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The permissive effect of sebum in seborrhoeic dermatitis: an explanation of the rash in neurological disorders.

The hypothesis that sebum permits the growth of Pityrosporum ovale, and hence the development of seborrhoeic dermatitis, was tested by observing whether a reduction of sebum production by isotretinoin would improve the disorder. In 10 male patients with seborrhoeic dermatitis, treatment with isotretinoin for 6 weeks reduced the mean sebum excretion rate by 70% and improved the severity of the rash, but with a site difference in magnitude of response. It is concluded that the residual pool of sebum is important for the growth of P. ovale and that, within the physiological range, sebum has a permissive effect on the growth of this yeast. Variation in the pools of residual sebum explains a number of features of the disease such as site of involvement and greater prevalence in males than females. The pathological increase in the residual pool of sebum due to immobility explains the frequent occurrence of seborrhoeic dermatitis in patients with a variety of neurological disorders.

Adult↗

Female pattern hair loss, sebum excretion and the end-organ response to androgens.

BACKGROUND: Although female pattern hair loss can be a feature of hyperandrogenism, many women with hair loss show no clinical or biochemical features of androgen excess. It is possible that hair loss in nonhyperandrogenic women is due to a high level of response to androgens by scalp hair follicles. In this study we explored this idea using sebum excretion as a marker of the cutaneous end-organ response to androgens. OBJECTIVES: To test the hypothesis that hair loss in nonhyperandrogenic women is due to an increased cutaneous end-organ response to androgens. METHODS: We studied 100 women, 41 with female pattern hair loss (without hirsutism), 29 with hirsutism (with and without scalp hair loss) and 30 subjects without hair problems. We measured hair density on the frontal scalp, forehead sebum excretion, serum free androgen index (FAI), and body mass index (BMI). RESULTS: The mean FAI was significantly raised in hirsute women compared with nonhirsute women (P < 0.001), but there was no difference in FAI levels between nonhirsute women with and without hair loss. The mean BMI was also significantly elevated in hirsute women (P < 0.01) but there was no difference in BMI between nonhirsute women with and without hair loss. The mean sebum excretion was higher in hirsute women than nonhirsute women but the difference was not statistically significant. There was no difference in sebum excretion between nonhirsute women with and without hair loss. There was no correlation between hair density and sebum excretion. CONCLUSIONS: Our results show that sebum excretion is not elevated in women with female pattern hair loss. This may indicate that different androgen-response pathways operate in controlling hair growth and sebum excretion. The alternative explanation is that nonandrogenic mechanisms are involved in mediating hair loss in some women.

Adolescent↗

MK-386, an inhibitor of 5alpha-reductase type 1, reduces dihydrotestosterone concentrations in serum and sebum without affecting dihydrotestosterone concentrations in semen.

Two isozymes (types 1 and 2) of 5alpha-reductase (5alphaR; EC 1.3.99.5), with differential tissue distribution, catalyze the reduction of testosterone (T) to dihydrotestosterone (DHT) in humans. This study examined sequentially increasing oral doses of MK-386 (4,7beta-dimethyl-4-aza-5alpha-cholestan-3-one), an azasteroid that specifically inhibits the human 5alphaR1 isozyme in vitro. Finasteride, a selective inhibitor of 5alphaR2, was included for comparison. One hundred men were evaluated in a double blind, randomized, placebo-controlled, sequential, increasing dose, parallel group trial. Ten to 20 subjects received MK-386, and 2 to 5 received placebo in each of 6 panels. In 1 panel, 10 subjects received finasteride (5 mg), and 5 received placebo. Treatments were given once daily for 14 days, except in 1 panel in which MK-386 was administered 10 mg twice daily for comparison to 20 mg daily. Serum, sebum, and semen DHT concentrations and serum and sebum T concentrations were measured before and after treatment. The mean changes from baseline on day 14 for serum DHT after placebo and 0.1, 0.5, 5, 20, and 50 mg MK-386 were 6.9%, 4.6%, -2.7%, -1.2%, -14.1% (P < 0.05 vs. placebo), and -22.2% (P < 0.05 vs. placebo), respectively. No significant alterations in serum T were observed after any dose of MK-386. Serum DHT fell 65.8% from the baseline 14 days after finasteride treatment (P < 0.05 vs. placebo). The mean changes from baseline on day 14 in sebum DHT were 5.0%, 3.0%, -25.4% (P < 0.05 vs. placebo), -30.1% (P < 0.05 vs. placebo), and -49.1% (P < 0.05 vs. placebo) for the placebo and 0.5, 5, 20, and 50 mg MK-386 groups, respectively. Finasteride also reduced sebum DHT, but to a lesser extent (- 14.9%; P < 0.05 vs. placebo). Reciprocal increases in sebum T concentration were noted at doses of 5 mg or more of MK-386, but not with finasteride. The mean reduction in semen DHT with 5 mg finasteride was approximately 88% (P < 0.01 vs. placebo); no significant change in semen DHT was noted with 20 or 50 mg MK-386. Serum 3alpha-androstanediol glucuronide values were also reduced after the 20- and 50-mg MK-386 treatments in parallel with the changes in serum DHT. No meaningful changes were observed in serum LH after MK-386 treatment. MK-386 was generally well tolerated by all subjects; reversible aspartate aminotransferase/alanine aminotransferase elevations were observed in two subjects at the 50-mg dose. The differential responses in serum, sebum, and semen DHT concentrations associated with MK-386 and finasteride treatments are consistent with those changes anticipated for selective inhibitors of the human 5alphaR isozymes. Dose-dependent suppression of sebum DHT by a 5alphaR1 inhibitor suggests the potential utility of such compounds in the treatment of acne.

5-alpha Reductase Inhibitors↗

Influence of vehicles on the phase transitions of model sebum.

It is hypothesized that vehicles that are miscible with sebum may concentrate drugs in the sebaceous follicle. This is important for the treatment of diseases like alopecia and acne. The main objective of the study was to identify different vehicles that affect the thermal behavior of sebum using differential scanning calorimetry (DSC). For this purpose, a model sebum mixture was prepared based on a composition reported in the literature. The test vehicle was added in a concentration of 15% of the weight of the sebum. Small portions of the above mixture were put in a pre-weighed DSC pan. These were run from -50 to 100 degrees C at 5 degrees C/minute. In the model sebum, four distinct transitions were observed: Mp-1 and Mp-2 occurred below 0 degrees C while Mp-3 and Mp-4 occurred above 30 degrees C. Vehicles that affected Mp-3 and Mp-4 were considered for further analysis. From the vehicles tested it was found that the hydrophobic materials were more effective in lowering Mp-3, while the ones that affected Mp-4 did not show any particular trend. Some of the vehicles tested are known skin permeation enhancers, and it is proposed that they interact with sebum and increase permeation by the follicular route. It was found that DSC may be used to identify vehicles that are miscible with sebum and that may deliver drugs preferentially to the sebaceous follicle.

Calorimetry, Differential Scanning↗

Ultraviolet a induces generation of squalene monohydroperoxide isomers in human sebum and skin surface lipids in vitro and in vivo.

At the outermost surface of human skin, skin surface lipids are first-line targets of solar ultraviolet radiation. Therefore, we hypothesized that ultraviolet A and ultraviolet B irradiation induce photo-oxidation of skin surface lipids. To test this, sebum samples were collected from facial skin of 17 healthy volunteers, weighed, and immediately irradiated with either ultraviolet B or ultraviolet A. Squalene, the major sebum lipid, as well as photo-oxidation products were identified in sebum lipid extracts by high-performance liquid chromatography analysis. Upon ultraviolet A exposures squalene was depleted in a concentration-dependent manner, whereas an unidentified sebum lipid photo-oxidation product was detected. Using high-performance thin layer chromatography, high-performance liquid chromatography, atmospheric pressure chemical ionization mass spectrometry, and nuclear magnetic resonance, unidentified sebum lipid photo-oxidation product was identified as a mixture of squalene monohydroperoxide isomers. Squalene monohydroperoxide isomers purified from sebum were identical with squalene monohydroperoxide isomers synthesized by preparative photo-oxidation of squalene. Squalene monohydroperoxide isomers were formed even after small suberythematogenic doses of ultraviolet A (5 J per cm2). Whereas physiologic baseline levels of squalene monohydroperoxide isomers in human skin were only slightly above detection limits, squalene monohydroperoxide isomer levels were strongly increased by suberythematogenic doses of ultraviolet A both in vitro and in vivo. High-performance liquid chromatography results could be complemented by a straightforward thin layer chromatography method for rapid screening of lipid peroxide formation in human sebum/skin surface lipids. In conclusion, specific squalene monohydroperoxide isomers were identified as highly ultraviolet A sensitive skin surface lipid breakdown products that may serve as a marker for photo-oxidative stress in vitro and in vivo.

Adult↗

Sebum output as a factor contributing to the size of facial pores.

BACKGROUND: Many endogenous and exogenous factors are known to cause enlarged pilosebaceous pores. Such factors include sex, genetic predisposition, ageing, chronic ultraviolet light exposure, comedogenic xenobiotics, acne and seborrhoea. This study was an attempt to determine the factors related to enlarged pores. OBJECTIVES: To assess the relationship of sebum output, age, sex, hormonal factors and severity of acne with pore size. METHODS: A prospective, randomized, controlled study was designed. A total of 60 volunteers, 30 males and 30 females, were recruited for this study. Magnified images of pores were taken using a dermoscopic video camera and measured using an image analysis program. The sebum output level was measured with a Sebumeter. RESULTS: Using multiple linear regression analysis, increased pore size was significantly associated with increased sebum output level, sex and age. Among the variables, sebum output level correlated most with the pore size followed by male sex. In comparing male and female participants, males had higher correlation between the sebum output level and the pore size (male: r = 0.47, female: r = 0.38). Thus, additional factors seem to influence pore size in females. Pore size was significantly increased during the ovulation phase (P = 0.008), but severity of acne was not significantly associated with the pore size. CONCLUSIONS: Enlarged pore sizes are associated with increased sebum output level, age and male sex. In female patients, additional hormonal factors, such as those of the menstrual cycle, affect the pore size.

Acne Vulgaris↗

Formation of oiliness and sebum output--comparison of a lipid-absorbant and occlusive-tape method with photometry.

Sebum output and the development of oiliness formation were studied in 24 acne-prone volunteers. Sebutape and photometric measurement by the Sebumeter were compared. Tapes were taken 1, 2 and 3 h after degreasing. Tapes were scored, and light transmission was measured by a special densitometric device. Sebumeter recordings were performed after 3 h. Densitometric evaluation of tapes was accurate with a high correlation to scoring. Sebutape and Sebumeter assessments correlated. However, in some individuals the tape method overestimated the sebum output. Right-left comparison indicated that the tape method was less reproducible, particularly after longer sampling periods. It is suggested that Sebutape, due to water occlusion and temperature insulation during the sampling period, interferes with sebum droplet formation and spreading. However, such systematic interference may be advantageous since sweating and heat are important clinical prerequisites in the formation of oiliness. Thus, it is suggested that the Sebutape is a specialized method for the determination of 'oiliness', the very last phase of sebum output, in which sebum droplets spread over the skin surface. The tape is not automatically comparable to other methods for determining sebum output from the follicular reservoir.

Acne Vulgaris↗

Responses of tsetse to ox sebum: a video study in the field.

The behaviour of tsetse (mainly Glossina pallidipes Austen) around odour-baited targets, with or without a coating of ox sebum, was recorded in the field using video. The addition of sebum increased the total time a fly was in contact with the target, as well as the time spent flying around and landing on it. When carbon dioxide was released as part of the attractant odour plume, the presence of sebum on the target increased the number of landings made by each fly, but did not significantly affect the duration of each contact. When carbon dioxide was absent from the odour plume, sebum did not affect the number of landings made by flies but the duration of each contact with the target did increase. Evidence for an interactive effect of sebum and carbon dioxide was obtained. In addition, the presence of sebum on the target increased the percentage of landed flies which walked on its surface; such behaviour may represent an 'inspection' of the artificial host. The potential tsetse control application of the current findings are discussed.

Animals↗

Zileuton, an oral 5-lipoxygenase inhibitor, directly reduces sebum production.

BACKGROUND: Zileuton, a 5-lipoxygenase inhibitor, reduces the number of inflammatory lesions in moderate acne and inhibits the synthesis of sebaceous lipids. OBJECTIVE: To detect whether zileuton directly reduces sebum synthesis. METHODS: A 40-year-old female with mild disseminated sebaceous gland hyperplasia and seborrhea was treated with zileuton 4 x 600 mg/day over 2 weeks, was followed-up for 6 weeks after discontinuation of zileuton and was re-treated with low-dose isotretinoin 10 mg/2nd day over 5 weeks. Casual skin surface lipids and sebum synthesis were determined. RESULTS: Under treatment with zileuton increased casual skin surface lipids were normalized and synthesis of facial sebum was decreased. Six weeks after discontinuation of treatment casual skin surface lipids were increased again and synthesis of sebum returned to baseline. Subsequent low-dose isotretinoin treatment led to similar changes of casual skin surface lipids and sebum synthesis with zileuton already after 2 weeks. CONCLUSION: Zileuton directly inhibits sebum synthesis in a transient manner with a potency similar to low-dose isotretinoin at least in our patient.

Administration, Oral↗

Kinetics of sebum excretion evaluated by the Sebutape--Chromameter technique.

We present a novel method for studying the changing characteristics of sebum excretion of facial skin over a 3-hour period. Sebum production can be quantified by analysis of the pore patterns formed on a sebum-sensitive tape (Sebutape). We applied the CIE principles of reflectance colorimetry by measuring L*, a* and b* of Sebutapes every 15 min during 3 h of sebum collection. This combined technique yielded valuable new informations on the kinetics of sebum excretion, allowing the distinction between the follicular reservoir effect and the sebum flow.

Adult↗

Sebum rheology evaluated by two methods in vivo. Split-face study of the effect of a cosmetic formulation.

Modulation of the rheological characteristics of sebum at the surface of the skin might represent a valuable strategy for the treatment of seborrhea. In this field, only a small number of studies have addressed sebum diffusion within the stratum corneum. In an open, split-face study conducted on 20 men, we measured the sebosuppressive effect of Effidrate cream which is based on a glycerol alkyl-ether. Measurements were made in the morning at three-week intervals for a total period of 3 months. Sebum casual levels and sebum excretion rates were measured using a SM810 Sebumeter. Lipid-absorbent Sebutape was also used to collect all the sebum released from infundibular reservoirs over a four-hour period. Clinical assessments were relatively uninformative but the photometric measurements showed that Effidrate cream had a sebosuppressive action. The underlying biological mechanism remains unclear but a hypothesis based on enhanced sebum absorption by the stratum corneum is discussed.

Administration, Cutaneous↗

Sebum-suppressing activity of the nonpolar arotinoid Ro 15-0778 in rodents.

Retinoids are known to modulate sebaceous gland activity in humans and animals. The nonpolar arotinoid Ro 15-0778 [(E)-1,2,3,4-tetrahydro-1,1,4,4-tetramethyl-6-(1-methyl-2-phenylethen yl) naphthalene] does not contain a polar end group and is devoid of the classical retinoid side effects of hypervitaminosis A. The favorable toxicological profile stimulated the evaluation of this arotinoid in animal models of sebum production. In castrated, testosterone-stimulated male rats, Ro 15-0778 is 50 times more potent than 13-cis-retinoic acid in inhibiting the production and subsequent secretion of sebum. The oral ED50 value of Ro 15-0778 is 30 micrograms/kg, while an oral dose of 0.5 mg/kg inhibited sebum secretion nearly 100%. In testosterone-stimulated female rats, Ro 15-0778 inhibits sebum secretion significantly with an oral ED50 of 140 micrograms/kg and an s.c. ED50 of 75 micrograms/kg. Ro 15-0778 was also evaluated for its ability to prevent testosterone induction of the immature hamster flank organ. The topical ED50 is 0.53 mg/kg and the oral ED50 is 38 mg/kg. This arotinoid is similarly active in mature male hamsters without testosterone treatment. In addition, the retinoid is active topically and orally in reducing the size of the gerbil abdominal sebaceous gland. The compound exhibits no antiandrogenic activity when tested in ventral prostrate and seminal vesicle assays in rats. Additionally, the compound does not have estrogenic activity when tested in the rat uterine weight assay. High doses of Ro 15-0778 in humans did not demonstrate significant sebum-suppressing activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen Antagonists↗

Fatty acid composition of sebum wax esters and urinary androgen level in normal human individuals.

To investigate the effects of androgens on the fatty acid compositions of sebum wax esters, we examined sebum and urinary samples from 36 healthy individuals, aged from 3 to 59 years. The percentages of C16:1 straight chain components in wax esters were correlated positively with the urinary testosterone levels in both sexes, and with the urinary levels of etiocholanolone and total 17-ketosteroids (17-KS) in females. These data suggest that more active sebaceous glands in lipid production excrete sebum with a higher proportion of C16:1 straight chain fatty acid, which is considered to be purely endogenous. It appears, therefore, that the proportion of C16:1 straight chain fatty acid in sebum wax esters may indicate the sebaceous gland activity in both sexes. In comparison of the amounts of various straight and terminally branched fatty acids in sebum with urinary androgen levels, the straight even fatty acids tended to change in a positive correlation with testosterone levels, in contrast to the changes of the iso even fatty acids in both sexes and to those of the iso odd fatty acids in males. The straight odd fatty acids showed a similar change to that of the straight even fatty acids in males, while in females, there was no significant correlation between the amounts of the fatty acids and testosterone levels. Anteiso fatty acids showed no notable change correlated with testosterone levels. This result suggests that the synthesis of iso or anteiso fatty acids may be controlled by complex factors and that there may be a unique source of anteiso fatty acids in human sebaceous glands.

17-Ketosteroids↗

Sustainable rates of sebum secretion in acne patients and matched normal control subjects.

Sustainable rates of sebum secretion were measured in twelve subjects with inflammatory acne and in twelve control subjects, matched in age and gender, who had no significant signs of acne. The measurements were made after first depleting the skin of an accumulation of previously secreted sebum by absorption into adherent layers of bentonite clay applied to the center of the forehead for 14 hours. Disks of fine Dacron mesh, embedded in fresh clay, were then applied to the forehead for 3 hours. The disks and adhering clay were then removed and extracted with ether to recover the collected lipids. The sebum recovered during the 3-hour period was measured by quantitative thin layer chromatography. The subjects with acne were found to have an average sustainable sebum secretion rate of 2.51 mg/10 cm2/3 hr, while the control group had an average of 0.81 mg/10 cm2/3 hr. Furthermore, all subjects with acne had secretion rates larger than those of their matched control subjects. The results indicate that a high sebum secretion rate is the decisive factor in inflammatory acne.

Acne Vulgaris↗

An analysis of sebum excretion rate, bacterial population and the production rate of free fatty acids on human skin.

Bacteria were sampled using a "scrub" technique from the skin surface of the faces of forty-nine female subjects aged 18-21 years. The sebum excretion rate was determined by a gravimetric method and the level of free fatty acids by titration. The production rate of free fatty acids was calculated from the product of the concentration of free fatty acids in the sebum and the sebum excretion rate. The date was analysed using Kendall's rank correlation method. Positive correlations existed between the number of Micrococcaceae and the skin propionibacteria (P < 0.001) and between both groups of organisms and the production rate of free fatty acids (P < 0.001). There was no significant correlation between the size of the bacterial population and the sebum excretion rate. The results support the view that free fatty acids are produced as a result of bacterial action, that the Micrococcaceae and skin propionibacteria do not compete to the detriment of their respective populations, and that the size of the bacterial population is not dependent upon the sebum excretion rate.

Adolescent↗

Effects of repetitive superficial chemical peels on facial sebum secretion in acne patients.

BACKGROUND: Glycolic acid and Jessner's solution are popular superficial chemical peel agents for the treatment of facial acne, and increased sebum secretion is one of the major aetiological factors of acne. OBJECTIVE: To compare the effects of 30% glycolic acid peels and Jessner's solution peels on sebum secretion in facial acne patients. METHODS: Thirty-eight patients with mild to moderate facial acne were included. Twenty-seven patients were treated with 30% glycolic acid peels and 11 patients with Jessner's solution peels. Each peel was performed twice with an interval of 2 weeks. Before and 2 weeks after each peel, sebum levels of forehead, nose, chin and cheeks were measured by using a Sebumeter (SM810 Courage & Khazaka, Cologne, Germany). RESULTS: The sebum levels were not significantly changed by two peels treatments of 30% glycolic acid peels or Jessner's solution peels on the facial skins of patients with facial acne. CONCLUSIONS: The two types of peels, 30% glycolic acid peels and Jessner's solution peels, did not affect sebum secretion of the facial skins of patients with facial acne after the two peels treatments. The accumulative effects of more than two peels treatments using these modalities need further evaluation.

Acne Vulgaris↗

L-dopa and the secretion of sebum in Parkinsonian patients.

Sebum secretion was studied in 14 parkinsonian patients before and after 3 months of treatment with L-dopa. An abnormality of sebum secretion was shown to exist in parkinsonism. In 7 patients, successfully treated with L-dopa, sebum secretion diminished and its pattern improved. In all patients, in whom L-dopa treatment did not result in noticeable clinical changes, there was no significant modification in sebum secretion. No change was observed in the secretion of sebum of 5 normal control subjects, who were given L-dopa for 1 week.

Adult↗

Lipoperoxides in sebum of substance users and controls.

Sebum was collected from forehead skin in five compulsive heroin and/or cocaine (substance) users and in five controls over three consecutive periods, each lasting three hours. The participants were adult black and white men similar in age and smoking habits, who did not consume alcohol. Lipoperoxides were determined in sebum as malondialdehyde by high performance liquid chromatography. Two participants were excluded in the control group: in both, urinary lipoperoxides were elevated; in one, urine tested positive for delta-9 tetrahydrocannabinol (THC). All other participants had negative urine drug screening tests. Relative to the controls, all substance users had elevated concentrations of lipoperoxides in urine. Compared to the controls, the rate of sebum excretion in the last collecting period was higher in substance users, but sebum had significantly lower lipoperoxide concentration. It is assumed that compulsive drug use may influence lipoperoxidation of incipient sebum, possibly by altered tissue perfusion.

Adult↗