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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

Observations on the progress of chlordane contamination in humans by blood and sebum analysis.

Chlordane residues were determined in human blood and sebum samples. The residue levels in both types of samples were remarkably increased in pest control operators and in the general population living in an area heavily contaminated with chlordane. The compound with the highest level among the residues in the blood of control subjects was oxychlordane followed by trans-nonachlor and trans-chlordane, while in the sebum, the highest levels found was that of trans-chlordane followed by cis-chlordane and trans-nonachlor. The sebum residue was similar to technical chlordane in its component pattern, but it largely originated from sources other than simple exogenous contamination. Thus, sebum might be a unique and available sample source for evaluating direct exposure to technical chlordane. A progressive state of contamination was observed in residents whose homes had been treated with chlordane.

Air Pollutants

Liquid chromatographic analysis of sebum lipids and other lipids of medical interest.

A technique is described for the high-pressure liquid chromatographic (HPLC) analysis of sebum lipid classes. The lipid present in sebum are separated by gradient elution HPLC from a microparticulate silica column and detected using a moving-wire detector. The system described can be linked to a computer. Quantitation can be carried out by comparing peak areas obtained with those of an internal standard. Peak trapping for further investigations of the separated components, for example by gas chromatography-mass spectrometry, is very easy. Sebum lipids are separated into the following lipid classes: hydrocarbons and squalene, cholesterol esters and wax esters, fatty acids as their methyl esters, triglycerides, 1,3-diglycerides, 1,2-diglycerides, free cholesterol, monoglycerides and other polar materials. Besides to sebum, the method has been successfully applied to other lipid mixtures, such as serum lipids. Examples of other applications are shown.

Chromatography, High Pressure Liquid

Estimation of sebum production rates in man by measurement of the squalene content of skin biopsies.

Previous studies have shown that lipids are synthesized at a constant rate in sebaceous glands and secreted onto the skin surface an average of 8 days after synthesis. As a result, measurement of the sebum content of a skin specimen of known surface area should allow calculation of the sebum production rate which had been occurring in vivo. In the present study, such measurements have been made on scalp skin specimens from 14 men. The amount of sebum in 4-mm punch biopsies was calculated from the squalene content of the specimens, as measured by quantitative thin-layer chromatography of lipid extracts. The average sebum production rate for the group was found to be 1.45 mg/10 sq cm/3 hr.

Humans

Local suppression of sebum secretion in rats by topical cyproterone acetate in ethanol.

Sebum production was measured on 2 symmetrically placed areas on the flanks of rats over alternating periods of 18 and 6 hr for 4 days, by absorbing the lipid on pads of cigarette paper held in place by a specially designed harness. Castrated rats receiving testosterone produced about twice as much sebum as untreated littermate controls. Once daily application of ethanol to one flank significantly reduced sebum production, in comparison with the other flank in testosterone-treated but not in untreated rats. Daily application of 5 mg cyproterone acetate in ethanol to one flank in a third group of rats significantly reduced sebum production in comparison with that of the other flank treated with vehicle only. The effects became significant within 24 hr. It seems likely that the sebaceous glands received the topically applied materials by way of the pilo-sebaceous orifices rather than by transepidermal absorption. The results demonstrate that one action of cyproterone acetate is at the target site and suggest that the anti-androgen may be effective when applied topically. The method could prove useful in assessing the local action on sebaceous activity of topically applied substances.

Administration, Topical

The effect of marked inhibition of sebum production with 13cis-retinoic acid on skin surface lipid composition.

Sebum production and skin surface lipid composition have been measured during the oral treatment with 13cis-retinoic acid of a group of patients with severe cystic acne. Two hundred and thirty-eight paired samples have been analyzed and compared. A marked, drug-induced decrease in sebum production was accompanied by a decrease in the concentration of wax esters, a slight decrease in the squalene concentration and in increase in the cholesterol concentration in the skin surface lipids. These changes were consonant with changes in the relative contributions of sebum and epidermal lipid to the surface film, except that at very low levels of sebum production there might be preferential preservation of squalene synthesis.

Acne Vulgaris

A modified photometric technique for measuring sebum excretion rate.

Accurate measurement of sebum excretion is necessary to evaluate drugs such as anti-androgen and the new retinoic acid derivatives. Existing techniques are good, but some are inaccurate at high levels of sebum and are time-consuming for technicians. We have therefore, re-examined sebum excretion methodology and have developed a modified photometric technique. This technique, which utilizes a robust, portable machine gives data which are accurate at all levels of sebum production and reduces the technician time of analysis without loss of accuracy or reproducibility.

Humans

Measurement of sebum output using a lipid absorbent tape.

A sebum absorbent tape is introduced as a reproducible and convenient method for estimation of sebaceous gland output. We have tested the reproducibility of this method by serial measurements of sebum excretion rates (SER) of 10 individuals over a 6-week period, and in addition we have correlated this method with the conventional hexane extraction technique. The sebum absorbent tapes gave consistent values for the SERs, and within subjects variation over the 6-week period was statistically nonsignificant. A coefficient of variation for the tapes was calculated as 16.25 +/- 6.78% based on these serial measurements. Furthermore, the amount of total lipid collected using this technique (n = 16) correlated well with the hexane extraction technique, r = 0.89. Free fatty acids (r = 0.87), triglycerides (r = 0.92), wax and cholesterol esters (r = 0.83), and squalene (r = 0.88) also showed a good correlation. Cholesterol occasionally suffered from incomplete separation on thin-layer chromatograms; however, a sample cleanup procedure was developed for tape extracts that removed interfering materials and allowed complete separation of all sebum components.

Absorption

Influence of oral metronidazole on the endocrine milieu and sebum excretion rate.

As part of a study of the mechanism of metronidazole's efficacy in the treatment of acne and rosacea, its effects on the endocrine milieu and sebum excretion rate were assessed. Thirteen healthy males received oral metronidazole treatment (500 mg/day) for 4 weeks. Serum sex hormone levels were determined in all 13 subjects and the sebum excretion rate was determined in seven of them, before and after treatment. We measured serum levels of estrone (E1), estradiol (E2), total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG). There were no significant changes in E1, T, FT, DHT, or SHBG levels, but E2 and DHEA-S levels decreased significantly after treatment. In all seven subjects in whom the sebum excretion rates were determined, the amount of facial skin surface lipids decreased significantly after treatment. These results suggest that metronidazole exerts its clinical effects through suppressing the sebum excretion by a mechanism other than anti-androgenic action.

Administration, Oral

A direct gravimetric technique for measuring sebum excretion rate.

The standard gravimetric method for measuring sebum excretion rates involves ether extraction of the collected sebum. We have evaluated a more direct method in which the collecting papers were pre- and post-weighed in glass beakers under conditions of stable temperature and humidity. Weights were adjusted allowing for control weight gain or loss, due mainly to day to day changes in weight room humidity. The direct method compared favourably with the ether extraction method in determining: (1) sebum collected from 43 subjects (r = 0.991, P less than 0.001), (2) left versus right forehead comparisons in 19 subjects (direct method: r = 0.966, P less than 0.001; ether extraction method: (r = 0.963, P less than 0.001), and (3) recovery of sebum from 32 premeasured standards (r = 0.997, P less than 0.001). The findings demonstrate the accuracy of the direct gravimetric procedure which is also simpler, safer and less expensive than methods currently in use.

Forehead

Genetic control of sebum excretion and acne--a twin study.

Sebum excretion and acne grades were measured in 20 pairs each of identical and non-identical like-sex twins. The identical twins had virtually identical rates of sebum excretion (P greater than 0.05), but they had a significantly different degree of acne severity (P less than 0.01). The non-identical twins had significantly different sebum excretion rates (P less than 0.01) and acne grades (P less than 0.01). These findings suggest that sebum excretion is under genetic control and the development of clinical lesions is modified by environmental factors.

Acne Vulgaris

Physiology of the vellus hair follicle: hair growth and sebum excretion.

The growth of vellus hair and the secretion of sebum from vellus hair follicles were measured on the forehead, cheek, chest, shoulder and back of healthy men and women aged 15-30 years. Hair growth was assessed by computerized image-analysis of photographs and sebum excretion by the use of Sebutape followed by image analysis. The density of vellus hairs and the percentage of growing hairs were higher on the face than on the thorax (439 hairs/cm2 with 49% growing hairs on the forehead compared with 85 hairs/cm2 with 31.5% growing hairs on the back). The rate of growth ranged from 0.03 mm/day on the forehead to 0.13 mm/day on the back. The maximum length of vellus hair significantly decreased with age; otherwise hair growth was not affected by age or sex. Some variations in hair growth and sebum secretion were observed over a period of 3 months, but no consistent rhythms were detected. There was no obvious link between vellus hair growth and sebum excretion.

Adolescent

Sebum secretion in idiopathic Parkinson's disease: effect of anticholinergic and dopaminergic drugs.

Sebum secretion was measured on the foreheads of 47 unmedicated patients with idiopathic Parkinson's disease, aged 50-81 years and 80 healthy, matched volunteers. Sebum secretion was significantly higher in men patients aged 50-59 years than in controls; no such difference was observed in women of the same age. There was also no difference between patients and volunteers of either gender older than 60 years of age. The effects of either biperiden, L-Dopa + benserazide (a decarboxylase inhibitor) or bromocriptine treatments on sebum secretion and on 5 parkinsonian signs were evaluated over 127 days. There was a significant reduction of all measures during the treatment with the dopaminergic drugs. The only observable effect with biperiden was reduction of tremor. It is discussed whether the sebum suppressive effect of the dopaminergic drugs may be explained through their central effects.

Aged

Arotinoid Ro 13-6298 and etretin: two new retinoids inferior to isotretinoin in sebum suppression and acne treatment.

Thirty patients have been treated with either etretin, the main derivative of etretinate, or arotinoid Ro 13-6298, a polyaromatic retinoid, or isotretinoin. Sebum production was measured before and during the treatments. While no change was observed in the patients treated with etretin, a reduction of 33% of the sebum excretion rate was observed for those treated with arotinoid Ro 13-6298 but only after long treatment periods of 20 to 30 weeks. The sebum excretion rate decreased by 92% in the patients treated with isotretinoin. Four patients suffering from severe nodulocystic acne were treated with arotinoid Ro 13-6298 for 2-5 months without improvement. Substantial improvement, however, resulted after a subsequent treatment with isotretinoin; sebum production decreased markedly as well. This study suggests that neither etretin nor arotinoid Ro 13-6298 will replace isotretinoin in the treatment of severe nodulocystic acne.

Acitretin

Changes in sebum secretion and the sebaceous gland.

New data have shown that sebum secretion is highest in young adults and then declines steadily throughout life in both men and women. This parallels the decline in androgen levels, but this cannot be the sole factor because there is so much overlap in sebaceous gland activity between men and women. The increased occurrence of dry skin in the elderly has been shown to be unrelated to the sebum secretion rate. This is not unexpected, as children, with even less sebum, rarely have this problem. Seborrheic dermatitis, which is also much more common in the elderly, is also unrelated to sebum secretion rate.

Aging

Changes in sebum secretion and the sebaceous gland.

New data have shown that sebum secretion is highest in young adults and then declines steadily throughout life in both men and women. This parallels the decline in androgen levels, but this cannot be the sole factor because there is so much overlap in sebaceous gland activity between men and women. The increased occurrence of dry skin in the elderly has been shown to be unrelated to the sebum secretion rate. This is not unexpected, as children, with even less sebum, rarely have this problem. Seborrheic dermatitis, which is also much more common in the elderly, is also unrelated to sebum secretion rate.

Adolescent

Studies on the critical period of neonatal life for the differentiation of sebum secretion in rats.

Sprague-Dawley rats were castrated at the age of 1, 3, 5, 10 or 21 days. A control group of male and female rats were also included for comparison. The secretion rate of sebum was assessed from the amount of skin-surface lipids that could be extracted by acetone and which had been produced during 2 days. Sebum production increased with age, particularly in male rats. Castration of male rats at the age of 1, 3, 5, or 10 days showed no differences from female rats in sebum secretion when measured at the age of 80 days. On the other hand, male rats that had been castrated at the age of 21 days secreted significantly more sebum than female rats.

Animals

A prospective study of the effect of isotretinoin on the follicular reservoir and sustainable sebum excretion rate in patients with acne.

BACKGROUND AND DESIGN: A prospective study of 30 patients with moderate to severe acne was performed. The follicular reservoir and sustainable sebum excretion rates were measured before and after a 4-month course of isotretinoin at a dose of 1 mg/kg per day. RESULTS: The follicular reservoir and sustainable sebum excretion rates were profoundly reduced at the end of the course of isotretinoin (79% and 83%, respectively) and remained significantly suppressed at 1 year following therapy (43% and 36%, respectively). Those patients who relapsed clinically at 1 year after treatment had a significantly higher follicular reservoir rate. CONCLUSIONS: These data support the concept that up to 1 year after therapy, there is a reduction in the sebum secretion rate accompanying the remission of acne. This suppressed sebum secretion may modulate the microenvironment of the pilosebaceous canal through an effect on the follicular reservoir.

Acne Vulgaris