerol, the barrier-damaging effect can be abolished. Also in stress tests with wash solutions, the damage to the horny layer is reduced by glycerol-containing O/W emulsions. Whereas the penetration-promoting effect of O/W emulsions without glycerol is best, only W/O emulsions or glycerol-containing O/W emulsions are suitable for atopic dermatitis. A hydrating effect on the stratum corneum was also found in a propylene glycol ointment., (2004 S. Karger AG, Basel.)

Unlabelled: BACKGROUND AND PROBLEM: It is well known that the damaging effect of surfactants on the stratum corneum varies according to the surfactant used. The present investigations aim to compare four standard commercial cleansing solutions (Esemptan Cleansing Lotion, Stephalen Shower Gel, Manipur Antimicrobial Cleansing Solution and Tork Mevon 55 Liquid Soap) with respect to their cleansing and skin barrier-damaging effects., Material and Methods: The cleansing effect of the solutions was determined in relation to their concentrations in a first experimental series involving 15 subjects using a standardised test method. The product concentrations with the most divergent cleansing effects were tested for their dehydrating (corneometry), epidermal barrier-damaging (TEWL) and irritating effects (laser Doppler) in a standardised washing test. In a second experimental series, the concentration used for the cleansing solutions was based on the quantity of cleansing solution obtained from dispenser actuations (six actuations/L). These concentrations were used to test the cleansing and damaging effect on the stratum corneum using the same methods as in the first experimental series., Results: There were no significant differences in the first experimental series. In the second experimental series, Stephalen Shower Gel showed disadvantages in terms of a small cleansing effect, but without evidence of a smaller stratum corneum-damaging effect, and Tork Mevon 55 Liquid Soap showed advantages in terms of a smaller stratum corneum-damaging effect, but without evidence of a smaller cleansing effect., Conclusions: These studies showed that the relationship between the cleansing and the damaging effect on the stratum corneum can be properly assessed only by testing different concentrations. Furthermore, this experimental approach allowed to differentiate the four tested cleansing solutions.

Twenty subjects with healthy skin were treated with the following formulations for two weeks: drug-free W/O vehicle, 5% ammonium lactate (CAS 52003-58-4) in W/O vehicle, 5% urea (CAS 57-13-6) in W/O vehicle, 3% ammonium lactate + 3% urea in W/O vehicle, 5% ammonium lactate + 5% urea in W/O vehicle. These formulations were applied in randomized order to 6 test areas on the forearms; one area was left untreated. Repetitive washings were additionally performed in the second treatment week. TEWL, stratum corneum water content (corneometry-determined electrical capacitance), and cutaneous blood flow (laser Doppler) were measured at baseline, day 7, and day 14. 5% urea and both ammonium lactate/urea combinations produced significant stratum corneum hydration and improved stratum corneum barrier function; there were no significant differences between these three treatments., (Copyright 2002 S. Karger AG, Basel)

Objective: To determine whether salicylic acid and high dose urea in five different NRF (New German Formulary) formulations have an effect on stratum corneum., Methods: 20 healthy volunteers had their stratum corneum blacked with silver nitrate and a photographic developer, and a chromameter (a*-value) was used to determine the amount of discoloration produced by the study products and the drug free vehicles after 24 hours semiocclusive application and 24 hours later. The change in fingerpad ridge width produced by the study formulations and drugfree vehicles was determined at the same time, using the Hikoscope Dermatoscope after 30 and 35 minutes' use under an occlusive dressing. The results obtained with the two methods were correlated., Results: All study formulations were effective. There were differences in the time course of the effects on the stratum corneum. The fingerpad ridge width method is not a measure of keratolytic activity because there were no significant correlations between the results obtained with the two methods. Also, 40% urea was keratolytic in the silver nitrate test, but had no effect of fingerpad ridge width., Conclusions: All NRF study formulations were effective in the stratum corneum. The fingerpad ridge width method is not a measure of keratolytic activity but rather of an other unknown effect of salicylic acid.

We carried out three studies to evaluate the effects of white zinc shake lotion (Zinkschüttelmixtur DAC), zinc oil ( Zinköl NRF 11.20), Lotio Cordes, PEG ointment (Polyethylenglykolsalbe DAB) and PEG paste on nonmoisturized and moisturized skin. The aim of the study was a clear indication for these vehicles in the clinical practice. Studies 1 and 2 were performed on 20 healthy volunteers. Study 1 was carried out on nonmoisturized skin, while test areas in study 2 were treated with the study products after 1-hour moisturization with hydrophilic aqueous ointment (hydrophile wasserhaltige Salbe DAB), covered with a semiocclusive film dressing. Study 3, carried out on 10 subjects, differed from study 2 by a longer follow-up period. The water content of the horny layer before and after application of the different vehicles was estimated by the capacitance measurement (Corneometer CM 820) and the conductance measurement (Skikon). The glycerol-containing zinc shake lotion and both PEG gels (with or without zinc oxide) produced hydration under the conditions of study 1 and 2. Zinc oil and moisturizer-free Lotio Cordes had little impact on stratum corneum hydration under the conditions of studies 1-3. Therefore, zinc shake lotion and the two PEG ointments can be used in the treatment of dry atopic skin, but not in overhydrated skin, e.g. in intertriginous regions. Zinc oil and Lotio Cordes can be used in overhydrated skin but not in dry skin, for the missing water-binding capacity in the horny layer. On the other hand an effective dehydrating effect cannot be expected.

The aim of this study was to establish the effect on barrier function in atopic dermatitis of topical evening primrose oil in an amphiphilic and a stable water-in-oil emulsion. The studies were vehicle-controlled in two populations of 20 atopic subjects. Barrier function was assessed in terms of transepidermal water loss and stratum corneum hydration after a 4-week treatment period and a 1-week treatment-free period. A barrier function test with sodium lauryl sulphate (SLS) and nicotinic acid ester was also carried out. Evening primrose oil proved to have a stabilising effect on the stratum corneum barrier, but this was apparent only with the water-in-oil emulsion, not the amphiphilic emulsion. The choice of vehicle is therefore an extremely important factor in the efficacy of topically applied evening primrose oil.

Background: Topical retinoic acid (RA) causes irritation of the skin. To prevent this side effect, natural precursors of RA have been proposed. The aim of the present study was to compare the local tolerance profiles of retinol (ROL), retinaldehyde (RAL) and RA., Methods: ROL, RAL and RA were studied using repeated insult patch tests for 14 days (n = 6). Similarly, RAL and RA were assessed in long-term clinical use for 44 weeks (n = 355). Clinical scoring on irritation, measurement of transepidermal water loss (barrier function) and laser Doppler blood flow perfusion units (irritation) were performed., Results: Under maximized conditions, an equally low irritation potential for ROL and RAL and a more pronounced irritant effect with RA could be demonstrated clinically (p < 0.05 in the intergroup analysis). Furthermore, RAL and RA induced more scaling than ROL (p < 0.05), and ROL and RA tended to induce more burning/pruritus than RAL (nonsignificant). The TEWL values were low with ROL and high with RAL and RA (nonsignificant, intergroup analysis). The laser Doppler measurements confirmed pro-irritating effects of RA and the nonirritating effects of ROL and RAL (p = 0. 001, intergroup analysis). The long-term clinical study showed that the study population developed a high frequency of erythema (44% of the population), scaling (35%) and burning/pruritus (29%) with RA in the first 4 weeks of treatment, whereas these 3 parameters were significantly less frequent with RAL (p < 0.0001 in the intergroup analysis)., Conclusion: The natural retinoids ROL and RAL do have a good tolerance profile, in contrast with the irritating potential of RA.

The influence of vitamin E (tocopherol, CAS 10191-41-0) on stratum corneum hydration was tested in O/W and W/O emulsions. Additionally, the O/W emulsion was used in an in vivo/in vitro method to gravimetrically obtain evidence concerning the water-binding capacity of the stratum corneum. In the W/O emulsion, 2.5%, 5%, and 7.5% vitamin E were compared. With both types of emulsions, vitamin E increased the stratum corneum hydration statistically significantly (p = 0.0002). In addition, we could provide evidence of an enhanced water-binding capacity after treatment with vitamin E (p = 0.05). For the hydrating effect of vitamin E. its concentration is of importance. The optimum concentration turned out to be 5%.

The effects of glycerol are discussed in detail. Glycerol can lead to a transition of crystalline lipid structures within the horny layer lipids into liquid crystalline states. Especially if applied in oil/water-emulsions it improves, the hydration of the horny layers better than urea. In addition, if facilitates the dissolution of desmosomes within the superior layers of the horny layer enhancing desquamation. Furthermore, by using glycerol, the mechanical properties of the skin can be influenced; long term used leads to increased elasticity. The roughness of the horny layer is reduced, which can be explained by the abrasive and/or the hydrating effect. Glycerol used in o/w-emulsions also protects against the influence of tensides or noxious lipophilic agents. Presumably a flux from the base of the epidermis towards its surface triggers the regeneration of the barrier. Finally, glycerol can lead--similarly to urea--to an improvement in active agent penetration, as has been proven for hexylnicotinate.

Damage to the skin following the repeated use of 2 different wash solutions was investigated. Stratum corneum capacitative resistance, stratum corneum lipids, transepidermal water loss, skin surface pH, laser Doppler flow and skin reddening were determined. All skin function parameters already showed a marked change after a single wash (e.g., the median of TEWL values increased by more than 0.5 g/m2 h). Repetitive washing for 1 week led to a further deterioration of TEWL and corneometry values (e.g., TEWL increased for about 2.9 g/m2 h after repetitive washing with sodium lauryl sulfate). The rate of skin function regeneration after repetitive washing was unaltered compared to regeneration after a single wash. The surfactants used showed quantitatively differing effects on corneometry, TEWL and laser Doppler flow (e.g., after repetitive washing with Geliderm, the median of TEWL values increased only up to 1.55 g/m2 h). However, damage arising from repetitive washing could not be completely prevented by the selection of a mild surfactant. Skin function regeneration showed no difference with the 2 surfactants used.

The influence of three different liposome formulations (NAT 106, NAT 50, NAT 89), as empty liposomes and loaded with 0.05% betamethasone, on blood circulation in the corium was investigated by means of laser Doppler flowmetry. All three empty liposomes brought about a decrease in circulation. The maximum effect was reached 90 min after a 30-min occlusive application of the test preparations. Loading with betamethasone resulted in a significant increase in circulation after only 15 min. This increase in interpreted as a steroid effect. No comparable symptoms appeared with the application of base cream DAC (an O/W emulsion) or of betamethasone in base cream under identical experimental conditions.

Infrared-spectroscopic investigations of the water content of the stratum corneum after application of emulsions and wash solutions are reported. As a methodologic variation infrared spectroscopy is applied after stripping the skin to determine the hydration of various depths of the stratum corneum by ointments. Using soap as an example, a method of correcting the overlap effects between the ointment and skin spectrums is presented which expands the application possibilities of infrared spectroscopy. An o/w emulsion with plenty of water and a w/o emulsion containing less water produce to almost the same degree a hydration of the deeper layers of the stratum corneum which lasts for at least 40 min. The report in the literature that soap solutions produced a stronger hydration of the stratum corneum and surfactant solutions is not supported.

This is a report on biochemical and physiological examinations carried out on 20 test persons who in the last 2 years had contacted and completely recovered from pityriasis versicolor and on 25 control persons of corresponding age and sex. The tests on the skin surface of the patients with pityriasis versicolor show, when compared with the corresponding control group, the following significant results: 1. Significantly more amino acids could be extracted from the skin of the pityriasis versicolor patients than from the skin of the control persons. 2. A significantly shorter alkali neutralisation time was to be found in the pityriasis versicolor patients than in the control persons. 3. The degree of water spreading on the skin was found to be significantly reduced in the pityriasis versicolor patients when compared with the control persons. It is probable that these results point to important predisposing factors for pityriasis versicolor.

Investigation on 60 volunteers are reported in whom the influence of salicylic acid and finely divided sulfur on the blanching effect of ointments with and without steroid was analysed. The higher the concentration of salicylic acid the greater is the decrease in the blanching effect of the steroid free ointment. At low concentrations finely divided sulfur also reduces the blanching effect of the steroid is reduced by salicylic acid as well as by sulfur. This effect is at least partly produced by the decrease of the blanching effect due to the base. An increase in the bioavailability of corticosteroids in the skin after local application cannot be achieved by addition of salicylic acid or sulfur under the conditions chosen.

Infrared spectroscopic measurements of hydration of the stratum corneum before and after stripping the skin five and ten times with scotch tape are reported. Investigations on 64 healthy persons show that for individuals over 45 and under 15 years of age the range of the measurement values is strikingly larger than for persons in the age group 15 - 45 years of age. A small, but not significant reduction in the measurement values is found in females as compared to males. A comparison of the clinically unaffected skin of atopic dermatitis patients with the skin of normal persons points to an increase in the hydration of the stratum corneum of atopic dermatitis patients, which is especially evident in patients who show clinical evidence of "dry" and rough skin.

The irritational disposition of the skin was studied in a control group of 12 healthy persons, 8 patients with neurodermitis, 11 hairdressers with occupational dermatitis and 11 nurses with occupational dermatitis by using the Duhring-chamber-scarification test. For comparison, the alkali resistance test was also carried out. The results show that with the alkali resistance test the irritational disposition towards tensides may not be judged. The present findings show that the increased irritational disposition toward detergent substances seems to be a constitutional factor which favors the development of occupational dermatitis in hairdressing and nursing jobs; with the patient suffering from atopic dermatitis, one must presume an increased irritational disposition towards tensides in most cases.

Ultraviolet (UV) light therapy was given over a period of several weeks to 19 test persons on one side of the back. The duration of the treatment was gradually increased from 30 sec to 7 min. After conclusion of the treatment quantitative lipid determination was made on both the treated and the untreated sides of the back, using the direct extraction method and the paper absorption method. The lipids obtained in this way were analysed by thin-layer chromatography. The following were the most important results: (1) The amount of skin surface lipids was significantly increased by UV irradiation. This results goth from an increase in the epidermal lipids as well as in the lipids of the sebaceous blands. (2) The percentage of free cholesterol in the skin surface lipids was significantly increased by UV irradiation. This increase is probably connected with a thickening of the stratum corneum. (3) The percentage of free fatty acids in the skin surface lipids is significantly increased by UV therapy. This shows that the living conditions of the saprophyte skin flora, which set free lipases, are improved as a result of this treatment or that this treatment leads to an increase of the activity of the bacterial lipases in the excretory ducts of the sebaceous glands.

The right lower inner arms of 22 healthy test persons in total have been treated either with 6% salicylic acid solution in 70% isopropyl alcohol, or with 5% precipitated sulphur mixture in white petrolatum, or with a surfactant mixture. The basic preparations without active agents have been applied to the corresponding skin area on the left arms. The thickness of the corneal layer on both arms was measured by means of the cantharidin blister method. Salicylic acid, sulphur, as well as the surfactant mixture all led to a more significant reduction of the corneal layer than the basic preparations. Under the chosen test conditions, the keratolytic effect of all three substances has thus been proven.

The morphological presentation of the stratum corneum and simultaneously measurements of the alkali resistance and alkali neutralization time of the skin have been carried out in 26 guinea pigs. Whereas we could not demonstrate any association between the alkali neutralization time and the structure of the stratum corneum, a significantly better alkali resistance of the skin could be found when the columnar structure of the stratum corneum was most pronounced. The structure of the stratum corneum on full thickness skin autografts was also compared to that of normal skin in 26 animals. The columnar structure can be just as well pronounced on grafts as on normal skin. Significant differences between graft and normal skin could not be demonstrated but random samples showed that a disturbance in the columnar structure occurred more often in the grafts.

The composition of the aerobic and anaerobic bacterial skin flora was investigated quantitatively and qualitatively in 25 patients with seborrheic eczema (SE) and in 35 healthy persons. In SE patients, the geometric mean count for propionibacteria in the pilosebaceous ducts of the forehead was reduced to a statistically significant extent in comparison with the control group. There was the same tendency with regard to the geometric mean count of the superficial anaerobic bacterial flora of the back, whereas the geometric mean counts of the coagulase-negative staphylococci were the same in the two groups. These results may explain earlier findings of a reduction of free fatty acids in the surface lipids in SE patients. According to the results of differentiation in 295 propionibacteria and 157 micrococcaceae, 7 biotypes and 10 phage types of propionibacteria which were so far unknown could be demonstrated. Significant differences between the groups with regard to the frequency of different biotypes, serotypes, and phage types could be demonstrated neither in propionibacteria nor in coagulase-negative staphylococci. The results of typing, however, showed that patients with SE displayed much more frequently several different propionibacterial species and types as well as different micrococcal species and types than persons with healthy skin.

Biochemical and physiological examinations were carried out on the skin surface of the following groups: on 16 newly diagnosed diabetics; on 26 diabetics receiving treatment; and on 2 control groups of 16 and 26 healthy persons respectively of corresponding age and sex. The tests on the surface of the skin of the newly diagnosed diabetics when compared with the corresponding control group show the following significant results: 1. An increase in the percentage of free cholesterol in the lipids of the skin's surface possibly as a result of an increased cell turnover in the epidermis. 2. An increase in the free fatty acid concentration to the disadvantage of the triglycerides in the lipids of the skin's surface as an expression of an improved bacterial lipolysis. 3. A decrease in the reducing substances as confirmed by the phenol-sulfuric acid method in the so called water solubles. 4. An increase in the amino acids as confirmed by the ninhydrin method in the so called water solubles. All the above mentioned changes were more pronounced in the newly diagnosed diabetics than in those already receiving treatment; it can be seen that these changes can partly be normalised under diabetic therapy.

Groups of 15 guinea pigs and 10 Syrian hamsters were treated with 5-fluorouracil (Fluoro-uracil "Roche") for 8, 22, and 36 days, respectively. 15 guinea pigs and 10 Syrian hamsters remained untreated. At the end of the experiment the hair root status of the guinea pig and the 3H-thymidine labelling index of the sebaceous glands and epidermis on the Syrian hamsters were determined. 5-Fluorouracil leads to a gradual reduction of both the 3H-thymidine labelling index in the epidermis and the sebaceous glands and the amount of anagenetic hair. The effect is slow at the onset, gradually increases, and is still increasing after 3 weeks of treatment. The reduction in the number of labelled cells is significantly larger in the epidermis than the sebaceous glands.

In 14 patients with atopic dermatitis the superficial bacteria from unaffected skin were extracted with the scrub method, aerobically cultured, and analysis qualitatively and quantitatively. For comparison, 12 healthy subjects served as control group. Staphylococcus aureus, as well as coagulase-negative staphylococci were significantly increased in patients with atopic dermatitis. It is assumed that special characteristics of the horny layer in atopic dermatitis favor the growth of aerobic bacteria. The qualitative biotyping and phage typing gave no support to the claim that special bacteria dominate the microbial flora of the skin of patients with atopic dermatitis.

The thymidine labelling index and the mitosis rate (blocked by colcemid) in the basal cell layer of the guinea pig were determined before and during treatment with 5-fluorouracil (1 mg i.p. in 2 day's interval/100 g body weight). Additionally, the epidermal area and thickness and the number and size of cells were measured. 5-Fluorouracil equally reduces the thymidine labelling index and the mitosis rate with the full effect after treatment of at least 22 days. From these findings it is concluded that the S-phase--calculated from the end of the thymidine synthesis--is not altered. Furthermore atrophy of the epidermis runs parallel with the reduction of the 3H thymidine labelling index and the mitosis rate.

Biochemical and physiological examinations were carried out on the healthy surface of the skin of 24 test persons who had had contracted common warts during the 2 years prior to examination and on a control group of 46 healthy persons of the same age and sex. The following significant results were obtained: (1) There was a significant reduction in the percentage amount of squalene in the lipids of the skin surface in the patients with common warts as compared with the healthy control persons. (2) The alkali neutralization time in the patients with common warts was significantly shortened as compared with the healthy control group. (3) The degree of moistening of the skin with water was significantly less in the patients with common warts than in the control persons. These results indicate important predisposing factors for common warts.

Thin-layer chromatographic investigations of the skin surface lipids have been performed on 10 healthy subjects before and after treatment with film masks containing 1% ethyl lactate and 50% ehtanol. From the results obtained it can be assumed that there is a reduction in the fraction of free fatty acids on the skin surface. Clinical studies with the same mask on 23 patients with acne vulgaris over a period of 3 weeks proved that this treatment led to a significant reduction in comedones and inflammatory acne efflorescences. No side effects whatsoever were obtained. This therapy, therefore presents a valuable element in the treatment of acne vulgaris. These investigations show also that a decrease in the free fatty acids of the skin surface lipids points to a favourable therapeutical effect on inflamed and not-inflamed efflorescens of acne vulgaris when testing antimicrobial agents.

The following report describes the results of biochemical and physiological examinations in 32 persons, who had suffered from impetigo contagiosa in the last 2 years, as well as 21 control persons of the same age and sex. The examination of the skin surface of the patient group, when compared with the corresponding control group, showed the following significant results: 1. an increase in the percentage of free cholesterol in skin surface lipids possibly as a result of an increased cell turnover in the epidermis, 2. a decrease in reducing substances as revealed by the ferricyanide and the phenolsulfuric acid methods in the so called water solubles, 3. a decrease in the alkali resistance of the skin possibly as a result of a decreased barrier function of the stratum corneum. It is most likely that these results indicate predisposing factors, localized in the epidermis, for impetigo contagiosa.

Biochemical and physiological examinations were carried out on the skin surface of a total of 115 healthy persons ranging from the age of 7-79 years. In these investigations the following striking findings were made: 1. There is a significant correlation between the results obtained by the ferricyanide, the phenol sulfuric acid and the ninhydrin methods in the so called water solubles. 2. The relationship between the fraction of wax and cholesterol esters and the squalene fraction in the skin surface lipids influences the release of free fatty acids by bacterial lipases. 3. With regards to most parameters tested there are great differences between the 8-12 year age group and the older age groups. 4. There are significant differences in the 8-12 year age group between the male and female test persons. 5. With regards to the parameters tested there are also significant differences between the various test areas.

A lipid-free preparation containing 0.076% dexamethasone-21-sodium-m-sulfobenzoate (corresponding to 0.05% dexamethasone) has been applied to the right side of the back and the same vehicle without the agent to the left side of the back of 16 male subjects without any skin diseases. The applications were made twice daily over a period of 26 days. Two days after the final application the skin surface lipids were analysed quantitatively by means of the direct extraction method and the paper absorption method. Thin layer chromatograpical analyses were also carried out. The sum of skin surface lipids is not altered by dexamethasone-21-sodium-m-sulfobenzoate. This agent does, however, induce a significant increase in the free fatty acids at the expense of the triglycerides. The importance of this result is discussed with reference to the pathogenesis of steroid acne.

Autologous full thickness skin autografts were carried out on 60 male guineapigs in such a way that the hair roots were destroyed. The light sensitivity of the skin towards UV B was then tested on the hairless skin by means of the Xenon lamp and the corresponding filter. Exploratory excisions were taken from another area of the graft and used to demonstrate the structure of the stratum corneum according to the method of Christophers. It could be shown that light erythema developed significantly less than when the columnar structure of the stratum cornuem was well developed.

In individuals free from skin diseases, the resistance and the neutralisation to alkali, and the quantity of lipids at the surface of the skin, are constitltional factors; these idiotypically (genetically) controlled factors are subject to paratypical (environmental) variations. The frequency of a reduced alkali neutralisation and of sebostasis in case of neurodermitis atopica and of ichthyosis vulgaris is not dealt with in the literature, but it results from literature findings that a pathologic alkali resistance is a facultative feature in neurodermitis atopica, while it is an obligatory one in ichthyosis vulgaris. The difference seems to be conditioned genetically. In neurodermitis atopica, the genotype is in itself of no pathogenic importance since the disease is induced exclusively by exogenous and endogenous, non hereditary agents. In ichthyosis vulgaris, the reduced alkali resistance falls into the pleiotropic character of the disease.