老年脂溢性角化患者血脂、脂蛋白、载脂蛋白的分析

为了探讨脂溢性角化和血脂代谢的关系。回顾分析了70例老年脂溢性角化患者总胆固醇，甘油三酯，高密度脂蛋白，低密度脂蛋白，载脂蛋白A－1和载脂蛋白B。结果发现脂溢性角化患者组甘油三酯和低密度脂蛋白明显高于正常对照组。脂溢性角化与血脂代谢的关系需要进一步研究。     

Lipid analysis of follicular casts from cyanoacrylate strips as a new method for studying therapeutic effects of antiacne agents

BACKGROUND: The cyanoacrylate follicular biopsy is an established method for the examination of the horny layer and quantitative assessment of microcomedones. We have optimized the method by separating follicular casts mechanically from the cyanoacrylate strips. OBJECTIVES: To use this method to analyse topical therapy-induced changes of the lipid composition in the sebaceous follicular infundibulum. METHODS: Both the follicular casts and the residual skin surface strip, the last representing a mixture of stratum corneum and surface lipids, were extracted twice with n-hexane-ethanol under ultrasonication, evaporated, redissolved in chloroform-methanol and separated by high-performance thin layer chromatography, using cholesterol sulphate, cerebroside, ceramide types 3 and 4, cholesterol, oleic acid, triolein, cholesterol oleate and squalene as standards. Identification was performed by computer-assisted densitometric analysis. Six patient groups receiving adapalene 0.1%, tretinoin 0.025%, clindamycin 1%, clindamycin 1% + tretinoin 0.025%, benzoyl peroxide 5% or benzoyl peroxide 5% + erythromycin 2% were investigated before and 12 weeks after application. RESULTS: A significant decrease in free fatty acid proportions combined with an increase in triglycerides was observed in the groups receiving antimicrobial therapy, supporting the hypothesis of lipolysis due to microbial colonization. The groups treated with topical retinoids showed an additional significant increase in ceramide subfractions, most probably reflecting their influence on epidermal keratinization. CONCLUSIONS: Our method proved suitable for the detection of quantitative and qualitative changes in lipid profiles of both infundibulum cast content and surface lipids. It enabled simple, non-invasive and objective assessment of the most relevant lipid classes in the sebaceous infundibulum, and efficient monitoring of drug effects on the follicular infundibulum.     

Ointment is evenly spread on the skin, in contrast to creams and solutions

BACKGROUND: The efficacy of topical therapy depends on the patient spreading the topical drug in an even layer to give a standard dose. Ointments are believed to be more effective than creams and solutions. OBJECTIVES: To compare the application and spreading of four different pharmaceutical vehicles. METHODS: Twenty-nine healthy volunteers applied a fixed amount (0.1 g) of solution (S), ointment (O), cream (C) and low-viscosity cream (LVC) to the abdominal skin. Area of spread, skin surface lipids (dependent on formulation) and changes in skin surface temperature (cooling due to evaporation of formulation water/alcohol) were measured. RESULTS: Area of spread: O = C = LVC = S. Skin surface lipids: O > C > LVC > S. Difference in skin surface lipids between centre and periphery: O < C = LVC = S. Cooling: O < C = LVC < S. CONCLUSIONS: The four formulations were spread to similar areas. The ointment was spread evenly in the treated area while the other formulations were unevenly spread, with a lower dose in the periphery. Creams and solutions have disadvantages as vehicles, as rapid evaporation of formulation water/alcohol, measured as cooling, influences spread, resulting in an uneven topical dose within the treated area. In contrast, ointment is evenly spread and is thus a more appropriate formulation. Patients should be instructed to apply creams and solutions to multiple sites and to spread them quickly.     

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.     

Human stratum corneum polar lipids and desquamation

Summary The ceramides and steryl-sulfate components from desquamated and cohesive human stratum corneum were examined using a combination of chemical and chromatographic means. Six structurally distinct series of ceramides were identified, and the relative amounts of these species, as measured by quantitative thin-layer chromatography, did not differ in cohesive and desquamated stratum corneum. In contrast, the level of cholesteryl sulfate was significantly reduced in the desquamated material. The results are in accord with the hypothesis that cholesteryl sulfate serves in cell-to-cell cohesion within the stratum corneum, and its hydrolysis may be necessary to permit shedding of cells from the surface.     

Investigation of the roles of the substances in serum lipids and their constitutive fatty acids in chronic urticaria

The newly-generated lipid mediators include products of arachidonate metabolism, prostaglandins and leukotrienes. In this study, serum lipids and fatty acids, including arachidonic acid (C20:4) were examined in 12 normal subjects (6 males and 6 females) and 23 subjects with chronic urticaria (6 males and 17 females), including 17 who made an excellent or good recovery (4 males and 13 females). The results indicated a relationship between chronic urticaria and serum lipids and fatty acids. The omega 6 (n-6) and omega 3 (n-3) series of polyunsaturated fatty acids and lipid peroxidation were suggested that may be one of the mediators in chronic urticaria. Pantethine, glutathione and ascorbic acid were effective in controlling chronic urticaria.     

The morphologic changes in lamellar bodies and intercorneocyte lipids after tape stripping and occlusion with a water vapor-impermeable membrane

It has been reported that artificial restoration of barrier function by a water vapor-impermeable membrane after tape stripping induces barrier abrogation in hairless mice, impeding rather than enhancing barrier recovery. To address this issue, we examined the morphologic changes in the epidermis after tape stripping and occlusion with a water vapor-impermeable membrane in murine skin. Male hairless mice were used for all studies of barrier perturbation and occlusion. Barrier disruption was achieved by repeated application of cellophane tape. Immediately after tape stripping the animals were wrapped in a tightly fitting water vapor-impermeable membrane. Transepidermal water loss (TEWL) was measured 20 min after tape stripping and 14, 24, 36, 48 and 60 h after occlusion. For electron microscopy the samples were treated with osmium tetroxide (OsO ₄ ) or ruthenium tetroxide (RuO ₄ ). When tape-stripped animals were wrapped in a water vapor-impermeable membrane, thereby preventing water flux, barrier function did not recover normally. These results demonstrate that an artificial block to TEWL with an impermeable membrane did not enhance barrier recovery. By electron microscopy many transitional cells and lacunae of various sizes were seen within the intercellular spaces of the stratum corneum after occlusion following tape stripping. Occlusion also caused alterations in both lipid lamellar membrane structures in the stratum corneum interstices and the lamellar bodies in the cytosol of granulocytes and transitional cells. Secreted lamellar body contents also appeared to be abnormal in the stratum corneum-stratum granulosum junction. Received: 17 December 1996 / Accepted: 14 November 1997     

Mass spectrometric characterization of cholesterol esters and wax esters in epidermis of fetal, adult and keloidal human skin

Abstract:  Mass spectrometry (MS) with chemical ionization was found to be a useful tool for characterizing epidermal cholesterol esters (CE) and wax esters (WE), and was applied to analyse them in the epidermis of fetal, adult and keloidal human skin. Increases in the concentrations of CE and WE had occurred by 20 weeks of gestation in association with increasing concentrations of ceramides and cholesterol sulphate. Although adult epidermis contained them in similar concentrations at 25–28 weeks of gestation (13–14% of the total less polar lipids), the molecular species were shown to differ between fetal and adult epidermis by MS. Cholesterol oleate comprised 45% of the total molecular species in adult CE, whereas saturated fatty acids with chain lengths of 15–19 were abundant in fetal CE. Also, unsaturated and shorter chain WE were abundant in adult epidermis in comparison with that in the fetal epidermis, the total chain lengths of fetal and adult WE being 34–42 with a mean chain length of 38.6, and 27–41 with a mean chain length of 34.0, respectively, and the unsaturated molecules in fetal and adult WE amounting to 29% and 45%, respectively. Also, CE and WE in the epidermis of keloidal skin were reduced to 67% and 20% of the levels in normal skin, respectively. Thus, epidermal CE and WE were shown to carry eligible structures for construction of the hydrophobic barrier at the skin and amniotic fluid interface as well as that at the skin and air interface.     

Quantitative Analysis of Stratum Corneum Lipids in Xerosis and Asteatotic Eczema

Sphingolipids, a major constituent of intercellular lipids, are an important determinant for both water-holding and permeability barrier function in the stratum corneum. To assess the pathogenic role of sphingolipids in the stratum corneum of dry skin disorders such as xerosis and asteatotic eczema in leg skin, ceramides were quantified by thin layer chromatography after n-hexane/ethanol extraction of resin-stripped stratum corneum and evaluated as μg/mg stratum corneum. In healthy leg skin (n=49), there was age-related decline in the total ceramide, whereas xerosis (n=25) and asteatotic eczema (n=16) suffering significantly reduced water-holding properties, exhibited no definite decrease, rather slight increase in ceramide quantity with the same composition of each individual ceramide as compared to healthy age-matched controls. These data indicate that the seemingly elevated level of ceramide is an artificial effect due to inflammatory processes which result from susceptibility to dryness. Analysis of sebum-derived lipids present in the stratum corneum revealed that there was a significant decline in free fatty acids in xerosis and asteatotic eczema as compared to age-matched healthy controls, and a similar decline in triglycerides in the above three groups when compared to younger controls. Although the observed decrease in the stratum corneum lipids may well explain the high incidence of winter dry skin in older people, the progression toward asteatotic eczema can not be accompanied solely by a decrease in ceramide quantity, suggesting that the evolution of xerotic skin is associated with other moisturizing factors and/or environmental stimuli.     

Zileuton prevents the activation of the leukotriene pathway and reduces sebaceous lipogenesis

Please cite this paper as: Zileuton prevents the activation of the leukotriene pathway and reduces sebaceous lipogenesis. Experimental Dermatology 2010; 19: 148–150. Abstract: Arachidonic acid (AA) activates the 5‐lipoxygenase, induces leukotriene‐B₄ (LTB₄) synthesis, enhances interleukin‐6 (IL‐6) release and increases intracellular neutral lipids in human sebocytes. Moreover, the enzymes of LTB₄ biosynthesis are activated in acne‐involved sebaceous glands. Zileuton a 5‐lipoxygenase inhibitor, reduces the number of inflammatory acne lesions and lipogenesis in patients with acne. In this study, we investigated the activity of zileuton on LTB₄ generation, lipid content and IL‐6 and ‐8 release from human SZ95 sebocytes in vitro. Pretreatment with zileuton partially prevented the AA‐induced LTB₄ and IL‐6 release and increased neutral lipid content. IL‐6 release and neutral lipid content were also reduced under long‐term zileuton treatment. In conclusion, zileuton prevents the activation of the leukotriene pathway and enhancement of lipogenesis by AA in human sebocytes in vitro.     

Age and skin structure and function, a quantitative approach (II): protein, glycosaminoglycan, water, and lipid content and structure

BACKGROUND/PURPOSE: The aging process has been studied with fervor recently, given our shifting demographics. As age's effects are so manifest in the skin's appearance, structure, mechanics, and barrier function, it is not surprising that much effort has been made in research to better understand them. Quantitative measurements permitted by bioengineering have allowed us to objectively and precisely study aging skin. These overviews piece together the immense amounts of information that have emerged from recent technological advances in dermatological research in order to develop a unified understanding of the quantitative effects of age on skin. METHODS: We performed a literature search on age-related changes in protein, glycosaminoglycan (GAG), water, and lipid content and structure, searching Pub-med, Em-Base, Science Citation Index, and the UCSF dermatological library's collection of books on the topic of aging skin. RESULTS: Collagen becomes sparser and less soluble in intrinsically aged skin, but is thickened and more soluble in extrinsically aged areas. Elastin is degraded slowly and accumulates damage with intrinsic aging; also, increased synthesis of abnormally structured elastin occurs in photoexposed areas. This leads to an age-related accumulation of aberrant elastoic material, clumped in the papillary dermis. Generally, age leads to increased folding and decreased interaction of proteins with water. Also, despite increased GAGs in aged skin, these are abnormally deposited on the elastoic material and cannot interact properly with water. Hence, in aged skin, water is found in the tetrahedron form, bound to itself rather than other molecules. Lipid content appears to decrease with age, although the proportion of different lipid classes seems to remain fairly constant. CONCLUSION: Much work remains to be carried out to reach a consensus on the effects of age on skin structure and function. Future studies would be benefited by increased standardization of skin sites tested, methodology, and increased sample sizes.     

Quantitative screening of human stratum corneum lipids by sequential one-dimensional thin layer chromatography

Abstract There is a need in many studies on the epidermal permeability barrier for practical and reliable separation of all major fractions of human stratum corneum lipids. Various methods have been described including thin layer chromatography, high performance thin layer chromatography and iatroscan. However, none of these methods seems to be applicable for an inexpensive, rapid and reliable analysis of a large number of samples. Here, such a method for the separation and quantification of all major stratum corneum lipid fractions is presented. This method employs the one-dimensional separation of stratum corneum lipids using thin layer chromatography. The systems used herein are based upon various modifications of the solvents, solvent ratio and developing distance of each system. For quantification of chromatographed and charred lipids a Desaga densitometer is used. The system described here had been successfully applied to 550 samples of human stratum corneum lipids.     

The stratum corneum: structure and function in health and disease

ABSTRACT:  Our understanding of the formation, structure, composition, and maturation of the stratum corneum (SC) has progressed enormously over the past 30 years. Today, there is a growing realization that this structure, while faithfully providing a truly magnificent barrier to water loss, is a unique, intricate biosensor that responds to environmental challenges and surface trauma by initiating a series of biologic processes which rapidly seek to repair the damage and restore barrier homeostasis. The detailed ultrastructural, biochemical, and molecular dissection of the classic "bricks and mortar" model of the SC has provided insights into the basis of dry, scaly skin disorders that range from the cosmetic problems of winter xerosis to severe conditions such as psoriasis. With this knowledge comes the promise of increasingly functional topical therapies.     

Saprophytic bacteria and fungi colonize stearoyl coenzyme-A desaturase-1 knockout skin

Lipids synthesized on the skin are critical to the antimicrobial barrier. Skin lipids also facilitate survival of lipophilic skin commensals in an otherwise dry and acidic ecological landscape. Thus, skin-specific stearoyl-coenzyme A desaturase 1 knockout mice (Scd1^ΔK14) with sebocyte atrophy and decreased synthesis of monounsaturated fatty acids, triglycerides and wax diesters have dry, inflamed skin. Here, we used 16S rRNA (V1-V2 and V1-V9) and internal transcribed spacer 1 (ITS1) amplicon sequencing to compare bacterial and fungal skin microbiomes between Scd1^ΔK14 mice and wildtype control mice (Scd1^fl/fl) in a barrier facility. Saprophytic bacteria including Sporosarcina spp. and Staphylococcus lentus and saprophytic fungi including Alternaria infectoria were found in higher relative abundance in the Scd1^ΔK14 group (ANCOM). Analysis of community diversity (Shannon index) revealed greater fungal alpha diversity in the Scd1^ΔK14 group (p = 0.009, Kruskal–Wallis). Principal coordinates analysis (Bray–Curtis dissimilarity) showed that both bacterial (p = 0.002, PERMANOVA) and fungal communities (p = 0.006, PERMANOVA) of the Scd1^ΔK14 group were unique from the wildtype group. Altogether, these results suggest that sebaceous gland-derived lipids normally restrict the skin microbiome, and in the absence of these lipids, a greater diversity of opportunistic organisms are able to colonize the surface of skin.     

524例青春期后女性痤疮患者的性激素和血脂分析

目的：检测青春期后女性痤疮患者血脂和性激素水平变化情况,探讨痤疮与性激素和血脂的关系。方法：收集青春期后女性寻常痤疮患者和健康对照者,检测BMI、甘油三酯、高密度脂蛋白、垂体泌乳素、促卵泡生成素、促黄体生成素、睾酮和硫酸脱氢表雄酮水平和盆腔超声。结果：共纳入524例青春期后女性痤疮患者（轻、中、重度痤疮分别为239例,207例和78例）及50名健康对照。轻、中、重度患者垂体泌乳素、雄烯二酮和硫酸脱氢表雄酮均显著高于健康对照者（P<0.05）。379例患者无多囊卵巢综合征（PCOS）,其中高雄烯二酮患者62例,雄烯二酮水平正常者317例。较雄烯二酮正常组,高雄烯二酮组垂体泌乳素、促黄体生成素、睾酮、硫酸脱氢表雄酮及高密度脂蛋白水平升高,甘油三酯水平降低（均P<0.05）。结论：青春期后女性痤疮患者易合并多种性激素异常,其中雄激素水平升高明显。     

脂类混合物对人体皮肤的生物学效应

本文阐述了利用从哺乳动物脑组织提取的脂类混合物对人体皮肤的生物学效应，结果表明，这种混合物能有效地提高皮肤角质层水分含量，降低皮肤水分丢失，维持皮肤的渗透屏障作用。     

Mechanisms of sebum production and delivery in man

Summary Utilizing a solvent extraction system and colorimetric analysis, surface lipid levels were determined on the forehead. To understand the mechanisms involved in the sebaceous gland apparatus, repeated sampling at varying timed intervals were made.The data suggest that frequent surface samplings produce higher rates of lipid replacement. The increasing lipid replacement rates seen with sampling intervals of greater frequency do not follow a linear pattern. Also, lipid replacement rates show a gradual decline with time. This data suggest the existence of a multifunctional sebaceous apparatus involved in sebum production (a rate function), sebum storage (a volume function) and surface delivery (a rate function).     

Epidermal barrier lipids in human vernix caseosa: corresponding ceramide pattern in vernix and fetal skin

BACKGROUND: Vernix caseosa is a protective biofilm covering the fetus during the last trimester. Vernix and epidermal barrier lipids (i.e. cholesterol, free fatty acids and ceramides) appear to share protective functions for fetal and neonatal skin. OBJECTIVES: To analyse vernix samples for epidermal barrier lipid content, and to compare lipid profiles of vernix with those of fetal and postnatal epidermis. METHODS: Vernix samples were collected from 21 healthy term neonates. Skin samples were collected from 10 fetuses aborted between gestational week (GW) 16 and 25, nine infants and 11 older children. Lipids were extracted according to standard protocols and analysed by high-performance thin-layer chromatography. RESULTS: Vernix contained 196.5 +/- 70.1 microg barrier lipids mg-1 protein (mean +/- SD). Cholesterol formed the major barrier lipid fraction (52.8%), followed by free fatty acids (27.7%) and ceramides (20.1%). The ceramide composition of vernix resembled that of mid-gestational (GW 23-25) fetal epidermis both qualitatively and quantitatively, while there were major differences from postnatal epidermis. The total epidermal ceramide concentration increased significantly between prenatal and postnatal samples. CONCLUSIONS: The composition pattern of ceramides mirrors that of mid-gestational fetal epidermis. Vernix thus represents a 'homologous' substitute for the immature epidermal barrier in fetal skin. The differential role of individual ceramides in this process remains to be established.