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PubMed2000

Combination azelaic acid therapy for acne vulgaris.

There is no topical antiacne medication that acts against all four of the major pathophysiologic features of acne: hyperkeratinization, sebum production, bacterial proliferation, and inflammation. Topical azelaic acid cream helps both to normalize keratinization and to reduce the proliferation of Propionibacterium acnes, and has proven to be effective against both noninflammatory and inflammatory lesions. The results of a recent study now demonstrate that its efficacy can be enhanced, and patient ratings of overall impression improved, when it is used in combination with other topical medications such as benzoyl peroxide 4% gel, clindamycin 1% gel, tretinoin 0.025% cream, and erythromycin 3%/benzoyl peroxide 5% gel. Furthermore, another study has shown that azelaic acid plus benzoyl peroxide achieves greater efficacy and higher patient ratings of convenience than monotherapy with erythromycin-benzoyl peroxide gel.

Acne Vulgaris↗
PubMed2003

A review of the use of combination therapies for the treatment of acne vulgaris.

Acne is a disease of the pilosebaceous unit, involving abnormalities in sebum production, follicular epithelial desquamation, bacterial proliferation, and inflammation. The major classes of therapeutic agents are topical and systemic retinoids, antimicrobial agents, and systemic hormonal drugs. Combination therapy with a topical retinoid and an antibiotic can normalize follicular epithelial desquamation and reduce bacterial proliferation. The new retinoids (eg, adapalene) have an additional antiinflammatory action along with their effect on the preclinical microcomedo and, coadministered with a topical or an oral antibiotic, are a rational initial therapy for all but the most severe forms of acne. Retinoids can also be used alone for long-term maintenance to prevent the reemergence of comedones and inflammatory acne lesions and to spare the use of antibiotics, thus helping to reduce the risk of bacterial resistance.

Acne Vulgaris↗
PubMed2001

Abnormal differentiation of epidermis in transgenic mice constitutively expressing cyclooxygenase-2 in skin.

In prostanoid biosynthesis, the first two steps are catalyzed by cyclooxygenases (COX). In mice and humans, deregulated expression of COX-2, but not of COX-1, is characteristic of epithelial tumors, including squamous cell carcinomas of skin. To explore the function of COX-2 in epidermis, a keratin 5 promoter was used to direct COX-2 expression to the basal cells of interfollicular epidermis and the pilosebaceous appendage of transgenic mouse skin. COX-2 overexpression in the expected locations, resulting in increased prostaglandin levels in epidermis and plasma, correlated with a pronounced skin phenotype. Heterozygous transgenic mice exhibited a reduced hair follicle density. Moreover, postnatally hair follicle morphogenesis and thinning of interfollicular dorsal epidermis were delayed. Adult transgenics showed a body-site-dependent sparse coat of greasy hair, the latter caused by sebaceous gland hyperplasia and increased epicutaneous sebum levels. In tail skin, hyperplasia of scale epidermis reflecting an increased number of viable and cornified cell layers was observed. Hyperplasia was a result of a disturbed program of epidermal differentiation rather than an increased proliferation rate, as reflected by the strong suppression of keratin 10, involucrin, and loricrin expression in suprabasal cells. Further pathological signs were loss of cell polarity, mainly of basal keratinocytes, epidermal invaginations into the dermis, and formation of horn perls. Invaginating hyperplastic lobes were surrounded by CD31-positive vessels. These results demonstrate a causal relationship between transgenic COX-2 expression in basal keratinocytes and epidermal hyperplasia as well as dysplastic features at discrete body sites.

Aging↗
PubMed2005

Identification of two novel human acyl-CoA wax alcohol acyltransferases: members of the diacylglycerol acyltransferase 2 (DGAT2) gene superfamily.

The esterification of alcohols such as sterols, diacylglycerols, and monoacylglycerols with fatty acids represents the formation of both storage and cytoprotective molecules. Conversely, the overproduction of these molecules is associated with several disease pathologies, including atherosclerosis and obesity. The human acyl-CoA:diacylglycerol acyltransferase (DGAT) 2 gene superfamily comprises seven members, four of which have been previously implicated in the synthesis of di- or triacylglycerol. The remaining 3 members comprise an X-linked locus and have not been characterized. We describe here the expression of DGAT2 and the three X-linked genes in Saccharomyces cerevisiae strains virtually devoid of neutral lipids. All four gene products mediate the synthesis of triacylglycerol; however, two of the X-linked genes act as acyl-CoA wax alcohol acyltransferases (AWAT 1 and 2) that predominantly esterify long chain (wax) alcohols with acyl-CoA-derived fatty acids to produce wax esters. AWAT1 and AWAT2 have very distinct substrate preferences in terms of alcohol chain length and fatty acyl saturation. The enzymes are expressed in many human tissues but predominate in skin. In situ hybridizations demonstrate a differentiation-specific expression pattern within the human sebaceous gland for the two AWAT genes, consistent with a significant role in the composition of sebum.

Acyltransferases↗
PubMed2001

Eye- and skin symptoms in German office workers--subjective perception vs. objective medical screening.

The question of whether perceived sensation correlates with medical tests was examined using data from the ProKlimA project (1994-1999) in which sensory perception and medical examination of Sick Building Syndrome related complaints were examined in 14 office buildings across Germany. Within the ProKlimA study, a subsample of 817 persons participated in ophthalmological examinations; dermatological tests were conducted on 925 persons using serni quantitative dermatological methods. Participants of both sub-samples responded to a questionnaire assessing sensory perception over 6 sub-scales (eyes, skin nose, mouth, throat and nervous systems) consisting of 9 to 11 items per sub-scale. Non-parametric analysis revealed a significant association between medical tests of symptoms and self-reported complaints regarding skin/eyes. Break up time, a measure of tear film stability, appeared to be the best indicator for self-reported eye complaints. In terms of skin symptoms, low sebaceous secretion and/or low stratum corneum hydration was associated significantly with increased skin complaints. But not all items of the sensory perception modules reflected the medical diagnoses in the same way. For instance the items "rough skin" and "dry skin" described the medical diagnosis "low sebum content" better than "irritated skin", "rash" or "spotty skin". However, sensory perception modules differed in their relationship to medical tests, so that questionnaires may be used as indicators not as substitutes for medical test data. The choice of method has to be determined by the purpose of the research project.

Environment, Controlled↗
PubMed2006

Skin bioavailability of dietary vitamin E, carotenoids, polyphenols, vitamin C, zinc and selenium.

Dietary bioactive compounds (vitamin E, carotenoids, polyphenols, vitamin C, Se and Zn) have beneficial effects on skin health. The classical route of administration of active compounds is by topical application direct to the skin, and manufacturers have substantial experience of formulating ingredients in this field. However, the use of functional foods and oral supplements for improving skin condition is increasing. For oral consumption, some dietary components could have an indirect effect on the skin via, for example, secondary messengers. However, in the case of the dietary bioactive compounds considered here, we assume that they must pass down the gastrointestinal tract, cross the intestinal barrier, reach the blood circulation, and then be distributed to the different tissues of the body including the skin. The advantages of this route of administration are that the dietary bioactive compounds are metabolized and then presented to the entire tissue, potentially in an active form. Also, the blood continuously replenishes the skin with these bioactive compounds, which can then be distributed to all skin compartments (i.e. epidermis, dermis, subcutaneous fat and also to sebum). Where known, the distribution and mechanisms of transport of dietary bioactive compounds in skin are presented. Even for compounds that have been studied well in other organs, information on skin is relatively sparse. Gaps in knowledge are identified and suggestions made for future research.

Administration, Oral↗
PubMed2003

Pathological mechanisms of acne with special emphasis on Propionibacterium acnes and related therapy.

Acne is a common disease that in cases of extreme disfiguration can have severe consequences for the personality development of young people and is associated with a relatively high prevalence of depression and suicide. Spontaneous regression is common, but acne can extend into the fourth and fifth decades of life. The pathogenesis is still not fully understood. Factors promoting the development of acne are: increased sebum production, ductal cornification, bacterial colonization of the pilosebaceus ducts and inflammation. However, there is evidence that inflammation is not a factor but rather a consequence of the interaction of the other three factors. Propionibacterium acnes releases pro-inflammatory cytokines as well as antigens and mitogen(s), with cellular and non-cellular responses to these products triggering inflammation. Treatment is often frustran. Therapeutical strategies are needed based on new understandings of the pathomechanisms involved in acne. The aim of this review is to summarize the data on aetiopathological factors in acne and their contribution to acne pathology and therapy.

Acne Vulgaris↗
PubMed2005

A randomized double-blind study to assess the effects of silicic acid compared to placebo in patients with mild to moderate acne.

OBJECTIVE: To establish the efficacy and safety of silicic acid in comparison to placebo in patients with mild to moderate acne vulgaris. PATIENTS AND METHODS: Forty adult patients with facial acne vulgaris were randomized to silicic acid or placebo applied twice daily for 8 weeks. Efficacy was assessed by number of acne lesions, acne grade and sebum excretion rate (SER). Clinical safety and tolerance were also assessed and global assessments and psychological profile questionnaires were completed. RESULTS: There were no significant differences between silicic acid and placebo in the number of inflamed lesions (the primary efficacy variable). In contrast, silicic acid significantly reduced the number of non-inflamed lesions, total acne lesions and the acne grade after 8 weeks and SER over 4 weeks when compared with placebo. There were no significant differences between silicic acid and placebo in the responses to the questionnaires or the global assessments after 8 weeks. Silicic acid was well tolerated with few adverse events. CONCLUSIONS: Silicic acid may have a positive treatment effect on the non-inflammatory component of mild to moderate facial acne. These preliminary findings now need to be confirmed by similar studies.

Acne Vulgaris↗
PubMed2000

A quantitative biometrological assessment of acne and hormonal evaluation in young women using a triphasic low-dose oral contraceptive containing gestodene.

OBJECTIVE: To investigate the effect of a triphasic low-dose oral contraceptive pill containing gestodene on acne severity and hormone levels in young women over 13 menstrual cycles. METHODS: A total of 33 subjects aged 16-25 years with moderate facial acne were enrolled in the study. The primary efficacy end-points used in the clinical assessment of acne were the overall severity and number of lesions, sebum secretion and superficial follicular biopsy. Both physicians and patients evaluated acne status. Blood levels of sex hormone binding globulin (SHBG), estradiol, progesterone and androgens were monitored. RESULTS: By cycle 13, the total lesion count had been reduced by 80%. Physicians and patients assessed acne status in 90% and 95% of cases, respectively, as better or much better (p < 0.001). At the end of the study, SHBG levels had increased by 229% and total and free testosterone levels had decreased by 41% and 70%, respectively. CONCLUSION: An oral contraceptive containing triphasic gestodene has a beneficial effect on the severity ofacne, decreases major circulating androgen levels and is well tolerated.

Acne Vulgaris↗
PubMed2004

The new age of acne therapy: light, lasers, and radiofrequency.

BACKGROUND: Current treatments for acne vulgaris include topical and oral medications that counteract microcomedone formation, sebum production, Propionibacterium acnes, and inflammation. Concerns about the short- and long-term consequences of these medications, along with technological advancements, have to significant progress in the management of acne. These developments include light, laser, and radio frequency, which may offer faster onset of action, equal or greater efficacy, and greater convenience than traditional approaches. CONCLUSION: Research emphasizing long-term follow-up and comparative, randomized trials is necessary to determine whether these emerging technologies will become a viable alternative to standard therapies such as antibiotics.

Acne Vulgaris↗
PubMed2004

420 nm intense continuous light therapy for acne.

BACKGROUND: Topical antibiotics, isotretinoin or systemic antibiotics are usually used for acne therapy. However, isotretinoin cannot be used during pregnancy because it can cause significant birth defects while systemic antibiotics can have adverse side effects such as gastrointestinal irritation, photosensitivity and tetracycline sensitivity. Describe here is a high-intensity, narrow-band, blue light (ClearLight) system, and its therapeutic clinical effect is investigated on acne using cutaneous measurements, bacterial observations and ultrastructural changes. MATERIALS AND METHODS: A total of 28 adult healthy volunteers with facial acne (mean age 28.1 years, range 16-56 years) were recruited for this study. They were treated with a total of eight serial biweekly 15-minute treatment sessions. Clinical counts of acne, as well as moisture, sebum and pH measurements were taken between each session. Nine of the 28 patients were followed for 2-3 months after the last treatment. Detection of bacteria in acne pustules was analyzed by culture and by polymerase chain reaction (PCR). Ultrastructural changes were examined in eight patients after four sessions of the light therapy. RESULTS: All patients completed the study. Overall, there was a 64.7% improvement in acne lesions. There were no bacterial changes before or after the therapy, although damaged Propionibacterium acnes were observed at the ultrastructural level. CONCLUSIONS: ClearLight performed eight times over 4 weeks can be useful in the treatment of acne. Further investigation will be needed to elucidate the mechanism of action of ClearLight.

Acne Vulgaris↗
PubMed1951

Histogenesis of sebaceous gland carcinomas produced in rats by 2-acetylaminofluorene.

1. Tumors of the external auditory canal region were produced by oral administration of 2-acetylaminofluorene in 71 rats out of 124 which survived a 6 month period of administration of the compound. In 12 animals the tumors were bilateral. Tumors in other locations, such as the liver, breast, etc., were less frequent. 2. Tumors were found to originate in the compound sebaceous gland located at the medial end of the external auditory canal. 3. Histologically the tumors were sebaceous or keratinizing squamous-cell carcinomas. 4. The tumors were found to arise in cystic lobules of the gland, produced by stasis of secretion. 5. Cystic lesions of the sebaceous glands appear to be a frequent condition in older rats. The outward bulging of the tympanic membrane with interference in drainage from the gland seems to be a promoting factor in the stasis of sebum. 6. The localizing effect of the preexisting cystic lesions in the sebaceous glands on the carcinogenic action of 2-acetylaminofluorene is discussed.

2-Acetylaminofluorene↗
PubMed2001

Nutritional skin care: health effects of micronutrients and fatty acids.

Human skin is continuously exposed to internal and external influences that may alter its condition and functioning. As a consequence, the skin may undergo alterations leading to photoaging, inflammation, immune dysfunction, imbalanced epidermal homeostasis, or other skin disorders. Modern nutritional science is developing new insights into the relation between food intake and health, and effects of food ingredients may prove to be biologically relevant for optimal skin condition. The objective of this review was to evaluate the present knowledge about the interrelation of nutrients and skin, particularly the photoprotective effects of nutrients, the influences of nutrients on cutaneous immune responses, and therapeutic actions of nutrients in skin disorders. The nutrients of focus were vitamins, carotenoids, and polyunsaturated fatty acids. Supplementation with these nutrients was shown to provide protection against ultraviolet light, although the sun-protection factor was relatively small compared with that of topical sunscreens. An increase in delayed-type hypersensitivity skin responses after supplementation with nutrients has proven beneficial, especially in elderly people, and may boost cell-mediated immunity. Dietary consumption of certain plants or fish oil is known to modulate the balance of lipid inflammatory mediators and, therefore, is valuable in the treatment of inflammatory skin disorders. It was concluded that nutritional factors exert promising actions on the skin, but information on the effects of low-to-moderate doses of nutrients consumed long term by healthy individuals is obviously lacking, as are data on direct effects on basal skin properties, including hydration, sebum production, and elasticity.

Animals↗
PubMed2006

Fatty acid ethyl esters (FAEE); comparative accumulation in human and guinea pig hair as a biomarker for prenatal alcohol exposure.

AIMS: To compare the incorporation rate (ICR) of fatty acid ethyl esters (FAEE) in hair between guinea pigs and humans, and to assess the relationship between ethanol exposure and FAEE concentrations in hair. METHODS: Published data from pregnant guinea pigs, including maximum blood ethanol concentration (BEC), dosage regimen, and total hair FAEE concentration, were compared with published data from alcoholic patients, where dose of ethanol consumed and total hair FAEE concentration were reported. Mean values of ethanol Vmax for pregnant guinea pigs and humans were obtained from published data (26.2 and 24 mg/dl/h, respectively). RESULTS: Total and individual FAEE ICRs, defined as the ratio of hair FAEE to the area under the BEC-time curve (total systemic ethanol exposure), were found to be on average an order of magnitude lower in the guinea pig than in the human. The profiles of ester incorporation also differed slightly between species, with ethyl stearate being highly incorporated in guinea pig hair and less so in human hair. The results may reflect in the human greater FAEE production, greater FAEE deposition in hair, slower FAEE catabolism, differential sebum production and composition, or a combination thereof. Also, ethyl oleate was found to correlate with total systemic ethanol exposure for both guinea pigs and humans, correlation coefficients equalling 0.67 (P < 0.05) and 0.49 (P < 0.05), respectively. No other ethyl esters, nor total FAEE, were found to correlate with systemic ethanol exposure. CONCLUSION: When extrapolating FAEE concentrations in hair from guinea pigs to humans, an order of magnitude difference should be considered, with humans incorporating more FAEE per unit of ethanol exposure. Also, the results suggest caution should be taken when interpreting values of single esters because of their differential incorporation among species. Lastly, our findings suggest ethyl oleate may be of keen interest in FAEE hair analysis, particularly across species.

Adult↗
PubMedDate not supplied

Incorporation of isotopically labeled cocaine and metabolites into human hair: 1. dose-response relationships.

Deuterium-labeled cocaine (cocaine-d5) was administered intravenously and/or intranasally in doses of 0.6-4.2 mg/kg to 25 human volunteers under laboratory clinical conditions. Sequential blood samples were collected for up to 3 days, and hair samples were collected for up to 10 months. Samples were analyzed by gas chromatography-mass spectrometry (GC-MS) for cocaine-d5 and its major metabolite, benzoylecgonine-d5 (BZE-d5). The parent drug, cocaine-d5, was the predominant analyte in hair, whereas BZE-d5 was the major analyte in blood, especially at later time periods. The amount of cocaine-d5 incorporated into hair ranged from 0.1 to 5 ng/mg hair, whereas the amount of BZE-d5 was approximately one-sixth of that concentration. The threshold dose for detection was estimated to be 25-35 mg of drug administered intravenously. A single dose could be detected for 2-6 months. Subjects receiving the same dose differed (from two to 12 times as much depending upon how it was measured) in the amount of cocaine-d5 incorporated into their hair. Non-Caucasians, in particular, incorporated more cocaine-d5 in hair than did Caucasians. Also, segmental analysis of the samples revealed considerable intersubject variability in the time drug first appeared in hair and the rate at which the drug moved along the hair shaft with time. These interindividual differences could not be explained by differences in plasma pharmacokinetics. Considered together, these results suggest that cocaine incorporation into hair may occur by way of multiple mechanisms--by way of sweat and sebum, for example--and at various times during the hair growth cycle. Thus, hair analysis using GC-MS appears to be a very sensitive method for detecting cocaine ingestion. However, within the range of doses used in the present study, hair does not provide a particularly accurate record of either the amount, time, or duration of drug use.

Administration, Intranasal↗
PubMed1999

Drug testing with alternative matrices II. Mechanisms of cocaine and codeine deposition in hair.

A 10-week inpatient study was performed to evaluate cocaine, codeine, and metabolite disposition in biological matrices collected from volunteers. An initial report described drug disposition in plasma, sebum, and stratum corneum collected from five African-American males. This report focuses on drug disposition in hair and sweat collected from the same five subjects. Following a three-week washout period, three doses of cocaine HCl (75 mg/70 kg, subcutaneous) and three doses of codeine SO4 (60 mg/70 kg, oral) were administered on alternating days in week 4 (low-dose week). The same dosing sequence was repeated in week 8 with doubled doses (high-dose week). Hair was collected by shaving the entire scalp once each week. Hair from the anterior vertex was divided into two portions. One portion was washed with isopropanol and phosphate buffer; the other portion was not washed. Hair was enzymatically digested, samples were centrifuged, and the supernatant was collected. Sweat was collected periodically by placing PharmChek sweat patches on the torso. Drugs were extracted from sweat patches with methanol/0.2 M sodium acetate buffer (75:25, v/v). Supernatants from hair digests, hair washes, and sweat patch extracts were processed by solid-phase extraction followed by gas chromatography-mass spectrometry analysis for cocaine, codeine, 6-acetylmorphine, and metabolites. Cocaine and codeine were the primary analytes identified in sweat patches and hair. Drugs were detected in sweat within 8 h after dosing, and drug secretion primarily occurred within 24 h after dosing. No clear relationship was observed between dose and drug concentrations in sweat. Drug incorporation into hair appeared to be dose-dependent. Drugs were detected in hair within 1-3 days after the last drug administration; peak drug concentrations generally occurred in the following 1-2 weeks; thereafter, drug concentrations decreased. Solvent washes removed 50-55% of cocaine and codeine from hair collected 1-3 days after the last drug dose. These data may reflect removal of drug that was deposited by sweat shortly after dosing. Drug removed by washing hair collected 1-3 weeks after the last dose was minimal for cocaine but variable for codeine. Drug in these specimens was likely transferred from blood to germinative hair cells followed by emergence of drug in growing hair. These findings suggest that drug deposition in hair occurs by multiple mechanisms.

Cocaine↗
PubMedDate not supplied

MR imaging of retroperitoneal teratoma: correlation with CT and pathology.

A retroperitoneal teratoma was studied with CT and magnetic resonance (MR) imaging. The images were correlated with the pathologic findings. The tumor was composed of five portions: adipose tissue, bone, hair, sebum, and loose edematous fibrofatty tissue with skin. Computed tomography and MR both demonstrated a well defined mass with separate cystic and solid components and all five tissue elements of the tumor. Magnetic resonance was superior to CT in delineating the relationship of blood vessels to the tumor.

Adolescent↗
PubMed1983

Texture of the skin graft, with special reference to the hydration state of the stratum corneum.

The water contained in the superficial portion of the stratum corneum plays an important role in keeping the skin surface soft and smooth. In an attempt to study the true nature of the "texture" of grafted skin, in vivo water sorption-desorption tests were performed on grafts, on normal skin adjacent to grafts, and on normal skin surrounding the donor sites. The results showed that skin grafted to sites other than the face maintained a functional similarity to normal skin surrounding the donor site. However, in skin grafted to the face, the functions of the stratum corneum, as measured in terms of hydration state, increased, and this was associated with an improved water-holding capacity that probably results from the effect of abundant sebum and sweat excretion in adjacent skin. From these results it is suggested that the recipient site plays an important role in determining the difference in the function of the stratum corneum, i.e., the "texture" between grafts on the face and those on other sites.

Adolescent↗