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• W2040459675 abstract "SummaryThe existence of a flux of proton donors from skin (inner part of the forearm) to the electrode was observed in 12 male and female volunteers. This flux was used to collect and identify the ionic species responsible for skin acidity. It was then found that: (i) pK of these proton donors (pK = 6.13 ± 0.07) was quasi-identical to that of trans-urocanic acid (6.10), and (ii) the amount of urocanic acid present in stratum corneum was sufficient in itself to explain the acidic level as measured with pH meter (R = 0.8484, n = 10, p =0.00136). As a result, the contribution of other ionic species can be considered as negligible in normal human skin. The data recorded led us to identify three groups (Fast, Medium, and Slow) characterized by different skin surface pH values (low, medium, and close to neutral) and showing a pH gradient in the outer layers of the stratum corneum, or not. Data analysis suggests that these characteristics depend on urocanic acid production rate within the stratum corneum and that this production rate is self-regulated by its urocanic acid content. The existence of a flux of proton donors from skin (inner part of the forearm) to the electrode was observed in 12 male and female volunteers. This flux was used to collect and identify the ionic species responsible for skin acidity. It was then found that: (i) pK of these proton donors (pK = 6.13 ± 0.07) was quasi-identical to that of trans-urocanic acid (6.10), and (ii) the amount of urocanic acid present in stratum corneum was sufficient in itself to explain the acidic level as measured with pH meter (R = 0.8484, n = 10, p =0.00136). As a result, the contribution of other ionic species can be considered as negligible in normal human skin. The data recorded led us to identify three groups (Fast, Medium, and Slow) characterized by different skin surface pH values (low, medium, and close to neutral) and showing a pH gradient in the outer layers of the stratum corneum, or not. Data analysis suggests that these characteristics depend on urocanic acid production rate within the stratum corneum and that this production rate is self-regulated by its urocanic acid content. urocanic acid The acidic nature of skin has been well documented since it was first described (Heuss, 1892Heuss E. Die Reaktion des Schweiβes beim gesunden Menschen.Monatsschr Prakt Dermatol. 1892; 36: 305-308Google Scholar) and since the term acid mantle was coined (Schade and Marchionini, 1928Schade H. Marchionini A. Der Saüremantel der Haut.Klin Wochenschr. 1928; 7: 12-14Crossref Scopus (71) Google Scholar). Such an interest is mainly due to the part played by pH in epidermal homeostasis (Forslind, 1995Forslind B. The skin: upholder of physiological homeostasis. A physiological and (bio) physical study program.Thrombosis Res. 1995; 80: 1-22Abstract Full Text PDF PubMed Scopus (19) Google Scholar). Hydrolytic enzymes such as phosphatase, which are stored in the lamellar bodies (pH 7) of stratum granulosum, are released to extracellular space during cornification. They are activated by acidic pH (Meyer et al., 1990Meyer J. Grundmann H. Knabenhans S. Properties of acid phosphatase in human stratum corneum.Dermatologica. 1990; 180: 24-29Crossref PubMed Google Scholar). Numerous hydrolases such as proteases (chymotrypsin, trypsin, cathepsin, etc.) have been shown to be involved in the desquamation process that require a controlled degradation of desmosomes in the upper stratum corneum (Horokoshi et al., 1999Horokoshi T. Igarashi S. Uchiwa H. Brysk H. Brysk M.M. Role of endogenous cathepsin D-like and chymotrypsin-like proteolysis in human epidermal desquamation.Br J Dermatol. 1999; 141: 453-459Crossref PubMed Scopus (96) Google Scholar; Ekholm et al., 2000Ekholm I.E. Brattsand M. Egelrud T. Stratum corneum tryptic enzyme in normal epidermis: a missing link in the desquamation process?.J Invest Dermatol. 2000; 114: 56-63Abstract Full Text Full Text PDF PubMed Scopus (194) Google Scholar). Lipases and enzymes such as glucosylcerebrosidases (Takagi et al., 1999Takagi Y. Krienhuber E. Imokawa G. Elias P.M. Holleran W.M. Beta-glucocerebrosidase activity in mammalian stratum corneum.J Lipid Res. 1999; 40: 861-869PubMed Google Scholar), and ceramidases (Jin et al., 1994Jin K. Higaki Y. Takagi Y. Higuchi K. Yada Y. Kawashima M. Imokawa G. Analysis of beta-glucocerebrosidase and ceramidase activities in atopic and aged dry skin.Acta Derm Venereol. 1994; 74: 337-340PubMed Google Scholar), which play a significant part in epidermal homeostasis and barrier function, are also influenced by pH level (Freinkel and Aso, 1969Freinkel R. Aso K. Esterification of cholesterol in the skin.J Invest Dermatol. 1969; 52: 148-154Abstract Full Text PDF PubMed Scopus (14) Google Scholar; Törmä and Vahlquist, 1990Törmä H. Vahlquist A. Vitamin A esterification in human epidermis: a relation to keratinocyte differentiation.J Invest Dermatol. 1990; 94: 132-138Crossref PubMed Scopus (47) Google Scholar). The activity of transglutaminase, which catalyzes the cross-linking of cell envelope precursor protein (Nemes and Steinert, 1999Nemes Z. Steinert P.M. Bricks and mortar of the epidermal barrier.Exp Mol Med. 1999; 31: 5-19Crossref PubMed Scopus (414) Google Scholar), and the attachment of hydroxyceramides to cell envelope (Nemes et al., 1999Nemes Z. Marekov L.N. Fesus L. Steinert P.M. A novel function for transglutaminase 1: attachment of long chain omega-hydroxyceramides to involucrin by ester bond formation.Proc Natl Acad Sci USA. 1999; 96: 8402-8407Crossref PubMed Scopus (207) Google Scholar), was also shown to be pH dependent, and transglutaminase activation requires an hydrolase activity. Recently,Redoules et al., 1999Redoules D. Tarroux R. Assalit M.F. Peri J.J. Characterisation and assay of five enzymatic activities in the stratum corneum using tape-strippings.Skin Pharmacol Appl Skin Physiol. 1999; 12: 182-192Crossref PubMed Scopus (59) Google Scholar have confirmed the presence of five enzymatic activities in the stratum corneum that are involved in the edification of the skin barrier, and suggested that these activities were controlled by pH. Despite the number of studies reported in this field (Jolly et al., 1961Jolly H.W. Hailey C.W. Netick J. pH determination of the skin.J Invest Dermatol. 1961; 36: 305-308Abstract Full Text PDF PubMed Scopus (17) Google Scholar; Turek and Dikstein, 1985Turek B.A. Dikstein S. Skin pH. Workshop report from the 4th International Symposium on Bioengineering and the Skin.Bioeng Skin. 1985; 1: 57-58Google Scholar; Dikstein and Zlotogorski, 1994Dikstein S. Zlotogorski A. Measurement of skin pH.Acta Derm Venereol (Stockh). 1994; 185: 18-20Google Scholar), the origin of acidity of human outer epidermal layers is still under debate. It was recently suggested (Öhman and Vahlquist, 1998Öhman H. Vahlquist A. The pH gradient over the stratum corneum differs in X-linked recessive and autosomal dominant ichthyosis: a clue to the molecular origin of the ‘‘acid skin mantle’'.J Invest Dermatol. 1998; 111: 674-677Crossref PubMed Scopus (142) Google Scholar) that the ‘‘acid mantle of the skin’' was the result of a combined effect of acidic excretion products from sweat and sebum, and hydrolytic products of filaggrin originating in the granular layer and further concentrated in the upper stratum corneum partly as the result of desiccation. In an attempt to test the validity of this hypothesis and obtain complementary information on the factors involved in the regulation of skin acidity, a dynamic method similar to the one previously developed (Anjo and Maibach, 1981Anjo D.M. Maibach H.I. Transepidermal chloride flux through hydrated skin: combination chloride electrode.Br J Dermatol. 1981; 105: 39-44Crossref PubMed Scopus (8) Google Scholar; Lo et al., 1990Lo J. Oriba H. Maibach H. Bailin P. Transepidermal potassium ion, chloride ion, and water flux across delipidized and cellophane tape-stripped skin.Dermatologica. 1990; 180: 66-68Crossref PubMed Scopus (26) Google Scholar) was used for measuring skin pH. A theoretical model illustrating the transport of solute through the stratum corneum has been designed to analyze and explain the data obtained. Healthy male and female volunteers aged 23–56 y, with no apparent skin disease took part in the study after giving informed consent. They were asked not to apply ointments on the skin on the day of the experiment, which was carried out at room temperature (21–22°C) and relative humidity, ≈50–60%. The inner part of the forearm was chosen considering the low density of sebaceous glands and sweat fluid in this anatomic site. Skin surface pH was measured with a combined flat membrane pH glass electrode (Metrohm, Herisau, Switzerland) connected to a SA 520 pH meter (Orion, Küsnacht, Switzerland). The tip of the electrode was moistened with 20 μl of water (Milli-Q, Millipore, Molsheim, France) and pressed firmly against the skin (inner part of forearm, 10 cm from elbow) before recording pH for 30 min. The output signal from pH meter was recorded on a Compaq 386 data system via an analogic/digital converter and a designed software (Ginkosoft data system, Ginkotek, Germering, Germany). Calibration of the system was performed before and after each experiment with two buffer solutions (pH 4.01 and 7.00, respectively). Fifteen successive tape strippings (4 cm2 area) using adhesive disks (Haas, Sumoreau, France) were performed on the same area of the inner part of volunteers forearm. Teflon cell (3 cm2 contact area with skin surface), containing 3.5 ml of water was pressed against the skin for 30 min with an adhesive tape. To determine pK value, a classical chemical approach consisting of titrating weak acids with a strong base was used. Briefly, in the case of a monoprotic acid (XH), the slope of titration curve reach a maximum when the respective amounts of acid and base are equivalent (equivalence point), i.e., when v = v* · v* value is used to determine pK from the titration curve since halfway to the equivalence point: pK = pH, when v = v*/2. After 1 h contact with skin surface, the water solution was transferred to a glass vial. The tip of the electrode was then immersed in the stirred solution. When the signal was stabilized, a 0.01 M NaOH solution was added with a Harvard 44 syringe pump (Ealing, Orsay, France) at a flow rate of 1 μl per min. Validation of the method was performed with diluted solutions of pure acids. pK values obtained were 4.82 and 6.10 for acetic acid and trans-urocanic acid (trans-UA), respectively, which is in agreement with reported values (pK = 4.76 for acetic acid;Lide, 1999Lide D.R. CRC Handbook of Chemistry and Physics. ed. CRC Press, London1999Google Scholar) and 6.1 for trans-UA,Roberts et al., 1982Roberts J.D. Yu C. Flanagan C. Birdseye T. RA nitrogen-15 nuclear magnetic resonance study of the acid-base and tautomeric equilibria of 4-substitued imidazoles and its relevance to the catalytic mechanism of α-lytic protease.J Am Chem Soc. 1982; 104: 3945-3949Crossref Scopus (68) Google Scholar). The amount of UA was estimated using high-performance liquid chromatographic system consisting of a 400 solvent delivery system (Applied Biosystem, Ramsey, NJ), a Gina 160 autosampler (Ginkotek), a UVD 320 photodiode array detector (Ginkotek) and a DESKpro 386/25M Compaq data system. The column was a 100 × 30 mm ID glass column packed with 5 μm Hypersil APS (Chrompack, Middleburg, The Netherlands). The mobile phase consisted of a phosphate buffer (1 mM) adjusted to pH 5 with a flow rate of 0.5 ml per min. Calibration of the analytical system and recovery studies was performed with pure compounds; mean recovery was 98 ± 3% and the limit of detection was 3 nM (i.e., 60 fmol injected) for both isomers. To quantify the amount of UA present in a tape stripping, the sample was placed into a screw-capped glass tube containing 2 ml of 0.1 M NaOH for 2 min. The tape stripping was thereafter removed and orthophosphoric acid was added to adjust pH to 5. Before analysis, the solution was filtered through a 0.22 μm Millex-GV membrane filter (Millipore, Bedford, MA). In order to interpret data quantitatively, we used theoretical model software previously developed to describe interactions between UA and stratum corneum (Krien and Moyal, 1994Krien P.M. Moyal D. Sunscreens with broad-spectrum absorption decrease the trans to cis photoisomerization of urocanic in the human stratum corneum after multiple UV light exposures.Photochem Photobiol. 1994; 60: 280-287Crossref PubMed Scopus (37) Google Scholar). In this model, the movement of particles represents the stratum corneum turnover (a homogeneous membrane with thickness, h) with a velocity v = h/θ where θ represents the turnover time (from:Rotberg et al., 1961Rotberg S. Crousne R.G. Lee J.L. Glycine C14 incorporation into the proteins of normal stratum corneum and the abnormal stratum corneum of psoriasis.J Invest Dermatol. 1961; 37: 497-505Crossref PubMed Scopus (77) Google Scholar; Weinstein and Van Scott, 1965Weinstein G.D. Van Scott E.J. Autoradiographic analysis of turnover times of normal and psoriatic epidermis.J Invest Dermatol. 1965; 45: 257-262Crossref PubMed Scopus (155) Google Scholar), θ= 13–14 d. When a solute molecule is bound within the corneocytes, it moves with the same velocity (convective transport). When this molecule is freely diffusible, it moves through the membrane according to the law of passive diffusion (Fick's law). To take account of both modes of transport, a parameter (K) representing the bound solute/free solute ratio was introduced in the model. Furthermore, solute production was assumed to occur in the deeper layers of epidermis and in the membrane. Under these conditions, the evolution of the solute (concentration, n) in the membrane is described by the equation: ∂n∂t=D′∂2n∂x2-V′∂n∂x+k(1) Where D′ represents the apparent diffusion coefficient, V′ the apparent velocity and k the rate of solute production within the membrane. Equation 1 was solved using the Cranck–Nicholson method (Crank, 1975Crank J. The Mathematics of Diffusion. Clarendon Press, Oxford1975Google Scholar) and a Compaq Deskpro data system). A Microcal Origin software (Microcal, Northampton, MA) was used to differentiate the experimental function pH (v) for the determination of v* and pK. Linear or nonlinear curve fitting parameters were also determined using this software. The diffusion lag time was discussed byBarrer, 1939Barrer R.M. Permeation, diffusion and solution of gases in organic polymers.Trans Faraday Soc. 1939; 35: 628-656Crossref Scopus (402) Google Scholar in the context of solute permeation through a membrane (stratum corneum) separating an upstream compartment (viable epidermis) containing a saturated solution and a downstream compartment (electrode compartment) that is initially free of solute. It was demonstrated that if the membrane was initially free of solute, then the lag time would be positive and reflect the characteristic time required for solute to permeate the membrane. In this case, lag time (Lt1) depends on the thickness of the membrane (h) and the diffusion coefficient of solute (D) through the membrane according to the equation: Lt1=h2/6.D(2) Another situation is when membrane initially is at equilibrium with the upstream solution. In this case a ‘‘rush’' of solute flow into the downstream compartment and a negative lag time is observed (Barrer, 1939Barrer R.M. Permeation, diffusion and solution of gases in organic polymers.Trans Faraday Soc. 1939; 35: 628-656Crossref Scopus (402) Google Scholar; Siegel, 1986Siegel R.A.A. Laplace transform technique for calculing diffusion time lags.J Membrane Sci. 1986; 26: 251-262Crossref Scopus (30) Google Scholar): Lt=-h2/3D(3) Equation 3 was used to determine the apparent diffusion coefficient, assuming a 13 μm thickness for stratum corneum (Scheuplein, 1967Scheuplein R.J. Mechanism of percutaneous absorption. II Transient diffusion and the relative importance of various routes of skin penetration.J Invest Dermatol. 1967; 48: 79-88Abstract Full Text PDF PubMed Scopus (393) Google Scholar; Corcuff et al., 1993Corcuff P. Bertrand C. Leveque J.L. Morphometry of human epidermis in vivo by real-time confocal microscopy.Arch Dermatol Res. 1993; 285: 475-481Crossref PubMed Scopus (115) Google Scholar; Schwindt et al., 1998Schwindt D.A. Wilhelm K.P. Maibach H.I. Water diffusion characteristics of human stratum corneum at different anatomic sites in vivo.J Invest Dermatol. 1998; 111: 385-389Crossref PubMed Scopus (100) Google Scholar). When a water solution contains monoprotic acids, pH value can be calculated when ionization constants (ki) and concentrations (ci) are known, as: pHc=-log(Hc+)=-12⋅log[∑i=1n(ki⋅ci)](4) When water solution contains a single proton donor, Eqn 4 takes a simplified form: pHc=12⋅[pk-log(C)](5) These equations are used to compare the measured and calculated (predicted) pH values. When the tip of the electrode was in contact with a cellulose filter paper wetted with a pH ≈5 solution, pH values remained quasi-stable for hours. Such stability was no longer observed when the electrode was placed in contact with the skin surface. In this situation, the proton concentration in the electrode compartment increased to reach a linear asymptote after few minutes of contact time as shown in Figure 1. Similar evolution was observed in all the volunteers (n = 12). The slope of the linear asymptote (proton concentration increase) and the intersection of the time axis with the asymptote (lag time) were calculated using a linear regression, and summarized in Table 1. The only differences observed concerned time delay for signals to reach the asymptote (from 2 to 10 min) and the slope of asymptote (from 1.25 × 10-8 to 23 × 10-8 N per min). To test the reproducibility of the observed phenomenon, triplicate experi-ments were performed on volunteers 3 and 7. No consistent difference was observed between the different slope values obtained for a given volunteer. We also noticed that rinsing the skin surface with tap water or the use of a cleansing agent did not significantly modify the slope value. Only the initial pH value was sensitive to these treatments. We concluded that the phenomenon observed was not due to some artifactual exchange between electrode and the surrounding atmosphere, but to a proton donor transfer from the stratum corneum to the electrode compartment. This is the reason why the term ‘‘proton donor flux’' is thereafter used instead of ‘‘proton concentration increase’'. To get complementary information about the molecular species involved in the process, we estimated the apparent diffusion coefficient using lag times values and Eqn 3. No consistent difference was observed between the calculated value (mean ± SD; 9.68 ± 9.06 × 10-14 m2 per s; n = 12) and mean diffusion coefficient value (D ≈4.3 × 10-14 m2 per s) obtained previously when studying in vivo percutaneous absorption of different chemicals (Rougier et al., 1990Rougier A. Rallis M. Krien P. Lotte C. In vivo percutaneous absorption: a key role for stratum corneum/vehicle partitioning.Arch Dermatol Res. 1990; 282: 498-505Crossref PubMed Scopus (42) Google Scholar). This concordance means that both mechanisms occur in the same biologic matrix: stratum corneum. We therefore considered that the observation of proton donor transfer was a key field of information, giving access to possible identification of the main sources of protons in normal human stratum corneum.Table 1Evidence for the existence of a flux of protons from the skin surface to the electrode compartmentVolunteerProton concentration increaseaBest linear fit for a time of contact > 10 min. (N per min) × 108Lag time (min)bIntercept of the linear fit with the time axis.Apparent diffusion CoefficientcCalculated using lag-time values, Eqn 3, and a 13 μm thickness for stratum corneum. (m2 per s) × 101418.20-70.181.3426.04-13.816.8031.25-46.692.01410.1-5.0618.5658.03-4.6520.1964.70-2.9631.7278.30-18.485.0884.12-22.844.1196.20-13.766.82105.0-13.516.951118.5-14.086.67128.80-16.015.86Mean7.44-20.179.68SD4.3-19.459.06a Best linear fit for a time of contact > 10 min.b Intercept of the linear fit with the time axis.c Calculated using lag-time values, Eqn 3, and a 13 μm thickness for stratum corneum. Open table in a new tab Seven volunteers (three male and four female) participated in the study. pH was measured after few minutes of contact of the electrode with skin surface before any, and after 15 successive tape strippings on the same area of the skin. Data analysis (Figure 2) distinguished three groups of response related to the initial proton donor flux: Slow (< 5 × 10-8 N per min), Medium (5 × 10-8 N per min < > 16 × 10-8 N per min), and Fast (> 16 × 10-8 N per min). Partial abrasion of stratum corneum had no significant influence on the magnitude of flux for type Slow. In volunteers typed Medium, successive tape strippings induced a slight but significant decrease in flux value. The magnitude of flux decrease was much more significant for type Fast. At the limit; the flux of proton donors was almost identical for all the volunteers after 15 successive tape strippings. Two volunteers (male and female) from types Slow and Medium, respectively, were asked not to wash during two periods of 3 d each. pH was measured on the same area of forearm twice a day (Figure 3). A significant increase in the acidity of skin surface was noticed with the type Slow volunteer (R = 0.989, n = 8, p <0.0001). The slight acidification observed with the type Medium volunteer was not considered significant (R = 0.3744, n = 10, p =0.287). A new set of experiments was performed with 10 volunteers. The purpose of which was to collect proton donors in a sufficient amount to be identified. A compartment was therefore filled with distilled water (collecting chamber) and placed in contact with skin surface for 1 h. This time was considered as a best compromise in the consideration of the welfare of volunteers and the need to collect an optimal amount of proton donors as the final pH of water solution (5.53 ± 0.26; mean ± SD) was comparable with that of stratum corneum (pH 5.18) measured with a direct contact between the electrode and the surface of the forearm (Yosipovitch et al., 1998Yosipovitch G. Xiong G.L. Haus E. Sackett-Lundeen L. Ashkenazi I. Maibach H.I. Time-dependent variations of the skin barrier function in humans: transepidermal water loss, stratum corneum hydration, skin surface pH, and skin temperature.J Invest Dermatol. 1998; 110: 20-23Crossref PubMed Scopus (210) Google Scholar). Titration curves being less ‘‘noisy’' than expected, no major difficulties were encountered when determining pK. A typical titration curve and its first derivative are shown in Figure 4. The shape of the derivative was almost the same for all the volunteers, and was indicative of a broad single peak that suggested either the contribution of a unique proton donor or contribution of different proton donors, which have an almost identical pK. From data reported in Table 2, because the experimental pK value (6.13 ± 0.07 mean ± SD) corresponded to the second ionization and deprotonation of the trans-UA imidazole ring (pKa2 = 6.1) (Roberts et al., 1982Roberts J.D. Yu C. Flanagan C. Birdseye T. RA nitrogen-15 nuclear magnetic resonance study of the acid-base and tautomeric equilibria of 4-substitued imidazoles and its relevance to the catalytic mechanism of α-lytic protease.J Am Chem Soc. 1982; 104: 3945-3949Crossref Scopus (68) Google Scholar), we decided to focus on UA isomers, which were isolated and their amount estimated. Finally, as the relative amount of cis-UA was less than 1%, contribution of trans-UA only was taken into account to calculate pH using Eqn 5. All the data obtained are summarized in Table 2. Using a linear regression, an unexpected but significant correlation between measured and calculated pH was observed. Best adjustment of data was obtained when neglecting deprotonation of carboxylic group. Paired t-test indicated that at 0.01 level, the two means were not significantly different: t = 0.435, p =0.674.Table 2Determination of the contribution of UA on the pH of water after 30 min of contact with skin surface (see text for details)VolunteerMeasured pKa2trans-UA (M) × 106Calculated pH 2apH2 was calculated taking into account the two ionization constants for UA according to the following equations: H = k2 + [- k1 + (k12 + 4 k1 C)1/2]/2. k1 = 10-4 (first ionization constant) and the experimental values for ka2 and C (UA concentration).Calculated pH 1bpH1 was calculated when neglecting the first ionization constant, i.e., using Eqn 5 and experimental values for pKa2 and UA concentration.Measured pHRelative difference (%)cRelative difference = 100* (calculated pH 1 - measured)/measured.136.1845.355.795.81-0.36146.10154.855.465.254.04156.13204.755.415.48-1.20166.161.85.615.955.930.38176.182.275.545.915.615.38186.1128.74.625.325.35-0.56196.279.445.045.655.87-3.75206.09344.565.285.221.14216.0229.64.615.275.29-0.30226.0312.04.935.485.51-0.63Mean6.1315.74.995.555.530.41SD0.0711.90.390.260.262.61a pH2 was calculated taking into account the two ionization constants for UA according to the following equations: H = k2 + [- k1 + (k12 + 4 k1 C)1/2]/2. k1 = 10-4 (first ionization constant) and the experimental values for ka2 and C (UA concentration).b pH1 was calculated when neglecting the first ionization constant, i.e., using Eqn 5 and experimental values for pKa2 and UA concentration.c Relative difference = 100* (calculated pH 1 - measured)/measured. Open table in a new tab Although the role of trans-UA as a major proton donor in human stratum corneum was then evident, we tried to detect whether other proton donors may also play a significant part in the acidity of normal skin. The response was achieved using Eqn 5 to fit the data under a simplified form: pHm=-12log[A+(kua⋅cua)](5) where A, the variable parameter to be determined, represents the contribution of proton donors different from UA, kua and cua represent the ionization constant and concentration for UA, respectively. From the fit, the parameter A value is not significantly different from zero (A = 4.9 ± 9.4 × 10-13). It was thus possible to confirm that UA appears to be governing the process. Seventeen volunteers (eight male and nine female) participated in the study of pH gradient in stratum corneum (with one volunteer of each type Slow, Medium, and Fast). Skin surface pH was recorded before and after five to 20 successive tape strippings on the same area of the inner part of forearm. Figure 5 shows that the three types are clearly different. The more acidic skin surface (pH 4.4) was observed in type Fast (six males). This value did not vary significantly with tape strip number (R = - 0.09812, n = 5, p =0.8753). A more neutral skin surface (mean pH 5.27) was observed in type Medium (seven females) and Slow (two males). A significant decrease in pH value (an increase in proton concentration) with tape strip number was also observed in these two types (R > 0.975, n = 5, p <0.0035). We also observed (data not shown) that pH increases in all the volunteers when the tape strip numbers exceed ≈50 as previously observed by others (Öhman and Vahlquist, 1994Öhman H. Vahlquist A. In vivo studies concerning a pH gradient in human stratum corneum and upper epidermis.Acta Derm Venereol (Stockh). 1994; 74: 375-379PubMed Google Scholar; Öhman and Vahlquist, 1998Öhman H. Vahlquist A. The pH gradient over the stratum corneum differs in X-linked recessive and autosomal dominant ichthyosis: a clue to the molecular origin of the ‘‘acid skin mantle’'.J Invest Dermatol. 1998; 111: 674-677Crossref PubMed Scopus (142) Google Scholar) in human skin. Similar type distribution (groups 1 and 2) was observed with UA content in 10 successive tape strips (Figure 6). A significant increase in the amount of UA collected (R = 0.9912, n = 5, p <0.001) was observed with volunteers from group 2 (four of six volunteers) only. Comparison between Figure 5 and 6 strengthens the validity of our hypothesis concerning the role of UA in the acidity of the stratum corneum. Table 3 summarizes the different factors (surface pH, pH gradient, and rate of production) characterizing each of the three types of skin observed.Table 3Summary of the characteristics of three groups evidencedGroupSkin surface pHProton donor flux (magnitude)Influence of tape-stripping on fluxpH gradient in the outer layers of the stratum corneumTime required to reach equilibrium after cleansingSlow> 5.5SlowNo significant decreaseStatistically significant≥ 3 dMedium[5–5.5]MediumSlight decreaseStatistically significant< 10 hFast[4.3–4.5]FastHigh decreaseNo significantNot determined Open table in a new tab The validity of the term ‘‘acid mantle’' of human skin has been discussed byÖhman and Vahlquist, 1994Öhman H. Vahlquist A. In vivo studies concerning a pH gradient in human stratum corneum and upper epidermis.Acta Derm Venereol (Stockh). 1994; 74: 375-379PubMed Google Scholar). According to the authors, this term is a misnomer because its implies something that can be readily removed from the skin: pH values are quite constant in a given individual and unaffected by delipidation with organic solvents (Lo et al., 1990Lo J. Oriba H. Maibach H. Bailin P. Transepidermal potassium ion, chloride ion, and water flux across delipidized and cellophane tape-stripped skin.Dermatologica. 1990; 180: 66-68Crossref PubMed Scopus (26) Google Scholar). The acidic level extends well below the lipid film, suggesting that compounds within the horny layer contribute to the low surface pH (Wilhelm et al., 1" @default.
• W2040459675 created "2016-06-24" @default.
• W2040459675 creator A5034226774 @default.
• W2040459675 creator A5049199894 @default.
• W2040459675 date "2000-09-01" @default.
• W2040459675 modified "2023-10-03" @default.
• W2040459675 title "Evidence for the Existence of a Self-Regulated Enzymatic Process Within the Human Stratum Corneum –An Unexpected Role for Urocanic Acid" @default.
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