Antifungal activity of selected Malassezia indolic compounds detected in culture

Background: Malassezia yeasts produce bioactive indolic substances when grown on L‐tryptophan agar. A panel of these substances was tested against commensal and opportunistic fungi, the Minimum Inhibitory Concentration (MIC) was determined and the potential for in loco antifungal activity on the skin was assessed. Materials and Methods: Eight indoles were included (malassezin, pityriacitrin, indirubin, indolo[3,2‐b]carbazole, 6‐formylindolo[3,2‐b]carbazole, tryptanthrin, 6‐hydroxymethylindolo[3,2‐b]carbazole and 6‐methylindolo[3,2‐b]carbazole) and were tested against 40 fungal strains [yeasts: Malassezia spp.(N = 9); Cryptococcus spp.(N = 10); Candida spp.(N = 7); Yarrowia lipolytica(N = 1); Exophialla dermatitidis (N = 2); moulds: Aspergillus spp.(N = 7); Fusarium spp.(N = 2); Rhizopus oryzae(N = 2)]. The concentration of 5/8 of the tested indoles on diseased skin was calculated from published data. Kruskal‐Wallis and Mann‐Whitney U tests were employed for group susceptibility evaluation in 33 strains. Results: The MIC range was 0.125‐32 μg/mL, and the median log2MIC was four. Indirubin was the most potent antifungal agent and differed significantly from the others. The highest median MIC was found for FICZ. Malassezia with Candida strains were more susceptible compared to Cryptococcus and Aspergillus, and this inhibitory activity was predicted to be valid also on human skin. Conclusions: Malassezia yeasts produce indolic species that inhibit an array of clinically significant yeasts and moulds

No Evidence of Persisting Unrepaired Nuclear DNA Single Strand Breaks in Distinct Types of Cells in the Brain, Kidney, and Liver of Adult Mice after Continuous Eight-Week 50 Hz Magnetic Field Exposure with Flux Density of 0.1 mT or 1.0 mT

BACKGROUND: It has been hypothesized in the literature that exposure to extremely low frequency electromagnetic fields (50 or 60 Hz) may lead to human health effects such as childhood leukemia or brain tumors. In a previous study investigating multiple types of cells from brain and kidney of the mouse (Acta Neuropathologica 2004; 107: 257-264), we found increased unrepaired nuclear DNA single strand breaks (nDNA SSB) only in epithelial cells of the choroid plexus in the brain using autoradiographic methods after a continuous eight-week 50 Hz magnetic field (MF) exposure of adult mice with flux density of 1.5 mT. METHODS: In the present study we tested the hypothesis that MF exposure with lower flux densities (0.1 mT, i.e., the actual exposure limit for the population in most European countries, and 1.0 mT) shows similar results to those in the previous study. Experiments and data analysis were carried out in a similar way as in our previous study. RESULTS: Continuous eight-week 50 Hz MF exposure with 0.1 mT or 1.0 mT did not result in increased persisting unrepaired nDNA SSB in distinct types of cells in the brain, kidney, and liver of adult mice. MF exposure with 1.0 mT led to reduced unscheduled DNA synthesis (UDS) in epithelial cells in the choroid plexus of the fourth ventricle in the brain (EC-CP) and epithelial cells of the cortical collecting duct in the kidney, as well as to reduced mtDNA synthesis in neurons of the caudate nucleus in the brain and in EC-CP. CONCLUSION: No evidence was found for increased persisting unrepaired nDNA SSB in distinct types of cells in the brain, kidney, and liver of adult mice after continuous eight-week 50 Hz magnetic field exposure with flux density of 0.1 mT or 1.0 mT

Advanced keratinocyte skin cancer is a tumor with considerable disease burden and aggressiveness

In a 2013 study published in this Journal, Dacosta Byfield et al. used MediCare data to extract reliable estimations of the incidence (I = 6.16) and prevalence (P = 10.31) rates of advanced keratinocyte skin cancer (aKSC) per 100,000 US population. These data unmask a considerable disease burden of aKSC (tumor stages ≥ 3) compared to the corresponding projected SEER predictions in 2019 of all invasive cases (tumor stages ≥ 1). According to its incidence, aKSC ranks 19th out of 29 major SEER registered neoplasms and has an average disease duration of 1.67 years, which is the second shortest disease duration next only to pancreatic carcinoma. Furthermore, in support of the high disease aggressiveness of aKSC and using a calibration approach, we calculated a mortality estimate of 4.64 per 100,000 and a 5-year survival rate of 21.8% for this tumor, which corresponds to positions of 13th and 5th out of 29 cancers among the SEER tracked malignancies, respectively. Taken together, these data indicate a considerable disease burden and biologic aggressiveness of aKSC

Psoriasis and inflammatory bowel disease: links and risks

Christoforos Vlachos,1 Georgios Gaitanis,1 Konstantinos H Katsanos,2 Dimitrios K Christodoulou,2 Epameinondas Tsianos,2 Ioannis D Bassukas1 1Department of Skin and Venereal Diseases, 2Division of Gastroenterology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece Abstract: Psoriasis and the spectrum of inflammatory bowel diseases (IBD) are chronic, inflammatory, organotropic conditions. The epidemiologic coexistence of these diseases is corroborated by findings at the level of disease, biogeography, and intrafamilial and intrapatient coincidence. The identification of shared susceptibility loci and DNA polymorphisms has confirmed this correlation at a genetic level. The pathogenesis of both diseases implicates the innate and adaptive segments of the immune system. Increased permeability of the epidermal barrier in skin and intestine underlies the augmented interaction of allergens and pathogens with inflammatory receptors of immune cells. The immune response between psoriasis and IBD is similar and comprises phagocytic, dendritic, and natural killer cell, along with a milieu of cytokines and antimicrobial peptides that stimulate T-cells. The interplay between dendritic cells and Th17 cells appears to be the core dysregulated immune pathway in all these conditions. The distinct similarities in the pathogenesis are also reflected in the wide overlapping of their therapeutic approaches. Small-molecule pharmacologic immunomodulators have been applied, and more recently, biologic treatments that target proinflammatory interleukins have been introduced or are currently being evaluated. However, the fact that some treatments are quite selective for either skin or gut conditions also highlights their crucial pathophysiologic differences. In the present review, a comprehensive comparison of risk factors, pathogenesis links, and therapeutic strategies for psoriasis and IBD is presented. Specific emphasis is placed on the role of the immune cell species and inflammatory mediators participating in the pathogenesis of these diseases. Keywords: psoriasis, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, immune cells, inflammatio