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Relationship between dermato-physiological changes and hormonal status in pre-, peri-, and postmenopausal women.

We previously reported that hormonal changes in perimenopausal women are associated with dermatologic changes. In the present study, we evaluated such dermatologic changes by means of dermato-physiological testing methods in perimenopausal women with various types of hormonal conditions. The study group consisted of 46 consecutive women 41-70 years of age (mean, 54.0 years), attending a climacteric outpatient clinic for a healthy check-up is whom no abnormalities were recognized. The women were divided into four groups according to menstrual history and sex-related steroid hormone values: a premenopausal group (n = 9); a perimenopausal group (n = 8); an early menopausal group, in which 5 years or less had elapsed since menopause (n = 12); and a late menopausal group, in which 6 years or more had elapsed since menopause (n = 17). We found that: (1) after menopause the sebum cutaneum content of the forehead decreased significantly, but that of the subocular region was unchanged; (2) the water content of the stratum corneum of the forehead was significantly higher in the late menopausal group than in the premenopausal group and the perimenopausal group, but there were no significant differences among the four groups at the other sites studied; (3) on psychological stimulation, sweat production was found to decrease significantly after menopause; (4) the skin temperature of the forehead and cheek fell significantly after menopause, but that of the nose, back of the foot, and tips of the toes, did not differ significantly among the four groups; (5) The perimenopausal period was associated with increased skin permeability and vascular responsiveness; (6) fingertip plethysmography revealed significant decreases in peripheral circulatory function in the perimenopausal group and the late menopausal group.

Adult↗

Topical transport of hydrophilic compounds using water-in-oil nanoemulsions.

A variety of water-in-oil nanoemulsions were prepared using sorbitan monooleate (Span80), polyoxyethylene 20 sorbitan monooleate (Tween80), olive oil and water. The nanoemulsions were tested for their ability to facilitate transport of a model hydrophilic solute, inulin, across hairless and hairy mouse skin and hairy rat skin following topical in vitro application. The transport of inulin incorporated in water-in-oil nanoemulsions was found to be significantly higher (5- to 15-fold) than that obtained with micellar dispersions or aqueous controls. The rate and extent of inulin transport across hairy mouse skin was found to be highly dependent on the hydrophile-lipophile balance (HLB) of the surfactant mixture in the nanoemulsion. Nanoemuslions prepared using mixtures with lower HLB exhibited significantly higher rate and extent of transport. It was also found that nanoemulsion-mediated transport was independent of molecular size of the hydrophilic solute and the nature of the aqueous phase. More importantly, transport of inulin from nanoemulsions was independent of animal skin characteristics such as stratum corneum thickness and follicle-type. The combined results suggest that water-in-oil nanoemulsions that are compatible with the lipophilic sebum environment of the hair follicle facilitate efficient transport of incorporated hydrophilic solutes and imply that such transport is predominantly transfollicular in nature.

Administration, Topical↗

Analysis of fatty acid ethyl esters in hair as possible markers of chronically elevated alcohol consumption by headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS).

Fatty acid ethyl esters (FAEE) are products of the nonoxidative ethanol metabolism, which are known to be detectable in blood only about 24h after the last alcohol intake. After deposition in hair they should be suitable long-term markers of chronically elevated alcohol consumption. Therefore, a method for the analysis of ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate from hair was developed based on the extraction of the hair sample by a dimethylsulphoxide (DMSO)/n-hexane mixture, separation and evaporation of the n-hexane phase and application of headspace solid-phase microextraction (HS-SPME) in combination with gas chromatography-mass spectrometry (GC-MS) to the extract. For use as internal standards, the corresponding D(5)-ethyl esters were prepared. The HS-SPME/GC-MS measurements were automatically performed using a multi-purpose sampler. The detection limits of the FAEE were between 0.01 and 0.04ng/mg and the reproducibility was between 3.5 and 16%. By application of the method to hair samples of 21 fatalities with known heavy alcohol abuse 0.045-2.4ng/mg ethyl myristate, 0.35-13.5ng/mg ethyl palmitate, 0.25-7.7ng/mg ethyl oleate and 0.05-3.85ng/mg ethyl stearate were measured. For social drinkers (30-60g ethanol per week), the concentrations were about one order of magnitude smaller. For 10 teetotalers negative results or traces of ethyl palmitate were found. It was shown by supplementary investigations in single cases that FAEE are also present in sebum, that there is no strong difference in their concentrations between pubic, chest and scalp hair, and that they are detectable in hair segments after a 2 months period of abstinence. From the results follows that the measurement of FAEE concentrations in hair is a useful way for a retrospective detection of alcohol abuse.

Adolescent↗

Effect of hair care and hair cosmetics on the concentrations of fatty acid ethyl esters in hair as markers of chronically elevated alcohol consumption.

Fatty acid ethyl esters (FAEE) can be used as alcohol markers in hair. It was investigated in this study whether this diagnostic method is disturbed by hair care and hair cosmetics. Traces of ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate were detected in all of 49 frequently applied hair care products by headspace solid phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS). The highest concentration was 0.003% in a hair wax. From experiments with separated hair samples of alcoholics as well as from the evaluation of the FAEE concentrations and the data about hair care of 75 volunteers (alcoholics, social drinkers and teetotalers) follows that usual shampooing, permanent wave, dyeing, bleaching or shading are of minor importance as compared to the drinking amount and other individual features. However, false positive results were found after daily treatment with a hair lotion containing 62.5% ethanol, with a deodorant and with a hair spray. As an explanation, it is assumed that FAEE are formed in the sebum glands also after regular topical application of products with a higher ethanol content.

Alcohol Drinking↗

[Pathophysiology of acne].

Acne is a disease that develops in pilosebaceous follicles. Acne was long considered was an infectious disease related to Propionibac-terium acnes, but studies show that the production of inflammatory substances in situ was much more important to the action of this bacterium than was simple infection. It was once thought that only the androgens could stimulate the seba-ceous gland, but today we know that neuromediators can also stimulate sebum production. This finding provides physiological support to the clinical observation that stress can induce acne.

Acne Vulgaris↗

Generation of oxidative stress in human cutaneous models following in vitro ozone exposure.

Ozone, one of the main components of photochemical smog, represents an important source of environmental oxidative stress. The skin, being the outermost barrier of the body, is directly exposed to environmental oxidant toxicants. Skin sebum and cellular plasma membrane lipids contain polyunsaturated fatty acids which are primary targets for ozone and free radical attack induced lipid peroxides. These ozonation processes in skin can also generate aldehydes, hydroxyhydroperoxides and specific Criegee's ozonides. In order to evaluate in vitro human skin susceptibility to ozone, we have exposed cultured immortalized human keratinocytes (DK7-NR) and the reconstructed human epidermis Episkin to 10 ppm of ozone in a specific incubator. We measured the formation of protein carbonyls by an ELISA method and monitored the oxidative stress using the fluorogenic probe 2',7'-dichlorofluorescin-diacetate (DCFH-DA). Results showed a time-dependent increase of fluorescence levels (linked to oxidative stress) in both models exposed to ozone. Using this protocol, we investigated the protective potential of different products including vitamin C, a thiol derivative and a plant extract. All products dramatically reduced oxidative responses during ozone exposure. Decreases observed in fluorescence levels were between 60 and 90% as compared to non-protected controls. These results demonstrate: (a) cutaneous in vitro models are remarkably susceptible to oxidative stress generated by an environmental air pollutant as ozone, and (b) raw antioxidants, thiols and vitamin C were efficient products to prevent ozone induced cellular oxidative damage.

Acetylcysteine↗

Quantitative evaluation of skin condition in an epidemiological survey of females living in northern versus southern Japan.

Image analysis and biophysical methods were used to compare the skin condition of a group of females ranging in age from 5 to 65 years who had lived all of their lives in either Kagoshima (n=300), located in southern Japan, or Akita (n=302), located in northern Japan. Kagoshima annually receives approximately 1.5 times more solar UVB radiation than Akita. The methods used and corresponding skin parameters reported in this survey were: high resolution digital imaging followed by computer analysis of facial images for facial skin wrinkling and hyperpigmentation; silicone skin replicas followed by Moiré interferometry for facial skin surface roughness (texture); the Minolta Chromameter for skin color (L*a*b*) on sun-exposed (forehead) and sun-protected (upper inner arm) skin sites; the Corneometer for skin capacitance (hydration) on the cheek and ventral forearm; the Sebumeter for sebum excretion rate on the forehead; and the Minolta Spot Thermometer for skin temperature on the upper cheek. Compared with Japanese women living in Akita, Japanese women living in Kagoshima had significantly longer facial wrinkles, higher number of wrinkles, larger hyperpigmented spots, higher number of spots, rougher facial skin texture, more yellow foreheads and upper inner arms, darker foreheads, and less stratum corneum hydration in the cheeks and arms. When compared on an age-for-age basis, the average 40-year-old Kagoshima women has the same level of facial wrinkling as a 48-year-old Akita women, a delay of 8 years for living in the northern latitude. For facial hyperpigmentation, the delay is 16 years; the average 40-year-old Kagoshima women has the same level of facial hyperpigmentation as a 56-year-old Akita women. The results further testify to the skin damaging effects of sun exposure and may be useful in public health education to promote everyday sun protection.

Adolescent↗

Photocontact dermatitis and chloracne: two major occupational and environmental skin diseases induced by different actions of halogenated chemicals.

Among occupational and environmental disorders, contact or photocontact dermatitis and an acneiform eruption are two major skin disorders. Photocontact dermatitis was historically caused by various halogenated salicylanilides, while the acne is induced by halogenated aromatic hydrocarbons and thus called chloracne. Therefore, it should be noted that halogenated chemical compounds are important causative agents in the occupational and environmental medicine. In photocontact dermatitis, photoconjugation of epidermal cells with a photohaptenic halogenated chemical is the initial step. Langerhans cells serve as antigen-presenting cells and T cells sensitized by photoantigen-bearing Langerhans cells induce this photosensitivity. On the other hand, in chloracne, halogeneted hydrocarbons render keratinocytes of the outer root sheath and sebaceous duct hyperplastic. The dilated infundibulum of most hair follicles is then filled with comedone that consist of many accumulated layers of keratinized cells and sebum. Therefore, halogenated chemicals exhibit different actions, i.e. the induction of an immunologic consequence and the modulation of keratinocyte biology. These two conditions also provide good experimental models for investigating dermatology.

Acne Vulgaris↗

Identification of Propionibacterium acnes by polymerase chain reaction for amplification of 16S ribosomal RNA and lipase genes.

Propionibacterium acnes belongs to the cutaneous flora and is present in sebaceous follicles. The fatty acids that are released from sebum triglycerides by the action of this bacterial lipase play an important role in the pathogenesis of acne vulgaris. P. acnes is also involved in postoperative disorders and opportunistic infections in immunosuppressed hosts. Recently, it has been proposed that P. acnes causes sarcoidosis. Therefore, rapid isolation and identification of P. acnes is important. This study evaluated the polymerase chain reaction (PCR) for the detection of the 16S rRNA and lipase genes of P. acnes. The PCR used to detect the 16S rRNA gene could amplify the gene of P. acnes, but not the genes of the other tested strains of P. avidum, P. granulosum, P. lymphophilum, P. jensenii, P. acidipropionici and P. thoenii. The PCR to detect the lipase gene of P. acnes, however, could amplify not only the gene of P. acnes but also that of P. avidum. The PCR product of this lipase gene was not found in the strains of the other species tested. Therefore, the organism that has both the 16S rRNA gene and lipase gene was identified as P. acnes, while the strain with the lipase gene but not the 16S rRNA gene of P. acnes was characterized as P. avidum. These findings were confirmed by the conventional biochemical tests including lipase activity. Furthermore, out of the seven clinical isolates from acne vulgaris, four were identified as P. acnes and three as P. avidum by the PCR method and biochemical tests. The combination of two PCR, one for the detection of the 16S rRNA and the other of lipase genes was shown to be an easier, faster and more accurate method to identify P. acnes and P. avidum than conventional methods.

Journal Article↗

[Bacterial contamination of platelet concentrates by Propionibacterium acnes].

In this study, three incidents of platelet contamination by Proprionibacterium acnes and an investigation of the transfusion process have been reported, which occurred at the Nord-Pas-de-Calais Blood Center over a period of several months. P. acnes is a bacterium that is present in the cutaneous flora; it does not produce any toxin, and is rarely considered as a pathogenic agent; its occurrence is widespread, in particular in those regions that are rich in sebum (face, back, scalp), and it is extremely apparent during adolescence. The three incidents occurred following the transfusion of a pool of leucodepleted platelet concentrates obtained from immunodeficient patients. The clinical outcome was in all cases positive. It was considered that the bacterial contamination of platelet concentrates could reflect insufficient skin disinfection at the site of the venipuncture and a minimal bacterial risk involving the blood collection procedure.

Adolescent↗

Midline sublingual dermoid cyst.

The case of an 18-year-old man who presented with a large cystic mass in the floor of the mouth extending into the left submandibular triangle of the neck is reported. Histopathology of this mass, which was totally excised by a combined intra-oral and cervical approach, confirmed it to have originated in ectodermal remnants (congenital dermoid cyst) and to be actively secreting sebum. This case is reported both because dermoids at this site are rare because they may present some problems in management.

Adolescent↗

Low intensity ultrasound as a probe to elucidate the relative follicular contribution to total transdermal absorption.

PURPOSE: To investigate the effect of ultrasound on the histological integrity and permeability properties of whole rat skin in vitro. METHODS: A defined, field-free source of ultrasound was used to irradiate excised rat skin prior to in vitro transport studies in Franz-type cells using sucrose, mannitol, hydrocortisone, 5-fluorouracil and aminopyrine. RESULTS: High intensity ultrasound irradiation (1 to 2 W cm-2) irreversibly damaged cutaneous structures and increased the percutaneous transport rate of permeants. In contrast, skin integrity was largely maintained with low intensity ultrasound (0.1 to 1 W cm-2) which merely discharged sebum from the sebaceous glands so as to fill much of the hair follicle shafts. This effect caused the transfollicular absorption pathway to be blocked for hydrophilic molecules that penetrate via this route and reduced the transport rate significantly. CONCLUSIONS: This phenomenon may be used as a probe to elucidate the relative follicular contribution to total penetration for hydrophilic permeants. It was demonstrated that the shunt pathway was responsible for virtually all mannitol and sucrose penetration, perhaps half of hydrocortisone transport but negligible aminopyrine and 5-fluorouracil penetration.

Aminopyrine↗

Evolution of the mammary gland defense system and the ontogeny of the immune system.

A decisive event in the evolution of mammals from synapsid reptiles was the modification of ventral thoracic-abdominal epidermal glands to form the mammary gland. The natural selection events that drove the process may have been the provision of certain immunological agents in dermal secretions of those nascent mammals. This is mirrored by similar innate immune factors in mammalian sebum and in protherian and eutherian milks. On the basis of studies of existing mammalian orders, it is evident that immune agents in milk such as immunoglobulins, iron-binding proteins, lysozyme, oligosaccharides, and leukocytes compensate for developmental delays in early postnatal production of antimicrobial factors. At least in human milk, anti-inflammatory and immunomodulating agents also evolved to provide different types of protection for the offspring. In addition, investigations reveal that the types or concentrations of immunological agents in milk vary depending upon the type of placenta, lactation pattern, and environment of the species.

Animals↗

Relevance of multiparametric skin bioengineering in a prospectively-followed cohort of junior hairdressers.

There is conflicting evidence concerning predictors of individual susceptibility to develop irritant contact dermatitis in wet work. A cohort of initially 92 hairdresser apprentices was prospectively followed for 3 years. The association between anamnestic and clinical findings, and multiparametric skin bioengineering data (transepidermal water loss [TEWL], microcirculation, capacitance, pH, sebum, temperature) was investigated. The observation intervals were 3 months in the 1st year of training and 12 months thereafter. Of the 92 apprentices, 6 had already developed hand dermatitis on 1st examination, 20 dropped out or had occupational exposure longer than 7 weeks prior to investigation. Of the remaining 66 participants considered here, 19 (29%) developed moderate or severe dermatitis ("cases"), 32 minimal skin changes, 15 none within the observation period. Average incidence rate of hand dermatitis was 21.1 cases per 100 person years. Atopy score was not associated with the development of dermatitis, nor were the investigated basal bioengineering parameters, including TEWL, in a multivariable model. However, there was a significant increase in TEWL within the 1st year of training in presumptive "cases". The aim to develop an objective and predictive instrumentary for pre-employment counselling in wet work, by a combination of (a) clinical and (b) relevant non-invasive bioengineering parameters, has not yet been accomplished. Skin-provocation tests employing bioengineering seem to be required. Notwithstanding, work-related monitoring of basal biophysical skin-functions may become useful in the secondary prevention of occupational dermatitis.

Adolescent↗

Insights from the asebia mouse: a molecular sebaceous gland defect leading to cicatricial alopecia.

The primary cicatricial alopecias have proven to be challenging for the clinician, dermatopathologist and the researcher--let alone the patient. If we are to improve our diagnostic and therapeutic tools for these very difficult disorders, we will need greater insight into their etiology. Recent work with the mouse mutant, asebia, provides a model for cicatricial alopecia. In this model the pathology--perifollicular inflammation, sebaceous gland "destruction", hair shaft granuloma, and cicatricial follicle drop-out--results from the mutation of one very important sebaceous gland gene. In the absence of this gene, the sebaceous gland is hypoplastic and normal sebum production is minimal to absent. In this paper the relevance of this mutant to human alopecias is discussed and the point emphasized that the pathogenesis of some forms of human cicatricial alopecia could involve the sebaceous gland.

Alopecia↗

Chloracne: histopathologic findings in one case.

BACKGROUND: Chloracne is an acneiform eruption due to poisoning by halogenated aromatic compounds having a specific molecular shape. This condition is always a symptom of systemic poisoning by chemical chloracnegens and not just a cutaneous disorder. METHODS: We have studied a patient with severe chloracne who showed cutaneous lesions involving mostly the face and the axillae. RESULTS: Histopathologic study of the facial lesions demonstrated that almost every vellus hair follicle was involved, showing a dilated infundibulum filled by a keratotic plug. This keratotic material was mostly composed of orthokeratotic basket-weave basophilic corneocytes, namely infundibular keratin, although there were also some dilated infundibula containing eosinophilic laminated or granular sebum at their center. Small infundibular cysts were more numerous than comedones. Mature and well-developed sebaceous glands were seen at the base of many of the dilated infundibula and no squamous metaplasia of the sebaceous glands or ducts could be demonstrated. Hyperpigmentation of the lesions resulted from hyperproduction of melanin by a normal number of melanocytes along the basal layer of the epidermis and infundibular epithelium. Abundant melanin granules also impregnated the corneocytes of the infundibular plugs. CONCLUSIONS: Our findings support the notion that tiny infundibular cysts rather than comedones represent the basic lesions of chloracne.

Acneiform Eruptions↗

The biological actions of estrogens on skin.

There is still extensive disparity in our understanding of how estrogens exert their actions, particularly in non-reproductive tissues such as the skin. Although it has been recognized for some time that estrogens have significant effects on many aspects of skin physiology and pathophysiology, studies on estrogen action in skin have been limited. However, estrogens clearly have an important function in many components of human skin including the epidermis, dermis, vasculature, hair follicle and the sebaceous, eccrine and apocrine glands, having significant roles in skin aging, pigmentation, hair growth, sebum production and skin cancer. The recent discovery of a second intracellular estrogen receptor (ERbeta) with different cell-specific roles to the classic estrogen receptor (ERalpha), and the identification of cell surface estrogen receptors, has provided further challenges to understanding the mechanism of estrogen action. It is now time to readdress many of the outstanding questions regarding the role of estrogens in skin and improve our understanding of the physiology and interaction of steroid hormones and their receptors in human skin. Not only will this lead to a better understanding of estrogen action, but may also provide a basis for further interventions in pathological processes that involve dysregulation of estrogen action.

Animals↗

Involvement of the SREBP pathway in the mode of action of androgens in sebaceous glands in vivo.

Androgens have profound effects on the physiology of the sebaceous gland. Using the hamster ear sebaceous gland model, we performed a detailed kinetic study to clarify the mechanism of androgen action on sebaceous gland function. We demonstrated that the growth of sebaceous glands observed after androgen treatment was due to both an increase in sebocyte proliferation and a parallel induction of sebocyte terminal differentiation, as evidenced by the induction of the synthesis of specific sebaceous lipids such as cholesterol esters, triglycerides, and squalene. Accordingly, the effect of androgen treatment on the mRNA expression of several key enzymes involved in the synthesis of sebaceous lipids has been studied using semi-quantitative RT-PCR. Up-regulation by androgens of mRNA expression of HMG coenzyme A synthase and reductase, acetyl coenzyme A carboxylase (ACC), glycerol 3-phosphate acyl transferase (GPAT), and FAR-17c (stearoyl coenzyme A desaturase homologous), was demonstrated. Because sterol-response element(s) (SREs) are known to be present in the promoters of these genes, we analyzed the expression by RT-PCR and the activation of the transcription factor sterol regulatory element binding protein (SREBP) using immunoblotting experiments. Our results showed that SREBP-1 was up-regulated and rapidly activated after androgen treatment. Altogether, these results demonstrate for the first time that in sebaceous glands, in vivo, androgen regulates the synthesis of sebum lipids through the SREBP pathway.

Androgens↗