Stratum corneum and nail lipids in patients with atopic dermatitis. Decrease in ceramides--a pathogenetic factor in atopic xerosis?

Dry skin is seen in many patients with atopic dermatitis and correlates with a disturbed epidermal barrier function demonstrated by such features as increased transepidermal water loss and diminished stratum corneum hydration. With regard to the importance of stratum corneum lipids for the permeability barrier, we have analysed plantar (n = 8) and lumbar (n = 20) stratum corneum and nail lipids (n = 15) of atopic subjects by high-performance thin-layer chromatography (HPTLC). Compared with controls our investigations show a decrease in the ceramide fraction as a percentage of total lipid and a diminished ratio of ceramides and free sterols in atopic subjects. This implies that impaired ceramide synthesis may be a factor in the pathogenesis of atopic xerosis.     

Stratum corneum lipids serve as a bound-water modulator

Stratum corneum lipids have been found to be an important determinant involved in the water-holding function of the stratum corneum. In order to further elucidate the significance of stratum corneum lipids in the water-holding properties, the hydration behavior of the stratum corneum following depletion and replenishment of the lipids has been studied, using an isolated human forearm stratum corneum sheet, by differential scanning calorimetry parallel to ultrastructural changes of intercellular lipids in the stratum corneum. Extraction of the stratum corneum sheet with acetone/ether (1/1) decreased the bound-water content from 33.3% to 19.7%, where the melting temperature of ice remained constant. Further extraction with water, which released a large amount of water-soluble materials such as amino acids, did not change the bound-water content, but definitely raised the melting temperature of ice. The application of the stratum corneum lipids, which were solubilized in squalane containing 1% alpha-monomethyl heptadecyl glyceryl ether to the lipid-depleted stratum corneum sheet, caused a significant recovery of bound-water content to the previous, almost normal level. In accordance with the hydration behavior, electron microscopic analysis of the acetone/ether-treated stratum corneum sheet revealed selective depletion of lipids from the intercellular spaces, accompanied by a marked disruption of multiple lamellar structures. In contrast, the application of stratum corneum lipids into the lipid-depleted stratum corneum sheet resulted in the restoration of the lamellar structure between the stratum corneum cells. These findings strongly suggest that stratum corneum lipids serve a water-holding function through the formation of lamellar structures within the stratum corneum.     

Stratum corneum lipid abnormalities in surfactant-induced dry scaly skin

Sodium dodecyl sulfate (SDS) has been used to induce a dry scaly skin condition in human subjects. Measurements of stratum (s.) corneum hydration, scaliness, and lipid composition reveal in vivo surfactant perturbations on desquamation. Subjects (n = 10) were briefly treated daily with a 4% aqueous solution of SDS on one lower leg over a period of 2 weeks. The other control leg received no treatments. At the end of the treatment period, both lower legs were evaluated for hydration using an electrical impedance technique and examined by an independent dermatologist using a visually based grading scale for surface roughness and scaliness. Shave biopsies were then excised from each lower leg for analysis of s. corneum lipids. Treatment resulted in decreased s. corneum hydration and increased surface scale/roughness. These physical changes were accompanied by significant changes in s. corneum lipid composition. While surfactant treatments did not alter the total quantity of lipids per gram s. corneum protein, significant changes in specific lipid classes were observed. The free cholesterol to cholesterol ester ratio increased while the quantity of total sterols remained constant. The distribution of certain ceramide species were altered while the quantity of total ceramides remained constant. Free fatty acids were resolved into 2 distinct bands, only one of which diminished upon treatment. These results are interpreted in terms of a model for surfactant-induced perturbation of keratinization which leads to abnormal s. corneum lipids and altered desquamation.     

Stratum corneum hydration and amino acid content in xerotic skin

The relationship between clinical severity, the hydration state of the skin surface as assessed by a conductance with a 3.5 MHz high frequency impedance meter, and the amino acid content of the stratum corneum (SC) of six patients with ichthyosis vulgaris and 30 elderly persons with varying degrees of xerosis was investigated. With an increase in the severity of xerosis the SC showed a decrease in hydration and in its extractable amino acid content. There was a significant correlation between the hydration state and amino acid content of the SC. Although there was a significant correlation between the amino acid content of the lower leg SC and that of the forearm SC in the same subject, the former was generally lower, corresponding to the greater incidence of xerosis on the lower leg. These results suggest that a decreased amount of amino acids may be the result of low profilaggrin biosynthesis in the epidermis and that this is involved in the pathogenesis of these xerotic skin conditions. Clinical improvement of the xerosis following treatment with a urea-containing cream was not accompanied by any significant change in the amino acid content of the SC.     

Stratum corneum lipids: the effect of ageing and the seasons

Stratum corneum lipids play a predominant role in maintaining the water barrier of the skin. In order to understand the biological variation in the levels and composition of ceramides, ceramide 1 subtypes, cholesterol and fatty acids, stratum corneum lipids collected from tape strippings from three body sites (face, hand, leg) of female Caucasians of different age groups were analysed. In addition, we studied the influence of seasonal variation on the lipid composition of stratum corneum from the same body sites. The main lipid species were quantified using high-performance thin-layer chromatography and individual fatty acids using gas chromatography. Our findings demonstrated significantly decreased levels of all major lipid species, in particular ceramides, with increasing age. Similarly, the stratum corneum lipid levels of all the body sites examined were dramatically depleted in winter compared with spring and summer. The relative levels of ceramide 1 linoleate were also depleted in winter and in aged skin whereas ceramide 1 oleate levels increased. The other fatty acid levels remained fairly constant with both season and age, apart from lignoceric and heptadecanoic acid which showed a decrease in winter compared with summer. The decrease in the mass levels of intercellular lipids and the altered ratios of fatty acids esterified to ceramide 1, are likely to contribute to the increased susceptibility of aged skin to perturbation of barrier function and xerosis, particularly during the winter months. Received: 17 October 1995     

头皮屑与角质层功能障碍第二部分:角质层与头皮屑

健康角质层形成了一层保护屏障,防止头皮水分散失并保湿,同时保护头皮不受外界损伤(如包括马拉色菌在内的微生物或者有毒物质).严重的或慢性的屏障损伤会减少应有的水分从而导致非典型的表皮细胞增殖、角化细胞分化及成熟,从而引起头皮屑症状的产生.头皮屑人群的头皮角质层中结构脂质缺失、无序排列,与高经皮水分丢失所表征的头皮屏障脆弱状态相一致.头皮屑人群头皮屏障功能脆弱的证据包括亚临床炎症和对局部刺激的高敏感性.     

Stratum corneum sphingolipids and free amino acids in experimentally-induced scaly skin

Summary Stratum corneum sphingolipids are of particular importance in maintaining the water permeability barrier of mammalian epidermis. Free amino acids also play an important role in water retention in the stratum corneum. To clarify the way in which these substances affect scaly skin, stratum corneum sphingolipids and free amino acids collected from artificially-induced scaly skin were analysed. Scaly skin was induced by tape stripping. The total amount of sphingolipids was quantified by gas chromatography and five of sphingolipid fractions were isolated and quantified by thin-layer chromatography. Free amino acids were analysed using a high-speed amino analyser. The total amount of sphingolipid in scaly skin did not differ statistically from that in control skin. However, a significant change in the distribution of the five sphingolipid species was observed in scaly skin and the total amount of amino acids was decreased in scaly skin. These results suggest that the distribution of these five types of sphingolipid and the total amount of amino acids are responsible for scaly skin.     

Stratum corneum hydration and skin surface pH in patients with atopic dermatitis

Atopic dermatitis (AD) is a chronically relapsing skin disease with genetic predisposition, which occurs most frequently in preschool children. It is considered that dryness and pruritus, which are always present in AD, are in correlation with degradation of the skin barrier function. Measurement of hydration and pH value of the stratum corneum is one of the noninvasive methods for evaluation of skin barrier function. The aim of the study was to assess skin barrier function by measuring stratum corneum hydration and skin surface pH of the skin with lesions, perilesional skin and uninvolved skin in AD patients, and skin in a healthy control group. Forty-two patients were included in the study: 21 young and adult AD patients and 21 age-matched healthy controls. Capacitance, which is correlated with hydration of stratum corneum and skin surface pH were measured on the forearm in the above areas by SM810/CM820/pH900 combined units (Courage AND Khazaka, Germany). The mean value of water capacitance measured in AD patients was 44.1 ± 11.6 AU (arbitrary units) on the lesions, 60.2 ± 12.4 AU on perilesional skin and 67.2 ± 8.8 AU on uninvolved skin. In healthy controls, the mean value was 74.1 ± 9.2 AU. The mean pH value measured in AD patients was 6.13 ± 0.52 on the lesions, 5.80 ± 0.41 on perilesional skin, and 5.54 ± 0.49 on uninvolved skin. In control group, the mean pH of the skin surface was 5.24 ± 0.40. The values of both parameters measured on lesional skin were significantly different (capacitance decreased and pH increased) from the values recorded on perilesional skin and uninvolved skin. The same held for the relation between perilesional and uninvolved skin. According to study results, the uninvolved skin of AD patients had significantly worse values of the measured parameters as compared with control group. The results of this study suggested the skin barrier function to be degraded in AD patients, which is specifically expressed in lesional skin.     

Stratum corneum integrity as a predictor for peristomal skin problems in ostomates

Background Peristomal skin problems are common, most often the result is disruption of the skin barrier and this may account for more than one in three visits to ostomy nurses. Therefore a specific assessment of individual risk factors relating to the skin barrier function would be of great interest. Methods Skin barrier integrity in ostomy patients with peristomal skin problems (PSP) was compared with that of ostomy patients with normal skin (controls) using transepidermal water loss (TEWL). Mechanical barrier disruption was determined by a tape stripping test and chemical barrier disruption [sodium lauryl sulphate (SLS) 0·25%]. Results Patients and controls had a highly significant increase in TEWL value in the peristomal area compared with nonperistomal contralateral abdominal skin (P < 0·0001 for both groups). The skin barrier of normal‐looking contralateral skin of ostomates was found to be borderline impaired in patients with PSP compared with those without. A linear association was seen between the number of tape strips removed and TEWL for both cases and controls. Tape stripping suggested that patients with PSP had less resilient skin (P = 0·002). A significant difference in TEWL value between cases and controls was also seen for the SLS patch test on the dorsal skin (P = 0·02). Conclusion Successive tape stripping, a situation analogous to the normal use of a pouching system, caused a higher degree of barrier damage more rapidly in patients with PSP, indicating an impaired mechanical quality of the barrier. The SLS exposure test suggested a generally increased susceptibility to irritant dermatitis as assessed by TEWL. Our findings suggest tape stripping and SLS testing may have a role as predictive tests to identify patients at risk of PSP.     

Stratum corneum acidification is impaired in moderately aged human and murine skin

Aged skin commonly is afflicted by inflammatory skin diseases or xerosis/eczema that could be triggered or exacerbated by impaired epidermal permeability barrier homeostasis. This defect is linked to reduced epidermal lipid synthesis in humans and in mice of advanced age (i.e., >75 years in human or >18-24 months in mice). We now report that barrier defects in moderately aged humans (50-80 years) or analogously aged mice (12-15 months) are linked instead to defective stratum corneum (SC) acidity. In moderately aged mouse epidermis, we find that abnormal acidification, in turn, is linked to decreased Na+/H+ antiporter (NHE1) expression. Decreased NHE1 levels lead to increased SC pH, which results in defective lipid processing and delayed maturation of lamellar membranes, due to suboptimal activation of the pH-sensitive essential, lipid-processing enzyme, beta-glucocerebrosidase. Conversely, impaired SC integrity in moderately aged mice is due to increased pH-dependent activation of serine proteases, leading to premature degradation of corneodesmosomes. These abnormalities were normalized by exogenously acidifying the SC, suggesting a basis for the well-known acidification therapies that are widely used to treat the pathologic xerosis/eczema seen in moderately aged humans.     

Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate

Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.     

Stratum corneum lipid morphology and transepidermal water loss in normal skin and surfactant-induced scaly skin

Stratum corneum lipid morphology was evaluated using attenuated total reflectance infrared spectroscopy (ATR-IR) in normal skin and surfactant-induced scaly skin to evaluate skin barrier function. To evaluate the degree of order of the intercellular lipid alkyl chain conformation, we measured the wavenumbers (frequency shifts) of the symmetrical and asymmetrical C-H stretching vibrations observed at approximately 2850 cm^–1 and 2920 cm^–1, respectively. There was a correlation between the wave-number and transepidermal water loss in normal skin. However, no difference was observed in surfactant-induced scaly skin from the baseline value in the wavenumbers of the C-H vibrations. These results suggest that in normal skin, lipid morphology plays an important role in the barrier function of the stratum corneum. However, the decline in barrier function in scaly skin is not due to conformational disorder of the lipid alkyl chain.     

Morphologie des Stratum corneum

Ohne Zusammenfassung     

Functional analyses of the superficial stratum corneum in atopic xerosis

Dermatologists universally recognize that the unaffected skin of patients with atopic dermatitis tends to be dry and slightly scaly. To characterize the functional properties of the superficial stratum corneum in atopic xerosis, we studied the forearms of 28 patients with atopic dermatitis, aged 14 to 30 years, and 18 age-matched controls, with the use of mainly noninvasive methods. Patients with atopic xerosis showed markedly higher transepidermal water loss and markedly lower skin surface hydration levels than did the controls. The corneocytes in atopic xerosis tended to desquamate in clumps of cell aggregates instead of as individual cells. They contained a substantially lower amount of water-soluble amino acids, which play a role in the water-retaining capacity of stratum corneum, than did those of controls. Although the number of stratum corneum cell layers in atopic xerosis (21 +/- 4) was substantially larger than that in controls (15 +/- 1), its turnover time (7 +/- 2 days) was appreciably shorter than that for controls (14 +/- 2 days). Like those noted in the skin with increased epidermal proliferation, the size of superficial corneocytes in patients with atopic xerosis was substantially smaller than in controls. Histopathologic examination revealed acanthotic epidermis, mild perivascular mononuclear cell infiltrate, and pigment incontinence. Atopic xerosis, the dry skin of patients with atopic dermatitis, shows various stratum corneum functional impairments, probably reflecting increased epidermal proliferation due to a low-level ongoing dermatitis.     

Stratum corneum chymotryptic enzyme in psoriasis

Abstract Stratum corneum chymotryptic enzyme (SCCE) is a serine protease which may function in the turnover of the stratum corneum by means of degradation of intercellular adhesive structures between corneocytes. It is also potentially an epidermal activating enzyme for cytokines such as interleukin-1β. The aim of this work was to study the expression of SCCE in psoriatic epidermis by means of immunohistochemistry, and to elucidate the nature of the SCCE present in psoriatic scales by means of biochemical analyses. In comparison to normal skin the number of cell layers expressing SCCE in psoriatic lesions was consistently increased. In nonlesional psoriatic skin the pattern of SCCE expression varied. It was similar to the pattern in normal skin in some biopsies, whereas in other biopsies evidence of an increased expression of SCCE was found. By means of zymography and immunoblotting, extracts of psoriatic scales were found to contain active SCCE as well as enzymatically inactive SCCE precursor. Also the effects of inhibitors on the activity towards a chromogenic protease substrate in the extracts after partial purification by gel exclusion chromatography were compatible with the presence of enzymatically active SCCE. We conclude that the expression of SCCE in psoriasis may be upregulated, and that the conversion of inactive SCCE-precursor to active SCCE occurs in the psoriatic lesion. The possible role of SCCE in the pathophysiology of psoriasis remains to be elucidated, but should be considered in future studies. Received: 24 April 1998 / Received after revision: 1 October 1998 / Accepted: 16 October 1998     

Zur Morphologie des Stratum corneum

Ohne Zusammenfassung

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Stratum corneum lipid function.

The stratum corneum contains a complex mixture of polar and nonpolar lipids in its intercellular spaces. These lipids, present in form of multiple lamellae, have been investigated for their role in providing the epidermal barrier to transcutaneous water loss, the selective barrier from the inside to the outside of the organism and partly the process of physiological desquamation. The composition of these lipids varies from species to species, with the body region and the degree of keratinocyte differentiation. The most undifferentiated layers of the epidermis contain typical membrane lipids, phospholipids, while more differentiated layers contain ceramides, cholesterol and free fatty acids. Essential fatty acids are essential for the maintenance of the lamellar structures and epidermal barrier function. Epidermal linoleic and arachidonic acids derive from exogenous sources. Only recently attempts have been made to elucidate the timing and regulation of epidermal fatty acid metabolism. Keratinocytes do not express a low molecular weight fatty acid binding protein like other cells active in lipid metabolism, but may employ alternative ways in fatty acid uptake and metabolism.     

Stratum corneum lipid abnormalities in atopic dermatitis

Summary Patients with atopic dermatitis (AD) often present with a dry skin. To clarify the relationship between dry skin and lipid abnormalities within stratum corneum, stratum corneum lipids were collected from six AD patients aged 15 to 25 years and from sex- and age-matched controls. All major stratum corneum lipid classes were separated and quantitated by high-performance thin-layer chromatography/photodensitometry. Six ceramide fractions were also isolated and quantitated by thin-layer chromatography/photodensitometry. Esterified fatty acids of both ceramide 1 (acylceramides) and wax esters were analysed by capillary gas chromatography. The relative amounts of all the stratum corneum lipid classes including squalene, cholesterol esters, wax esters, triglycerides, free fatty acids, cholesterol, ceramides, cholesterol sulphate and phospholipids did not differ statistically between AD patients and controls. However, a significant decrease in proportion of ceramide 1, which is believed to be a carrier of linoleate responsible for a water-barrier function, and increased levels of esterified C₁₈₁ fatty acids (oleate) of ceramide 1 were observed in AD patients. On the other hand, the fatty acid compositions as well as the proportions of C₁₆₁ straight-chain component in sebum wax esters of AD patients were very similar to those of controls. These results suggest that a significantly reduced amount and/or structural alterations of ceramide 1 deriving from epidermal keratinocytes may be responsible for the impaired water-barrier function of the skin in AD.     

Stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: preparation and in vitro permeation study

Background  

Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs) in order to optimize its skin delivery in Photodynamic Therapy (PDT) of skin cancers.