经表皮水分流失与皮肤屏障的遗传学研究

经表皮水分流失（Transepidermal water loss?,TEWL）测量的是水分从真皮和表皮的水合层向皮肤表面扩散的通量密度,是用于评估皮肤屏障功能的一项成熟无创的方法,最新的一项研究发现TEWL值与9号染色体9q34.3基因突变密切相关,本文总结了TEWL与皮肤屏障功能的遗传学研究进展。     

面部糖皮质激素依赖性皮炎患者经皮水分丢失和皮肤含水量分析

目的 分析面部糖皮质激素依赖性皮炎患者的皮肤屏障功能。方法 将面部分为额部、鼻尖、下颌、双面颊、双侧口角的皮损区及左耳后无皮损区共8个点，分别测量95例面部糖皮质激素依赖性皮炎患者及25例健康对照者的经皮水分丢失（TEWL）和皮肤含水量。结果 与健康组相比，面部糖皮质激素依赖性皮炎组下颌、双侧口角、双面颊TEWL值均显著升高（t值分别为4.90，2.60，2.57，2.54，3.77，P < 0.01）；双侧口角、右面颊及额部的皮肤含水量均显著降低（t值分别为3.27，3.81，2.02，2.78，P < 0.05）。在8个测量点中，面部糖皮质激素依赖性皮炎组与健康组TEWL值均为下颌及双侧口角 > 双面颊及额部 > 耳后无皮损区；皮肤含水量降低均为下颌及双侧口角 > 双面颊及额部 > 耳后无皮损区。结论 面部糖皮质激素依赖性皮炎患者下颌、双侧口角、双面颊区域皮肤屏障功能受损，口周区域TEWL值较高，而面颊皮肤水分含量较少。     

Changes in basal cell mitosis and transepidermal water loss in skin cultures treated with vitamins C and E

Three variants of the living skin equivalent cultures were compared in order to determine the most suitable to grow human differentiated epidermis to test beneficial properties of nutrients. Criteria of culture quality were mitotic index and transepidermal water loss (TEWL) assayed by means of a ServoMed Evaporimeter EP-2TM (ServoMed, Kinna, Sweden). Standards were donor skin mean mitotic index 11.1% and TEWL of living subjects mean 6.4 g/m(2)/h. Cultures (i) in 5% serum, 10 ng/ml of epidermal growth factor (EGF) at 37 degrees C and 95% relative humidity (RH); mitotic index on day 14, 19.2%, but on day 21, 1.8% and TEWL 9.5 g/m(2)/h on day 18. (ii) In 1% serum, no EGF, 33 degrees C and 95% RH, mitotic index on day 21, 9.1% and TEWL, 9.5% on day 18. (iii) Culture in same medium, 33 degrees C and 60% RH, mitotic index on day 28, 9.5% and TEWL 6.1 g/m(2)/h on day 18 as in vivo. Incubation in 60% RH was achieved using a novel chamber and dishes exposing only the corneum, sealing the medium. Vitamins C and E were used as model test nutrients. Culture conditions were 1% serum, no EGF at 33 degrees C and 95% RH. Vitamin C at 142 and 284 microM increased the mitotic index after 10- and 15-day treatment, but at 586 microM it was weakly toxic. Vitamin E at 20 and 40 microM did not. Both vitamins reduced TEWL providing functional data in support of previous reports on barrier properties. These are functional biomarkers of skin benefit relevant to skin in vivo.     

A closed unventilated chamber for the measurement of transepidermal water loss

Background/aims Open chamber systems for measuring transepidermal water loss (TEWL) have limitations related to ambient and body‐induced airflows near the probe, probe size, measurement sites and angles, and measurement range. The aim of the present investigation was to develop a closed chamber system for the TEWL measurement without significant blocking of normal evaporation through the skin. Additionally, in order to use the evaporimeter to measure evaporation rates through other biological and non‐biological specimens and in the field applications, a small portable, battery‐operated device was a design criteria. Methods A closed unventilated chamber (inner volume 2.0 cm³) was constructed. For the skin measurement, the chamber with one side open (open surface area 1.0 cm²) is placed on the skin. The skin application time was investigated at low and high evaporation rates in order to assess the blocking effect of the chamber on normal evaporation. From the rising linear part of the relative humidity (RH) in the chamber the slope was registered. The slope was calibrated into a TEWL value by evaporating water at different temperatures and measuring the water loss of heated samples with a laboratory scale. The closed chamber evaporation technique was compared with a conventional evaporimeter based on an open chamber method (DermaLab^®, Cortex Technology, Hadsund, Denmark). The reproducibility of the closed chamber method was measured with the water samples and with volar forearm and palm of the hand in 10 healthy volunteers. Results The skin application time varied between 7 and 9 s and the linear slope region between 3 and 5 s at the evaporation rates of 3–220 g/m² h. A correlation coefficient between the TEWL value from the closed chamber measurements and the readings of the laboratory scale was 0.99 (P < 0.001). The reproducibility of the evaporation measurements with the water samples was 4.0% at the evaporation rate of 40 g/m² h. A correlation coefficient of the TEWL values between the closed chamber and open chamber measurements was 0.99 (P < 0.001) in the range where the response of a conventional evaporimeter was linear (until 120 g/m² h). With volar forearm and palm of the hand of 10 healthy volunteers the reproducibility of the measurements was 8.0 and 10.1%. Conclusion The closed chamber technique solves the drawbacks related to open chamber evaporimeters. Especially, it extends the measurement range to high evaporation rates and TEWL measurements can be performed practically at any anatomical sites and measurement angle. By the use of a closed chamber the disturbance related to external or body‐induced air flows on the measurement can be avoided.     

Comparability and reproducibility of the results of water loss measurements: a study of 4 evaporimeters

A study was made of the comparability and reproducibility of the results of measurements of water loss, both in vitro and in vivo, using 4 ServoMed Evaporimeters (3 single-probe and 1 double-probe instrument). The optimum time for recording transepidermal water loss (TEWL) after the initial application of the probe to the skin (in vivo), and the best technique for optimizing the accuracy of measuring TEWL were determined. An evaporation device with a constant level of water loss was constructed for in vitro studies. The volar aspect of the right forearm skin of one subject was used in vivo. Both in vitro and in vivo measurements showed that there were some differences between the results of 4 of the 5 probes. The other probe was distinctly out of range. For all probes, the reproducibility of results of successive measurements was high. Stabilization of TEWL values was reached for all probes from 30-45 s after their initial application to the skin. It is recommended that TEWL be recorded for a further 30-s period, after the initial stabilization (45 s), and that this be taken as the true value. The manufacturer's recommended calibration procedure is based only on adjustments for the standard specified humidities and zero water loss. The importance of incorporating an additional calibration procedure which includes adjustments for an actual standard constant water loss is thus strongly stressed.     

Guidelines for transepidermal water loss (TEWL) measurement

This report reviews individual-related variables, environment-related variables and instrument-related variables, with a focus on the Evaporimeter EP1 (ServoMed). Start-up and use is described, and guidelines for good laboratory practice given.     

International guidelines for the in vivo assessment of skin properties in non‐clinical settings: Part 2. transepidermal water loss and skin hydration

Background

There is an emerging perspective that it is not sufficient to just assess skin exposure to physical and chemical stressors in workplaces, but that it is also important to assess the condition, i.e. skin barrier function of the exposed skin at the time of exposure. The workplace environment, representing a non‐clinical environment, can be highly variable and difficult to control, thereby presenting unique measurement challenges not typically encountered in clinical settings.

Methods

An expert working group convened a workshop as part of the 5th International Conference on Occupational and Environmental Exposure of Skin to Chemicals (OEESC) to develop basic guidelines and best practices (based on existing clinical guidelines, published data, and own experiences) for the in vivo measurement of transepidermal water loss (TEWL) and skin hydration in non‐clinical settings with specific reference to the workplace as a worst‐case scenario.

Results

Key elements of these guidelines are: (i) to minimize or recognize, to the extent feasible, the influences of relevant endogenous‐, exogenous‐, environmental‐ and measurement/instrumentation‐related factors; (ii) to measure TEWL with a closed‐chamber type instrument; (iii) report results as a difference or percent change (rather than absolute values); and (iv) accurately report any notable deviations from this guidelines.

Conclusion

It is anticipated that these guidelines will promote consistent data reporting, which will facilitate inter‐comparison of study results.     

The barrier component and the driving force component of transepidermal water loss and their application to skin irritant tests

BACKGROUND/AIM: According to Fick's law of diffusion, the rate of transepidermal water loss (TEWL) is determined by a barrier component and a driving force component. The objective of this study is to propose novel indicators for the assessment of skin irritation potential from chemicals using these components. METHODS: Before and after acetone/ether (AE), sodium lauryl sulfate (SLS) and nicotinic acid methyl ester (NME) treatments, the apparent mass transfer coefficient of water, K, of the stratum corneum (SC) and the apparent water vapor pressure, P(d), at the interface between SC and epidermis were estimated as measures of the SC barrier and the driving force, respectively. RESULTS: After AE treatment, K showed marked increase and P(d) remained approximately constant. All participants reacted to NME with erythema and the laser-Doppler flowmetry (LDF) value peaked at around 30 min. While there was a change in P(d), which parallels with LDF changes, K showed little variation. Repeated SLS treatment induced a slight increase in P(d) besides an increase in K. In the meantime, all participants reacted with subtle erythema. CONCLUSIONS: Our results suggest that not only the SC barrier but also the driving force determines variations in the TEWL rates during skin irritant tests. Together, K and P(d) will provide us with invaluable information about skin condition.     

Impact of stress of marital dissolution on skin barrier recovery: tape stripping and measurement of trans-epidermal water loss (TEWL)

Background: Psychological stress of marital disruption is associated with significant increases in a variety of psychological and physical disorders . The effect of stress on the immune system is well documented and skin disorders have been reported to exacerbate during stressful situations. This study was designed to observe the effects of stress on skin barrier strength and recovery. Twenty-eight healthy females age 21–45 who were in the process of marital separation were tested for skin barrier strength and recovery. The panel was chosen on the basis of the intensity of self perceived stress. The control group was an age-matched group of self perceived 'happy' subjects. Servomed evaporimeter was used to measure trans -epidermal water loss (TEWL) from cheek area of the face, before and after removing stratum corneum layers with tape strippings. Skin barrier strength was defined as the number of tape strippings required to disrupt skin barrier, which is a TEWL of 18 g/m2/h or more. Barrier recovery was denoted by the level of TEWL, 3 h and 24 h after barrier disruption.
Results: There was no correlation between the degree of stress and barrier strength. However, individuals with high stress recovered slower than the individuals with low stress after 3 h ( R  = 0.64) and 24 h ( R  = 0.74).
Conclusions: Psychological stress of marital dissolution does not appear to change skin barrier strength but has a negative impact on skin barrier recovery.     

Measurement of transepidermal water loss in localized scleroderma

Localized scleroderma (LS) is a disease characterized by fibrotic changes in the dermis. Connective tissue growth factor and transforming growth factor β2 are the main mediators of fibrogenesis; this, along with excessive connective tissue production, affects epidermal keratinocytes, and thereby contributes to the changed quality of skin barrier. The objective of this article was to study the objective measurement of the skin barrier quality in LS with transepidermal water loss (TEWL) meter. The measurements of TEWL were performed on LS plaques in all three stages of various body locations. Control measurements were made on the contralateral side of healthy skin. The difference between TEWL in LS area and the contralateral side of the healthy skin was evaluated. A higher average TEWL 7.86 g/m²/h (SD 5.29) was observed on LS plaques compared with the control measurements on healthy skin 6.39 g/m²/h (SD 2.77). TEWL average values decreased from the inflammatory stage, through the sclerotic and to the atrophic stage. The mean difference 1.301 g/m²/h (SD 5.16) was found between TEWL on LS plaques and on the contralateral healthy skin in 82 measurements, i.e., a higher TEWL was observed in LS. The difference was statistically significant with p = 0.0250. Although fibrogenesis in scleroderma is localized in dermis, the skin barrier changes can be detected.     

Artificial reduction in transepidermal water loss improves skin barrier function

BACKGROUND: Artificial reduction of abnormal transepidermal water loss (TEWL) is considered to improve skin diseases associated with a defective barrier function. Treatment of the skin with moisturizers is also known to influence skin barrier function. Whether or not differences in occlusion between creams contribute to their effects on the skin barrier function is unknown. OBJECTIVES: To investigate the long-term effects of a semipermeable membrane on the skin barrier function in normal skin. In addition, the occlusive properties of two creams were studied. METHODS: The study was randomized, controlled and evaluator-blind using measurement of TEWL and skin susceptibility to sodium lauryl sulphate as indicators of skin barrier function. RESULTS: Coating of the skin with a silicone membrane for 23 h per day for 3 weeks improved skin barrier function, whereas no significant changes were found after using the membrane for 8 h per day. CONCLUSIONS: Differences between creams in terms of their effect on skin barrier function cannot be solely explained by their occlusive properties.     

Improved barrier function observed in cultured skin substitutes developed under anchored conditions

Background/purpose: The current method of producing cultured skin substitutes (CSS) is focused on providing treatments for severe skin wounds/burns. We have developed a modified growth method to make them more suitable for in vitro product‐testing/toxicity‐testing purposes. Method: CSS grown in Petri dishes were either transferred to Franz diffusion cells on day 5 (modified method) or left in the Petri dish (standard method) and maintained in these environments for the remainder of the growth phase. Mitochondrial metabolism (MTT assay) was measured on days 5, 10 and 14 and histology was studied on days 5, 10 and 14. Barrier function for all tissues was evaluated by transferring them to Franz cells (standard method) and measuring transepidermal water loss (TEWL), ³H₂O penetration and ¹⁴C‐niacinamide permeability on days 7, 14 and 21. Results: CSS grown by the standard and modified methods showed comparable cell viability and tissue morphology. Barrier function, however, was markedly improved in CSS grown by the modified method. The average improvement at days 7 and 14 was 1.3‐fold for TEWL, 2.1‐fold for ³H₂O penetration and 6.4‐fold for ¹⁴C‐niacinamide permeability. The barrier function of CSS grown by the modified method was still significantly lower than that of human cadaver skin tested by the same methods. Conclusions: CSS developed using the anchored multi‐cell system showed similar cell viability and morphology and improved barrier function compared with CSS produced by the standard Petri dish method, thereby improving its potential as an in vitro skin permeability and toxicity model.     

经皮水分丢失与健康人性别、年龄、解剖部位的关系

通过经皮水分丢失（TEWL）来评价皮肤的屏障功能，并研究经皮水分丢失与性别，年龄，解剖部位的关系，参加本次实验的为健康志愿者共104名，其中女性53名，男性51名，分为5个不同年龄组，用与计算机相连的蒸发测定仪Darmalab TEWL探头测量。结果发现不同年龄组男女性别之间TEWL值均无显著性差异（P＞0．05），新生儿组TEWL值明显高于其他各年龄组（P＜0．05），老年组TEWL值低于其他年龄组。在8个不同部位测量中，经统计得到TEWL值顺序为：手掌＞额部＞颊部＝手背＞小腿＝背部＞前臂＝胸部。说明TEWL与性别无明显相关性，而与年龄相关，以新生儿最高，老年人最低，在身体各部位的测量中，四肢末端和暴露部位经皮水分丢失较高。     

Basal transepidermal water loss, skin thickness, skin blood flow and skin colour in relation to sodium-lauryl-sulphate- induced irritation in normal skin

The influence of basal transepidermal water loss (TEWL), skin thickness, blood flow and skin colour on susceptibility to sodium-lauryl-sulphate(SLS)-induced irritant contact dermatitis was studied in 70 healthy volunteers. SLS 0.5% was applied as a patch test. For assessment of basal values and skin response to SLS, bioengineering methods were used: TEWL was measured by an evaporimeter, skin thickness by ultrasound A-scan, blood flow by laser Doppler flowmetry, and skin colour by a colorimeter, using the L*a*b* system of the Commission Internationale de l'Eclairage (CIE). By use of multiple regression analysis, it was demonstrated that basal TEWL was substantially related to skin susceptibility to SLS, high basal TEWL predicting an increased susceptibility to SLS. Also increased light reflection from the skin, indicating a 'fair' skin, was found to be associated with increased susceptibility to SLS.     

Time course of occlusive effects on skin evaluated by measurement of transepidermal water loss (TEWL) Including patch tests with sodium lauryl sulphate and water

The time course for transepidermal water loss (TEWL) for a period of 3 h after removal of occlusive patch tests with sodium lauryl sulphate (SLS), water and empty chambers was studied in healthy volunteers. Patches were applied to the upper arm for 24 h, TEWL was measured immediately after removal of the patches, and every 30 min up to 3 h. For SLS and water patches, TEWL remained significantly increased for 3 h. as compared to normal adjacent skin, while for empty chamber patches. TEWL was only significantly increased for 30 min. A significant decrease from 0 to 30 min and from 30 to 60 min was observed for all patches, and for water patches, a significant decrease in TEWL was found from 60 to 180 min, while SLS patches remained constant. The prolonged increase in TEWL observed after SLS exposure is a well-known occurrence. The prolonged increase in TEWL after exposure to water is interpreted as transient damage to the water harrier of the skin.     

Comparative evaporimetry in man

BACKGROUND/AIMS: Transepidermal water loss (TEWL) measurements are frequently used; the most widely utilized instrument has been the open chamber device. Traditional open-chamber systems for measuring TEWL have limitations related to ambient and body-induced airflows near the probe, probe size, measurement site and angles. Recent technology provides a portable and battery-operated closed chamber Evaporimeter. It is presumably less affected by external factors such as room- or body-induced airflows, breathing or heating of the probe by the operators' hand. This study compares this commercial instrument, a closed chamber device, with a traditional open-chamber device. METHODS: Two open chamber devices and one closed chamber device were used in such a way that each instrument could simultaneously measure TEWL in an identical experimental environment with known relative humidity and temperature values. TEWL values of seven locations on healthy volunteers were measured simultaneously with each instrument in the same room according to the guidelines of the standardization group of the European society of contact dermatitis. RESULTS: For TEWL values of all forearm locations, there was no statistically significant difference between the mean values measured by all three instruments. For TEWL values of forehead locations, there was a significant difference between the mean values of open chamber device and closed chamber device. For the forehead, values from closed chamber device were higher than the open one. CONCLUSION: The TEWL values measured by all instruments were constant with small standard deviations. These instruments appear sufficiently robust that a standardization group could document similarities and differences with in vitro models. We suspect that both techniques will continue to be used and that the closed method will find increasing use because of its ease of use.     

Transepidermal water loss, temperature and sebum levels on women's facial skin follow characteristic patterns

Background/aims: The aim of this study was to compare the biophysical properties of different facial zones. Methods: We investigated transepidermal water loss (TEWL), skin temperature and sebum casual level (CL) on 90 adjacent test sites distributed on the forehead, cheeks and chin of five women. Results: All three parameters showed a symmetrical distribution around the facial median line. Only minor variations of individual values were found within the forehead and the chin areas. In contrast, the cheeks exhibited a distinct gradient with highest values in the paranasal zones and lowest on the cheek bones for all of the three parameters. The mean values on both cheeks of a given individual were nearly identical, and the patterns within the two cheeks were superimposable. Both CL and skin temperature distributions pointed out a “T‐zone” with highest values on the forehead, on the chin and on the median part of the cheek. Conclusions: Our data demonstrate that biophysical skin properties differ considerably between different facial areas but that they follow a characteristic distribution.