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Effects of a multilamellar emulsion on glucocorticoid-induced epidermal atrophy and barrier impairment.

Skin atrophy is one of the most frequent side-effects of the topical glucocorticoid. Skin barrier impairment has also been reported as a steroid-induced side effect. Although there have been various studies on preventing or minimizing this atrophogenic effect, little has been reported about preventing barrier impairment. This study was performed to determine the effects of a multilamellar emulsion (MLE) that had a well-ordered lamellar structure on the steroid-induced barrier impairment and epidermal atrophy. To confirm these effects of MLE, 0.05% clobetasol-17-propionate (CP) and 0.05% clobetasol-17-propionate in MLE (MLE/CP) were topically applied to both flanks of hairless mice for 9 days. The topically applied CP induced a significant impairment of the epidermal permeability barrier, and MLE/CP also did not have a preventive effect on this change. However, skinfold thickness studies and histological studies showed that MLE/CP significantly reduced the steroid-induced atrophy. The topical application of MLE/CP was also shown to have a preventive effect on the steroid-induced increase of the stratum corneum (SC) surface pH. In addition, the electron microscopic findings showed relatively well-conserved lamellar bilayers in the skin treated with MLE, as compared to CP only. The results showed that the topical application of MLE immediately after CP treatment prevented the glucocorticoid-induced transepidermal water loss values increase. Light microscopy measurements showed that the skin treated with MLE immediately after CP treatment for 1 week had a slightly lower decline of skin thickness than did the CP-treated skin. These results suggest that MLE should be effective for preventing glucocorticoid-induced epidermal atrophy and for repairing the barrier impairment.

Administration, Topical↗

Skin barrier function in healthy volunteers as assessed by transepidermal water loss and vascular response to hexyl nicotinate: intra- and inter-individual variability.

This study assesses the variability of two non-invasive methods of measuring stratum corneum barrier function in vivo. Transepidermal water loss (TEWL), and the vascular response to hexyl nicotinate (HN) penetration as determined by laser-Doppler flowmetry, were measured in a group of 21 healthy volunteers. Each time profile of the vascular response to HN penetration was analysed using the following parameters: the baseline cutaneous blood flow, the lag-time between application and initial response (t0), the time between application and maximum response (tmax), the maximum response, and the slope of the curve. TEWL measured on the left volar forearm showed a normal range of 3.9-7.6 g/m2h and a small inter-individual variability [coefficient of variation (CV) 19.4%]. TEWL values at three other forearm sites did not show differences of clinical importance compared with the left volar forearm. The parameters of the vascular response to HN penetration spanned a wider normal range than the TEWL values (CV between 33 and 52%). Repeat measurements after a 1-2 month interval showed highly reproducible individual TEWL values. The mean difference between first and second measurements was only 0.03 g/m2h; the relative difference 0.6%. The intra-individual reproducibility of t0 and tmax. for HN penetration was also high (relative differences of 2.8 and 3.1%, respectively). The other vascular response parameters were less reproducible (relative differences of 6.9-18.6%). We conclude that TEWL and selected parameters of HN penetration, as non-invasive tests of the stratum corneum barrier function, yield reproducible results and are hence useful for investigations assessing the skin barrier function in various disorders.

Adolescent↗

Cutaneous barrier function after cold exposure in hairless mice: a model to demonstrate how cold interferes with barrier homeostasis among workers in the fish-processing industry.

Dry skin and eczema only seldomly occur in workers in the Danish fish-processing industry (FPI) during work, when their fingers and palms have a low skin surface temperature, low transepidermal water loss (TEWL), and a high capacitance. However, shortly after work, when the skin temperature has become normal, TEWL levels increase to above normal, and capacitance decreases to below normal, followed by the development of dry skin or chapping, which subsequently revert to normal over a period of hours. These observations suggest that workers in the FPI may have a defect in skin barrier function, which is, however, masked by a low skin temperature, resulting in misleadingly low TEWL levels during work. To test this hypothesis, we disrupted the permeability barrier in hairless mice with topical acetone, and exposed the treated skin to ice for 3.5 h. Although TEWL rates immediately after cold exposure were low, suggesting normal barrier recovery, TEWL increased to levels slightly above pre-cold exposure levels (i.e. levels just after the barrier was disrupted with acetone) when the skin temperature reverted to normal (> or = 15 min). The changes in TEWL were paralleled by equivalent changes in percutaneous penetration of the electron-dense tracer lanthanum nitrate. This indicates that cold masks a defective barrier, and inhibits barrier repair. After a few hours at ambient temperatures, normal barrier recovery was observed. Electron microscopy revealed empty or partially empty lamellar bodies during the first 30 min post-cold exposure. After 1 h the majority of nascent LBs displayed normal morphology. Moreover, histochemical studies showed a delayed reappearance of stratum corneum intercellular lipids following cold exposure. These results demonstrate that cold exposure prevents barrier recovery after acetone disruption, and provide an explanation for the occupational dermatosis observed in the fish-processing industry and related occupations.

Acetone↗

Experimental irritant contact dermatitis due to cumulative epicutaneous exposure to sodium lauryl sulphate and toluene: single and concurrent application.

In clinical practice, cutaneous exposure to a variety of irritants such as surfactants and solvents is frequent. Although the induction of irritant dermatitis by single irritants has been extensively studied in recent years, our knowledge of the effects of simultaneous application of different irritants is limited. Using non-invasive techniques for measurements of transepidermal water loss (TEWL) and skin colour reflectance, we quantified the irritant effects of single and concurrent application of 0.5% sodium lauryl sulphate (SLS) and undiluted toluene (TOL) in vivo. The irritants were applied twice daily for 30 min to the volar forearms of 20 volunteers. Repeated application of SLS and TOL induced an irritant reaction, as indicated by an increase in TEWL and skin redness. In contrast to SLS alone, the application of TOL alone induced only a moderate increase in TEWL, confirming previous results. Concurrent application of SLS/TOL and TOL/SLS induced significantly stronger reactions than those caused by twice daily application of each irritant on its own. Our results demonstrate that a mixed application of an anionic detergent and an organic solvent has an additive effect on skin irritation. It is suggested that pretreatment with SLS causes an increased susceptibility to TOL irritation and vice versa. Thus, the necessity for special precautions against skin absorption of TOL when handling detergents such as SLS is emphasized.

Administration, Cutaneous↗

Stratum corneum adhesive tape stripping: influence of anatomical site, application pressure, duration and removal.

BACKGROUND: Tape stripping is a common method for investigating stratum corneum (SC) physiology as well as bioavailability and bioequivalence of topical drugs. OBJECTIVES: To investigate the influence of procedures (anatomical site, pressure, pressure duration, tape removal rate) inherent in each stripping protocol on changes in skin physiology. METHODS: Tape stripping was performed using tapes on the forearm, forehead and back. On the forearm different pressures (165 and 330 g cm(-2)), durations of pressure (2 and 10 s), and removal rate (slow and rapid removal) were used. Changes in skin physiology were evaluated by measurement of transepidermal water loss (TEWL) and hydration. RESULTS: A significant influence of all parameters on the TEWL increase as a function of tape strip number was observed. The fastest increase was demonstrated on the forehead, followed by the back and, lastly, the forearm. Rapid removal produced a protracted increase in comparison with slow removal. Pressure for 10 s induced a faster increase in TEWL than 2 s pressure. Likewise, pressure at 330 g cm(-2) induced an earlier increase than pressure at 165 g cm(-2). Skin hydration was not influenced by the variables tested. CONCLUSIONS: Tape stripping results are influenced dramatically by all investigated parameters. A dynamic SC stress test to investigate SC cohesion more closely is proposed based on the present observations.

Adhesives↗

Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study.

BACKGROUND: For many years topical progesterone has been prescribed by gynaecologists as an antiageing and skin-firming treatment, without any clinical scientific evidence of its effects, tolerability and safety when applied to skin. OBJECTIVES: To evaluate the influence of 2% progesterone cream on function and texture of the skin in peri- and postmenopausal women. METHODS: A double-blind, randomized, vehicle-controlled study was conducted in 40 subjects. Objective methods for measuring skin elasticity, epidermal hydration and skin surface lipids, clinical monitoring and self-assessment, and determination of blood hormone levels (luteinizing hormone, follicle-stimulating hormone, oestrogen and progesterone) were used to determine effects and side-effects of this treatment at four visits over a 16-week period. RESULTS: The study demonstrated a significant (P < or = 0.05) increase of the elastic skin properties in the treatment group, as demonstrated by objective measurements of three skin elasticity parameters, whereas in the control group no such effect was observed. This effect in the treatment group was further paralleled by the results of the clinical monitoring, where the 2% progesterone cream yielded consistent superiority over vehicle in counteracting different signs of ageing in the skin of peri- and postmenopausal women. Clinical monitoring showed a greater reduction in wrinkle counts (29.10% vs. 16.50%) and wrinkle depth (9.72% vs. 7.35%) around the right eye, a greater decrease in nasolabial wrinkle depth (9.72% vs. 6.62%) and a significantly higher (P < 0.05) increase in skin firmness (23.61% vs. 13.24%) in the treatment group. Epidermal hydration and skin surface lipids did not change significantly in either group during the study. Progesterone was well absorbed in the systemic circulation: mean blood levels rose minimally, but statistically significantly (P = 0.001), by 0.53 ng mL(-1). No serious side-effects of the treatment were observed. CONCLUSIONS: The results of this study demonstrate that topical 2% progesterone acts primarily in increasing elasticity and firmness in the skin of peri- and postmenopausal women. These effects in combination with good tolerability make progesterone a possible treatment agent for slowing down the ageing process of female skin after onset of the menopause.

Double-Blind Method↗

Variation in barrier impairment and inflammation of human skin as determined by sodium lauryl sulphate penetration rate.

BACKGROUND: Skin irritability after a brief exposure to the model skin irritant, sodium lauryl sulphate (SLS), is known to vary considerably between individuals. A difference in the skin barrier to SLS may contribute to this variation. To date, no human in vivo data have been available on SLS penetration into the skin. OBJECTIVES: We studied whether the SLS penetration rate into the stratum corneum (SC) is related to impairment of the water barrier function and inflammation of the skin. METHODS: The penetration of SLS into the SC was assessed using a noninvasive tape-stripping procedure in 20 volunteers after a 4-h exposure to 1% SLS. Additionally, the effect of a 24-h exposure to 1% SLS on the skin water barrier function was assessed by measuring the transepidermal water loss (TEWL). The accompanying inflammation was quantified by measuring erythema. RESULTS: The mean +/- SD diffusivity of SLS (D) and the SLS permeability coefficient (Kp) were 1.4 +/- 0.6 x 10(-8) cm2 h(-1) and 1.5 +/- 0.7 x 10(-3) cm h(-1), respectively. A multiple regression analysis showed that the baseline TEWL, SC thickness and SLS penetration parameters K (SC/water partition coefficient) and D clearly influenced the increase in TEWL after the 24-h irritation test (explained variance: r2 = 0.80). Change in erythema was mainly influenced by SC thickness. CONCLUSIONS: We found that variation in the barrier impairment and inflammation of human skin depends on the SLS penetration rate, which was mainly determined by SC thickness.

Adolescent↗

Skin pharmacokinetics.

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Administration, Cutaneous↗

Liposomes.

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Antineoplastic Agents↗