Olopatadine hydrochloride accelerates the recovery of skin barrier function in mice

BACKGROUND: The skin barrier function in patients with atopic dermatitis is disrupted and prolonged topical steroid therapy produces epidermal barrier disturbance. Olopatadine hydrochloride (olopatadine; Allelock; Kyowa Hakko Kogyo Co., Ltd, Shizuoka, Japan) is an antiallergic drug with histamine H(1) receptor antagonistic action. This drug alleviates skin inflammation and decreases the number of scratching episodes in a murine model of chronic contact dermatitis. OBJECTIVES: To investigate the effects of olopatadine and a steroid on the recovery of skin barrier function after barrier disruption in mice. METHODS: The skin barrier of the ears of mice was disrupted by tape stripping. The recovery of skin barrier function was monitored by measurement of transepidermal water loss (TEWL) after barrier disruption. Epidermal hyperplasia was induced by repeated tape stripping for 7 days. Olopatadine was administered orally once daily from 3 days before the first barrier disruption. Betamethasone 17-valerate (betamethasone) was applied topically once daily from 3 days before barrier disruption. RESULTS: Tape stripping led to a significant increase in TEWL. TEWL decreased with time after tape stripping and the skin barrier function recovered by over 60% within 9 h after tape stripping. The recovery of skin barrier in olopatadine-treated mice was significantly accelerated, compared with that in vehicle-treated mice. In contrast, the skin barrier recovery in mice treated with topical betamethasone was significantly delayed, compared with that in vehicle-treated mice. Combined treatment with olopatadine and betamethasone ameliorated the delay in barrier recovery induced by topical treatment with betamethasone. In addition, olopatadine significantly prevented the increase in epidermal thickness induced by prolonged barrier disruption. CONCLUSIONS: These results suggest that systemic administration of olopatadine accelerates the recovery of skin barrier function and ameliorates the adverse effects of topical steroids on skin barrier recovery.     

Impact of ultraviolet radiation and ozone on the transepidermal water loss as a function of skin temperature in hairless mice

Exposure to ultraviolet radiation or ozone leads to skin damage including oxidation of skin biomolecules, as well as to depletion of constitutive antioxidants. The highly organized stratum corneum forming the main barrier against most xenobiotics is particularly susceptible to such damage and possible barrier perturbation may be the consequence. Whereas ample evidence exists for an increased permeability for different solutes including water after exposure to ultraviolet radiation, such an effect has not yet been reported for ozone. This study reports on the effect of such oxidative stressors using the hairless mouse as the skin model and measuring temperature-controlled transepidermal water loss (TEWL) as an indicator for skin barrier integrity. First, a strong dependency of the TEWL on skin temperature was observed, an effect that was clearly more pronounced than that found in man. Given this temperature dependency in untreated animals, we proceeded to determine the effects of both ultraviolet radiation and ozone on TEWL over a relevant physiological skin temperature range. Solar-simulated ultraviolet radiation (0.75-3 minimal erythemal dose) resulted in a delayed and dose-dependent skin barrier disruption over the entire temperature range investigated. Conversely, daily ozone exposure at 2 ppm for 1 week, however, did not significantly alter TEWL up to 72 h after the last exposure. The results demonstrate a differential response of the epidermis to two environmental stressors associated with oxidative damage; they suggest that chronic ozone exposure at relevant environmental levels does not lead to a detectable skin barrier defect, while solar UV exposure was demonstrated to increase epidermal water loss. Furthermore, experimental evidence clearly suggests that future studies applying TEWL measurements in animal models should be performed under carefully controlled skin temperature conditions.     

Faecal enzymes: in vivo human skin irritation

Digestive enzymes in faeces have been reported to posses skin irritation potential. The present study was designed to investigate the in vivo irritant potentials of faecal concentrations of proteolytic and lipolytic digestive enzymes in bile salt mixtures. In a 21-day cumulative irritation assay, clinical evaluation and noninvasive bioengineering techniques were used. 5 days occlusive exposure to phosphate buffer (pH = 8) caused no visual skin damage but reflectance spectroscopy demonstrated significant vasodilation ( p < 0.01) and increases in transepidermal water loss (TEWL) and skin pH were also observed ( p < 0.01). These increases were still present at days 12 and 19. Occlusive exposure to physiologic concentrations of faecal enzymes resulted in significant visual and objective scores at day 5, 12, and 19, with increased readings as a function of exposure time ( p < 0.01). The enzyme mixture containing lipase caused delayed onset of skin erythema and epidermal barrier disruption compared to elastase and chymotrypsin containing solutions. Prolonged occlusive exposure to digestive enzymes in faecal concentrations caused severe skin erythema and epidermal barrier disruption in a human model, suggesting a possible etiologic role of digestive enzymes in perianal, circumstomal or diaper dermatitis.     

Improvement of skin barrier function during treatment of atopic dermatitis

Background: Active dermatitis causes a disturbance in skin barrier function. This can be evaluated by the measurement of transepidermal water loss (TEWL) and percutaneous absorption of hydrocortisone.Objective: The study objective was to evaluate changes in skin barrier function during treatment of atopic dermatitis.Methods: Nine patients with widespread atopic dermatitis were studied longitudinally by measuring the severity of the dermatitis and TEWL at intervals of 1 to 3 days. Percutaneous absorption of hydrocortisone was measured at entry and during treatment.Results: At entry, both TEWL and percutaneous absorption of hydrocortisone were elevated. Four to six days later, a significant decline was observed in both variables, indicating rapid improvement in skin barrier function. Individual changes in TEWL correlated with the changes in the systemic absorption of hydrocortisone.Conclusion: TEWL reflects changes in the systemic absorption of topical hydrocortisone during treatment of atopic dermatitis.     

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 delect 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 3–5h. 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 (≥ 15min). 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 barrierrepair. 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 occupatonal dermatosis observed in the fish-processing industry and related occupations.     

Transepidermal water loss in dry and clinically normal skin in patients with atopic dermatitis

To obtain data on the function of the epidermal barrier in patients with atopic dermatitis (AD) the transepidermal water loss (TEWL) was studied. Measurements were made on three body locations in two clinically well defined groups of patients with AD and in a control group. The TEWL was found to be increased both in dry non-eczematous skin and in clinically normal skin in patients with AD. The TEWL was highest in patients with dry skin. The result of the study may indicate a primary defect in the epidermal barrier: the stratum corneum.     

Transepidermal water loss after photodynamic therapy, UVB radiation and topical corticosteroid is independent of inflammation

Background/purpose: Photodynamic therapy (PDT) and ultraviolet radiation cause an inflammatory reaction of the skin. This may lead to disruption of the skin barrier function. We examined the acute effect of PDT and short-wave ultraviolet radiation (UVB) on the barrier function of the epidermis. Furthermore, we explored the effect on the skin barrier of topical corticosteroid previous to UVB exposure.
Methods: Eight patients with acne vulgaris of the face were treated with PDT two times, and eight patients were left untreated. The transepidermal water loss (TEWL) was measured before treatment and at three control visits after PDT over 12 weeks. Twenty healthy volunteers were irradiated with UVB in two areas on the back. One area was treated with topical high-potency corticosteroid before irradiation. TEWL was measured before, 15 min and 24 h after UVB exposure.
Results: TEWL did not differ significantly between the various visits in each acne group and no significant difference in the TEWL between PDT-treated patients and the control group was found at any visit ( P >0.05). TEWL was not significantly altered 15 min and 24 h after a single exposure to UVB and no positive relationship was found between UV-induced erythema and change in TEWL ( P >0.05). Application of topical corticosteroid before UVB did not affect the skin barrier function significantly ( P >0.05).
Conclusion: Neither PDT nor a single exposure to UVB damaged the permeability barrier function of the skin and no effect on the TEWL was found when topical corticosteroid was applied previous to UVB irradiation.     

The transient and cumulative effect of sodium lauryl sulphate on the epidermal barrier assessed by transepidermal water loss: inter-individual variation

The aims of the investigation were: 1) to study the inter-individual variation in time course of TransEpidermal Water Loss and of clinical manifestations after a 24-h single exposure to Sodium Lauryl Sulphate. This TEWL time course (expressed as the difference in TEWL between the day of patch removal and a subsequent day) reflected the epidermal barrier response to the damage caused by SLS; 2) to investigate the association between the TEWL time course after the single SLS exposure and the TEWL value after 4-day repeated SLS exposure (as a model for cumulative irritation). The 35 healthy subjects tested could be divided into four sub-groups according to the day of their maximum TEWL value after the single SLS exposure (days 2 to 5). For the whole group, inter-individual variation in TEWL course was most pronounced in the first days following the single SLS application. Moreover, there was an inverse relationship (R = -0.61) between TEWL course during the first days after the single exposure and the TEWL value after 4-day repeated exposures. It is concluded that this association illustrates the importance of an adequately responding barrier function against the continuous exposure to irritants in daily life.     

On the course of the irritant reaction after irritation with sodium lauryl sulphate

Background: The sodium lauryl sulphate (SLS) irritation test is a well-established model for irritant contact dermatitis after the effects of surfactants.
Aim of the study: The course of changes in corneometric measurements (stratum corneum hydration), in transepidermal water loss (TEWL), in laser Doppler measurements (epidermal perfusion) and in colorimetric measurements (skin redness), after a single SLS irritation, should be studied over time.
Methods: Twenty healthy volunteers were studied. Irritation with 1% SLS solution was applied to the side of one forearm for 24 h under occlusive conditions, while the symmetrical experimental site remained untreated. Measurements were made for 9 days after completion of SLS irritation.
Results: Stratum corneum hydration was reduced immediately after irritation, and subsequently a hyper-hydration was observed. The increase in TEWL, laser Doppler measurements and skin redness persisted for 7–9 days. With regard to skin redness, a mild blanching effect was noticeable after 9 days.
Discussion: The evidence of very short-term exsiccation of the stratum corneum with persistent barrier damage, as well as reactive hyper-hydration and blanching of the skin, is remarkable. These first findings suggest that exsiccation of the stratum corneum is not caused by a damage to barrier lipids.     

【开放获取】皮肤干燥是通透屏障功能受损的表现吗？

【摘要】 有学者认为,皮肤干燥是表皮通透屏障功能受损的表现,但目前尚没有足够的证据证明这一观点。实际上,皮肤干燥是角质层含水量降低的表现。角质层含水量主要由角质层天然保湿因子的量决定,而表皮通透屏障功能则主要由角质层脂质的质和量以及结构蛋白决定。如果皮肤干燥是由表皮通透屏障功能降低所致,那么,角质层含水量应当与透皮失水率呈负相关性。但是研究表明,无论是正常人皮肤、鱼鳞病皮损或皮脂腺缺乏的小鼠皮肤,角质层含水量与透皮失水率均无负相关性。相反,有研究显示,人角质层含水量与透皮失水率呈正相关性。因此,皮肤干燥似乎不是表皮通透屏障功能受损的表现。     

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.     

Biophysical and morphological changes in the stratum corneum lipids induced by UVB irradiation

BACKGROUND: UV irradiation induces a variety of responses in the epidermis, including sunburn cell formation, epidermal hyperplasia, and epidermal permeability barrier disruption. OBJECTIVE: The aim of present study was to assess the effects of UVB irradiation in the intercellular lipids in murine stratum corneum. METHODS: Adult hairless mice were exposed to a single UVB dose (0.15 J/cm(2)), the Fourier transform infrared (FT-IR) spectroscopic study was performed to investigate the effect on the biophysical changes in the stratum corneum lipids, barrier function was monitored by transepidermal water loss (TEWL) measurement, and the morphological alterations of stratum corneum was examined by electron microscopy using ruthenium tetroxide postfixation. RESULTS: The FT-IR spectroscopic study revealed that there was the shift to higher wavenumbers of the symmetric and asymmetric stretching peaks near 2850 and 2920 cm(-1) respectively at days 3-4 after a single UVB irradiation, reflecting to the increase in motional freedom of lipids hydrocarbon chains, call as disordering of lipids. Moreover, A single UVB irradiation also caused a significant increase in TEWL, the increase in TEWL began after 2 days and peaked at day 4. Electron microscopic observations revealed that marked morphological abnormalities in the intercellular domains, including abnormal profile of lamellar granules and its contents at the interface between stratum corneum and stratum granulosum and the persistence of the nuclei in the stratum corneum. Moreover, the separated fragmentary lipid lamellae, excessive numbers of lamellae in stacks, both the elongated and enlarged lacuna as well as the extracellular whorls were present within the widen space of the stratum corneum. CONCLUSION: The both of biophysical and morphological changes of the stratum corneum lipids may reflect to the mechanisms of perturbation of the epidermal permeability barrier induced by UVB irradiation.     

Dynamics of skin barrier repair following preconditioning by a biotechnology-driven extract from samphire (Crithmum maritimum) stem cells

Background With aging, the barrier repair kinetics following any weakening of the epidermal permeability barrier function is commonly slowed down. Objective To assess the recovery rate of the epidermal permeability barrier function following controlled stripping and applications of samphire and control formulations. Method In 12 healthy subjects older than 50 years, controlled stratum corneum (SC) strippings were used to increase the transepidermal water loss (TEWL) just above 15 g/m²/h. This procedure followed a 14‐day skin preconditioning by daily applications of formulations enriched or not with a samphire (Crithmum maritimum) biomass. An untreated skin site served as control. The epidermal permeability repair kinetics was assessed for 14 days by daily measurements of both TEWL and the colorimetric value a*. Results A rapid (96 h) recovery to lower TEWL values was obtained at each of the samphire‐preconditioned sites (0.1% serum, 0.05% cream, the serum–cream association, and 0.5% silicone oil). This process was significantly (P < 0.001) faster than that on both the placebo‐preconditioned (silicone oil) and the untreated sites. No adverse inflammatory and sensory reactions were recorded. At the sites preconditioned by samphire formulations, the SC moisture (capacitance) was higher at completion of the study compared to inclusion. Conclusions The present experimental pilot study brings some clues supporting a beneficial boosting effect of samphire cell biomass on the kinetics of epidermal permeability barrier repair.     

The influence of repeated exposure to surfactants on the human skin as determined by transepidermal water loss and visual scoring

The purpose of this study was to develop a new model for the induction of chronic irritant contact dermatitis, which would reflect well the conditions of daily practice. Various weak irritant agents were tested for irritating potency on the skin and the sensitivity of transepidermal water loss (TEWL) measurements in the detection of early skin changes was also studied. 10 widely used surfactants and 1 solubilizer were applied to the skin of the forearms of healthy volunteers in aqueous solutions of 12.5 millimoles/l for 45 min twice daily for 3 weeks. The effect on the skin was evaluated daily by means of TEWL measurements and by a visual scoring system. Each solution caused an increase in TEWL value over time due to the cumulative irritating action on the epidermal barrier. This increase in TEWL was different for the various solutions, resulting in different mean TEWL values on the last day of the experiment. Thus, it was possible to rank the agents according to irritating potency. This ranking order was the same in almost every individual and remained constant during the 3 weeks. In comparison with the visual scoring system, the TEWL measurements were more sensitive in the detection of early changes in the skin.     

Non‐invasive assessment of tryptophan fluorescence and confocal microscopy provide information on skin barrier repair dynamics beyond TEWL

The stratum corneum (SC) serves a primary function of skin barrier and understanding the kinetics of SC formation may provide great insight for skin diagnosis and evaluation of therapies. Besides trans‐epidermal water loss (TEWL), few methods have been characterized to assess skin barrier non‐invasively in vivo, particularly for dynamic measurements on the same specimen over time. The objective of this study was to characterize alternative non‐invasive methods to evaluate the dynamic processes involved in the recovery of normal human SC after total removal. TEWL, tryptophan fluorescence and reflectance confocal microscopy (RCM) were used to determine skin barrier function, cell turnover and epidermal morphology over a period of 10 days after total removal of the SC by tape stripping. The results show a biphasic recovery of TEWL over time, which contrasted with a linear increase of 2.3 μm/day in SC thickness. Tryptophan assessment of cell turnover also demonstrated a biphasic pattern attaining a maximum three to four times the levels of the control site 3 days after injury that slowly returned to baseline and displayed great correlation (R² > 0.95) to viable epidermis thickness that also achieved a maximum about 3 days after injury with an approximate increase of 55%. When plotting the change of TEWL versus SC thickness, a single exponential function is observed [Δ‐TEWL = 55 exp (?0.157×)] which contrasts with other proposed models. These methods were able to present rates for SC recovery processes beyond skin barrier (TEWL) that may provide new insights on kinetics of barrier formation for evaluation of skin conditions and treatments.     

Skin permeability barrier and occlusion: no delay of repair in irritated human skin *

It has been reported that occlusive treatment of irritated skin results in a reduction of barrier repair activities in hairless mice. In contrast, the clinically observed benefit of occlusion in the treatment of hand eczema and other chronic skin diseases with a perturbed barrier function is well–known. While the beneficial effect of occlusion has been proven for the treatment on psoriasis there are no controlled clinical studies of the effect of occlusion on irritated human skin. We have therefore evaluated the effect of various occlusive treatments on repair of the human skin permeability barrier under controlled experimental conditions. Barrier perturbation was induced either by application of sodium lauryl sulfate (SLS) or by repeated tape stripping. This was followed by treatment with different occlusive and semipermeable dressings, partly alter pre-treatment with petrolatum. Repair of water barrier function was evaluated by daily measurements of transepidermal water loss (TEWL) for 1 week. SLS irritation and tape stripping led to a 6-fold increase in TEWL as a sign of severe water barrier perturbation, followed by a stepwise decrease over the following days. Occlusion did not significantly delay barrier repair as measured by TEWL. Only in tape-stripped skin did TEWL stay at high levels during treatment with self-adhesive dressings. This may be explained by damage of newly formed stratum corneum caused by changing of these membranes. Our results indicate that, in contrast to earlier observations in hairless mouse skin, permeability barrier repair activities are not significantly delayed by occlusive treatment in human skin.     

Air flow at different temperatures increases sodium lauryl sulphate-induced barrier disruption and irritation in vivo

BACKGROUND: Combined exposure to dry climatic conditions and local heat sources together with detergents represents a common workplace situation. These conditions may support the induction of chronic barrier disruption leading subsequently to irritant contact dermatitis (ICD). OBJECTIVES: To test the irritant and barrier disrupting properties of air flow at different temperatures and velocities. METHODS: Using noninvasive biophysical measurements such as transepidermal water loss (TEWL) (TM 210; Courage & Khazaka, Cologne, Germany) we assessed the effects of short-term exposure to air flow at different temperatures (24 degrees C and 43 degrees C) in combination with sodium lauryl sulphate (SLS) 0.5% on the skin of 20 healthy volunteers in a tandem repeated irritation test. Chromametry was used to control the accuracy of the SLS irritation model. RESULTS: In our study air flow alone did not lead to a significant increase in TEWL values. Sequential treatment with air flow and SLS led to an impairment of barrier function and irritation stronger than that produced by SLS alone. The two different air flow temperatures led to different skin temperatures but had no influence on permeability barrier function. CONCLUSIONS: Warm air flow has an additional effect on the SLS-induced barrier disruption in a tandem irritation test with sequential exposure to SLS/air flow. This combination is suspected to promote ICD in workplace and household situations, especially in short-term applications as tested in our model.     

Baseline transepidermal water loss in patients with acute and healed irritant contact dermatitis

To examine the skin harrier function of patients with acute and healed irritant contact dermatitis ( n = 80) baseline transepidermal water loss (TEWL) was quantitatively measured using an evaporimeter. Healthy subjects served as controls ( n = 40). Test areas were the forearm and the thigh. A significant increase in TCVV'L was observed in the patients with acute and with healed irritant contact dermatitis (ICD) as compared LO healthy volunteers ( P ≤ 0.01). TEWL values in both test areas were com parable and markedly correlated ( p ≤ 0.01). with each other in every group. Thus, it is possible that basal TEWL depends more on the intrinsic skin barrier function of the subjects rather than the 2 anatomical regions examined. TEWL at the forearm with acme ICD was significantly higher ( P ≤ 0.01). than that of the group with healed ICD, but not for TCWL at the thigh suggesting that ICD may aggravate the barrier function of the adjacent involved skin. It is assumed, that increased basal TEWL in patients with ICD may relied a constitutional deviation of epidermal barrier function. This event seems to be comparable with the well-known symptom of atopic individuals. Using a detailed atopic scoring system in such a study may clarify the question of whether a proportion of patients with hand ICD may indeed be atopic individuals.