Assessment of the water content of the stratum corneum using a sorption-desorption test.

BACKGROUND/AIM: Various instruments based on electrical properties of the skin are currently used to assess the stratum corneum (SC) hydration state or water holding capacity. However, no direct relation with the quantity of water measured is provided. The objective of the present study was to calibrate the Corneometer, a device displaying electrical-capacitance-related values (which reflect the skin hydration state), and the amount and behaviour of the water taken up by the outer part of the SC during a sorption-desorption test. METHODS: The experiment was performed on the ventral forearms of 20 healthy volunteers after a rest in an environmentally controlled room. Corneometer and transepidermal water loss (TEWL) values were measured at intervals over the desorption process. The areas under the TEWL-versus-time curve provided the absolute amounts of residual sorbed water. RESULTS: The decrease kinetics of both signals after subtraction of prehydration values were very similar and bi-exponential, both showing a rapid, then a slower phase. The absolute amount of water taken up by the SC (hygroscopicity) and the two desorption rates were obtained. The Corneometer values were mono-exponentially related to the amount of water remaining within the SC. This allowed the in vivo calibration of the Corneometer in terms of absolute amount of water over the desorption range. CONCLUSION: The method may be used to calibrate in vivo other electrical devices aimed at assessing SC hydration during a sorption-desorption test. It may also provide new ways to measure SC water uptake and water holding capacity following application of products.

A new method to measure in vivo human skin hydrophobia.

Until now, the wettability of the skin has been only estimated through the measurement of its critical surface tension (Zisman), or surface free energy. These methods give information on the behaviour of the surface with water, but cannot quantify its behaviour with other polar liquids. In this paper we propose to express both the hydrophilia of the skin (Hi) by the ratio of its critical surface tension (gamma(c)) to the water surface tension (gamma(H(2)O)), and its hydrophobia (Ho) by the ratio of the difference between the critical surface tension (gamma(c)), and the value of the water surface tension (gamma(H(2)O)) normalized by the latter. By using this proposed parameter, it should be possible to classify skin surfaces according to their affinities to water, which is of major importance in Cosmetology as well as in biology. We also discuss the relationship between surface hydrophilia (Hi) and polarity (P) as defined by Wu, and water adhesion tension (tau(o)) as described by Vogler. The gamma(c) of untreated skin was 27.3 +/- 3.6 mJ m(-2), confirming previous data, and consequently basal Hi was 38%. Either cleaning with ether or hydration by occlusion induced a diminution of the wetting capacity of the surface and consequently a decrease of Hi to 29% and 33%, respectively. In contrast, washing the skin surface with soap and water increased surface Hi to 43%.

Isotretinoin improves the appearance of photodamaged skin: results of a 36-week, multicenter, double-blind, placebo-controlled trial.

Photodamaged skin occurs as a result of long-term exposure to ultraviolet radiation. The incidence of photodamage in European and North American populations with Fitzpatrick skin types I, II, and III is estimated at 80% to 90%. We conducted a double-blind clinical trial to test the efficacy and safety of 0.1% isotretinoin versus vehicle cream in 800 patients with moderate to severe photodamaged skin. Patients applied either 0.1% isotretinoin or matching vehicle cream to the face, forearms, and hands once nightly for 36 weeks. Local irritation and adverse events were assessed, and plasma retinoid levels were measured before and during treatment. Treatment response increased throughout the 36-week treatment period and the overall appearance of photodamaged skin was significantly better than with the vehicle alone. Topical application of 0.1% isotretinoin is an effective and well-tolerated treatment leading to clinically apparent improvement in the appearance of photodamaged skin of the face, forearms, and hands.

Inhibition of caffeine metabolism by 5-methoxypsoralen in patients with psoriasis.

Eight patients with psoriasis were given 200 mg caffeine orally with or without 1.2 mg kg-1 of 5-methoxypsoralen. Blood and urine samples were collected over a 2-day period. During 5-methoxypsoralen coadministration, the apparent volume of distribution of caffeine remained unchanged, but oral clearance (CLp.o.) decreased from 9.5 +/- 3.8 (mean +/- s.d.) to 3.2 +/- 0.51 h-1 (P < 0.01). The area under the plasma concentration-time curve (AUC) increased from 24 +/- 9 to 73 +/- 29 mg 1(-1) h (P < 0.001). This decrease in CLp.o. with increased AUC was consistent with a CYP1A2-dependent inhibition of caffeine N-demethylation which was further supported by significant decreases in the (AFMU+1U+1X)/17U and (AFMU+1U+1X)/17X urinary metabolic ratios.

Simultaneous absorption of copper and zinc through human skin in vitro: influence of counter-ion and vehicle.

Copper and zinc percutaneous absorptions were assessed in vitro using sliced human skin and both petrolatum and hydrophilic gels as vehicles. Applied quantities were largely in excess for the duration of the experiment (72 h). The absorption of sulphates and chlorides was compared. The cumulated amount recovered in receptor fluid was below 50 micrograms/cm2. The apparent permeability constant values kept in the range of 10(-6) cm h-1, except for ZnCl2 in gel vehicle (2.9 10(-5) cm h-1). With the exception of CuCl2 in gel vehicle, chlorides gave higher absorption rates than sulphates. This can be related to the higher octanol-water partition coefficient of chlorides. Storage within the epidermis was found to be equal to or greater than, and within the dermis equal to or lower than the 72 hour cumulative amount in receptor fluid. No difference was found in this respect between copper an d zinc. This work confirms the poor absorption of electrolytes through normal human skin, whatever the vehicle used.

Skin critical surface tension: A way to assess the skin wettability quantitatively.

BACKGROUND/AIMS: Surface energy phenomena result from molecular interaction between substances. On the skin, they are involved in sweat and sebum dispersion, and in foreign substances, in spreading and absorption. However, they are unknown due to the scarce number of studies. The aim of this work was to find the skin critical surface tension (CST), an index of wettability, through a reliable technique, and to study the influence of skin lipid and of some oil-in-water (O/W) and water-in-oil (W/O) preparations. METHOD: The CST was calculated using the Zisman equation, from the contact angle at equilibrium, of droplets of liquids whose surface tension was known. Contact angles were computed from the base and the height of the droplets viewed from their side through an operating microscope provided with a slanted mirror. Both volar forearm and forehead were studied. RESULTS: On volar forearm, the skin CST was 27.5±2.4 dyne/cm (n=12) and normally distributed. Forehead CST was above 50.7 dyne/cm. On both areas, defatting with ether reduced CST down to 21.6±2.6 dyne/cm, and 29.3±1.7 dyne/cm, respectively (p<0.001). Washing with soap reduced forearm CST down to 23.7±1.0 dyne/cm (p<0.01), and occlusion down to 21.6±3.4 dyne/cm (p<0.001). O/W cream application strongly decreased both forearm and glass slide CST, whereas W/O cream application either raised CST or left it unchanged; in all cases, changes were less marked on skin than on glass. CONCLUSION: These data demonstrate that the skin surface is primarily hydrophobic and paradoxically becomes more wettable through its lipidic component, especially the sebum. Emulsions seemed to interact with the skin and change its CST as would do their continuous phase only.

Effect of a conjugated oestrogen (Premarin) cream on ageing facial skin. A comparative study with a placebo cream.

The effects of Premarin cream on ageing facial skin were studied in a randomised, double-blind, parallel group study. Fifty-four women aged 52-70 years who had moderate to severe facial cutaneous ageing, applied 1 g of either Premarin cream (0.625 mg conjugated oestrogens per gram of cream), or placebo cream (same composition with the exclusion of conjugated oestrogens) to the face nightly for 24 weeks. Each morning these women protected their face with a sunblock SPF 15. Skin thickness was measured by B-scan ultrasonic echography, and skin microrelief by profilometry. Each subject's facial appearance was also evaluated by the subject herself and by the clinician. A statistically significant difference (P = 0.013) in favour of Premarin cream was detected in skin thickness at week 24. Skin thickness (dermal plus epidermal) for the women who used Premarin cream increased from 1.56 +/- 0.20 mm at baseline to 1.68 +/- 0.19 mm, compared with 1.52 +/- 0.20 mm at baseline to 1.59 +/- 0.19 mm in the placebo group. Premarin cream was also significantly more effective than placebo cream in improving fine wrinkles according to the results at weeks 12 and 24 (P = 0.010 and P = 0.012, respectively). Significant improvement from baseline was detected in both groups for roughness, laxity and mottled pigmentation and/or lentigines; however, there was no significant difference in these parameters between the two treatment groups. No subjects discontinued treatment for a safety reason. In conclusion, Premarin cream produced better results than the placebo cream; the difference was statistically significant for skin thickness and fine wrinkles. Premarin cream was well tolerated locally, and its general safety was good.

Effects of a new psoralen, 5-geranoxypsoralen, plus UVA radiation on murine ATPase positive Langerhans cells.

5-geranoxypsoralen (5-GOP), commonly called bergamottin, is a highly photoreactive psoralen, which in contrast to most furocoumarins, does not strongly interact with DNA. 5-GOP gives the opportunity to study, in a more selective way, the mechanisms of phototoxic and immunological activities induced by psoralen and UVA radiation. We investigated the effects of repetitive treatments with 5-GOP plus UVA radiation (320-400 nm) on the number of ATPase+ epidermal Langerhans cells and on the induction of photoreactivity. These effects were compared with those of 8-methoxypsoralen (8-MOP) or 5-methoxypsoralen (5-MOP) plus UVA radiation and UVA radiation alone. C3H/HeN mice were treated topically with the psoralen three times/week for 4 consecutive weeks followed each time by 1 J/cm2 of UVA radiation. At the end of the treatment, mice treated with 8-MOP or 5-MOP plus UVA radiation exhibited severe gross phototoxicity and nearly total depletion of ATPase-stained Langerhans cells. Both treatments produced severe morphological alterations of Langerhans cells. No gross but a microscopic phototoxic effect was observed after 5-GOP plus UVA radiation treatment, while the number of ATPase+ Langerhans cells was also greatly reduced. Interestingly the latter treatment induced no morphological alterations of the remaining Langerhans cells in contrast to treatment with 8-MOP or 5-MOP plus UVA radiation. We conclude that phototoxicity and decrease in the number of ATPase-stained epidermal immune cells observed after treatment with 5-GOP plus UVA radiation are not related to the DNA binding activity of the psoralen.(ABSTRACT TRUNCATED AT 250 WORDS)

Hydration, transepidermal water loss, pH and skin surface parameters: correlations and variations between dominant and non-dominant forearms.

The aim of this study was to examine differences between the skin of both forearms with regard to several parameters: hydration (skin capacitance), transepidermal water loss (TEWL), pH and skin surface parameters. Possible correlations between measurements were investigated. Thirty-three healthy women (32.6 +/- 8.4 years) participated in the study. The different parameters were measured on each volar forearm (dominant and non-dominant) at precisely delineated sites. TEWL and developed length (DL) were significantly increased on the dominant forearm (P < 0.001 and P < 0.01, respectively). In addition, a correlation matrix was calculated with the differences between dominant and non-dominant forearms for all the parameters measured. Only the skin surface parameters were found to be interrelated with this statistical approach. These data confirm that randomization between forearms is essential in the design of a reliable experimental plan, and indicate the lack of relationship between these measurements as assessed in a group of healthy young women.

Treatment of psoriasis with a new micronized 5-methoxypsoralen tablet and UVA radiation.

Since 1974, phototherapy with psoralen and ultraviolet A (UVA) has been used successfully for the treatment of psoriasis. However, undesirable side effects, including phototoxicity, nausea, stomach pain and headaches, have led investigators to develop new psoralen compounds. 5-Methoxypsoralen (5-MOP) has thus been introduced as an alternative to 8-MOP because of its less pronounced side effects. Since the absorption kinetics and bioactivity of 5-MOP are known to be variable, a new micronized tablet form (5-MOPm) has been developed. In an open randomized study, oral treatments with 5-MOP or 5-MOPm plus UVA radiation were compared in 22 psoriatic patients. Skin type and initial psoriasis area severity index did not differ significantly between treatment groups. Serum concentrations were significantly higher (320 vs 85.82 ng/ml) and occurred earlier (51.8 vs 229.09 min) with 5-MOPm. In addition, a reduction in PASI of more than 90% was achieved sooner (10.63 vs 17.27 treatments) and with a lower cumulative UVA dose (145.89 vs 232.11 J/cm2), in the group treated with 5-MOPm. No side effects were observed with 5-MOPm. Our data indicate that 5-MOPm has a higher bioavailability, clinical efficacy and tolerability than the commonly used 5-MOP.

Treatment of scleroderma with oral 1,25-dihydroxyvitamin D3: evaluation of skin involvement using non-invasive techniques. Results of an open prospective trial.

1,25-dihydroxycholecalciferol (1,25 (OH)2 D3) causes dose-dependent inhibition of fibroblast growth and collagen synthesis and has numerous immunoregulatory activities. We assessed the effects of oral 1,25 (OH)2 D3 in the treatment of patients with systemic sclerosis (SS). Eleven patients with SS entered an open prospective study. Oral 1,25(OH)2 D3 was given at a mean dose of 1.75 micrograms/day. The effects of the treatment were evaluated using clinical examination and physical measurements. After the treatment period (6 months to 3 years), a significant improvement, as compared with baseline values, was observed. No serious side-effects were observed. These results suggest that high-dose 1,25 (OH)2 D3 may be a useful therapeutic agent for scleroderma.

Surface recovery and stripping methods to quantify percutaneous absorption of caffeine in humans.

The percutaneous absorption of caffeine from two vehicles, an emulsion and an acetone solution, was quantified by in vivo techniques in humans. A surface recovery technique over a 6-h application and a stripping method after a 30-min application were performed on the volar aspect of the forearm on 12 volunteers. Caffeine was assessed by HPLC. Two phases were distinguished in the percutaneous absorption of caffeine: a higher filling up of the stratum corneum with the oil-in-water emulsion than with the acetone solution, which was then followed by a steady-state flux corresponding to the penetration in the living tissues. The permeability constants (Kp) with emulsion and acetone were 1.59 x 10(-4) and 9.53 x 10(-8) cm/h, respectively. The stripping method showed concentrations of caffeine in stratum corneum that were five times higher with emulsion (212 ng/cm2) than with acetone (37 ng/cm2). With acetone as a vehicle, approximately 40% of caffeine of the cornfield layer was found around the treated area. This sizeable lateral spread within the stratum corneum was not observed with the emulsion.

Effect of pressure on in vitro percutaneous absorption of caffeine.

The effect of increased pressure, which is a mechanical property of massage, was investigated on the percutaneous absorption of an amphiphilic compound (caffeine) in vitro on Franz diffusion cells, using excised human skin. 50 microliters of either a 320 micrograms/ml or a 15 mg/ml acetone solution of caffeine were pipetted onto the surface of each skin sample, which represented caffeine skin deposits of 5 micrograms/cm2 and 240 micrograms/cm2 respectively. During each experiment, a pressure device delivering 0.25 bar over the atmospheric pressure was applied for the first 30 min on half of the cells. At 2, 4, 6, 8, 12 and 24 h the aqueous dermal bathing solution, containing 14 g/l albumin, was removed and chromatographed. With the applied dose of 5 micrograms/cm2 no statistical difference was found between the cumulated absorbed amount under atmospheric pressure and increased pressure. On the other hand, with the applied dose of 240 micrograms/cm2, the permeation of caffeine was 1.8 times higher under increased pressure than the permeation under atmospheric pressure (p < 0.05). This enhancing effect of increased pressure was probably connected to either an improved transappendageal route during the percutaneous absorption process or a higher stratum corneum filling-up.

Binding of 5-methoxypsoralen to blood fractions. Influence of albumin and free fatty acids: an in vitro study.

The binding of 5-methoxypsoralen (5-MOP) to human serum and blood fractions was studied by equilibrium dialysis associated to high-performance liquid chromatography. 5-MOP serum binding was 95% and kept constant in the range of therapeutic concentrations. Albumin was the main binding protein with one class of binding sites (n = 2.05) and with a moderate affinity constant (Ka = 10,270 M-1). Free fatty acids (FFA) enhanced 5-MOP binding to albumin. Binding to other proteins, alpha 1-acid glycoprotein, gamma-globulins and lipoproteins (LDL, HDL, VLDL) also occurred, but was negligible. 5-MOP bound to red blood cells (RBCs) with a binding index (ratio of intra- to extra-globular 5-MOP concentrations) of 3.84 and 1.48 in buffer and plasma, respectively. 5-MOP distribution in blood was simulated. The free fraction of 5-MOP in blood could be increased in hypoalbuminemia, unchanged in acute inflammation, and decreased by FFA.