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Seasonal variability in the biophysical properties of stratum corneum from different anatomical sites.

BACKGROUND/PURPOSE: A 10-month-long study on a panel of 24 young female subjects was carried out to determine whether various biophysical aspects of the stratum corneum (SC) varied with season. METHODS: Three different anatomical sites (calf, inner forearm and crow's foot wrinkle area of the face) were assessed in February, April, July and December of the same year. The assessments made were skin surface hydration using an electrical capacitance technique, transepidermal water loss by evaporimetry, number of corneocytes released using a turbine stimulation method, and skin surface topography using optical profilometry. RESULTS: The results showed significant anatomical differences: with the crow's foot site > forearm > calf, for skin surface hydration and corneocyte numbers; and the crow's foot site > forearm and calf, with no difference between the latter two sites, for TEWL measurements. With these techniques, seasonal differences were observed mainly in the calf, to a lesser extent in the forearm, but not in the crow's foot area. These mainly involved increases in these three parameters in July, as opposed to the other time-points. Parameters of skin surface topography however, showed no consistent seasonal pattern, but markedly higher values were observed for the forearm in comparison to the calf and crow's foot sites, which were similar. From meteorological data obtained, the average daily maximum temperature and hours of sunshine increased to peak values in July, as did the absolute humidity derived from relative humidity data. CONCLUSION: We conclude that the results are most likely to represent changes in the SC due to climatic factors, with the calf and forearm sites being most affected in comparison to the face (crow's foot wrinkle area), which seems unaffected. The reasons for this latter site remaining unchanged may be due to its greater UV exposure, sebum content, and that the use of facial cosmetics was allowed.

Journal Article↗

Odor modulation of ventral scent gland marking in the Mongolian gerbil.

Gerbil odors were allowed to accumulate in individual home cages for several months in order to provide stable olfactory stimuli that might modulate the number of ventral scent gland marks produced by both male and female Mongolian gerbils. Male marking levels for most test conditions were 2-3 times larger than those in females. In general, the relative patterns of responsiveness to particular odors were similar in both sexes. The number of scent marks in home cages was significantly smaller than the number obtained in clean cages. This suppression was not strongly dependent on the odors emanating from an individual's own ventral gland sebum. Marking levels in the home cages of other gerbils were substantially higher than those seen in the test animal's own cage and were maximal in the home cages of other males. Behaviorally receptive females marked at significantly higher levels in home, clean, and conspecific cages than did nonreceptive females. Conspecific urine odors, especially those from females, increased marking levels significantly over those obtained in home cages. In males, home cage marking was significantly enhanced by the presence of a female. Females, on the other hand, marked at similar levels in home cages whether a potential mating partner was present or not. Both sexes showed significant reductions in marking levels in another's cage if the resident animal was present. These results suggest that when sufficient gerbil-related odors are available to a test animal, its rate of scent-marking is altered, depending on the particular odor environment. Some gerbil-related odors increase marking levels, whereas others decrease marking. Scent-marking then, like other olfactory guided behaviors and odor preferences, is context specific.

Animals↗

Tear film lipid layer thickness and ocular comfort after meibomian therapy via latent heat with a novel device in normal subjects.

AIM: This study measures changes in tear film lipid layer thickness (LLT) and ocular comfort in normal subjects after 10 min use of a novel device, which delivers meibomian therapy with latent heat. The device is designed to promote the release of meibomian sebum into the tear film by delivering latent heat to the eyelids, thus thickening the lipid layer. Normal lid movements are maintained, facilitating resurfacing of the tear film. METHOD: A prospective, controlled, observer masked, single intervention trial in which 24 normal subjects were randomised into three groups. Group I underwent 10 min treatment with the activated device, Group II used the inactivated device for the same duration of time, and Group III had no intervention. The LLT of each subject was measured with a Keeler Tearscope prior and subsequent to the 10-min period. Subjective alteration in ocular comfort was also assessed. RESULTS: Seven of eight subjects (87.5%) in Group I exhibited an increase in LLT. The mean LLT in this group showed a statistically significant increase (left eyes 1.0 levels, P<0.001, right eyes 0.9 levels, P<0.003) compared to Groups II and III. Six of eight subjects (75%) using the activated device experienced subjective improvement in ocular comfort. CONCLUSION: Meibomian therapy with this device increases LLT in normal individuals. This implies a more stable tear film, reflected in subjective improvement in ocular comfort.

Adult↗

Gene array expression profiling in acne lesions reveals marked upregulation of genes involved in inflammation and matrix remodeling.

The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. In an attempt to understand the specific genes involved in inflammatory acne, we performed gene expression profiling in acne patients. Skin biopsies were obtained from an inflammatory papule and from normal skin in six patients with acne. Biopsies were also taken from normal skin of six subjects without acne. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays comparing lesional to nonlesional skin in acne patients and comparing nonlesional skin from acne patients to skin from normal subjects. Within the acne patients, 211 genes are upregulated in lesional skin compared to nonlesional skin. A significant proportion of these genes are involved in pathways that regulate inflammation and extracellular matrix remodeling, and they include matrix metalloproteinases 1 and 3, IL-8, human beta-defensin 4, and granzyme B. These data indicate a prominent role of matrix metalloproteinases, inflammatory cytokines, and antimicrobial peptides in acne lesions. These studies are the first describing the comprehensive changes in gene expression in inflammatory acne lesions and are valuable in identifying potential therapeutic targets in inflammatory acne.

Acne Vulgaris↗

13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes.

Isotretinoin (13-cis retinoic acid (13-cis RA)) is the most potent inhibitor of sebum production, a key component in the pathophysiology of acne, yet its mechanism of action remains largely unknown. The effects of 13-cis RA, 9-cis retinoic acid (9-cis RA), and all-trans retinoic acid (ATRA) on cell proliferation, apoptosis, and cell cycle proteins were examined in SEB-1 sebocytes and keratinocytes. 13-cis RA causes significant dose-dependent and time-dependent decreases in viable SEB-1 sebocytes. A portion of this decrease can be attributed to cell cycle arrest as evidenced by decreased DNA synthesis, increased p21 protein expression, and decreased cyclin D1. Although not previously demonstrated in sebocytes, we report that 13-cis RA induces apoptosis in SEB-1 sebocytes as shown by increased Annexin V-FITC staining, increased TUNEL staining, and increased cleaved caspase 3 protein. Furthermore, the ability of 13-cis RA to induce apoptosis cannot be recapitulated by 9-cis RA or ATRA, and it is not inhibited by the presence of a retinoid acid receptor (RAR) pan-antagonist AGN 193109. Taken together these data indicate that 13-cis RA causes cell cycle arrest and induces apoptosis in SEB-1 sebocytes by a RAR-independent mechanism, which contributes to its sebosuppressive effect and the resolution of acne.

Alitretinoin↗

Metabolic fate and selective utilization of major fatty acids in human sebaceous gland.

The sebaceous gland is an integral part of the pilosebaceous unit of mammalian skin, which produces and secretes a unique mixture of lipids, known as sebum. Wax esters, which account for approximately 25% of human sebaceous lipids, are unique in that they are not synthesized by other cells in the body. To explore the biosynthesis of wax esters, the metabolic fate of exogenously supplied saturated (16:0, 18:0), mono-unsaturated Delta9 (16:1, 18:1), and polyunsaturated (18:2, Delta9,12) fatty acids was followed in biopsy punches from human facial skin rich in sebaceous glands. Acetate was incorporated into all of the cellular and secreted lipids and 16:0 was incorporated into all of the fatty-acid-containing lipids. The 16:0 was elongated to 18:0 and the 16:1 was incorporated primarily into polar lipids, secondarily into triglycerides, but not into other lipids and was elongated to 18:1 (Delta11). As proven by HPTLC analysis, both 18:0 and 18:1 were incorporated into the cellular lipids but at a lower rate into wax esters. Moreover, addition of exogenous 18:1 was not further processed following initial incorporation. Linoleic acid (18:2, Delta9,12) was the only fatty acid tested that appeared to be subjected to beta-oxidation. This was proven to be specific to linoleic acid, as it did not induce the oxidation of other fatty acids. The ability of the sebaceous cells to synthesize wax esters correlated with the beta-oxidation activity in these cells. Thus, the oxidation of linoleic acid is specific for the sebaceous cells and correlates with their function and differentiation. Our results provide evidence that the sebaceous gland selectively utilizes fatty acids as 16:0 is the preferred fatty acid that is incorporated into wax esters and linoleic acid undergoes beta-oxidation.

Aged↗

The integral role of topical and oral retinoids in the early treatment of acne.

This article will review the rationale for early use of topical retinoids alone or in combination with topical antimicrobials in light of the pathogenesis of microcomedones and later lesions. Knowledge of the pathogenic processes in acne vulgaris has risen dramatically over the last three decades. It is now widely accepted that acne is the result of four distinct processes: increased proliferation, cornification, and shedding of follicular epithelium; increased sebum production; colonization of the follicle with Propionibacterium acnes; and induction of inflammatory responses by bacterial antigens and cell signals. Clinical focus of disease management has shifted toward earlier treatment targeting these fundamental processes. Elimination of microcomedones, the precursor to all subsequent lesions, would optimize acne therapy by preventing the later inflammatory stages of disease. With the exception of oral isotretinoin, no single first-line agent addresses all pathogenic mechanisms. Topical retinoids have comedolytic and in some cases anti-inflammatory effects, but have no direct impact on P. acnes. Thus treatment with a combination of topical retinoid and topical antimicrobial is warranted. The former can also enhance penetration of the latter by increasing microcomedonal extrusion. In selecting a combination, one must consider efficacy, cost, and likelihood of compliance. Once thought to be effective primarily for treating comedones, topical retinoids have also been demonstrated to be effective in reducing inflammatory lesions. The activity of a topical retinoid combined with an antimicrobial agent has been shown to clear more lesions and to clear them more rapidly than antimicrobial therapy alone. Topical retinoids are also used effectively to maintain remissions.

Acne Vulgaris↗

Differences of skin irritation between Japanese and European women.

BACKGROUND: After using cosmetics, Japanese women frequently complain about sensitive, stinging skin. We wondered whether Japanese women's skin is more sensitive than that of Caucasians. OBJECTIVES: To examine possible racial differences of skin irritation and subjective sensations. METHODS: We performed patch testing on the forearm with sodium lauryl sulphate (SLS) at different concentrations (0.25%, 0.5%) and 24-h exposure time. Skin reaction was evaluated by measurement of transepidermal water loss (TEWL), stratum corneum hydration, sebum secretion, laser Doppler flowmetry (LD), content of melanin and erythema. During a stinging test with 10% lactic acid (applied to one side of the cheeks) the subjects were asked to describe the present intensity of any sensation. We used a Chromameter to measure skin colour before and after application of lactic acid. This study was performed in Marburg, Germany, with healthy Japanese and German women living in Marburg. RESULTS: After SLS testing, we found no significant differences of the barrier function in the stratum corneum, but we found significant subjective sensory differences between Japanese and German women. CONCLUSIONS: Japanese women may complain about stronger sensations reflecting a different cultural behaviour rather than measurable differences in skin physiology; however, a faster penetration of SLS in Japanese cannot be excluded.

Adult↗

Modelling the remission of individual acne lesions in vitro.

BACKGROUND: Acne lesions spontaneously remit, but the mechanism of this remission has not been elaborated. It is known, however, that the remission is associated with a de-differentiation of sebocytes, causing a cessation of sebum secretion specific to that particular pilosebaceous unit. We have previously described the cytokines that will promote in vitro the lesions of acne. OBJECTIVES: To show that those same cytokines may also promote a de-differentiation of sebocytes analogous to that seen during remission of some lesions. METHODS: Human chest sebaceous glands were maintained in vitro as whole organs. We then chronicled the effects of the appropriate cytokines and growth factors on the glandular rates of (i) lipogenesis and (ii) DNA synthesis, as well as on (iii) glandular morphology, (iv) the expression patterns of the proliferation marker Ki-67, (v) keratinocyte-specific markers, and (vi) the sebocyte marker epithelial membrane antigen. RESULTS: We have shown that the same cytokines that promote comedogenesis (interleukin-1alpha), expression of infundibular intercellular adhesion molecule-1 and human leucocyte-associated antigen-DR (tumour necrosis factor-alpha and interferon-gamma), and infundibular disruption (epidermal growth factor/transforming growth factor-alpha) in human infundibula in vitro, will also inhibit sebaceous lipogenesis in vitro and will also induce, histologically, a de-differentiation of human sebocytes into a keratinocyte-like phenotype. CONCLUSIONS: These results confirm our hypothesis that the cytokines that induce the infundibular changes in acne may also inhibit the secretion of lipid from the sebaceous gland and thus, on diffusing down to the gland, contribute to the remission of the individual lesions. These findings help to explain the known natural history of the disease.

Acne Vulgaris↗

Congenital adrenal hyperplasia and acne in male patients.

Seborrhoea is one pathogenic factor for acne. Androgens induce sebum production, and excess androgen may provoke or aggravate acne. In women an androgen disorder is frequently suspected when acne is accompanied by hirsutism or menstrual irregularities. In men acne may be the only symptom of androgen excess. We report three male acne patients in whom hormonal screening revealed irregularities of androgen metabolism suggestive of late-onset congenital adrenal hyperplasia and who benefitted from low-dose glucocorticoids. Disorders of androgen metabolism may influence acne not only in women, but also in men, and these patients may benefit from low-dose glucocorticoid therapy.

Acne Vulgaris↗

Digital image analysis of the effect of topically applied linoleic acid on acne microcomedones.

A major pathogenic factor of acne is the disturbed keratinization of the follicular infundibulum. It has been hypothesized that a relative decrease in linoleic acid in the sebum could be responsible, in part, for this. The aim of the present study was objectively to evaluate the effects of topically applied linoleic acid on the size of microcomedones in patients with mild acne. The design was a double-blind placebo-controlled randomized cross-over study. Evaluations were performed by digital image analysis of cyanoacrylate follicular biopsies. There was a significant effect of topically applied linoleic acid on the size of follicular casts and microcomedones, an almost 25% reduction in their overall size being achieved over a 1-month treatment period. In contrast, no change was found at placebo-treated sites. It is concluded that topical linoleic acid might play a role as a comedolytic agent in acne-prone patients.

Acne Vulgaris↗

Responses of Glossina austeni to sticky panels and odours.

The responses of male tsetse Glossina austeni Newstead (Diptera: Glossinidae) towards blue and white sticky legged panels, baited with odour attractants, and towards modified panels were studied in the Jozani forest of Unguja Island, Zanzibar. Increasing the height of the body of a standard panel from 30 to 60 or 90 cm, increased the catch two-fold. Increasing the height of the legs (from 15 to 60 or 120 cm) or raising the device more than 5 cm above the ground reduced the catch significantly. The legs of the panels were the preferred landing sites of the flies, irrespective of the height of the body of the panel. Acetone (300 mg/h) combined with cow urine (60-130 mg/h) significantly increased the catches two- to threefold during the rainy season, but not during the dry season. Acetone had no effect during the dry season and its effect during the rainy season was less consistent. There was no effect of octenol (2.5-12.5 mg/h), used alone or in combination with acetone. Likewise, the catch did not increase through the addition of cow sebum, pig urine (60-860 mg/h), pig urine combined with acetone and octenol. The observed seasonal differences in the response of G. austeni towards odours are discussed in relation to host location strategies.

Acetone↗

Skin wrinkling for the assessment of sympathetic function in the limbs.

BACKGROUND: Wrinkling of the skin of the palm and sole is considered to be dependent on the presence of intact sympathetic nervous activity. Loss of sympathetic integrity could be simply and usefully assessed by the absence of wrinkling. To test this hypothesis, the skin wrinkle test was compared with the starch-iodine sweat test and sympathetic skin response (SSR) in patients with abnormal sympathetic function. METHODS: The three tests were carried out in 34 patients (68 limbs) undergoing temporary or permanent disruption of the sympathetic chain to upper or lower limbs. Included in this group were six diabetics undergoing chemical or surgical sympathectomy, lumbar epidural infusions following vascular surgery, and patients for whom sympathectomy was being considered. Sensitivity and specificity analysis and predictive values of the wrinkling response and the starch-iodine test were related to the SSR as the standard. RESULTS: The wrinkle test showed a sensitivity of 97% and specificity of 95%, and bore good correlation to the SSR. The starch-iodine test showed sensitivity of 55% and specificity of 93%. A hypothesis for the mechanism of wrinkling based on the observations of the present study is proposed. CONCLUSION: The wrinkle test is a reliable test of sympathetic function, is inexpensive and is easy to perform at the bedside. The sweat gland myo-epithelial cells and absence of sebum could play an important role in the wrinkling response. It can be used to select patients who will benefit from sympathectomy, and can adequately evaluate sympathetic blockade.

Adolescent↗

Defolliculated (dfl): a dominant mouse mutation leading to poor sebaceous gland differentiation and total elimination of pelage follicles.

Defolliculated is a novel spontaneous mouse mutation that maps to chromosome 11 close to the type I keratin locus. Histology shows abnormal differentiation of the sebaceous gland, with the sebocytes producing little or no sebum and undergoing abnormal cornification. The hair follicles fail to regress during catagen leading to abnormally long follicles. In contrast the hair shafts are shorter than normal, suggesting altered differentiation or proliferation of matrix cells during anagen. The shafts emerge from the follicle with cornified material still attached. The dermis contains increased numbers of immune cells, including T cells (CD4-positive), macrophages, and mast cells, at all time points examined. Complete elimination of all pelage and tail follicles occurs after two to three hair cycles, apparently by necrosis. Defolliculated may be a useful model for determining further functions of the sebaceous gland, and for understanding the regulation of catagen and hair follicle immunology.

Alopecia↗

[Treatment of acne with antiandrogens--an evidence-based review].

BACKGROUND: Increased sebaceous gland activity with seborrhea is one of the major pathogenetic factors in acne. Antiandrogen treatment targets the androgen-metabolizing follicular keratinocytes and the sebaceous gland leading to sebostasis, with a reduction of the sebum secretion rate of 12.5-65%. Antiandrogens can be classified based on their mechanism of action as androgen receptor blockers, inhibitors of circulating androgens by affecting ovarian function (oral contraceptives), inhibitors of circulating androgens by affecting the pituitary (gonadotropin-releasing hormone agonists and dopamine agonists in hyperprolactinemia), inhibitors of adrenal function, and inhibitors of peripheral androgen metabolism (5alpha-reductase inhibitors, inhibitors of other enzymes). METHODS: All original and review publications on antiandrogen treatment of acne as monotherapy or in combination included in the MedLine system were extracted by using the terms "acne", "seborrhea", "polycystic ovary syndrome", "hyperandrog", and "treatment" and classified according to their level of evidence. RESULTS: The combinations of cyproterone acetate (2 mg)/ethinyl estradiol (35 microg), drospirenone (3 mg)/ethinyl estradiol (30 microg), and desogestrel (25 microg)/ ethinyl estradiol (40 microg) for 1 week followed by desogestrel (125 microg)/ethinyl estradiol (30 microg) for 2 weeks showed the strongest anti-acne activity. Gestagens or estrogens as monotherapy, spironolactone, flutamide, gonadotropin-releasing hormone agonists, and inhibitors of peripheral androgen metabolism cannot be endorsed based on current knowledge. Low dose prednisolone is only effective in late-onset congenital adrenal hyperplasia and dopamine agonists only in hyperprolactinemia. Treatment with antiandrogens should only be considered if none of the contraindications exist. CONCLUSION: Antiandrogen treatment should be limited to female patients with additional signs of peripheral hyperandrogenism or hyperandrogenemia. In addition, women with late-onset or recalcitrant acne who also desire contraception can be treated with antiandrogens as can those being treated with systemic isotretinoin. Antiandrogen treatment is not appropriate primary monotherapy for noninflammatory and mild inflammatory acne.

Acne Vulgaris↗

The evolving role of Propionibacterium acnes in acne.

Propionibacterium acnes is a member of the resident cutaneous flora. Sebaceous follicles involved in acne are characterized by the accumulation of abnormally desquamated corneocytes and excess sebum-the microcomedo. This environment provides ideal growth conditions for P acnes. Several orders of magnitude level of P acnes are found in microcomedos. P acnes produces a variety of chemotactic factors and proinflammatory molecules that are responsible for the inflammatory phase of acne. Antibiotic therapy works by reducing the viable number of P acnes as well as by reducing the production of inflammatory stimuli. Antibiotic therapy has been a mainstay of treatment for more than 30 years. In the last decade, decreased sensitivity to antibiotics has developed and clinical resistance has been described. This development threatens the usefulness of antibiotic therapy in the future.

Acne Vulgaris↗

Adhesives and emollients in the preterm infant.

This chapter focuses on recent advances in preterm infant skin care related to skin adhesion and skin emolliency. Different types of adhesives and hydrating agents are reviewed. Clinical applications are best guided by understanding the biology of epidermal barrier development. The role of xeric stress in accelerating formation of the stratum corneum is discussed along with the effects of occlusive agents and emollients on wound healing and epidermal barrier repair. The principles of skin moisturization are introduced. The concept is advanced that programmatic changes in skin adhesion and water handling occur during the normal ontogeny of superficial biofilms (sebum, sweat, acid mantle).

Adhesives↗

[Hyperplasia of sebaceous glands (Fordyce's disease) in an oral mucocutaneous graft: 45-year follow-up].

BACKGROUND: Diffuse sebaceous gland hyperplasia in transplanted buccal mucosa is a very rare condition. We report on a further patient with this entity. PATIENT: In 1953, a now 68-year-old man suffered a severe alkali burn. Transplantation of oral mucosa was performed that same day in order to prevent perforation of the eye. Over the following 45 years, the patient developed multiple yellowish nodules within the grafts. Histologically, these nodules proved to be normally differentiated sebaceous glands. CONCLUSIONS: Diffuse sebaceous gland hyperplasia originating from within oral mucosa and developing over an extended period of time is a clinical entity known as Fordyce's disease. It is this a late complication of mucocutaneous transplantation, and although it constitutes mainly a problem of cosmesis, functionally it can lead to aberrant secretion of sebum.

Aged↗