In vitro and in vivo evidence of tyrosinase inhibitory activity of a synthesized (Z)‐5‐(3‐hydroxy‐4‐methoxybenzylidene)‐2‐thioxothiazolidin‐4‐one (5‐HMT)

Tyrosinase is a key enzyme that catalyses the initial rate‐limiting steps of melanin synthesis. Due to its critical role in melanogenesis, various attempts were made to find potent tyrosinase inhibitors although many were not safe and effective in vivo. We evaluated tyrosinase inhibitory activity of six compounds. Among them, (Z)‐5‐(3‐hydroxy‐4‐methoxybenzylidene)‐2‐thioxothiazolidin‐4‐one (5‐HMT) had the greatest inhibitory effect and potency as the IC₅₀ value of 5‐HMT was lower than that of kojic acid, widely‐known tyrosinase inhibitor. Based on in silico docking simulation, 5‐HMT had a greater binding affinity than kojic acid with a different binding conformation in the tyrosinase catalytic site. Furthermore, its skin depigmentation effect was confirmed in vivo as 5‐HMT topical treatment significantly reduced UVB‐induced melanogenesis in HRM2 hairless mice. In conclusion, our study demonstrated that 5‐HMT has a greater binding affinity and inhibitory effect on tyrosinase and may be a potential candidate for a therapeutic agent for preventing melanogenesis.     

Authors’ willingness for second‐opinion teledermatology in difficult‐to‐manage cases: ‘an online survey’

Background Expert non‐availability for an instant difficult‐to‐manage case may limit the online discussion group to provide second‐opinion teledermatology for registered dermatologists. Author‐based second‐opinion teledermatology (AST) is proposed and assessment of authors’ response to answer queries and their willingness to participate in teledermatology consultation is analysed. Materials and methods Authors of 292 articles from seven non‐open access dermatology and three general medical journals addressing difficult‐to‐manage cases from June 2007 to December 2008 participated in this online dermatology authors’ survey. Authors’ response to reprint requests, answer literature queries and willingness to offer second‐opinion teledermatology were the main outcome measures. Perceived views were also documented. Results The scores for reprints requests vs. received were (χ² = 13.57, n = 292), P = 0.000. The scores for articles read, analysed and literature queries sent vs. authors answered were (χ² = 11.09, n = 190), P = 0.001. The scores for authors responded to reprints vs. willing to offer second‐opinion teledermatology consultation were (χ² = 5.65, n = 190), P = 0.017 and authors responded to reprint requests, answered queries and willing to offer second‐opinion (χ² = 5.65, n = 190), P = 0.017. Conclusion A dermatologist obtains literature, answered queries and constructive suggestions with additional informative material and pools second‐opinions from the authors using their e‐mail to deliver quality health care. AST is an alternative to online discussion group for second‐opinion teledermatology practice in difficult‐to‐manage cases. Uniform international laws are to be framed to facilitate telemedicine care for a difficult‐to‐manage case.     

Connexin‐26‐Mutation bei „Keratitis‐Ichthyosis‐Deafness”‐Syndrom (KID‐Syndrom)

Background: Keratitis‐ichthyosis‐deafness syndrome (KID syndrome) is an extremely rare disorder. Inheritance is autosomal dominant but many cases occur sporadically following a spontaneous mutation. The cause of KID syndrome are missense mutations of the gene GJB2, encoding connexin 26. Patients and Methods: We clinically studied two cases of KID syndrome and extracted genomic DNA from peripheral blood. Results: The patients showed different heterozygous mutations of the connexin 26 gene and had quite different clinical courses. Conclusions: Both patients showed heterozygous mutations of the connexin 26 gene; a different Cx26 dominant mutation can cause a very different clinical course.     

The single‐chain anti‐TNF‐α antibody DLX105 induces clinical and biomarker responses upon local administration in patients with chronic plaque‐type psoriasis

It is not clear whether TNF‐α antagonists used in the treatment of psoriasis need to act systemically, or whether local inhibition of skin‐produced TNF‐α would be sufficient to silence skin inflammation. To answer this question, we conducted two multicentre, double‐blinded, randomized, placebo‐controlled clinical trials with the novel single‐chain anti‐TNF‐α‐PENTRA^®‐antibody DLX105. Upon intra‐dermal injection, DLX105 induced a mean local PASI decrease of 33% over baseline after 2 weeks of treatment, while the placebo response was only 12% (P = 0.001). The clinical response was accompanied by changes in biomarkers such as reductions in K16, Ki67 and epidermal thickness as well as decreased mRNA levels of IL‐17, TNF‐α, IL‐23p19, IL‐12p40 and IFN‐γ. Next, we applied the drug topically twice daily in a 0.5% hydrogel formulation. While the local PASI did not change, topical DLX105 mediated significant reductions of mRNA levels of key proinflammatory cytokines when compared to placebo, and this effect was further enhanced after weekly tape stripping of plaques to increase drug penetration. These results suggest that longer treatment periods and/or increased local drug concentrations might result in better therapeutic efficacy of topically applied DLX105. In sum, we can show for the first time that local inhibition of TNF‐α is sufficient to mediate a biological response in psoriasis that translates into clinical efficacy.     

Thymoma‐associated multi‐organ autoimmunity: A case of graft‐versus‐host disease‐like erythroderma complicated by Good syndrome successfully treated by thymectomy

Thymoma‐associated multi‐organ autoimmunity disease (TAMA) is a rare paraneoplastic disorder, clinicopathologically similar to graft‐versus‐host disease (GVHD). Many reported cases follow a difficult course; half of them die from serious infectious diseases subsequent to immunosuppression induced by chemotherapy for unresectable thymoma, or intensive therapies including systemic steroids for complicating autoimmune diseases and GVHD‐like symptoms. We report a patient whose skin symptoms were improved subsequently to total thymectomy. The patient also presented with hypogammaglobulinemia, which led to the diagnosis of complicated Good syndrome. Taking account of her immunodeficient condition, antibiotics and i.v. immunoglobulin were administrated promptly on onset of bacterial pneumonia, which was successfully treated. According to a review of the published work, treatments with systemic steroids for skin symptoms have limited effects and may contribute to serious infection. Our case indicates that successful treatment of thymoma itself may lead to the amelioration of the disease. The management priority should be given to the treatment of thymoma and the control of subsequent immune abnormality other than GVHD‐like erythroderma.     

Composite cutaneous lymphoma of diffuse large B‐cell lymphoma‐leg type and subcutaneous panniculitis‐like T‐cell lymphoma

Composite lymphoma (CL) is a rare disease defined by the occurrence of two distinct lymphomas within a single tissue at the same time. We present the case of an 89‐year‐old male with a clinical history of immunoglobulin M monoclonal gammopathy of undetermined significance. The patient presented cutaneous eruption of nodules on the right bottom and arm. An excisional biopsy revealed cutaneous infiltration composed of two components. The first one consisted of large B‐cells with CD20+/MUM1+/BCL2+ phenotype whereas the second one involved the subcutaneous fat in a panniculitic manner, and was CD3+/CD8+/granzyme B+/TCRβF1+. The final diagnosis was CL of primary cutaneous large B‐cell lymphoma‐leg type (PCLBCL‐leg type) and subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL). We report and characterize for the first time coexistent PCLBCL‐leg type and SPTCL in a patient.     

A liposome‐based formulation containing equol,dihomo‐γ‐linolenic acid and propionyl‐l‐carnitine to prevent and treat hair loss: A prospective investigation

Hair loss is a common aesthetic disorder that can be triggered by genetic, inflammatory, hormonal, and environmental factors acting on hair follicles and their life cycle. There are several types of hair loss that differ in causes, symptoms, and spatial and temporal progression. Androgenic alopecia, a common form of hair loss, is the consequence of a decreased microcirculation of the scalp as well as the toxic action of elevated dihydrotestosterone levels on the hair bulbs. In the present study, the lotions TRINOV Lozione Anticaduta Uomo and TRINOV Lozione Anticaduta Donna, containing dihomo‐γ‐linolenic acid (DGLA), S‐equol, and propionyl‐l ‐carnitine, were tested on 30 men and 30 women (mean age of men was 46.6 ± 6.4 years; mean age of women was 49.5 ± 9.0) with signs of androgenic alopecia, respectively. DGLA is a precursor of the prostaglandin PGE1, which acts by improving microcirculation; S‐equol inhibits 5α‐reductases, thus preventing the transformation of testosterone into dihydrotestosterone; and propionyl‐l ‐carnitine promotes lipid metabolism, stimulating energy production. These three molecules are loaded into liposomes for their effective transdermal delivery. Daily topical applications of the lotions resulted in a hair count that significantly increased for women and marginally increased for men after 6 months of treatment. Furthermore, significant increase in anagen hair and a significant decrease in telogen hair were observed starting from 3 months in male and 1 month in female patients. Thus, the formulations under investigation were effective in attenuating androgenic alopecia‐related hair loss in men and women.     

Neue und etablierte Indikationen der UV‐B‐311‐nm‐Phototherapie

Phototherapy with ultraviolet (UV) irradiation of wavelengths between 280 and 320 nm (UV‐B) is a safe and effective treatment for a variety of inflammatory skin diseases. In addition to standard broad band UVB, narrow band phototherapy with fluorescent bulbs emitting near monochromatic UV between 310 – 315 nm has become an important treatment for diseases such as psoriasis, atopic dermatitis or vitiligo. Other diseases respond favorably to narrow band UV‐B phototherapy, the number of potential indications for such phototherapy is continuously growing. The differential effects of narrow band UV‐B phototherapy in comparison to other UV phototherapies, as well as new and established indications for this treatment modality are reviewed.     

Reduction in the appearance of facial hyperpigmentation by topical N‐undecyl‐10‐enoyl‐l‐phenylalanine and its combination with niacinamide

Objectives N‐undecyl‐10‐enoyl‐l ‐phenylalanine (Sepiwhite^®, N‐undecylenoyl phenylalanine), a reported alpha‐melanocyte‐stimulating hormone (MSH) receptor antagonist, has been observed to reduce melanin production in cultured melanocytes. In other testing, niacinamide has been found to inhibit melanosome transfer in cultured cells and to reduce the appearance of hyperpigmented spots in clinical studies. Since these two agents function by different mechanisms, we conducted two studies to determine if their combination is more effective than niacinamide alone in reducing facial hyperpigmentation. Methods  Two double‐blind, 10‐week (2‐week washout + 8‐week treatment), left‐right randomized, split‐face clinical studies were conducted. In one, two groups of Japanese women applied one of two pairs of test emulsion formulations: a vehicle control and a 5% niacinamide formulation (n= 40), or a 5% niacinamide and a 5% niacinamide plus 1%N‐undecylenoyl phenylalanine formulation (n = 40). Each formulation was applied to the randomly assigned side of the face. In the second study, Caucasian women applied one of three emulsions: vehicle control, 5% niacinamide formulation, or combination 5% niacinamide plus 1%N‐undecylenoyl‐phenylalanine formulation to the randomly assigned side of the face (n = ～60 treatment sites per formulation). In both studies, hyperpigmented spots were evaluated at weeks 4 and 8 by quantitative image analysis. Results  In both studies, the combination formulation was significantly more effective than the vehicle and the 5% niacinamide formulation in reducing the appearance of hyperpigmentation after 8 weeks. Conclusions  The combination of 5% niacinamide and 1%N‐undecylenoyl phenylalanine is an effective anti‐aging technology for use on facial skin.