Role of BMP-4 and Its Signaling Pathways in Cultured Human Melanocytes

Bone Morphogenetic Protein (BMP-4) was shown to down-regulate melanogenesis, in part, by decreasing the level of tyrosinase [Yaar et al. (2006) JBC:281]. Results presented here show that BMP-4 down-regulated the protein levels of TRP-1, PKC-β, and MCI-R. When paired cultures of human melanocytes were treated with vehicle or BMP-4 (25 ng/ml), MAPK/ERK were phosphorylated within one hour of BMP-4 treatment. Then the activated MAPK/ERK caused an acute phosphorylation of MITF, followed by proteosome-mediated degradation of MITF, the key transcription factor for melanogenic proteins [Wu et al. (2000) Gene & Development:14]. However, prolonged exposure of melanocytes to BMP-4 (up to 48 hours) caused a decrease in the level of MITF-M transcript. In addition, BMP-4 decreased the intracellular level of cAMP, the key regulator of MITF expression. These results demonstrate that BMP-4 activates MAPK/ERK signaling pathway to transiently activate MITF; however, chronic treatment of BMP-4 to melanocytes causes a down-regulation of the expression of MITF, possibly in a cAMP-dependent pathway

Skin, hair and beyond: the impact of menopause.

The skin is an endocrine organ and a major target of hormones such as estrogens, androgens and cortisol. Besides vasomotor symptoms (VMS), skin and hair symptoms often receive less attention than other menopausal symptoms despite having a significant negative effect on quality of life. Skin and mucosal menopausal symptoms include dryness and pruritus, thinning and atrophy, wrinkles and sagging, poor wound healing and reduced vascularity, whereas skin premalignant and malignant lesions and skin aging signs are almost exclusively caused by environmental factors, especially solar radiation. Hair menopausal symptoms include reduced hair growth and density on the scalp (diffuse effluvium due to follicular rarefication and/or androgenetic alopecia of female pattern), altered hair quality and structure, and increased unwanted hair growth on facial areas. Hormone replacement therapy (HRT) is not indicated for skin and hair symptoms alone due to the risk–benefit balance, but wider potential benefits of HRT (beyond estrogen’s effect on VMS, bone, breast, heart and blood vessels) to include skin, hair and mucosal benefits should be discussed with women so that they will be able to make the best possible informed decisions on how to prevent or manage their menopausal symptoms.post-print1529 K

Budget impact analysis of ustekinumab in the management of moderate to severe psoriasis in Greece

BACKGROUND: The purpose of this study was to estimate the annual and per-patient budget impact of the treatment of moderate to severe psoriasis in Greece before and after the introduction of ustekinumab. METHODS: A budget impact model was constructed from a national health system perspective to depict the clinical and economic aspects of psoriasis treatment over 5 years. The model included drug acquisition, monitoring, and administration costs for both the induction and maintenance years for patients in a treatment mix with etanercept, adalimumab, infliximab, with or without ustekinumab. It also considered the resource utilization for non-responders. Greek treatment patterns and resource utilization data were derived from 110 interviews with dermatologists conducted in February 2009 and evaluated by an expert panel of 18 key opinion leaders. Officially published sources were used to derive the unit costs. Costs of adverse events and indirect costs were excluded from the analysis. Treatment response was defined as the probability of achieving a PASI 50, PASI 75, or PASI 90 response, based on published clinical trial data. RESULTS: The inclusion of ustekinumab in the biological treatment mix for moderate to severe psoriasis is predicted to lead to total per-patient savings of €443 and €900 in years 1 and 5 of its introduction, respectively. The cost savings were attributed to reduced administration costs, reduced hospitalizations for non-responders, and improved efficacy. These results were mainly driven by the low number of administrations required with ustekinumab over a 5 year treatment period (22 for ustekinumab, compared with 272 for etanercept, 131 for adalimumab, and 36 for infliximab). CONCLUSIONS: The inclusion of ustekinumab in the treatment of moderate to severe psoriasis in Greece is anticipated to have short- and long-term health and economic benefits, both on an annual and per-patient basis.Georgia Avgerinou, Ioannis Bassukas, Georgios Chaidemenos, Andreas Katsampas, Marita Kosmadaki, Hara Kousoulakou, Athanasios Petridis, Brad Schenkel, Dimitrios Sotiriadis, Theofanis Spiliopoulos, Panagiotis Stavropoulos, Evgenia Toumpi, and Loukas Xaplanteri

Topical treatments for acne

Topical drugs have been used successfully to treat acne for decades. This review discusses the use, efficacy, and safety of options available via prescription. Topical antibiotics, dapsone, benzyl peroxide, azelaic acid, and topical retinoids are included. Topical antibiotics should not be used as monotherapy but rather be combined with other agents to avoid resistant Propionibacterium acnes strains. Benzoyl peroxide is effective in preventing bacteria resistance. Topical retinoids address primarily the comedonal but also the inflammatory lesions of acne. Azelaic acid is useful in treating acne lesions and for lightening postinflammatory hyperpigmentation that may accompany inflammatory acne lesions. Combinations of agents that address different aspects of acne pathogenesis may offer higher benefit to acne patients. © 2016 Elsevier Inc

A proposed scoring system for assessing the severity of actinic keratosis on the head: actinic keratosis area and severity index

Background: Actinic keratosis (AK) severity is currently evaluated by subjective assessment of patients. Objectives: To develop and perform an initial pilot validation of a new easy-to-use quantitative tool for assessing AK severity on the head. Methods: The actinic keratosis area and severity index (AKASI) for the head was developed based on a review of other severity scoring systems in dermatology, in particular the psoriasis area and severity index (PASI). Initial validation was performed by 13 physicians assessing AK severity in 18 AK patients and two controls using a physician global assessment (PGA) and AKASI. To determine an AKASI score, the head was divided into four regions (scalp, forehead, left/right cheek ear, chin and nose). In each region, the percentage of the area affected by AKs was estimated, and the severities of three clinical signs of AK were assessed: distribution, erythema and thickness. Results: There was a strong correlation between AKASI and PGA scores (Pearson correlation coefficient: 0.86). AKASI was able to discriminate between different PGA categories: mean (SD) AKASI increased from 2.88 (1.18) for âlightâ to 5.33 (1.48) for âmoderateâ, 8.28 (1.89) for âsevereâ, and 8.73 (3.03) for âvery severeâ PGA classification. The coefficient of variation for AKASI scores was low and relatively constant across all PGA categories. Conclusions: Actinic keratosis area and severity index is proposed as a new quantitative tool for assessing AK severity on the head. It may be useful in the future evaluation of new AK treatments in clinical studies and the management of AK in daily practice

The Greek experience with efalizumab in psoriasis from a University Dermatologic Hospital

Background Efalizumab (anti-CD11a antibody) targets T cell-mediated steps important in the immunopathogenesis of psoriasis. As efalizumab is intended to be administered on a continuous long-term basis in psoriasis, it is important to share experience concerning issues commonly occurring during its use in real daily practice. Objective To evaluate the efficacy and safety of efalizumab treatment in Greek patients with moderate-to-severe plaque psoriasis, and to investigate whether there are specific characteristics that predict the clinical outcome of therapy. Patients Seventy-two patients with moderate-to-severe plaque psoriasis, who had failed to respond to, or had a contraindication to, or were intolerant to other systemic therapies, received efalizumab (I mg kg(-1) per week) for 12 weeks or more. Results After 12 weeks of efalizumab treatment, 65% of patients achieved 50% or more improvement from baseline Psoriasis Area and Severity Index (PASI) and 39% achieved at least 75% reduction in PASI score. The mean percentage PASI improvement from baseline was 62%. The most common side effects were a flu-like syndrome, a transient localized papular eruption, leucocytosis and lymphocytosis. There was no correlation between the occurrence of these side effects and the clinical response. Patients with a past history of unstable types of psoriasis were likely poor responders to efalizumab, and at an increased risk of developing generalized inflammatory flare. Conclusion These results confirm previous reports suggesting that treatment with efalizumab is an efficacious and safe option for patients with moderate-to-severe plaque psoriasis. A detailed previous history of psoriasis is important in order to select possible candidates for efalizumab therapy