Secukinumab for Psoriasis in Obese Patients: Minireview and Clinical Experience.

Psoriasis (PsO) has been associated with obesity, and its severity increases in obese subjects. The link between psoriatic condition and obesity is based on shared pathophysiological pathways where local and systemic inflammation promote each other; PsO is an inflammatory, immune-mediated disease, and the adipose tissue is the source of proinflammatory adipokines. Moreover, psoriatic arthritis (PsA) is an important comorbidity of PsO that reduces quality of life and makes difficult the patient's management. Treatment of obese subjects with moderate to severe PsO, even more if PsA is present, is challenging because of reduced efficacy of several systemic drugs and increased risk of adverse events. Secukinumab, a monoclonal antibody that selectively binds to and neutralizes interleukin 17A, shows efficacy on PsO in all body weight groups, even in the highest, whose response has a slight downward trend. Clinical features of two obese subjects, affected by PsO and PsA, successfully treated with secukinumab, are described.

Anti-oxidative effects of 17 ß-estradiol and genistein in human skin fibroblasts and keratinocytes.

BACKGROUND: Estrogens and phytoestrogens can hinder the aging process through mechanisms related to estrogen receptors (ERs), guanine nucleotide-binding protein-coupled receptor (GPER30), mitochondria function and nitric oxide (NO) release. Up to date, however, the above issues are a matter of debate. OBJECTIVE: To examine the effects elicited by 17 ß-estradiol and genistein against peroxidation in human keratinocytes/fibroblasts and evaluate the role played by ERs, GPER30, mitochondria and NO. METHODS: Human fibroblasts/keratinocytes, either subjected to peroxidation or not, were exposed to 17 ß-estradiol/genistein in the absence or presence of the NO synthase (NOS) inhibitor, the ERs and GPER30 blockers, fulvestrant and G15, the phosphatidyl-inositol-3-kinase (PI3K-Akt), the p38 mitogen-activated protein (MAP) kinase and the extracellular signal-regulated kinases (ERK) 1/2 inhibitors. Specific kits were used for cell viability, NO, ROS and glutathione (GSH) detection and mitochondrial membrane potential measurement. Western Blot analysis was performed for kinases expression/activation detection. RESULTS: In physiological and peroxidative conditions, 17 ß-estradiol/genistein respectively increased and reduced NO release by fibroblasts/keratinocytes. Moreover, both agents prevented the ROS release and the fall of cell viability and mitochondrial membrane potential, while increasing GSH levels and the proliferation rate. Fulvestrant and G15 counteracted all above responses. Also, the NOS, and the kinases blockers reduced the protection exerted by 17 ß-estradiol/genistein on cell viability/mitochondria function. The involvement of PI3K-Akt and p38-MAPK was confirmed by Western blot. CONCLUSION: 17 ß-estradiol/genistein protected fibroblasts/keratinocytes against peroxidation by modulating oxidant/antioxidant system and mitochondria membrane potential, through mechanisms related to ERs and GPER30 and kinases activation.

Extemporaneous transposition flap for closing two contiguous surgical excision.

The authors present a surgical procedure to remove two contiguous cutaneous lesions using a single transposition flap and suture line without an evident scar. This method is useful when rhomboid surgical exeresis could not represent the best choice to obtain an optimum aesthetic result.

Basal Cell Carcinoma of the Nipple in a Male Patient: A Particular Case Report.

Basal cell carcinoma (BCC) is a common skin cancer worldwide. However, BCC of the nipple and areola complex is rare. Men are more affected than women. Most of the cases were treated with simple excision. We report a case of BCC of the right nipple-areola complex in a 75-year-old man, treated with Mohs surgery and simple mastectomy.

Selective release of cytokines, chemokines, and growth factors by minced skin in vitro supports the effectiveness of autologous minced micrografts technique for chronic ulcer repair.

A new effective surgical procedure to repair chronic ulcers called minced micrografts technique has been recently reported. The technique consists in spreading a finely minced skin sample upon the wound bed. In this study, we investigate the in vitro release of cytokines (interleukin-6, tumor necrosis factor-α, interleukin-1α, and granulocyte-colony stimulating factor), chemokines (monocyte chemoattractant protein-1 and growth-related oncogene-α), and growth factors (platelet-derived growth factor, basic fibroblast growth factor, vascular endothelial growth factor, hepatocyte growth factor, and nerve growth factor) by minced (referred to as the minced sample) vs. not minced (referred to as the whole sample) human skin biopsy samples from the same donor. Factor release in the culture medium at different time points was detected using a multiplexed protein assay. The minced sample, which could behave like the skin fragments used in vivo in the autologous minced micrografts technique, expressed higher levels of tumor necrosis factor-α, interleukin-1α, platelet-derived growth factor, and basic fibroblast growth factor, and lower levels of interleukin-6, monocyte chemoattractant protein-1, growth related oncogene-α, and vascular endothelial growth factor compared with the whole sample. In conclusion, mincing of healthy skin may allow appropriate regulation of the inflammatory phase of wound healing and could induce overexpression of some growth factors, which facilitates the proliferative phase of healing.

A Mycobacterium ulcerans toxin, mycolactone, induces apoptosis in primary human keratinocytes and in HaCaT cells.

The pathogenicity of Mycobacterium ulcerans (Buruli ulcer) depends on cytotoxic effect of its exotoxin mycolactone. Since epidermis represents a barrier against infectious agents and balanced apoptosis is essential in epidermal homeostasis, we explored if mycolactone A/B induces apoptosis on two human keratinocyte populations, stem cells (KSC) and transit amplifying cells (TAC), and on human keratinocyte line, HaCaT. Treatment of TAC with 1 and 10 ng/ml mycolactone-induced 60 and 90% apoptosis. KSC were more resistant than TAC: 50 and 75% of cells underwent apoptosis after 10 and 100 ng/ml toxin-treatment. Higher doses (1000 ng/ml) induced about 30% apoptosis on HaCaT. In contrast, mycolactone A/B was devoid of toxicity neither on human hepatoma HuH7 nor on human embryonic kidney HEK 293 T cell lines. In conclusion, mycolactone induces apoptosis in human keratinocytes, thus contributing to Buruli ulcer lesions development.

Estrogen and beta-amyloid toxicity: role of integrin and PI3-K.

Beta-amyloid peptide (betaAP) induces apoptosis and down-regulation of alpha(1)beta(1) integrin in neuronal cells, indicating a relationship between betaAP neurotoxicity and modulation of integrin expression. Estrogen may play a role in protecting women from Alzheimer Disease (AD). It is here reported that both 17beta-estradiol (17betaE(2)) and its non-estrogenic stereoisomer 17alpha-estradiol (17alphaE(2)) rescue neuronal cells from betaAP-induced apoptosis. As cellular model, the human neuroblastoma cell line SK-N-BE was used, which responds to retinoic acid by growth arrest and differentiation toward the neuronal phenotype (RA-SK-N-BE). Estrogen receptor antagonist does not hinder estrogen protection. Inhibition of phosphatidylinositol 3-kinase (PI3-K), but not of tyrosine kinases or mitogen-activated protein kinases (MAPK) blocks 17betaE(2) protection against betaAP-induced apoptosis. 17betaE(2) up-regulates alpha(1)beta(1) integrin expression and completely abolishes betaAP-induced alpha(1)beta(1) down-regulation. Inadequate cell cycle control may contribute to neuronal death in AD. betaAP induces RA-SK-N-BE cells to enter cell cycle, which remains incomplete. 17betaE(2) induces betaAP-treated cells to complete cell cycle. Our data suggest that estrogen protects from betaAP neurotoxicity by restoring integrin expression and cell cycle control.