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At least 595 records · Page 33Linked to original sources
PubMed2003

Inducible mEDA-A1 transgene mediates sebaceous gland hyperplasia and differential formation of two types of mouse hair follicles.

EDA splice isoforms EDA-A1 and EDA-A2 belong to the TNF ligand family and regulate skin appendage formation by activating NF-kappa B- and JNK- promoted transcription. To analyze their action further, we conditionally expressed the isoforms as tetracycline ('Tet')-regulated transgenes in Tabby (EDA-negative) and wild-type mice. Expression of only the mEDA-A1 transgene had two types of effects during embryogenesis: (1) determinative effects on sweat glands and hair follicles. In Tabby mice, one type of hair follicle ('guard hair') was restored, whereas a second type, the dominant undercoat hair follicle ('zigzag') was not; furthermore, the transgene sharply suppressed zigzag hair formation in wild-type mice, with the overall numbers of back hair follicles remaining the same; and (2) trophic effects on sebaceous and Meibomian glands. Marked hyperplasia resulted from expansion of the sebocyte-producing zone in sebaceous glands, with particularly high expression of the transgene and the replication marker PCNA, and correspondingly high production of sebum. The phenotypic effects of mEDA-A1 on sebaceous glands, but not on hair follicles, were reversed when the gene was repressed in adult animals. The results thus reveal both initiating and trophic isoform-specific effects of the EDA gene, and suggest a possible balance of isoform interactions in skin appendage formation.

Animals↗
PubMed1989

Changes in the relative amounts of endogenous and exogenous fatty acids in sebaceous lipids during early adolescence.

Skin surface lipid samples were collected from the scalps of 40 males, aged 9-15, and the lipid class composition of each was analyzed by quantitative thin layer chromatography. The ratio of wax esters/[cholesterol + cholesterol esters] (WE/[CH + CE]) increased with age. The wax ester, cholesterol ester, triglyceride, and free fatty acid classes were isolated from each sample and the fatty acid compositions were determined by capillary gas chromatography of fatty acid methyl esters (FAME) prepared from each lipid class. The concentrations of most of the different types of fatty acids were found to be correlated with the WE/[CH + CE] ratio. Those straight chain fatty acids that are thought to be synthesized mainly within the sebaceous glands, such as 14:0, 14:1, 16:1, and 18:2 delta 5, 8 tended to increase with increasing WE/[CH + CE], while fatty acids which circulate in the blood, such as 18:0, 18:1, and 18:2 delta 9, 12, tended to decrease with increasing WE/[CH + CE]. For the majority of straight chain fatty acid types, the data could be fitted to the equation y = a + b/[x + 1], which can be derived from simple assumptions concerning the origins of the various sebum components. The FAME from the wax esters were separated into saturated and monounsaturated fractions and analyzed by capillary gas chromatography to determine the concentrations of the different types of branched chain FAME present. In the wax esters, straight chain fatty acids tended to increase with increasing WE/[CH + CE], while terminally branched (iso and anteiso) fatty acids tended to decrease. Other branched chain fatty acids increased up to a WE/[CH + CE] ratio of about 2 and then decreased at higher ratios.

Adolescent↗
PubMed1989

The hamster flank organ model: is it relevant to man?

The critical role that androgens play in the etiology of acne has led to a search for topically active antiandrogens and the frequent use of the flank organ of the golden Syrian hamster as an animal model. 17-alpha-propyltestosterone (17-PT) has been identified as having potent antiandrogenic activity in the hamster model, and this report describes its clinical evaluation. Two double-blind placebo controlled studies comparing 4% 17-PT in 80% alcohol versus vehicle alone were conducted. One study examined 17-PT sebosuppressive activity in 20 subjects. The second study examined its efficacy in 44 subjects having mild to moderate acne. A third study measured in vitro percutaneous absorption of 17-PT through hamster flank and monkey skin, and human face skin in-vivo, using radioactive drug. 17-PT was found to be ineffective in reducing either the sebum excretion rate or the number of inflammatory acne lesions. Failure of 17-PT to show clinical activity was not a result of poor percutaneous absorption. Total absorption in man was 7.7% of the dose and only 1.0% in the hamster. The sebaceous gland of hamster flank organ is apparently more sensitive to antiandrogens than the human sebaceous gland.

Acne Vulgaris↗
PubMed1986

Qualitative and quantitative changes in cutaneous bacteria associated with systemic isotretinoin therapy for acne conglobata.

Quantitative cultures in 40 patients treated with systemic isotretinoin demonstrated a significant reduction in the anaerobic diphtheroid, Propionibacterium acnes within one month of therapy and a continued suppression during 5 months of treatment. This reduction persisted after discontinuation of isotretinoin therapy despite a return of sebum excretion to pretreatment levels. Surface aerobic bacteria showed a significant reduction in the total number of organisms and significant qualitative changes. Gram negative bacteria were sharply reduced in both the anterior nares and skin while Staphylococcus aureus recovery increased significantly.

Acne Vulgaris↗
PubMed1993

19-Aldehydo-4-androstene-3,17-dione: an estrogen precursor that inhibits sebaceous secretion in a rat model.

19-aldehydo-4-androstene-3,17-dione (A; R = CHO), a biogenetic precursor of estrone in the body, has been found to suppress sebum secretion in the ovariectomized testosterone-treated Wistar rat at 1/2000 times the dose of cyproterone acetate required to produce an equivalent effect. The action of this steroid must therefore be analogous to that of an estrogen even though, in striking contrast to estradiol, it is without effect on uterine weight or vaginal cornification. It is postulated that 19-aldehydo-4-androstene-3,17-dione (A; R = CHO) is converted locally into estrone (B) by aromatase present in skin but only in low concentrations in vagina and uterus. The potential of biogenetic precursors (I) of estrogens for therapy of acne or alleviation of the worst effects of skin aging is worth investigation.

Androstenedione↗
PubMed1994

Characterization of low-temperature (i.e., < 65 degrees C) lipid transitions in human stratum corneum.

This study aims to characterize human stratum corneum (SC), focusing on those lipid transitions that occur at or below physiologically relevant temperatures. In the past, a lipid transition near 35 degrees C had been thought to be variable and a consequence of superficial sebaceous lipid contamination. However, analysis here indicates that it is widely present, and cannot be attributed to sebum production. We demonstrate that this transition represents a solid-to-fluid phase change for a discrete subset of SC lipids. The reversibility of this transition upon reheating, and its absence in extracted lipid samples imply that these lipids are not uniformly present throughout the SC, but would appear to be differentially distributed in response to terminal differentiation. Further, such an arrangement could involve a close association with other nonlipid (e.g., protein) components. Evidence for a new transition at approximately 55 degrees C is presented that suggests the loss of crystalline orthorhombic lattice structure. The existence of orthorhombic structure at physiologic temperature is reasoned to involve ceramides and/or free fatty acids. Localization of these lipids at the level of the corneocyte envelope supports a comprehensive picture of water transport across the SC, whereby diffusion occurs primarily via the intercellular lipids. This view, coupled with the hydration-induced changes in lipid disorder observed here provides additional insight into the mechanism by which skin occlusion increases permeability. Summarily, these results i) emphasize the inherent danger of over-interpreting experiments with isolated SC lipids, ii) emphasize the potential advantage(s) of employing several biophysical techniques to study SC structure, and iii) indicate that a full characterization of lipid phase behavior is requisite to our eventual understanding of SC structure and permeability function, particularly those phase transitions that occur near or at normal skin temperature.

Calorimetry, Differential Scanning↗
PubMed1976

Octadecadienoic acids in the skin surface lipids of acne patients and normal subjects.

Measurements were made of the proportions of octadeca-5,8-dienoic acid and octadeca-9,12-dienoic acid in the scalp surface lipids of 6 normal subjects, 5 subjects with slight acne, and 9 subjects with severe acne. The group averages for the delta5,8 isomer were: 0.74, 0.85, and 0.61% and for the delta9,12 isomer were 0.56, 0.27, and 0.19%, respectively. The differences in the levels of the delta9,12 isomer between the normal subjects and the groups with slight and with severe acne were statistically significant (p less than 0.02 and 0.001), respectively) but there was no significant difference in the content of the delta5,8 compound. The ratio of the delta5,8/delta9,12 isomers showed no correlation with the rate of sebum production in 12 subjects.

Acne Vulgaris↗
PubMed1975

The effects of a nonsteroid antiandrogen, flutamide, on sebaceous gland activity.

Flutamide (alpha,alpha,alpha-trifluoro-2-methyl-4'-nitro-m-propionotoluidide), at daily oral doses of 20 mg/day for 24 days, reduced the number and size of skin sebaceous gland cells, and reduced sebum production in ovariectomized, testosterone-stimulated rats. The weight of the preputial glands was also reduced. Unilateral topical application of flutamide (0.1-3.0 mg/day) to flank organs (androgen-sensitive cutaneous sebaceous structures) of testosterone propionate-treated female hamsters for 14 days resulted in bilateral reductions in flank organ weight and in inhibition of in vitro incorporation of 14-C from sodium [1--14C]acetate into lipids. Flutamide inhibition of flank organ weight paralleled the drug effect on lipogenesis. Unilateral topical application of flutamide to flank organs of intact male hamsters for 14 days resulted in significant bilateral reductions of flank organ weight at doses as low as 0.375 mg/day (the lowest dose tested). These weight changes were marked by reduction in sebaceous gland size, accompanied by focal cytoplasmic degeneration, and reductions in cytoplasmic organelles and in the size of the lipid bodies. Flutamide did not, however, seemingly alter the pattern of endogenous total lipids in sebaceous glands, nor did it alter the pattern of 14-C-incorporation into the lipids of male flank organ epidermis and isolated sebaceous glands, when compared to control, untreated preparations.

Acetates↗
PubMed1983

The relationship between the vitro activity of 3 beta-hydroxysteroid dehydrogenase delta 4-5-isomerase in human sebaceous glands and their secretory activity in vivo.

3 beta-hydroxysteroid dehydrogenase delta 4-5-isomerase (delta 5-3 beta-HSD) catalyzes an early step in the synthesis of testosterone from dehydroepiandrosterone (DHA). We compared enzyme activity in back skin biopsies with sebum excretion rate (SER) in 14 individuals. The rate of conversion of [7 alpha-3H]DHA into [3H]-4-androstene-3,17-dione was measured in cryostat sections of skin and compared with the sebaceous gland content of the same biopsies. Reaction rate was proportional to the volume of sebaceous gland tissue in the sections. Enzyme activity was absent from sections without histologically identifiable sebaceous gland tissue. This suggests that the delta 5-3 beta-HSD is localized in sebaceous glands. SER, measured by a modified photometric technique at the biopsy site, correlated highly with sebaceous gland volume and with the rate of conversion of DHA into androstenedione in the biopsy. For each biopsy, specific activity of delta 5-3 beta-HSD in sebaceous glands was calculated by dividing the rate of formation of [3H]-4-androstene-3,17-dione by sebaceous gland volume. Specific activity of delta 5-3 beta-HSD did not correlate significantly with SER, suggesting that variations in concentration of delta 5-3 beta-HSD in sebaceous glands probably do not underlie variations in sebaceous gland activity.

3-Hydroxysteroid Dehydrogenases↗
PubMed1980

In vitro effects of skin lipid extracts on skin bacteria in relation to age and acne changes.

Skin lipid extracts of 185 persons of different age were tested in vitro against single representatives of skin bacteria: Staphylococcus aureus, S. epidermidis, Propionibacterium acnes, P. granulosum and Corynebacterium sp. in order to find differences in their inhibitory effects. Percentages of the extracts inhibiting the first 4 bacteria were nearly the same (about 20%) while corynebacteria were inhibited by only 3 extracts. Extracts showing these properties were isolated mainly from adolescents with acne changes, young adults, about 20 yr old, and from children 8--10 yr old, but not from elderly people. The age-related differences in growth inhibition may be related to known differences in relative composition of the sebum constituents according to age. Forty-two extracts of acne patients and healthy adults and adolescents showed an inverse effect in vitro: they enhanced bacterial growth. Growth enhancement was demonstrated only for P. granulosum.

Acne Vulgaris↗
PubMed2005

The role of sebaceous gland activity and scalp microfloral metabolism in the etiology of seborrheic dermatitis and dandruff.

Most common scalp flaking disorders show a strong correlation with sebaceous gland (SG) activity. Early SG activity in the neonate results in microfloral colonization and cradle cap. After maternal hormonal control subsides, there is little SG activity until puberty, when the SG turns on under sex hormone control. When the SG activity increases, the present but low Malassezia population has a new food source and proliferates, resulting in the scalp itching and flaking common to greater than 50% of adults. Dry scalp flaking, dandruff, and seborrheic dermatitis are chronic scalp manifestations of similar etiology differing only in severity. The common etiology is a convergence of three factors: (1) SG secretions, (2) microfloral metabolism, and (3) individual susceptibility. Dandruff and seborrheic dermatitis (D/SD) are more than superficial stratum corneum disorders, including alteration of the epidermis with hyperproliferation, excess lipids, interdigitation of the corneal envelope, and parakeratosis. The pathogenic role of Malassezia in D/SD has recently been elucidated, and is focused on their lipid metabolism. Malassezia restricta and M. globosa require lipids. They degrade sebum, free fatty acids from triglycerides, consume specific saturated fatty acids, and leave behind the unsaturates. Penetration of the modified sebaceous secretions results in inflammation, irritation, and scalp flaking.

Dermatitis, Seborrheic↗
PubMed1975

The sebotrophic action of growth hormone (BGH) in the rat.

Sebum production of rats was assessed by measuring the levels of fat extractable by diethyl ether from samples of hair clipped immediately after shampooing with sodium lauryl sulphate and 2 days later. By the use of matched litter mates in was unequivocally demonstrated that the response of the sebaceous glands to testosterone is virtually abolished by hypophysectomy and that it can be completely restored by pure bovine growth hormone.

Animals↗
PubMed1976

The lipid composition of sebaceous glands as a reflection of gland size.

Following 4 h incubation in vitro, the patterns of incorporation of [I-14C] acetate into the lipid classes of human sebaceous glands which were dissected from small skin biopsies have been established for glands of different size. It has been shown that in the larger sebaceous glands proportionately more of the labelled acetate is incorporated into squalene at the expense of triglycerides. Experiments are presented as a result of which we conclude that this in vitro phenomenon, observed with [I-14C] acetate incorporation, does reflect parallel changes in the proportions of these lipids actually present in glands of different size. It is suggested that the larger sebaceous glands of the acne patient elaborate sebum which has an enhanced potential for inducing comedo formation by virtue of an increased concentration of squalene. This work also demonstrates that, in the interpretation of in vitro studies of sebaceous gland lipogenesis utilizing labelled precursors, the size of the sebaceous glands must be carefully considered whenever patterns of incorporation are being compared.

Acne Vulgaris↗
PubMed1977

An acne-free naevus.

Investigation of rare disorders may sometimes help in the understanding of common problems. We describe a patient with an unusual and previously unreported acne-free naevus occurring in an area severely affected by acne. Investigation revealed smaller sebaceous glands, a reduced sebum excretion rate, decreased number of Corynebacterium acnes in the pilosebaceous ducts and a reduced conversion of testosterone to 5 alphadihydrotestosterone in the areas which were free of acne compared with acne-bearing skin. The results of these investigations support some of the suggested mechanisms responsible for the development of acne.

Acne Vulgaris↗
PubMed1984

The mode of action of ethyl lactate as a treatment for acne.

We have shown that an alcoholic lotion containing ethyl lactate when applied topically to rat skin under occlusion became localized in the follicles and sebaceous glands. When applied to human facial skin the ethyl lactate was hydrolysed to ethanol and lactic acid, and thereby lowered the skin pH. Under such conditions the growth of recoverable skin bacteria, in particular the anaerobe Propionibacterium acnes, was inhibited, and the hydrolysis of sebum to free fatty acids by lipase derived from the bacteria was greatly impaired. These effects of ethyl lactate would account for its observed clinical efficacy in acne vulgaris.

Acne Vulgaris↗
PubMed1984

Effect of low dose cyproterone acetate on the response of acne to isotretinoin.

Twenty-seven males with severe acne were treated for 12 weeks with 0.05 mg/kg/day isotretinoin (ten patients) or 5 mg daily cyproterone acetate (eight patients) or both drugs together in these doses (nine patients). With isotretinoin, the sebum excretion rate (SER) fell by 45% +/- 9% s.e.m. (P less than 0.0025), lesion count fell by 65% +/- 10% (P less than 0.0005) and median clinical 17% +/- 12% (NS) fall in SER, a 15% +/- 10% (NS) fall in lesion count and the median severity was unchanged. Patients unchanged. Patients treated with both drugs showed a 42% +/- 13% reduction in SER (P less than 0.005), a 68% +/- 11% decrease in lesion count (P less than 0.0005) and a decrease in median severity from 8 to 4 (P less than 0.01) which was no different from the response to isotretinoin alone. Isotretinoin increased serum cholesterol from 4.4 mmol/l +/- 0.3 s.e.m. to 4.7 mmol/l +/- 0.3 s.e.m. (P less than 0.01), serum triglyceride from 0.73 mmol/l +/- 0.07 s.e.m. to 0.96 mmol/l +/- 0.14 s.e.m. (P less than 0.05) and gamma-glutamyltransferase (GGT) from 15.9 i.u./l +/- 2.1 s.e.m. to 19.0 i.u./l +/- 2.4 s.e.m. (P less than 0.01). Comparison of the area under the concentration-time curve for triglyceride and high density lipoprotein (HDL)-cholesterol showed that the changes were smaller when isotretinoin was combined with cyproterone acetate. We conclude that the effect of isotretinoin in acne was not enhanced by the antiandrogen, but the increase in serum triglyceride and decrease in HDL-cholesterol produced by the retinoid were reduced by combination with the antiandrogen.

Acne Vulgaris↗
PubMed1986

Evaluation of a therapeutic strategy for the treatment of acne vulgaris with conventional therapy.

Four hundred and twenty patients with moderate to severe acne vulgaris were treated with oral erythromycin and topical benzoyl peroxide to determine the optimum dose regimes. Our results show that the response was significantly less in patients with a greater severity of acne, with truncal acne and in those with a higher sebum excretion rate. There was a significantly better clinical result in patients given Ig erythromycin daily than in those given 0.5 g daily (plus topical therapy in both groups). The relapse rate on stopping antibiotics is also significantly less in patients given I g daily and this dosage did not produce any increase in side effects. We suggest that any patient requiring oral antibiotics should initially be given I g daily of erythromycin (or tetracycline) for up to six months, plus topical therapy.

Acne Vulgaris↗