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Skin surface lipids of the mole Scalopus aquaticus.

Skin surface lipids of the mole Scalopus aquaticus were found to consist principally of squalene (70%), wax esters (15%), and sterol esters (5%), together with small amounts of triglycerides, free fatty acids, free fatty alcohols, and free sterols. Analysis of the fatty acids occurring free and as wax esters and sterol esters showed these to consist of approximately equal amounts of saturated and monounsaturated compounds. The saturated fatty acids consisted predominantly of odd-carbon anteiso and even-carbon straight-chain compounds, with minor amounts of even-carbon iso-branched chains. The unsaturated fatty acids had double bond positions that would have been produced by delta 9-desaturation of C14, C16 and C18 straight chain saturated precursors. Both the free and the esterified fatty alcohols had chain structures corresponding with those of the fatty acids but of somewhat greater average chain length. Discovery of a major proportion of squalene in the sebum of this animal extends the number of non-human species that have this characteristic to four, all of which inhabit a damp environment, suggesting that squalene conveys some biological advantage under these conditions.

Animals↗

Analysis of all stratum corneum lipids by automated multiple development high-performance thin-layer chromatography.

An optimized gradient enabling the separation of all stratum corneum lipids by automated multiple development on HPTLC plates is presented. An initial isocratic step separates sebum lipids. This is followed by a 25-step development using a gradient with a polarity range of methanol-water to hexane. Application to in-vivo extracted and isolated stratum corneum lipids demonstrates the possible quantification of the lipid classes with a "one-experiment" separation.

Adult↗

Quantitative evaluation of skin surface lipids.

More than 50 years of noninvasive studies of epidermal and sebaceous lipids has revealed a vast amount of information concerning secretion and regulation of SSLs. The first techniques developed (solvent extraction and cigarette paper) required very long experimental procedures to obtain valuable parameters; however, a great part of the knowledge on SSL production and regulation was obtained by these pioneers. Because of the difficulties encountered in these multistep procedures, applicability was restricted to a limited number of research centers. The sampling procedures in the newly developed techniques are significantly reduced and are followed by a fast and accurate evaluation. Moreover, the new sampling procedures permit us to study other aspects of sebum secretion, as demonstrated with the Sebutape method. When using photometric techniques an estimate of the SSL can be obtained within minutes (casual level measurements). After such a screening procedure, more standardized parameters can be accurately determined. Whatever the parameter under investigation, strictly controlled experimental procedures are required. Control of temperature and relative humidity of the experimental room, of the acclimatization periods, and of the volunteers during the collection periods is of capital importance. The studies discussed in this article clearly demonstrate the applicability of the new techniques not only for research and cosmetic purposes but also for clinical use.

Chemistry Techniques, Analytical↗

Sebaceous gland activity and urinary androgen levels in children.

Sebum and 24-h urine samples were collected from 17 children, aged 10-17 years. Wax ester (WE) secretion rates were measured as the index for sebaceous gland activity. The fatty acid methyl esters were analyzed by capillary gas chromatography. Urinary testosterone as well as 17-ketosteroids (androsterone, dehydroepiandrosterone (DHEA), and etiocholanolone) were separated from the urine samples and analyzed by gas chromatography. WE secretion rates increased with age and there were correlated changes in the monounsaturated fatty acids of WEs. Straight chain types such as 14:1 and 16:1 tended to increase, while 18:1 tended to decrease. There was a negative correlation between iso even fatty acids and WE secretion rates. However the other chain types such as straight odd, iso odd and anteiso odd showed no statistically significant change in relation to WE secretion rates. WE secretion rates were correlated positively with testosterone levels in both sexes, with DHEA in males, and with etiocholanolone in females. The results suggest that sebaceous gland activity is stimulated by adrenocortical androgens in prepuberty, in addition to the strong effect of testosterone during puberty.

Adolescent↗

Biological purpose of acne.

It is argued that the close endocrine control of human sebaceous glands and the likely effects of acne on selection indicate that both gland and disease have persisted because they are biologically useful. Two possibilities are proposed: sebum may provide precursor substrates for metabolism and synthesis by the epidermis of compounds of both local and systemic importance; and the adjuvent properties of corynebacteria which colonise the active sebaceous glands of acne may facilitate certain general immunological membrane.

Acne Vulgaris↗

13-cis retinoic acid and acne.

Patients with very severe acne which had not responded to conventional treatment were given 13-cis retinoic acid (0.1 mg-1.0 mg/kg body-weight) in a double-blind dose response study. Sebum excretion rate was reduced by 75% at 4 weeks, and all patients had an 80% improvement in their acne severity after 4 months treatment. There were dose-related side-effects, particularly dryness of the skin and mucous membranes. No patient wished to stop treatment.

Acne Vulgaris↗

Isotretinoin versus placebo in the treatment of cystic acne. A randomized double-blind study.

Thirty-three patients with treatment-resistant cystic and conglobate acne entered a randomized, double-blind protocol testing the efficacy of isotretinoin versus placebo. There was an overall 57% increase in the number of cystic lesions in seventeen patients who initially received placebo. Sixteen of these seventeen patients then received isotretinoin, with a resultant 98% improvement. The sixteen patients who had been randomly assigned to receive initial therapy with isotretinoin had a 95% improvement. Twenty-seven of the thirty-two patients treated with isotretinoin cleared completely. The average maximum dosage of isotretinoin received by these patients was 1.2 mg/kg/day. Eighteen patients received only one 4-month course of isotretinoin. Fifteen patients received two courses. These included twelve patients with predominantly truncal acne who responded partially to the first course, and three patients who had cleared completely after one course of therapy but had mild relapses after an average of six months off of treatment. All patients are now in remission averaging 38 months in duration. Skin biopsies and quantitative measurement of sebum production during therapy indicated a profound inhibition of sebaceous gland size and function, which may be central to the mechanism of action of isotretinoin in acne.

Acne Vulgaris↗

Capillary gas chromatographic analysis of human skin surface lipids after microsampling on ground-glass platelets.

Small amounts of human skin surface lipids, in the 1-20 micrograms range, sampled on ground-glass platelets are investigated using capillary gas chromatography. A first system allows the separation of the neutral lipids, up to the triglyceride fraction. A second system reveals the distribution of the free fatty acids or of the free + glyceride fatty acids, after a methylation or transesterification step. Examination of samples from nine subjects shows that the unsaturation of the free fatty acids increases during a four-day period of accumulation. Comparison of the free fatty acid fraction and the free + glyceride fatty acid fraction shows that the fraction is more saturated than the latter. It is concluded that the bacterial lipases which cleave the fatty acids from the ester bond favor the liberation of straight-chain saturated fatty acids from sebum triglycerides. This result is confirmed by comparison of the free fatty acid fraction with the glyceride fatty acid fraction separated from bulk samples of skin surface lipids from hair and scalp.

Chromatography, Gas↗

Dolichol: a solar filter with UV-absorbing properties which can be photoenhanced.

Dolichol, the polyisoprenoid lipid found in all eukaryotic cells and suggested to represent a biomarker of aging, is inserted into cell membranes, also in tissues exposed to light such as the skin. A general question about its physiological role is whether dolichol may play the role of a natural barrier for the noxious components of solar radiation. In order to clarify this point, we established that dolichol is a component of human sebum and we performed an " in vitro " study of the effects of UV radiation on the spectral properties of dolichol in isopropanol. Our data clearly show that, following UV irradiation, the optical absorption spectrum of dolichol undergoes remarkable modifications below 400 nm: a significant, strongly dose-dependent, increase of the optical density around 320 nm and a minor, very slightly dose-dependent, raise of the absorbance at 250 nm. On the contrary, UV irradiation causes only minor changes in HPLC profiles and the formation of photooxidative products can be considered negligible in our experimental conditions. These results suggest that dolichol can be considered an innate, unusually efficient and promising UV screen for skin protection.

2-Propanol↗

Peroxidated squalene induces the production of inflammatory mediators in HaCaT keratinocytes: a possible role in acne vulgaris.

In order to investigate whether products derived from the oxidation of sebum can be responsible for the induction of inflammatory processes, HaCaT keratinocytes were treated with peroxidated squalene. NF-kappaB activation, secretion, and expression of IL-6, as well as peroxisome proliferator-activated receptor alpha (PPARalpha) mRNA and protein levels, were measured at the end of the treatment and after 24 and 48 hours of recovery. Squalene peroxidation products were administered in amounts able to elicit significant hyperproliferation and to induce lipoxygenase (LOX) activity. The results showed an early activation of NF-kappaB followed by an increase in PPARalpha mRNA and protein levels. Moreover, squalene peroxides induced an initial upregulation of IL-6 production and secretion that was counteracted by PPARalpha activation, as suggested by the subsequent decrease of NF-kappaB nuclear translocation and IL-6 levels. Inflammatory processes play an important role in the development of acne vulgaris. In combination with our own previous findings, which indicated an association between LOX stimulation and increased percentage of proinflammatory lipids in acne as well as a correlation between increased cytokine levels in the infundibulum, pilosebaceous duct hyperkeratinization, and augmented sebogenesis, the present data further support the involvement of lipid peroxides, in particular squalene peroxides, in establishing an inflammatory process in acne.

Acne Vulgaris↗

Differential response of sebaceous glands to exogenous testosterone.

To test the hypothesis that the seborrhoea of acne is an end-organ hyper-response to androgens, a standardized dose of 2% testosterone cream was applied to the forehead of eight prepubertal boys for 6 weeks and the effect determined by measurements of sebum excretion rate (SER). Three boys showed a 15-fold increase in SER and three boys were non-responders, whereas two boys had SER values between those of the responders and non-responders. These data show that sebaceous glands are stimulated by androgens to varying degrees and support the theory of an end-organ response in acne.

Acne Vulgaris↗

Itchy folliculitis and human immunodeficiency virus infection: clinicopathological and immunological features, pathogenesis and treatment.

The predominant itchy folliculitis associated with human immunodeficiency virus (HIV) infection appears to be an eosinophilic folliculitis (EF). This is characterized by lytic degeneration of sebaceous glands and an inflammatory infiltrate in which eosinophils and CD8+ T lymphocytes predominate. All patients have low CD4 counts and present late on in their HIV disease. Lesional distribution is mainly truncal, with a significant proportion also having facial involvement. Our prospective survey has shown that it is impossible to differentiate clinically between infective folliculitis and EF, and we recommend therefore that all cases are biopsied. We review the clinicopathological and immunological aspects of HIV-associated itchy folliculitis, in particular HIV-associated EF as well as current theories on pathogenesis and treatment. We suggest that HIV-associated EF is an autoimmune disease with the sebocyte or some constituent of sebum acting as the autoantigen.

AIDS-Related Opportunistic Infections↗

Changes in skin physiology during bath PUVA therapy.

BACKGROUND: Frequent bathing leads to a skin barrier damage with various changes in physiological skin parameters. Conversely, ultraviolet (UV) irradiation may improve the impaired skin barrier by reducing inflammatory reactions. OBJECTIVES: The aim of this study was to investigate the changes of physiological skin parameters during a therapy with 8-methoxypsoralen (8-MOP) bathing and subsequent UVA irradiation. METHODS: Thirty patients with a skin disease without barrier disruption were treated with daily bathing in a 8-MOP solution (0.0005%) and subsequent UVA irradiation. Multiple physiological skin parameters (transepidermal water loss, skin blood flow, skin colour, sebum content, skin hydration) were measured repeatedly on clinically non-affected skin on the back, forearm and forehead. In addition, patch testing with sodium lauryl sulphate (SLS) (0.5%) was performed on the forearm and on the back. RESULTS: We found a moderate but significant disturbance of skin barrier and hydration on the forearm and the back (bathing + irradiation) after increasing dosages of therapy. In addition, SLS testing leads to stronger reactions. CONCLUSIONS: We conclude that on clinically healthy skin the impairment of skin barrier by frequent bathing cannot be completely compensated by subsequent UVA irradiation. When conducting a treatment with 8-MOP bathing and UVA irradiation a concomitant therapy supporting the recovery of skin barrier, e.g. with moisturizer, should be performed.

Adult↗

Very low dose isotretinoin is effective in controlling seborrhea.

BACKGROUND: Excessive seborrhea, coarse-pored skin, minimal acne and oily scalp hair comprise a well-known clinical entity. It causes considerable concern, has social impact, and affects the quality of life in some individuals. Some patients seek treatment for seborrhea. No effective topical sebosuppressive medication is available. Oral isotretinoin is the only remedy for men. In women, oral isotretinoin is the most effective remedy, followed by antiandrogens. PATIENTS AND METHODS: Eleven patients in three groups were treated for 6 months with very low dose isotretinoin. The influence on seborrhea was measured during oral treatment with 5 mg/d, 2.5 mg/d, or 2.5 mg 3x weekly. RESULTS: Sebum production, measured with Sebutape, was reduced by up to 64%. Acne lesions regressed by as much as 84%. Follicular filaments were reduced by 66%. Microcomedones were reduced on average up to 86%. Quantitative bacteriology showed a reduction of Propionibacterium acnes but no increase of Staphylococcus epidermidis. Biopsies revealed a 51% reduction in sebaceous gland size. With Bentonite, a reduction of lipids was demonstrated with 2.5 and 5 mg isotretinoin/d but not with 2.5 mg 3x weekly. There was a shift within the lipid fractions: triglycerides dominated, followed by squalenes and free fatty acids. CONCLUSIONS: Good results were achieved in all patients. The small number of patients did not permit a statistical analysis of the three isotretinoin doses studied, but there was a tendency toward better results with the two higher doses.

Administration, Oral↗

Identification of the delta-6 desaturase of human sebaceous glands: expression and enzyme activity.

Delta-6 desaturase, also known as fatty acid desaturase-2 (FADS2), is a component of a lipid metabolic pathway that converts the essential fatty acids linoleate and alpha-linolenate into long-chain polyunsaturated fatty acids. Isolation of Delta-6 desaturase/FADS2 cDNA from human skin predicts an identical protein to that expressed in human brain and Southern analysis indicates a single locus, together suggestive of a single Delta-6 desaturase/FADS2 gene. Within human skin, Delta-6 desaturase/FADS2 mRNA and protein expression is restricted to differentiating sebocytes located in the suprabasal layers of the sebaceous gland. Enzymatic analysis using CHO cells overexpressing human Delta-6 desaturase/FADS2 indicates catalysis of a "polyunsaturated fatty acid type" reaction, but also an unexpected "sebaceous-type" reaction, that of converting palmitate into the mono-unsaturated fatty acid sapienate, a 16-carbon fatty acid with a single cis double bond at the sixth carbon from the carboxyl end. Sapienate is the most abundant fatty acid in human sebum, and among hair-bearing animals is restricted to humans. This work identifies Delta-6 desaturase/FADS2 as the major fatty acid desaturase in human sebaceous glands and suggests that the environment of the sebaceous gland permits catalysis of the sebaceous-type reaction and restricts catalysis of the polyunsaturated fatty acid type reaction.

Animals↗

Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue.

The secretion and the blood levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) decrease profoundly with age, and the question is posed whether administration of the steroid to compensate for the decline counteracts defects associated with aging. The commercial availability of DHEA outside the regular pharmaceutical-medical network in the United States creates a real public health problem that may be resolved only by appropriate long-term clinical trials in elderly men and women. Two hundred and eighty healthy individuals (women and men 60-79 years old) were given DHEA, 50 mg, or placebo, orally, daily for a year in a double-blind, placebo-controlled study. No potentially harmful accumulation of DHEAS and active steroids was recorded. Besides the reestablishment of a "young" concentration of DHEAS, a small increase of testosterone and estradiol was noted, particularly in women, and may be involved in the significantly demonstrated physiological-clinical manifestations here reported. Bone turnover improved selectively in women >70 years old, as assessed by the dual-energy x-ray absorptiometry (DEXA) technique and the decrease of osteoclastic activity. A significant increase in most libido parameters was also found in these older women. Improvement of the skin status was observed, particularly in women, in terms of hydration, epidermal thickness, sebum production, and pigmentation. A number of biological indices confirmed the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging, but does not create "supermen/women" (doping).

Absorptiometry, Photon↗

Loss of keratin 10 is accompanied by increased sebocyte proliferation and differentiation.

Here, we present strong evidence that the targeted deletion of keratin 10 (K10) alters sebocyte differentiation in mice, mediated by an increased proliferation and differentiation of cells located in the periphery of the glands. This was not accompanied by the induction of the proliferation-associated keratins K6, K16 and K17. Sebaceous gland cells of K10-/- mice showed an accelerated turnover and secreted more sebum including wax esters, triglycerides, and cholesterol esters. The levels of the major epidermal lipids ceramides and cholesterol were also increased, whereas glycosylceramides and sphingomyelin were decreased which was not based on altered sphingolipid biosynthesis. The amount of Cer(OS), covalently bound to the cornified envelope, remained unchanged, as well as the amount of loricrin and involucrin. In agreement with the unaltered expression of beta-catenin and its targets cyclin D1 and c-Myc, we conclude that the altered composition of the suprabasal intermediate filament cytoskeleton in K10-/- mice increased the differentiation of epidermal stem cells towards the sebocyte lineage.

Animals↗

An analysis of the reduction of elasticity on the ageing of human skin and the recovering effect of a facial massage.

Based on a study of human hand movements during practical diagnosis, evaluation patterns of softness and elasticity were observed. The evaluation models were extracted from these analyses and applied to the developing a method of detecting the dynamic properties of human skin. The device consisted of a robot arm controlled by microcomputer system and a probe with a mounted mechanical strain gauge. A method was developed to measure the dynamic properties of human skin. Correlations were obtained between parameters from the measurements and the values evaluated by experts. The dynamic properties of the cheek skins of a panel of 86 people, aged from 20 to 75 years, were measured. A remarkable reduction in elasticity was observed in older people and the lack of sebum was analysed. From these results the metabolism in the skin surface and the muscles of the cheeks were analysed. The effects of skin care products were then confirmed by measuring cheeks before and after continual use of facial treatment systems for a month. Significant recovery effects were observed in a less soft-skinned group and a less elastic-skinned group over 30 years of age. These experiments suggest a protecting effect of facial treatments and skin care products.

Adult↗