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PubMed1988

Pharmacokinetic profile of orally administered itraconazole in human skin.

Itraconazole is an orally effective antifungal agent with a high affinity for tissues. The skin kinetics in human volunteers have been studied after administration of 100 and 200 mg of itraconazole daily. From day 7 onward, tissue levels in the beard region and on the back were consistently higher than the corresponding plasma levels. The levels in the palmar stratum corneum were lower than the corresponding plasma levels but persisted for 3 weeks after discontinuation of therapy. Stratum corneum levels in the beard area were still measurable 4 weeks after the end of therapy. With the 200-mg dose, sweat levels became detectable 24 hours after the first drug intake. The sweat levels were usually lower than the corresponding plasma levels and followed the same curve as the plasma levels. Sebum levels of itraconazole were 10 times as high as the corresponding peak plasma levels. Sebum levels were undetectable 14 days after discontinuation of therapy. The results indicate that oral intake of itraconazole will result in therapeutic levels in the skin and these levels vary, depending on the region of skin tested. There are at least three routes of delivery of itraconazole to the skin: (1) passive uptake by keratinocytes in the basal layer (as shown by the continued presence of the drug in the palmar stratum corneum at a moment when plasma, sebum, and sweat levels are again undetectable); (2) a less significant excretion through the sweat glands (as shown by the lower drug levels compared with the plasma levels); and (3) a massive excretion through the sebaceous glands (as shown by the sebum levels compared with the plasma levels).

Administration, Oral↗
PubMed1998

The size of sebaceous glands in relation to the size of hair follicles on the heads of some small mammals (Insectivora, Chiroptera, Rodentia).

Many large sebaceous glands have been described, and functions such as scent production suggested, but gland size has seldom been studied in relation to the surface area of their hair follicles. However, investigating this relationship is essential for establishing whether glands produce more sebum than would be required for lubricating associated hair alone. Here, the relationship between sebaceous gland size and the surface area of the associated hair follicles has been studied. Glands on the heads of 20 species from three orders were compared with those associated with fur hairs. In all species, the fur hairs had small hair follicles with small sebaceous glands, as had the mystacial and submandibular hairs of Rodentia. Medium-sized glands and hairs were found in the mystacial and submandibular region in Insectivora, and in the circumoral region in Chiroptera and Rodentia. Large glands and hairs were found on a pad in the corner of the mouth in Rodentia. Although the size of glands was not directly proportional to hair size, some gross trends were noted. Vibrissae had either no or very small sebaceous glands. It is likely that sebum has to be provided from elsewhere to lubricate their surfaces. The glands on the snout of Insectivora and Chiroptera are clearly enlarged and could probably produce more sebum than would be required for grooming vibrissae alone. In Rodentia, vibrissae were surrounded by small hair and glands, and the nearest glands large enough to provide sebum were the glands on the pad in the mouth corner.

Animals↗
PubMed2001

Analysis of circadian and ultradian rhythms of skin surface properties of face and forearm of healthy women.

Biologic rhythms of cells and organisms are well documented and have been extensively studied at the physiologic and molecular levels. For the skin, many circadian changes have been investigated but few systematic studies comparing skin at different body sites have been reported. In this study we investigated facial and forearm skin circadian rhythms in eight healthy Caucasian women. Noninvasive methods were used to assess skin capacitance, sebum excretion, skin temperature, transepidermal water loss, and skin surface pH on fixed sites of the face and the volar forearm during a 48 h span under standardized environmental conditions. Using the cosinor or ANOVA methods, circadian rhythms could be detected for sebum excretion (face), transepidermal water loss (face and forearm), skin temperature (forearm), pH (face), and capacitance (forearm). No circadian rhythmicity was found for the other biophysical parameters. In addition to the 24 h rhythm component, rhythms with periods of 8 h were found for sebum excretion, of 8 and 12 h for transepidermal water loss (face and forearm), and of 12 h for skin temperature (forearm). Our study confirms that rhythms of skin surface parameters are readily measurable and that these rhythms differ between different sites. Furthermore, we demonstrate for the first time that, for transepidermal water loss (face and forearm), sebum excretion, and skin temperature (forearm), in addition to circadian rhythms, ultradian and/or component rhythms can be detected.

Activity Cycles↗
PubMed1999

Sebaceous gland secretion is a major physiologic route of vitamin E delivery to skin.

Skin plays an important part in the protection against oxidative stressors, such as ultraviolet radiation, ozone, and chemicals. This study was based on the observation that upper facial stratum corneum contained significantly higher levels of the antioxidant alpha-tocopherol than corresponding layers of arm stratum corneum. We hypothesized that the underlying mechanism involves sebaceous gland secretion of vitamin E. To test this, we examined in eight human volunteers: (i) stratum corneum levels and distribution profiles of vitamin E in sites with a different sebaceous gland density (arm versus cheek); (ii) whether vitamin E is a significant constituent of human sebum; and (iii) if there is a correlation between levels of vitamin E and squalene, a marker of sebum secretion, in skin surface lipids. Using standardized techniques for stratum corneum tape stripping and sebum collection, followed by high-performance liquid chromatography analysis of tocopherols and squalene, we found that: (i) the ratio of cheek versus upper arm alpha-tocopherol levels was 20 : 1 for the upper stratum corneum and decreased gradually with stratum corneum depth; (ii) vitamin E (alpha- and gamma-tocopherol forms) is a significant constituent of human sebum and is continuously secreted at cheek and forehead sites during a test period of 135 min; and (iii) vitamin E correlates well with levels of cosecreted squalene (r2 = 0.86, p < 0.001). In conclusion, sebaceous gland secretion is a relevant physiologic pathway for the delivery of vitamin E to upper layers of facial skin. This mechanism may serve to protect skin surface lipids and the upper stratum corneum from harmful oxidation.

Adult↗
PubMed2000

Effect of a desogestrel-containing oral contraceptive on the skin.

OBJECTIVE: This pilot study evaluated the effects of a desogestrel-containing oral contraceptive (DSG-OC) on facial seborrhea (oiliness), acne and related factors in otherwise healthy women with moderate facial acne vulgaris. METHODS: In this double-blind, placebo-controlled study, 41 women received DSG-OC (50/100/150 microg desogestrel plus 35/30/30 microg ethinylestradiol given in a 7/7/7 day regimen) and 41 received placebo for six cycles. Seborrhea and skin assessments, and hormone analyses were performed regularly. RESULTS: Analyses of sebum output (measured using Sebutape) indicated that the effect of DSG-OC on the skin varied with facial area. Compared with placebo, DSG-OC had a statistically significant effect on the cheeks (60% relative reduction in sebum output; p = 0.02), and a non-significant effect on the forehead (30% relative reduction in sebum output). Acne lesion counts did not differ significantly between groups. Both patient and investigator assessments of skin condition (visual analog scale) indicated significant improvements with DSG-OC compared with placebo. The reduced sebum output with DSG-OC is associated with a three-fold increase in sex hormone binding globulin, as well as an expected decrease in free testosterone and other androgens that were found in this group. CONCLUSION: These results suggest that DSG-OC reduces facial oiliness and may be a useful contraceptive choice for women with this problem.

Acne Vulgaris↗
PubMed2001

Polarized light photography and videomicroscopy greatly enhance the capability of estimating the therapeuic response to a topical retinoid (adapalene) in acne vulgaris.

Assessment of improvement in acne lesions following treatment is often based on clinical evaluation and photographs. However, limitations are associated with this sublective evaluation, making it difficult to accurately review individual acne lesions and to observe early response to therapy. Conventional photographs do not allow us to visualize small lesions, and it can be difficult to differentiate inflammatory lesions as papules or small nodules. Our objective was to evaluate a new standardized method for tracking individual acne lesions based on photographs. The effect of adapalene gel 0.1% on both inflammatory and noninflammatory acne lesions was evaluated using this technique. Polarized light photography and videomicroscopy were used to record the evolution of acne lesions over a 16-week period in 5 volunteers with moderate acne vulgaris. During the first 4 weeks before treatment, acne lesions were evaluated on a 3-times weekly basis to establish a pattern of progression and determine the length of time to resolution. Sebum secretion rates were monitored using Sebutape adhesive patches applied to the forehead and both cheeks for 1 hour. After 4 weeks, adapalene gel 0.1% was used once daily at bedtime for 8 weeks; polarized light photography, videomicroscopy, and assessment of sebum production followed treatment response. This treatment period was followed by a further 4-week phase, after which acne lesions and sebum secretion rates were evaluated. Our results showed that the new methodology was appropriate to track acne lesions and allowed an accurate and more oblective evaluation of individual lesions. Using this methodology demonstrated that adapalene gel 0.1% causes rapid resolution of inflammatory and noninflammatory lesions. The probability of clearing inflammatory and noninflamma tory lesions during the treatment period increased, and the probability of new lesions appearing decreased. Sebum secretion rates declined in patients while on study drug, returning to near pretreatment levels following therapy cessation. Using sophisticated photography and videomicroscopy every other day proved to be a valuable, noninvasive, and reliable method of following response to adapalene treatment in patients with moderate acne vulgaris.

Acne Vulgaris↗
PubMed1995

A double-blind controlled evaluation of the sebosuppressive activity of topical erythromycin-zinc complex.

In a double-blind randomised study, 14 volunteers applied 4% erythromycin plus 1.2% zinc (Zineryt lotion) and 4% erythromycin lotions, each on half of the forehead twice daily for 3 months. The sebum output was evaluated at 3-week intervals using the photometric and the lipid-sensitive film methods. Evaluations of casual level (CL) and sebum excretion rate (SER) were made with a Sebumeter, and total area of lipid spots (TAS) was measured on Sebutapes. Compared to baseline values, the formulation of the erythromycin-zinc complex induced significant reductions in SER after 6 and 9 weeks, and in CL and TAS at 3, 6, 9 and 12 weeks. The mean reduction in TAS was over 20% for four successive 1-h samplings on completion of the study. Significant reductions in CL, SER and TAS were observed for the erythromycin-zinc formulation compared to the control lotion at 6 and 9 weeks, and also at 3 weeks for SER and TAS, and at 12 weeks for CL and TAS. This study indicates that sebum output is significantly reduced by the erythromycin-zinc complex. This reduction is theoretically beneficial for the acneic patient.

Acetates↗
PubMed1987

Evaluation of a method for measuring the sustainable rate of sebaceous wax ester secretion.

Sebaceous wax ester secretion rates were measured in six subjects on six occasions each, using absorption into bentonite clay and analysis of the collected lipid by quantitative thin-layer chromatography. On each occasion eight samples were collected, four from the left and four from the right side of the forehead in four successive intervals. The first two intervals, which totaled 14 h, were intended to deplete the follicular reservoir of sebum so that a constant rate of absorption could be obtained during the third and fourth intervals, which were 3 h each. Thin-layer analysis of each sample was done in triplicate. The data were examined using analysis of variance techniques to determine the reproducibility of the measurement method and to identify possible sources of variability. The intraclass correlation coefficient (rI) for all 432 post-depletion determinations was 0.80. The reproducibility was considerably better for three of the subjects (rI = 0.93) than for the other three (rI = 0.75). Variability within the latter three subjects did not seem to be attributable to lack of reproducibility in the thin-layer analysis. Real biological variability also seems unlikely considering the holocrine mechanism of sebum secretion. Therefore, the variability probably arises from non-representative collection of sebum into the bentonite absorbent.

Adult↗
PubMed1982

Comparative effect of isotretinoin and etretinate on acne and sebaceous gland secretion.

Isotretinoin (13-cis-retinoic acid) was compared with the aromatic retinoid, etretinate, in patients with severe nodulocystic acne. Evaluation of fifty-six such men receiving 1 mg/kg of one or the other of these two drugs was performed with regard to clinical improvement and change in sebum production. Lesion counting demonstrated a significant improvement in patients receiving isotretinoin, particularly in facial lesions. There was significantly less improvement with etretinate. Similarly, isotretinoin produced a marked suppression of sebum production. There was little effect of etretinate on sebum production. Side effects were limited primarily to the skin and mucous membranes.

Acne Vulgaris↗
PubMed1997

On cosmetically treated hair--aspects and pitfalls of interpretation.

Popular hair cosmetic treatments like bleaching or permanent waving were found to affect the stability of incorporated drugs and to cause alterations of the fibers at an ultrastructural level. This may result in a partial or complete loss of drug substances, depending on the particular drug molecule and on its concentration prior to the cosmetic treatment. Moreover, from literature, there is some evidence that drug molecules are not only incorporated into the growing fiber by passive diffusion from blood into the matrix cells and melanocytes, but that the substances enter the hair also via perspiration such as sweat and sebum. Since permed and bleached hair shows an enhanced sorption capacity, the risk of false positives or an unusually high drug concentration in cosmetically treated hair was under investigation. Virgin, permed, mildly as well as severely bleached tresses were exposed to artificial sweat or sebum containing cocaine, benzoylecgonine, 6-acetylmorphine, morphine and codeine (500 ng/g). Except codeine, the concentrations measured by GC/MS were very small and quite close to the detection limit indicating a minor importance of drug uptake into hair fiber from the endogenous-exogenous shunt via sebum or sweat. From the results it is concluded that an increased risk of false positive results in hair analysis on bleached and permanent waved hair fibers does exist, but is not particularly severe.

Drug Interactions↗
PubMed2000

The melanocortin 5 receptor is expressed in human sebaceous glands and rat preputial cells.

Melanocortins regulate pigmentation, adrenal hormone secretion, immune functions, lipid metabolism, and feeding behaviors in rodents. These peptides include adrenocorticotrophic hormone, melanocyte stimulating hormone, beta-lipotrophin, and the endorphins. Lipid metabolism in sebaceous glands and preputial glands of rodents is regulated by alpha-melanocyte stimulating hormone, the major agonist for melanocortin receptors. Five melanocortin receptor subtypes have been identified that differ in their tissue localization and affinities for melanocortin ligands. Targeted disruption of the melanocortin 5 receptor in transgenic mice results in widespread dysfunction of exocrine glands, including a marked decrease in sebum production. A role for melanocortins in the modulation of human sebum production has not been established. The goal of this study is to determine which melanocortin receptors are expressed in human sebaceous glands. Messenger RNA was isolated from human sebaceous glands and the reverse transcriptase polymerase chain reaction was performed using primers specific for each of the melanocortin receptor subtypes. Transcripts were detected for the melanocortin 5 receptor. A polyclonal chicken antihuman antibody to the melanocortin 5 receptor localized to sebaceous glands, eccrine glands, hair follicles, and epidermis in human skin, rat skin, cultured human sebocytes, and rat preputial cells. Presence of the melanocortin 5 receptor protein in human sebaceous glands and rat preputial glands was further verified by Western blotting. These data support further investigation of the role of melanocortins in the regulation of human sebum production and support the use of the rat preputial system as an experimental model in sebaceous gland physiology.

Animals↗
PubMed1982

Variability in the fatty acid composition of wax esters from vernix caseosa and its possible relation to sebaceous gland activity.

Wax ester/sterol ester (WE/SE) ratios were measured in samples of vernix caseosa lipid obtained from 21 full-term infants. The mean WE/SE ratio was twice as high in males as in females, suggesting higher average fetal sebum production rates in males, but individual values varied widely and there was considerable overlap between the sexes. Wax esters (a class of lipid produced only by the sebaceous glands) were isolated from 6 of the 21 samples of vernix caseosa lipid and analyzed for fatty acid composition. The percentages of iso and anteiso branched saturated fatty acids and of delta 9-type monounsaturated fatty acids were found to be correlated negatively with the WE/SE ratios of the original lipid samples. Values for the percentages of the major delta 9-type monounsaturates, plotted as a function of WE/SE ratios, fell near a curve of the shape which would be expected if a limited quantity of delta 9-type monounsaturates were available for sebum synthesis, and were diluted with varying amounts of delta 6-type monounsaturates, the amount of the delta 6-type monounsaturates being proportional to the amount of wax esters synthesized by the sebaceous glands. The results suggested that the rate of sebum production may be the sole determinant of the percentage of delta 9-type monounsaturates in sebaceous wax esters and a partial determinant of the percentage of iso and anteiso branched saturates.

Esters↗
PubMed1977

Skin surface lipid composition, acne, pubertal development, and urinary excretion of testosterone and 17-ketosteroids in children.

Fifty-two children, age 5-10, from acne-prone families, were studied for a period of 1 year to examine the interrelationship between sebum, acne, pubertal development, and urinary steroid excretion. In each of the subjects, 30 boys and 22 girls, the composition of forehead skin lipid was determined 4 times yearly by thin-layer chromatography, with measurement of triglycerides, diglycerides, free fatty acids, wax esters, squalene, cholesterol, and cholesterol esters. Twice yearly, examination was made of the presence or absence of acne, pubertal maturation and the 24-hour urinary excretion of testosterone as determined by radioimmunnoassay, and of total 17-ketosteroids, dehydroepiandrosterone, androsterone, and etiocholanolone, as determined by paper chromatography. The relative amount of sebaceous lipids was positively correlated with age of the subjects (wax esters p less than .001, squalene p less than .05), as was the triglyceride-diglyceride component (p less than .05). No significant correlation was seen with the fatty acids. Acne, primarily comedonal, occurred in 27/52 subjects (15 girls, 12 boys) and was associated with higher sebum values. One-half of the children with acne had no signs of pubertal development. A significantly positive correlation was observed between the relative amount of sebaceous lipid and the urinary excretion of 17-ketosteroids, androsterone, and etiocholanolone in both sexes, and of testosterone and dehydroepiandrosterone in boys. The development of acne in children is an early pubertal event, often evident before other signs of pubertal maturation, and it is associated with an increase in sebum and in the urinary excretion of androgenic steroids.

17-Ketosteroids↗
PubMed1983

The local effects of topically applied estradiol, cyproterone acetate, and ethanol on sebaceous secretion in intact male rats.

Estradiol in ethanol was applied once daily to one flank of intact male rats and sebum production on both flanks was measured over periods of 18 h alternating with 6 h by absorbing the lipid on pads of cigarette paper held in place by a harness, starting on the 15th day. Sebum production was very significantly less on the treated flanks than on the contralateral flanks that received only vehicle, indicating an unequivocal local effect of the estradiol. At the same time, the values on the contralateral flanks were significantly below those of littermate rats which received vehicle only, indicating that the estrogen had been systemically absorbed to produce a distal action. The estradiol also significantly reduced plasma testosterone and the relative weights of the seminal vesicles, ventral prostate, and preputial glands, which demonstrated that part of the general action of the estrogen could have been by suppression of endogenous androgen production. In short-term experiments, in which measurements were started concurrently with treatment, the inhibitory action of estradiol, in contrast to that of cyproterone acetate, was not detected until the 4th day. Indeed, it appeared probable that the estrogen actually stimulated sebum secretion over the first 2 days, suggesting that it had a biphasic effect.

Administration, Topical↗
PubMed1978

Increased sebaceous gland activity in the adult rat after alpha-melanocyte-stimulating hormone treatment during early life.

Sebum secretion was measured in adult female and male rats given alpha-melanocyte stimulating hormone (alpha-MSH) during early life. Daily treatment with 40 microgram alpha-MSH/100 gm body weight for the first 5 weeks of life increased sebum secretion in female and male rats at 8, 11, and 15 weeks of age. A lower dose of alpha-MSH (10 microgram/100 gm body weight) produced similar changes in male but not in female rats. No effect on sebum secretion was found in female and male rats aged between 8-28 weeks when alpha-MSH was given (1) from the day of birth to 3 weeks; (2) 3--5 weeks; (3) 1st and 5th weeks and (4) 7--12 weeks. Apparently alpha-MSH must be given throughout the first 5 weeks of life in order to produce a sustained effect on the sebaceous glands. The fact that males appear to be more sensitive than females, in that they responded to a lower dose of alpha-MSH, may indicate that MSH acts by enhancing the response to androgen. Early alpha-MSH treatment failed to alter the sebaceous gland response to testosterone in adult female and male rats but the possibility that alpha-MSH enhances the action of androgen in early life cannot be ruled out.

Age Factors↗
PubMed2005

Is endogenous glycerol a determinant of stratum corneum hydration in humans?

Although stratum corneum (SC) hydration has been primarily of concern to the cosmetic industry, it serves an important biosensor function. In murine models, not only deiminated products of filaggrin-derived amino acids ("NMF") but also endogenous glycerol from circulation into the epidermis via aquaporin 3 channel and from triglyceride turnover in sebaceous glands (SG) are important determinants. We assessed here whether endogenous glycerol could also be linked to SC hydration in humans. SG-enriched sites are more hydrated than SG-impoverished sites, and SC hydration correlates with both sebum production and SC glycerol content, but the correlation is more significant for SC glycerol content than for sebum content. Moreover, gender-related differences in sebum content are not associated with altered SC hydration. SC hydration is also linked to SC glycerol content in SG-impoverished sites, suggesting a role for non-SG-derived (? from circulation) glycerol in SC hydration. Finally, short-term water immersion produces a parallel decline in SC hydration and SC glycerol content, with glycerol levels returning to normal over several hours. These results suggest that endogenous glycerol of both circulatory and SG origin comprises an H2O-extractable pool that influences SC hydration in humans. These results also provide a rationale for the development of glycerol-containing therapeutic moisturizers.

Adult↗
PubMed1972

Further observations on the pathogenesis of acne.

The composition of the lipid of the forehead skin surface and the sebum excretion rate were determined in 217 subjects and controls. Acne was associated with an increase in serum excretion rate and in the squalene and wax and sterol esters in surface lipid. The changes in sebum excretion rate and squalene were statistically significant only in women, but acne in men was associated with a significant decrease in the free fatty acid content or surface lipid.The increased amounts of squalene and wax esters may lead to pilosebaceous obstruction in acne subjects. The increased sebum excretion rate in acne may ensure increased production of sebaceous triglyceride substrate available for lipolysis to irritant free fatty acids, which may then mediate the inflammatory changes of acne.

Acne Vulgaris↗
PubMedDate not supplied

Daily variations in skin surface properties using mixed model methodology.

In order to explore the variations over the course of a day in certain skin biophysical properties, a study was conducted on 8 female volunteers. An assessment of several skin biophysical properties was carried out on the face and the volar forearm every 4 h over a period of 48 h. The biophysical parameters were assessed on the face for sebum secretion, skin surface pH, skin colour, transepidermal water loss, capacitance and skin surface temperature. The same parameters were measured on the volar forearm (excepted for sebum secretion). A statistical analysis based on mixed effect models was conducted. Four models, with different covariance structures, were successively tested. The analysis allowed us to identify a structure that repeated itself over time in the same way over each 24-hour period for capacitance on the forearm and for sebum secretion, skin surface pH and skin colour (L* and a* parameters) on the face. Mixed effect methodology is a powerful tool to analyse longitudinal data involving correlations among repeated measurements made on the same subject.

Adult↗