Skin aging. Effect on transepidermal water loss, stratum corneum hydration, skin surface pH, and casual sebum content.

This study investigates the effect of cutaneous aging on transepidermal water loss, stratum corneum hydration (capacitance), skin surface pH, and causal sebum content. Because the physiologic condition of skin varies considerably with anatomic region and skin aging might demonstrate regional variability, all factors were studied on 11 anatomic locations in 14 young adult (seven female and seven male subjects; 26.7 +/- 2.8 years [mean +/- SD]) and 15 aged human volunteers (seven female and seven male subjects; 70.5 +/- 13.8 years). Significant anatomic variability was noted for all factors in both age groups. However, no significant differences between the two groups were noted for sebum, capacitance, and pH on most anatomic regions. Transepidermal water loss, however, was significantly lower in the aged population on all anatomic regions tested, except for the postauricular region and the palm. Comparing male and female volunteers, none of the four factors showed significant differences. Of all measured factors, only transepidermal water loss showed significant age-related differences on most anatomic regions studied. The additionally observed differences between the age groups on the ankle for pH and sebum might be related to the stasis frequently observed on the lower limbs in aged individuals.     

Assessment of skin barrier function in podoconiosis: measurement of stratum corneum hydration and transepidermal water loss

Background Podoconiosis is a common cause of lymphoedema in barefoot workers in Ethiopia and other countries. It has severe consequences for patients’ physical function, quality of life and economic status. Aims To investigate stratum corneum (SC) hydration and transepidermal water loss (TEWL) in patients with podoconiosis compared with controls. Methods In total, 55 patients and 20 controls were recruited. For each study subject, SC and TEWL measurements were taken, along with foot and lower leg circumferences. Measurements were compared between the patient and control groups. Results Foot circumferences tended to be higher in patients with podoconiosis, with the mean foot:leg circumference ratio being 1·19 (95% confidence interval 1·11–1·28) times that for controls (P = 0·001). There was no detectable difference between patients and controls in TEWL values (P > 0·05); however, SC hydration was significantly lower in patients vs. controls for the foot (P = 0·004) and lower leg (P = 0·046) sites. Conclusions Patients with podoconiosis have significantly lower SC hydration in the skin of their lower legs and feet than controls, which may lead to cracking and splitting, and increased risk of lymphoedema and infection.     

Development of a stratum corneum and barrier function in an organotypic skin culture

The stratum corneum of human skin is responsible for maintaining the epidermal permeability barrier. We have developed a bilayered skin culture (SC) which forms a corneum 35 ± 1 cell layers thick 21 days after being raised to the air-liquid (A/L) interface. By the 7th day after raising to the A/L interface the corneocytes were irregularly shaped and had cross-sectional areas (CSA) of 300 m². By the 21st day the corneocytes had assumed polygonal shapes and had a CSA (100–250 m²) similar to that of human foreskin. The total lipid (TL) content of the corneum averaged 5–7% of the lyophilized weight. Ceramide content increased from 20% of TL at day 7 of A/L interface culture to 30% at day 21. Triglycerides decreased from 43% to 17% of TL during the same period. Free fatty acids comprised 5.5% of TL at day 21 of A/L interface culture. The intercorneocyte spaces contained stacks of lipid lamellae. However, the stacks lacked the Landmann unit repeat. Abnormal lamellar structures were observed in both the intra- and extracorneocyte spaces. Transepidermal water loss (TEWL) was >4 mg/cm² per h throughout the culture period. Lipid supplementation of the culture medium and culturing in a low humidity environment improved barrier function by 50%. However, the effects were not additive. The SC developed a near-normal corneum, but did not achieve barrier competence, due at least partially to abnormalities in lipid composition and organization. Improvement of barrier function with lipid supplementation or low humidity indicates that modifications of the culture environment may facilitate the SC in assembling a permeability barrier equivalent to human skin.     

The effect of solvent extraction on the lipids of the stratum corneum in relation to observed immediate whitening of the skin

Irritant contact dermatitis along with an increased transepidermal water loss can result from exposing the skin to solvents. A study of the interaction of various solvents with human stratum corneum was made using thin-layer chromatography. Comparison of 10 solvents (trichloroethylene, toluene, dimethylsulfoxide, n-hexane, 1,2-propanediol, carbon tetrachloride, methyl ethyl ketone, ethanol, acetone, distilled water) showed that 3 solvents (dimethylsulfoxide, 1,2 propanediol, distilled water) did not extract lipids from intact human stratum corneum. The findings are discussed in relation to the visual appearance of skin (whitening) after exposure to solvents.     

Molecular interactions of plant oil components with stratum corneum lipids correlate with clinical measures of skin barrier function

Plant‐derived oils consisting of triglycerides and small amounts of free fatty acids (FFAs) are commonly used in skincare regimens. FFAs are known to disrupt skin barrier function. The objective of this study was to mechanistically study the effects of FFAs, triglycerides and their mixtures on skin barrier function. The effects of oleic acid (OA), glyceryl trioleate (GT) and OA/GT mixtures on skin barrier were assessed in vivo through measurement of transepidermal water loss (TEWL) and fluorescein dye penetration before and after a single application. OA's effects on stratum corneum (SC) lipid order in vivo were measured with infrared spectroscopy through application of perdeuterated OA (OA‐d₃₄). Studies of the interaction of OA and GT with skin lipids included imaging the distribution of OA‐d₃₄ and GT ex vivo with IR microspectroscopy and thermodynamic analysis of mixtures in aqueous monolayers. The oil mixtures increased both TEWL and fluorescein penetration 24 h after a single application in an OA dose‐dependent manner, with the highest increase from treatment with pure OA. OA‐d₃₄ penetrated into skin and disordered SC lipids. Furthermore, the ex vivo IR imaging studies showed that OA‐d₃₄ permeated to the dermal/epidermal junction while GT remained in the SC. The monolayer experiments showed preferential interspecies interactions between OA and SC lipids, while the mixing between GT and SC lipids was not thermodynamically preferred. The FFA component of plant oils may disrupt skin barrier function. The affinity between plant oil components and SC lipids likely determines the extent of their penetration and clinically measurable effects on skin barrier functions.     

Effects of prolonged occlusion on stratum corneum barrier function and water holding capacity.

PURPOSE OF THE STUDY: We aimed to evaluate whether prolonged occlusion can induce stratum corneum barrier damage, alterations in stratum corneum hydration or water-holding capacity (WHC) lasting longer than the occlusion time. MATERIALS AND METHODS: 12 subjects were occluded on the forearm for 24, 48, 72 and 96 h. Two hours after occlusion removal, transepidermal water loss (TEWL) and skin hydration were measured and a sorption-desorption test performed. RESULTS: TEWL showed an increase reaching a plateau on day 2. Hydration and WHC did not show significant changes. Hygroscopicity showed the highest level on day 1, decreasing during the following days. A highly significant correlation between capacitance values and the WHC could be detected (p < 0.0001, r = 0.8206). No correlation could be detected between hygroscopicity and TEWL. CONCLUSIONS: Prolonged occlusion induces barrier damage without skin dryness. Occlusion also induces an increased hygroscopicity. A correlation between these two findings could not be proven.     

The diffusion of water across the stratum corneum as a function of its water content

The flux of tritiated water (HTO) through pieces of stratum corneum at four different levels of hydration has been measured. The concentration of water in the stratum corneum, the concentration of HTO in the presenting solution, and the thickness, density, and weight per unit area of the dry stratum corneum are known. The thickness of the hydrated stratum corneum and the permeability and diffusion constants of HTO were calculated. From these in vitro data it is possible to calculate the in vivo thickness of the stratum corneum, its water concentration profile, and the flux of water (transepidermal water loss) at environments of different relative humidities. Both the transepidermal water loss and the water concentration profile change very little as the environmental relative humidity increases from 0 to 80%. The small decrease in the water concentration of the surface layers of cells as the relative humidity becomes very low, however, may cause an observable alteration in the physical characteristics of the surface layers.     

Incontinence induces stratum corneum vulnerability and impairs the skin barrier function in the perianal region

BACKGROUND: Incontinence leads to a reduced skin barrier function, while also increasing the risk of skin breakdown. AIM: To investigate the perianal skin barrier function of elderly patients with or without incontinence. METHODS: We compared the skin barrier function by investigating the skin hydration, the skin pH, the amount of ceramide and by making a dermatological skin inspection of the perianal region in patients with and without incontinence. RESULTS: Twenty-one incontinent patients (70.0%) showed a glossy skin, which indicates impairment of the skin barrier while none of the patients in the continence group did so. In the incontinence group, those who had a glossy skin showed a significantly greater skin pH and total amount of ceramide than those with a normal skin (p = 0.0099, p = 0.0179, respectively). CONCLUSIONS: These results demonstrate that a glossy skin may be a useful indicator of a reduced perianal skin barrier function.     

Epidermal hyperproliferation and decreased skin barrier function in mice overexpressing stratum corneum chymotryptic enzyme

Stratum corneum chymotryptic enzyme (SCCE; also known as kallikrein 7) is a serine protease that may have an important role in the skin desquamation process. We have recently described transgenic mice overexpressing human SCCE in suprabasal epidermal keratinocytes, leading to increased epidermal thickness, hyperkeratosis, dermal inflammation and signs of severe pruritus in older animals. In order to further evaluate the scce-transgenic mice as a potential disease model, we compared transgenic animals and wild-type littermates for patterns of epidermal keratin expression, in situ hybridization of scce-mRNA, scratching behaviour and measurements of transepidermal water loss (TEWL). In 3-day-old mice, despite readily detectable amounts of human scce-mRNA in the epidermis of transgenic animals, there were no histological differences in skin appearance, and no differences could be found in epidermal expression of the keratins 5, 6 and 10. In mice 7-8 weeks of age and older, there was strong suprabasal expression of keratins 5 and 6 in the epidermis of transgenic animals, suggesting that the thickened epidermis in these animals is the result of keratinocyte hyperproliferation. In transgenic animals 11 weeks of age and older there was an increased frequency of scratching, suggestive of pruritus, and also signs of a deteriorating skin barrier function, as reflected by an increased TEWL. There was no correlation between increased TEWL and increased frequency of scratching in individual animals, suggesting that the defect barrier function was not an effect of skin damage caused by scratching.     

Effect of lactic acid isomers on keratinocyte ceramide synthesis,stratum corneum lipid levels and stratum corneum barrier function

Alpha-hydroxy acids are effective agents for the treatment of skin xerosis and it is known that, following treatment with lotions containingd,l-lactic acid, the stratum corneum prevents xerosis more effectively. To date, the relative efficacy of the different isomers of lactic acid has not been evaluated and the mode of action of lactic acid in improving stratum corneum resilience is not known. The objective of the present studies was to determine the effects of lactic acid isomers on keratinocyte ceramide biosynthesis, stratum corneum barrier function and the resistance of the straum corneum to the appearance of skin xerosis. In vitro, lactic acid enhanced the production of ceramides by keratinocytes.l-Lactic acid was more effective than thed isomer (300% increase vs 100% increase). Carbon label from lactic acid was incorporated into all keratinocyte lipid species and a greater incorporation of label into ceramides was achieved withl-lactate than withd-lactate. In vivo, lactic acid increased the levels of stratum corneum ceramides. Whereas, lotions containingl-lactic acid resulted in the greatest increase (48% increase) followed byd,l-lactic acid (25% increase),d-lactic acid had no effect on stratum corneum ceramide levels. The increases in stratum corneum ceramide levels following lactic acid treatment also led to improvements in stratum corneum barrier function, measured by transepidermal water loss following a challenge to the skin with SLS and in the regression phase of a moisturization efficacy study. Significant improvements in barrier function and resistance to the appearance of skin xerosis were observed followingl-lactic acid andd,l-lactic acid, but not followingd-lactic acid treatment. From these results we believe that lactic acid, particularly thel isomer, stimulates ceramide biosynthesis leading to increased stratum corneum ceramide levels which results in superior lipid barrier and a more effective resistance against xerosis.     

Water content and thickness of the stratum corneum contribute to skin surface morphology

Abstract Skin surface morphology has long been recognized as reflecting skin pathology. In the present study, we evaluated skin surface morphology using hairless mice under contrasting conditions of humidity. The skin surface microrelief was recorded with opaque quick-drying silicone rubber, and examined under a microscope. A binary image was produced by density slicing. Within 3 days of exposure to dry conditions, skin roughness was significantly increased. The skin roughness was partially mitigated by topical application of an aqueous solution of glycerol or hydration by immersion in water. A significant correlation between skin roughness and stratum corneum thickness was also observed. These results suggest that skin surface morphology is associated with both water content and thickness of the stratum corneum. Received: 29 November 1999 / Received: 1 March 2000 / Accepted: 22 March 2000     

Skin barrier response to occlusion of healthy and irritated skin: Differences in trans‐epidermal water loss,erythema and stratum corneum lipids

Background. Occlusion of the skin is a risk factor for development of irritant contact dermatitis. Occlusion may, however, have a positive effect on skin healing. No consensus on the effect of occlusion has been reached. Objectives. To investigate skin barrier response to occlusion on intact and damaged skin. Methods. In study A, the response to occlusion (nitrile glove material) for either 8 hr daily for 7 days or for 72 consecutive hours, respectively, was determined and compared with that of non‐occluded skin. In study B, the response to occlusion of for 72 consecutive hours of skin that had been damaged by either sodium lauryl sulfate (SLS) or tape stripping, respectively, was determined and compared with that of to non‐occluded pre‐damaged skin. Skin barrier function was assessed by measurements of trans‐epidermal water loss (TEWL) and erythema. In study A, stratum corneum lipids were analysed. Results. Occlusion of healthy skin did not significantly influence skin barrier function, ceramide profile or the ceramide/cholesterol ratio. Occlusion of the skin after SLS irritation resulted in higher TEWL than in the control (P = 0.049). Occlusion of the skin after tape stripping resulted in lower TEWL than in control skin (P = 0.007). Conclusions. A week of occlusion did not significantly affect healthy skin, but was found to decrease healing of SLS‐damaged skin, and to improve healing of tape‐stripped skin.     

The impact of ultraviolet therapy on stratum corneum ceramides and barrier function

The ceramide profile as well as the barrier function is known to be deteriorated in atopic eczema and psoriasis, and ultraviolet (UV) light is known to improve the barrier function. The impact of UV light on ceramides, however, is not clarified. The aim of this study was to examine the effect of UV therapy in dermatological patients on ceramides and skin barrier function. We found that UV light treatment does not change the ratio of important stratum corneum lipids, but we confirm earlier findings of decreased susceptibility to irritants after UV- therapy.     

Importance of intercellular lipids in water-retention properties of the stratum corneum: induction and recovery study of surfactant dry skin

Summary In order to further clarify the role of intercellular lipids in the water-retention properties of the stratum corneum, forearm skin of six healthy male volunteers was treated with 5% sodium dodecyl sulfate (SDS) for 1, 10, and 30 min. All treatment periods induced chapping and scaling of the stratum corneum without any inflammatory reaction, accompanied by a significant decrease in its water-retention function. Electron-microscopic analysis of SDS-treated stratum corneum revealed selective depletion of the lipids from the intercellular spaces, accompanied by marked disruption of multiple lamellae structures. Lipid analysis also showed a considerable and selective loss of intercellular lipids such as cholesterol, cholesterol ester, free fatty acid, and sphingolipids. To evaluate the recovery potential for intercellular lipids, lipids which were separated as sebaceous-rich lipids (SLs) and stratum corneum lipids (SCLs) wer applied daily on SDS-treated forearm skin. Two daily applications of the SCLs which were emulsified at 10% concentration in W/O (water in oil) cream caused a significant increase in conductance, accompanied by a definite improvement in the level of scaling over no application or W/O emulsion base only, whereas SLs in the W/O emulsion base led to no significant recovery in either conductance value or scaling. When two daily topical applications of four chromatographically separated lipid fractions (cholesterol ester, free fatty acid, cholesterol, and sphingolipid) from the SCL were carried out at 1% concentration in the same system, the cholesterol ester and sphingolipid fractions were found to induce a significant increase in the conductance value over no application. In contrast, the free fatty acid and cholesterol fractions showed no significant increase in conductance value. Similarly, the scaling which occurred after SDS treatment had a tendency to decrease after the two daily applications with the fractions of cholesterol ester, sphingolipids, and free fatty acid as compared with that of the base emulsion. These findings strongly suggest that sphingolipids, possibly in combination with other neutral lipids, play an essential role in the establishment or maintenance of water-retention capacity in the stratum corneum.