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.     

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.     

4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol)‐induced melanocyte cytotoxicity is enhanced by UVB exposure through generation of oxidative stress

4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol, RD), a skin‐whitening agent, was reported to cause skin depigmentation in some users, which is attributed to its cytotoxicity to melanocyte. It was reported that cytotoxicity to melanocyte is possibly mediated by oxidative stress in a tyrosinase activity‐dependent manner. We examined the effect of UV radiation (UVR) on RD‐induced melanocyte cytotoxicity as an additional aggravating factor. UVR enhanced RD‐induced cytotoxicity in normal human epidermal melanocytes (NHEMs) via the induction of endoplasmic reticulum (ER) stress. Increased generation of intracellular reactive oxygen species (ROS) was detected. Pretreatment with N‐acetyl cysteine (NAC), antioxidant and precursor of glutathione significantly attenuated ER stress‐induced cytotoxicity in NHEMs treated with RD and UVR. Increase in cysteinyl‐RD‐catechol and RD‐pheomelanin in NHEMs treated with RD and UVR suggested that, after UVR excitation, RD or RD metabolites are potent ROS‐generating substances and that the tendency to produce RD‐pheomelanin during melanogenesis amplifies ROS generation in melanocytes. Our results help to elucidate the development mechanisms of RD‐induced leukoderma and provide information for innovation of safe skin‐whitening compounds.     

Peas,beans, and the Pythagorean theorem – the relevance of glucose‐6‐phosphate dehydrogenase deficiency in dermatology

Glucose‐6‐phosphate (G6PD) deficiency is a common disease characterized by acute hemolysis induced by oxidative stress. More than 400 million subjects throughout the world carry the hereditary enzyme defect with the highest prevalences in Africa, Asia, and the Mediterranean region. In individuals affected by the erythrocytic enzymatic disorder, besides infectious diseases and diet, acute hemolytic crisis can be triggered by numerous drugs frequently used for the treatment of dermatoses.Taking into account the increasing number of immigrants from geographic regions with high preva‐lences of G6PD deficiency, dermatologists should be alert to the presence of disease.     

5‐Bromo‐2′‐deoxyuridine induced effluvium via p53‐mediated CD326‐positive keratinocyte apoptosis in C57BL/6 mice

Anagen effluvium develops because of disturbances in the hair follicle cycle, leading to acute and severe hair loss in humans. The objective of this study was to establish a mouse model of anagen effluvium by 5‐bromo‐2′‐deoxyuridine (BrdU) treatment, and evaluate the pathological changes and underlying mechanisms. We treated 9–10‐day‐old pups and 3–7‐week‐old C57BL/6 mice with BrdU. After successfully inducing hair loss in the neonatal pups, microscopic, immunohistochemical and flow cytometry analyses were conducted. BrdU induced early onset alopecia in neonates and caused epidermal thickening and hair shaft breakage. BrdU appeared to incorporate the CD326‐positive keratinocyte layer and induced p53‐related apoptosis. Keratinocyte apoptosis caused immune cell infiltration in the dermal region; M2 macrophages and neutrophils were dominant. The BrdU‐induced hair loss was dose‐dependent, and alopecia was visible at a dose range of 25–200 μg/g bodyweight. The BrdU‐induced anagen effluvium mouse model is novel and easily established by administrating four simple BrdU injections to pups; these mice showed synchronized onset of alopecia symptoms with little individual variation. Moreover, this model showed an alopecia phenotype similar to that of human anagen effluvium with acute, severe and widespread hair loss.     

Primary cutaneous diffuse large B‐cell lymphoma,leg‐type,treated with a modified R‐CHOP immunochemotherapy – diagnostic and therapeutic challenges

Background: Primary cutaneous diffuse large B‐cell lymphoma (PCLBCL) represents a rare subtype among primary cutaneous B‐cell lymphoma exhibiting a characteristic genetic background, an aggressive clinical course and a high relapse rate under different therapeutic regimen. Therefore, PCLBCL has a rather restricted prognosis. Patients and methods: Four patients with PCLBCL were treated at our institution with age‐ and toxicity‐adapted first‐line immunochemotherapy with rituximab and modified CHOP (cyclophosphamid, vincristin, liposomal doxorubicin, prednisolon). On relapse, the same regimen with R‐CHOP or different antineoplastic strategies (radiation, polychemotherapy, immunotherapy, stem cell transplantation) were applied. Toxicity, clinical response and overall survival was documented. Results: Under this regimen, clinical response to modified R‐CHOP was achieved in all patients with tolerable toxicity – however, being characterized by a rapid disease progression with inconsistent response towards the subsequent therapeutic armentarium and unsecure impact on overall survival. Conclusions: So far, it is still unknown, if an extensive multimodal therapy for PBLBCL improves overall survival. Immunochemotherapy with R‐CHOP currently represents the most effective treatment.     

“Slime” dermatitis,a fad‐associated chronic hand dermatitis

“Slime” is the colloquial name for a non‐Newtonian viscoelastic putty‐like substance that is currently a popular plaything among pre‐teens and adolescents. Several ingredients in homemade slime recipes may cause irritant or allergic contact dermatitis. We report two children who developed slime‐associated chronic hand dermatitis, more prominently on their dominant hand. We review the potential for irritant and allergic contact dermatoses as the causes of dermatitis associated with homemade slime.     

Dermal non‐neural granular cell tumor in a 3‐year‐old child

Dermal non‐neural granular cell tumors, also known as primitive polypoid granular cell tumors, are a rare group of distinct cutaneous non‐neural granular cell tumors. Pediatric cases are rare, and to the best of our knowledge, we report the youngest patient with dermal non‐neural granular cell tumors.     

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.     

Combined treatment with 578‐/511‐nm copper bromide laser and light‐emitting diodes for post‐laser pigmentation: a report of two cases

Postinflammatory hyperpigmentation (PIH) developing after cosmetic procedures such as lasers and chemical peels is always a concern, especially in darker skin types. We report two cases of laser‐related PIH of the face successfully treated by combined therapy with 578‐/511‐nm copper bromide laser and light‐emitting diodes (LED). Good cosmetic results were achieved in both patients. The side effects during and after treatment included a mild stinging and redness, but these were resolved within several days without any treatment. Combined 578‐/511‐nm copper bromide laser with LED provided safe and effective treatment for post‐laser pigmentation in Korean patients.     

Non‐ablative 1550‐nm erbium‐glass and ablative 10 600‐nm carbon dioxide fractional lasers for acne scars: a randomized split‐face study with blinded response evaluation

Background Non‐ablative 1550‐nm erbium‐doped fractional photothermolysis systems (FPS) and 10 600‐nm carbon dioxide fractional laser systems (CO₂ FS) have been effectively used to treat scars. Objective We compared the efficacy and safety of single‐session treatments of FPS and CO₂ FS for acne scars through a randomized, split‐face, evaluator‐blinded study. Methods Eight patients with acne scars were enrolled in this study. Half of each subject’s face was treated with FPS and the other half was treated with CO₂ FS. We used a quartile grading scale for evaluations. Results At 3 months after the treatment, the mean grade of improvement based on clinical assessment was 2.0 ± 0.5 for FPS and 2.5 ± 0.8 for CO₂ FS. On each side treated by FPS and CO₂ FS, the mean duration of post‐therapy crusting and scaling was 2.3 and 7.4 days respectively and that of post‐therapy erythema was 7.5 and 11.5 days respectively. The mean VAS pain score was 3.9 ± 2.0 with the FPS and 7.0 ± 2.0 with the CO₂ FS. Conclusion We demonstrated the efficacy and safety of single‐session acne scar treatment using FPS and CO₂ FS in East Asian patients. We believe that our study could be used as an essential reference when choosing laser modalities for scar treatment.     

The outcome of 9 years of consecutive patch testing with 4,4′‐diaminodiphenylmethane and 4,4′‐diphenylmethane diisocyanate

Background. Two outbreaks of allergic contact dermatitis caused by isocyanates at two companies in southern Sweden initiated a research project focusing on contact allergy to isocyanates. Within the project, there was an interest in determining how often contact allergy to the most common isocyanate, diphenylmethane‐4,4′‐diisocyanate (4,4′‐MDI), occurred. Objectives. To determine and compare the occurrence of contact allergy to 4,4′‐MDI, its corresponding amine 4,4′‐diaminodiphenylmethane (4,4′‐MDA), and polymeric diphenylmethane diisocyanate (PMDI) in a Swedish and a Belgian study population. Patients and method. The study population consisted of 6190 consecutively patch tested dermatitis patients: 5690 patients from Malmö, Sweden, and 500 patients from Leuven, Belgium. Patch test results were analysed and compared. Results. None of the Belgian patients reacted positively to 4,4′‐MDI, but 5 Swedish patients did. Contact allergy to 4,4′‐MDA was more common in the Belgian patients than in the Swedish patients: 3.6% and 0.9%, respectively. This could possibly be explained by the fact that the prevalence of p‐phenylenediamine allergy was higher in the Belgian population. Conclusions. The prevalence of contact allergy to 4,4′‐MDI, 4,4′‐MDA and PMDI is not high enough to justify their inclusion in any baseline series. Isocyanate allergic individuals should be detected by aimed testing with an isocyanate series and work materials.