Silicone based water-in-oil emulsion fortified with anthocyanin: In-vitro, in-vivo study.

Skin care formulations with antioxidants are being widely explored for their benefits to human skin. The purpose of this study was to formulate a stable w/o emulsion containing anthocyanin derived from Malus dosmestica fruit extract and to further explore its beneficial effects on normal human skin. Anthocyanin was extracted using various solvents from the peel of Malus dosmestica fruit. w/o creams containing anthocyanin has been prepared and systematically characterized for various physiochemical properties in terms of stability at varying conditions of storage. An efficacy study has been carried out on 12 male healthy Asian subjects to determine effects of anthocyanin on skin melanin, erythema, skin moisture, trans-epidermal water loss (TEWL) and on skin sebum. Solvent system containing methanol/acetone/water (3.5: 3.5: 3 v/v/v) including 1% formic acid established a best recovery of anthocyanin from fruit peel. W/O emulsions presented promising stability profile when kept at different storage conditions over 90 days period. All skin parameters studied, anthocyanin has been found more efficacious (p<0.05) for its effects on skin melanin and erythema content of skin. It has been shown that a topical application of anthocyanin derived from Malus domestica has substantial potential for human skin system and needs some patient oriented studies could warrant its potential for damaged skin.

Amazake made from sake cake and rice koji suppresses sebum content in differentiated hamster sebocytes and improves skin properties in humans.

Amazake is a traditional Japanese health drink. Here, we examined the effects of amazake on skin in cells and humans. Treatment with sake cake or rice koji suppressed intracellular lipid accumulation in differentiated hamster sebocytes, likely through the reduced expression of peroxisome proliferator-activated receptor-gamma (PPARγ) mRNA. In double-blind, placebo-controlled trial, seventeen Japanese women ingested either amazake or placebo for 4 weeks. Ingestion of the amazake decreased the sebum content compared to the placebo. The questionnaires showed improvements in "face color," "dark circles under the eyes," "glossy hair," and "waking up well", only in the amazake. In accordance with the questionnaires, additional analysis revealed the change in the L* values under the eyes was statistically increased in the amazake compared to the placebo. These results indicate that amazake may decrease sebum content in cells and humans and increase the L* values under the eyes, with some additional beneficial effects in humans.

Non-Invasive Immunofluorescence Assessment of Lycopene Supplementation Status in Skin Smears.

Circulating lycopene level is negatively associated with the prevalence of cardiovascular disease, cancers (prostate and breast), type 2 diabetes mellitus, and aging. Traditionally, lycopene is measured in biological specimens by a combination of high-performance liquid chromatography (HPLC) and mass spectrometry methods. Moreover, as we recently reported, tissue/cell lycopene depositions can be observed by the immunohistochemistry method with a newly developed monoclonal antibody (mAb) against lycopene. A main objective of this study is to evaluate the performance of a new noninvasive immunofluorescence (IF) lycopene quantification skin test with mAbs against lycopene versus HPLC lycopene assay of serum lycopene in volunteers subjected to lycopene supplementation which represents a novel approach to lycopene measurement methodology. For this purpose, 32 healthy volunteers, 30-40 years old, were supplemented with lycopene (n = 15) or placebo (n = 17) for a period of 4 weeks. It was found that lycopene supplementation leads to a significant increase in serum lycopene concentration after 2 and 4 weeks by 2.6- and 3.4-fold over control, respectively. This was accompanied by a concordant step-wise rise in IF staining of skin corneocytes and sebum, quantifiable by arbitrary IF scores. Placebo supplementation did not affect serum lycopene values or intensity of IF staining of the skin samples. There was 86.6% agreement in paired HPLC/IF variants for the intermediate time point and 80.0% agreement at the end of the study in the lycopene group. Intraclass correlation between paired values in this group was +0.49 for the 2-week time point and +0.63 for the end point. These results indicate that the new antibody-based skin assay can be used for rapid detection of lycopene deficiencies. Moreover, the noninvasive nature of the skin swab test would allow using it to monitor, optimize, and personalize lycopene supplementation protocol of risk groups in the general population.

Comparative effects of a fixed Polypodium leucotomos/Pomegranate combination versus Polypodium leucotomos alone on skin biophysical parameters.

OBJECTIVES: Polypodium leucotomos extract is a commonly used systemic photoprotective agent. In an exploratory fashion, the current study aimed to compare the effects of oral supplementation with a fixed Polypodium leucotomos/pomegranate combination (PPmix®) versus Polypodium leucotomos alone (Fernblock®) on skin biophysical parameters of Caucasian adults. METHODS: Forty healthy adult volunteers (20 males and 20 females; mean age: 37.2±5.5 years) were randomized in a 1:1 fashion to a fixed Polypodium leucotomos/pomegranate combination (480 mg/day; n=20) or Polypodium leucotomos alone (480 mg/day; n=20) for 3 months. Six skin biophysical parameters (skin sebum content, hydration, transepidermal water loss [TEWL], erythema index, melanin index, and elasticity) were measured at baseline and after 3 months by personnel blinded to participant allocation. RESULTS: At the end of the study, hydration and elasticity were significantly improved and TEWL was reduced in both groups, without significant intergroup differences. The erythema index was decreased by both treatments, although the fixed Polypodium leucotomos/pomegranate combination was significantly more effective. Finally, melanin index and skin sebum content were reduced by the fixed Polypodium leucotomos/pomegranate combination, whereas Polypodium leucotomos alone did not affect them. CONCLUSIONS: Our results suggest that a fixed Polypodium leucotomos/pomegranate combination provides a greater improvement of skin biophysical parameters compared to Polypodium leucotomos alone in adult Caucasians. Our findings may have implications for optimizing systemic skin photoprotection and beautification strategies.

Evaluation of molecules or extracts modulating seborrhea and its consequences, using normal human culture of sebocytes and keratinocytes, skin explants models and in vivo methods: a case study.

Skin produces sebum through sebocytes. Hyper-seborrhea creates conditions for the development of inflamed cutaneous alterations through bacteria colonization triggering dead cell accumulation and pro-inflammatory mediator release. Study of sebum production, its modulation, and its consequences requires complementary in vitro models in order to evaluate the effect of molecules on cell metabolisms. Clinical studies need to be performed to confirm in vitro results. Effects of phenylpropanoids, obtained by elicitation and purification from plant cell culture of Syringa vulgaris (CCSV), were studied on sebocytes, keratinocytes, and explants, all derived from normal human skins. Normal human sebocytes (NHSs) expressed markers such as cytokeratin-7, cytokeratin-4, and perilipin-2 (PLIN-2) (1); the latter being colocalized with lipid droplets. Lipid droplets clearly appeared and their size increased rapidly when lipogenic agents were used. NHS, normal human keratinocytes (NHK), and explants reacted to presence of bacterial fragments which trigger pre-inflammatory mediator release. CCSV reduced lipid storage and release of pre-inflammatory mediators in NHS, NHK and explants. CCSV also reduced P. acnes growth and triggered beta-defensin-2 and cathelicidin synthesis by NHS, two natural antimicrobial peptides. On volunteers, sebum production, inflamed blemishes, and retentional lesions were significantly reduced after 1 month treatment with CCSV.

Acne: What's New.

Acne vulgaris is one of the most prevalent skin conditions. Antibiotics, when considered, are most effective in combination with other therapies, and limited evidence suggests that submicrobial doses of antibiotics may improve acne without increasing the risk for antibiotic resistance. A small but significant risk for inflammatory bowel disease has also been identified in children treated with multiple courses of antibiotics. New topical agents are expanding therapeutic options for acne. Semin Cutan Med Surg 35(supp6):S114-S116.

Inhibitory effect of imperatorin on insulin-like growth factor-1-induced sebum production in human sebocytes cultured in vitro.

AIMS: Acne is a common skin disease that originates in the sebaceous gland. The pathogenesis of acne is very complex, involving the increase of sebum production and perifollicular inflammation. In this study, we screened the anti-lipogenic material and demonstrated its effect using cultured human sebocytes. MAIN METHODS: Normal human sebocytes were cultured by explanting the sebaceous glands. To evaluate the anti-lipogenic effect, sebocytes were treated with test materials and (14)C-acetate incorporation assay was performed. KEY FINDINGS: To screen the anti-lipogenic materials, we tested the effect of many herbal plant extracts. We found that Angelica dahurica extract inhibited the insulin-like growth factor-1 (IGF-1)-induced sebum production in terms of squalene synthesis in sebocytes. Furthermore, imperatorin isolated from A. dahurica showed remarkable inhibitory effect on squalene production as well as squalene synthase promoter activity. To investigate the putative action mechanism, we tested the effect of imperatorin on intracellular signaling. The results showed that imperatorin inhibited IGF-1-induced phosphorylation of Akt. In addition, imperatorin significantly down-regulated PPAR-γ and SREBP-1, the important transcription factors for lipid synthesis. SIGNIFICANCE: These results suggest that imperatorin has a potential for reducing sebum production in sebocytes, and can be applicable for acne treatment.

Quantitative changes in skin composition parameters due to chemotherapy in breast cancer patients: a cohort study.

The objective of this study is to evaluate objective changes in water content, sebum content, transepidermal water loss (TEWL), and melanin due to breast cancer chemotherapy, and their association with subjective symptoms. Prospective cohort study of 61 patients 18 years of age or older with a postoperative diagnosis of stage I-III breast cancer, who received adjuvant chemotherapy between February and September 2012 at an outpatient breast cancer clinic in Korea. Objective skin parameters, measured using a noninvasive bioengineering device, and patient-reported dryness and dullness were assessed before chemotherapy, after two cycles of chemotherapy, and 1, 3, and 6 months after completion of chemotherapy. Water content (-6.5 %), sebum (-75.5 %), and TEWL (-22.4 %) significantly decreased during chemotherapy compared to pre-chemotherapy levels (all p values <0.001). These parameters were lowest at 1 month after completion of chemotherapy and recovered thereafter but did not return to baseline levels after 6 months of follow-up. Melanin increased during chemotherapy with respect to pre-chemotherapy levels (8.4 %; p < 0.001) but decreased from the first month after completion of chemotherapy through the end of follow-up (-17.1 %; p < 0.001). The patterns of skin changes were similar in patients with or without hormone therapy. Most of patients reported dryness (57.9 %) and dullness (49.1 %) after chemotherapy, and patient-reported dryness was significantly associated with decreased sebum content. Chemotherapy-induced substantial changes in objective skin composition parameters. These changes persisted after 6 months from completion of chemotherapy and were associated with patient-reported symptoms. Additional research is needed to translate these findings into interventions for improving the dermatologic quality of life of breast cancer patients undergoing chemotherapy.

Epigallocatechin-3-gallate improves acne in humans by modulating intracellular molecular targets and inhibiting P. acnes.

Acne vulgaris is a highly prevalent skin disorder characterized by hyperseborrhea, inflammation, and Propionibacterium acnes overgrowth. Only isotretinoin and hormonal therapy reduce sebum production. To identify a new drug candidate that modulates sebum, we examined the effects of EGCG, the major polyphenol in green tea, on human SEB-1 sebocytes and in patients with acne. In SEB-1 sebocytes, we found that EGCG reduced sebum by modulating the AMPK-SREBP-1 signaling pathway. EGCG also reduces inflammation by suppressing the NF-κB and AP-1 pathways. EGCG also induces cytotoxicity of SEB-1 sebocytes via apoptosis and decreases the viability of P. acnes, thus targeting almost all the pathogenic features of acne. Finally, and most importantly, EGCG significantly improved acne in an 8-week randomized, split-face, clinical trial, and was well tolerated. Our data provide a therapeutic rationale for the use of EGCG in acne.

Melanocortin-5 receptor and sebogenesis.

The melanocortins (α-MSH, ß-MSH, γ-MSH, and ACTH) bind to the melanocortin receptors and signal through increases in cyclic adenosine monophosphate to induce biological effects. The melanocortin MC(5) and MC(1) receptors are expressed in human sebaceous glands, which produce sebum, a lipid mixture of squalene, wax esters, triglycerides, cholesterol esters, and free fatty acids that is secreted onto the skin. Excessive sebum production is one of the major factors in the pathogenesis of acne. The expression of melanocortin MC(5) receptor has been associated with sebocyte differentiation and sebum production. Sebaceous lipids are down-regulated in melanocortin MC(5) receptor-deficient mice, consistent with the observation that α-MSH acts as a sebotropic hormone in rodents. These findings, which suggest that melanocortins stimulate sebaceous lipid production through the MC(5) receptor, led to our search for MC(5) receptor antagonists as potential sebum-suppressive agents. As predicted, an antagonist was shown to inhibit sebocyte differentiation in vitro, and to reduce sebum production in human skin transplanted onto immunodeficient mice. The melanocortin MC(5) receptor antagonists may prove to be clinically useful for the treatment of sebaceous disorders with excessive sebum production, such as acne.

[Hormonal antiandrogens in acne treatment]. / Hormonelle Antiandrogene in der Aknetherapie.

BACKGROUND: An enhanced sebaceous gland activity with production of proinflammtory sebaceous lipids belongs to the major pathogenetic factors of acne. Hormonal antiandrogen treatment targets the androgen-metabolizing cells of the pilosebaceous unit, i. e. follicular kertinocytes and sebocytes, and leads to sebostasis, with a reduction of the sebum secretion rate of 12.5 to 65 %. Concerning their mechanism of action, hormonal antiandrogens are classified in androgen receptor blockers, inhibitors of circulating androgens by affecting the ovarial function (oral contraceptives), inhibitors of circulating androgens by affecting the pituitary (gonadotrophin-releasing hormone agonists and dopamin agonists in hyperprolactinemia), inhibitors of the adrenal function, and inhibitors of peripheral androgen metabolism (5-reductase inhibitors, inhibitors of other enzymes). METHODS: In this study, all original and review publications on hormonal antiandrogen treatment of acne as monotherapy or in combination included in MEDLINE, EMBASE and COCHRANE libraries were extracted by using the terms "acne", "seborrhea", "polycystic ovary syndrome", "hyperandrog*" and "treatment" and classified according to their level of evidence. RESULTS: Antiandrogen treatment is overall active on acne lesions. The combinations of ethinyl estradiol with cyproterone acetate chlormadinone acetate, dienogest desogestrel and drospirenone have shown the strongest antiacne activity. Gestagens or estrogens as monotherapy, spironolactone, flutamide, gonadotrophin-releasing hormone agonists and inhibitors of peripheral androgen metabolism are not recommended according to the current stand of knowledge. Low dose prednisolone is to only be administered at late onset congenital adrenal hyperplasia and dopamine agonists at hyperprolactinemia. Treatment with hormonal antiandrogens requires missing of any contraindications. CONCLUSIONS: Hormonal antiandrogen treatment is limited to female patients who present additional signs of peripheral hyperandrogenism or hyperandrogenemia. In addition, females with acne tarda, persistent acne recalcitrant to treatment, with parallel wish of contraception, and as a requirement for a systemic isotretinoin treatment can be treated with hormonal antiandrogens. Hormonal antiandrogen treatment is not a primary monotherapy for uncomplicated acne.

Diphenyl ethers as androgen receptor antagonists for the topical suppression of sebum production.

A series of diphenyl ethers was prepared and evaluated for androgen receptor antagonist activity in human androgen receptor binding and cellular functional assays. Analogs with potent in vitro activities were evaluated for topical in vivo efficacy in the Golden Syrian Hamster ear model. Several compounds showed reduction in wax esters in this validated animal model.

Value of hormonal levels in patients with male androgenetic alopecia treated with finasteride: better response in patients under 26 years old.

BACKGROUND: Finasteride is a 5alpha-reductase inhibitor that has proved to be an effective treatment for men with androgenetic alopecia. OBJECTIVES: To investigate the hormonal influence of finasteride 1 mg daily on hormonal levels and hair growth in men of different ages and with different degrees of alopecia according to the Hamilton-Norwood scale. METHODS: Two hundred and seventy men aged 14-58 years with male androgenetic alopecia III-VI Hamilton-Norwood score (II-III Ebling score) were treated with finasteride 1 mg daily. Steroid hormone (free testosterone, 5alpha-dihydrotestosterone, dehydroepiandrosterone-sulphate, delta4-androstenedione, 17-hydroxyprogesterone), prostate-specific antigen (PSA) and sebum levels, and trichogram changes were determined at baseline, and at 6 and 12 months of treatment. RESULTS: According to significant hormonal statistical analysis, the patients were divided by age (up to or over 26 years). In the group of patients26 years. No variations in sebum levels were observed. CONCLUSIONS: High levels of 5alpha-dihydrotestosterone in patients

Surfactant protein expression in human skin: evidence and implications.

The presence of surfactant proteins (SPs), critical to local barrier and defense functions and usually associated with the lung, was revealed in adult and fetal human skin complementary deoxyribonucleic acid, in skin samples from three adult female donors and also in cultured fibroblasts, keratinocytes, and melanocytes. Using reverse transcription-PCR, SP-A, SP-B, SP-C, and SP-D messenger ribonucleic acid expression was detected to varying extents in the different skin sources. The stronger expression of SP-C in fetal skin, compared to adult skin, suggested that the role of this protein alters with age. Immunohistochemical studies showed variable distribution of SPs in human epidermis and dermis, confirming that these proteins are indeed translated and expressed in skin tissue. In vitro studies showed that the surface tension of SP-deficient artificial sebum is (a) lowered by skin-extracted SP-B and (b) further reduced to a level comparable to normal sebum by the additional presence of skin-extracted SP-A and SP-D, consistent with their surface tension-lowering capabilities in lung. The possible roles of SPs in skin, based on their known functions in the lung are discussed. However, their potential as therapeutic targets or diagnostic markers of skin disease remains to be elucidated.

Effects of benzoyl peroxide on lipogenesis in sebaceous glands using an animal model.

BACKGROUND: Benzoyl peroxide is the most widely used topical agent for acne since the 1960s. Concomitant treatment of benzoyl peroxide with oral, or topical antibiotics diminishes the multiplication of antibiotic-resistant strains of Propionibacteria acnes. Besides being antibacterial, the chemical also functions as a peeling agent, has comedolytic activity, reduces free fatty acid levels, and is touted to be sebosuppressive. OBJECTIVE: The purpose was to determine the ability of topically applied benzoyl peroxide to suppress lipogenesis of the sebaceous glands. METHODS: The data were obtained employing an animal model for human sebaceous glands, namely, the flank organs of female golden Syrian hamsters. RESULTS: Our results reveal no inhibition of lipogenesis in sebaceous glands by topical application of benzoyl peroxide. CONCLUSION: Despite many functions beneficial in acne therapy, benzoyl peroxide does not possess sebosuppressive capabilities. With the advent of water-soluble organic peroxides revealing similar antimicrobial activity to benzoyl peroxide, all therapeutic parameters (save for sebosuppression) will need to be assessed to weigh the benefits of these second-generation acne-fighting peroxides.

Effects of sex steroid deprivation/administration on hair growth and skin sebum production in transsexual males and females.

To investigate androgen effects on the skin pilosebaceous unit, we studied 21 male-to-female transsexuals and 17 female-to-male transsexuals receiving cross-sex hormones. At baseline and after 4, 8, and 12 months, hair growth was evaluated by the Ferriman-Gallwey score; acne by the Leeds classification; hair growth rate, density, and shaft diameter by image analysis; and sebum production by Sebutape. In males, estrogens and antiandrogens reduced plasma testosterone to below 1.0 nmol/L. Though all parameters of hair growth and sebum production declined, facial hair growth continued. After 4 months, the decrease in shaft diameter had reached its maximum and seemed inversely associated with changes in hair growth length and density. In females, testosterone increased hair growth rate and sebum production. After 12 months, hairs on the cheek and abdomen had not yet reached diameters found in males. 5alpha-Androstane-3alpha,17beta-diol glucuronide levels were only weakly associated with hair growth and sebum production. In conclusion, administration of estrogens and antiandrogens affects length and diameter of hairs at different rates. In the virtual absence of androgens, hair growth continues but at a slower rate. In women, after 12 months of androgen administration, hair diameters have not reached values of adult men.

The effect of silicol gel compared with placebo on papulopustular acne and sebum production. A double-blind study.

Altogether 30 patients (19 females and 11 males), mean age 19 years, were divided randomly into two groups. All patients had chronic papulopustular acne of the face. A total of 15 patients were treated topically with Silicol gel for 20 min twice daily for 6 weeks and the remaining 15 patients were treated with a placebo gel in a similar fashion. A clinical evaluation was carried out at baseline, and after 2, 4 and 6 weeks of treatment. The clinical variables evaluated were as follows: number of comedones, papules, pustules and cysts on a standard area of the left cheek (area 5 x 5 cm) and measurement of sebum production on the same area by the use of Sebumeter SM 810 PC (Courage and Khazaka, Ltd, Germany). No concomitant treatment was allowed during the study period. One patient using Silicol gel withdrew after 2 weeks of treatment because of severe irritation of the facial skin, leaving 29 patients who could be evaluated. In the active group, the number of comedones decreased from a mean of 48.5 to 15.1 after 6 weeks of treatment. The corresponding figures for papules were 10.7 and 1.0, for pustules 6.8 and 0, and for cysts 0.6 and 0. In the placebo group no improvement could be observed. There was a highly significant difference in efficacy between the two groups (P < 0.001) in favour of the actively treated group. The mean sebum index was 193 at baseline and 88 after 6 weeks. Correspondingly in the placebo group the mean sebum index at baseline was 187 and after 6 weeks 179. This difference between the two groups was also statistically significant (P < 0.001). After a short follow-up period (3 months) no deterioration was observed in the 14 'active' patients, showing either complete cure or improvement.

Treatment of photodamaged skin with trichloroacetic acid and topical tretinoin.

BACKGROUND: Photodamaged skin typically displays lentigines, actinic keratoses, wrinkles, and textural alteration. Chemical peeling has been used to treat these, but few controlled studies have been performed to determine its efficacy. OBJECTIVE: Our purpose was to compare the efficacy of a medium-depth chemical peel with and without tretinoin before and after treatment. METHODS: Sixteen men with actinic damage including actinic keratoses were treated with a 40% trichloroacetic acid(TCA) chemical peel. Half were pretreated for 6 weeks with topical tretinoin; they also used tretinoin after the peel. Photographs were obtained at baseline and at 6 weeks and 6 months after treatment. Changes in specific features were rated by a panel of three examiners. RESULTS: Some improvement was noted in all patients. More rapid and even frosting was observed in the patients pretreated with tretinoin. Solar lentigines, actinic keratoses, and skin texture were the features of photoaging most affected; wrinkles were least affected. No statistically significant difference was found between patients treated with TCA and tretinoin (before and after peel) and those with TCA alone. CONCLUSION: A medium-depth chemical peel with 40% TCA alone produced moderate improvement in some manifestations of actinic damage but had little effect on wrinkles. Treatment with tretinoin before and after TCA did not significantly enhance the efficacy of the peel.

L-dopa, biperideno e excreçäo sebácea na doença de Parkinson

A excreçäo sebácea frontal de 47 parkinsonianos "de novo" antes e após tratamento com anticolinérgico (biperideno), levodopa + IDAA e bromocriptina foi avaliada pelo método do ácido ósmico. Outros 100 parkinsonianos sob terapêutica crônica com biperideno, levodopa + IDAA ou associaçäo de ambos foram avaliados. Parkinsonianos "de novo" do sexo masculino apresentam valores de excreçäo sebácea significativamente mais elevados em relaçäo `as mulheres. Verificou-se que biperideno näo foi eficaz em reduzir o grau de excreçäo sebácea. Já, em relaçäo a L-dopa + IDAA constatou-se que a droga foi efetiva em reduzir o grau de excreçäo sebácea (NC e TRE) tanto no sexo masculino quanto no feminino. Em relaçäo `a bromocriptina (10mg/dia) também constatou-se que houve reduçäo da excreçäo sebácea no sexo masculino. Correlaçäo significante positiva foi verificada entre o NC, tremor, bradieinesia, hipertonia, alteraçöes da marcha e postura e incapacidade funcional, entre parkinsonianos do sexo masculino e faixa etária 50-59 anos, no período pré-tratamento. Após o período de tratamento näo mais havia correlaçäo entre excreçäo sebácea e as manifestaçöes neurológicas da doença de Parkinson. Entre parkinsonianos sob terapêutica crônica verificou-se correlaç-äo positiva e significante entre excreçäo sebácea e bradicinesia. O grau de excreçäo sebácea de parkinsonianos "de novo" sem tratamento näo difere do grau daqueles sob tratamento crônico, exceçäo feita a parkinsonianos com idade >= 60 anos, em que verificou-se maior ggrau de exreçäo sebácea (NC e TRE) em relaçäo ao mesmo sexo e faixa etária, sem tratamento. L-dopa + IDAA foi eficiente em reduzir o grau de excreçäo sebácea de parkinsonianos "de novo", tornando-a...