Efficacy and safety of narrowband ultraviolet B versus combined ultraviolet A/narrowband ultraviolet B phototherapy in the treatment of chronic atopic dermatitis: A randomised double-blind study.

Phototherapy is a useful treatment modality for atopic dermatitis (AD). This is a prospective randomised double-blind study comparing the clinical efficacy of combined ultraviolet-A (UVA)/narrowband ultraviolet-B (NBUVB) versus NBUVB phototherapy in the treatment of chronic AD. Patients with moderate-to-severe AD were randomised to receive either UVA/NBUVB or NBUVB phototherapy twice weekly over 12 weeks. At baseline, weeks 6 and 12, Eczema Area And Severity Index (EASI), itch score and adverse effects were assessed. At baseline and week 12, disease-related quality of life was evaluated using the Dermatology Life Quality Index (DLQI). Nine patients were randomised to receive UVA/NBUVB and 10 received NBUVB. At week 12, both groups showed significant improvement in EASI and itch scores (p < 0.05). Significant improvement in DLQI was seen in the UVA/NBUVB arm (p = 0.009) with a trend towards improvement in the NBUVB arm (p = 0.11). The efficacy of both modalities were comparable, as were reported adverse effects aside from skin dryness which was higher in the NBUVB arm (40% vs. 0%, p = 0.033). Combined UVA/NBUVB and NBUVB phototherapy have comparable clinical efficacy and safety in the treatment of chronic AD. NBUVB may induce greater skin dryness.

Pyrimethamine induces phototoxicity in human keratinocytes via lysosomal and mitochondrial dependent signaling pathways under environmental UVA and UVB exposure.

Pyrimethamine (PYR) is used to treat parasitic infections including toxoplasmosis, pneumonia and cystoisosporiasis in HIV patients. Various oral medicines have shown phototoxicity therefore, we aimed to study the phototoxicity of PYR and its molecular mechanism involving stress responsive lysosomal protein Lamp2 and mitochondrial mediated signaling pathway under normal UVA/B exposure. We found that photodegradation and subsequent photoproduct formation was evident through LCMS/MS analysis. Photosensitized PYR produces ROS that cause damage to DNA, cell membrane and membrane bound organelles in human keratinocytes. PYR triggered cytotoxicity and phototoxicity that was evident through MTT and NRU assay respectively. Intracellular ROS generation caused phosphatidyl serine (PS) translocation in cell membrane, lysosome membrane permeabilization (LMP) and mitochondrial membrane potential (MMP) collapse that was further validated through caspase3 activation. DNA damage was measured as tail DNA formation and cell cycle arrest in G1 phase. Photosensitized PYR induces oxidative stress in the form of overexpression of Lamp2 that ultimately led to cellular apoptosis. Moreover, the effects of UVB were higher than UVA, probably due to its direct interaction with various macromolecules. We propose that photoexcited PYR may be harmful to human health even at normal sunlight exposure. Therefore, protective procedures should be practiced during PYR medication.

Effects of UV Radiation on the Chlorophyte Micromonas polaris Host-Virus Interactions and MpoV-45T Virus Infectivity.

Polar seas are under threat of enhanced UV-radiation as well as increasing shipping activities. Considering the ecological importance of marine viruses, it is timely to study the impact of UV-AB on Arctic phytoplankton host-virus interactions and also test the efficacy of ballast water (BW) UV-C treatment on virus infectivity. This study examined the effects of: (i) ecologically relevant doses of UV-AB radiation on Micromonas polaris RCC2258 and its virus MpoV-45T, and (ii) UV-C radiation (doses 25-800 mJ cm-2) on MpoV-45T and other temperate algal viruses. Total UV-AB exposure was 6, 12, 28 and 48 h (during the light periods, over 72 h total). Strongest reduction in algal growth and photosynthetic efficiency occurred for 28 and 48 h UV-AB treatments, and consequently the virus production rates and burst sizes were reduced by more than half (compared with PAR-only controls). For the shorter UV-AB exposed cultures, negative effects by UV (especially Fv/Fm) were overcome without impacting virus proliferation. To obtain the BW desired log-4 reduction in virus infectivity, a UV-C dose of at least 400 mJ cm-2 was needed for MpoV-45T and the temperate algal viruses. This is higher than the commonly used dose of 300 mJ cm-2 in BW treatment.

Changes in Chromatin Organization Eradicate Cellular Stress Resilience to UVA/B Light and Induce Premature Aging.

Complex interactions among DNA and nuclear proteins maintain genome organization and stability. The nuclear proteins, particularly the histones, organize, compact, and preserve the stability of DNA, but also allow its dynamic reorganization whenever the nuclear processes require access to it. Five histone classes exist and they are evolutionarily conserved among eukaryotes. The linker histones are the fifth class and over time, their role in chromatin has been neglected. Linker histones interact with DNA and the other histones and thus sustain genome stability and nuclear organization. Saccharomyces cerevisiae is a brilliant model for studying linker histones as the gene for it is a single-copy and is non-essential. We, therefore, created a linker histone-free yeast strain using a knockout of the relevant gene and traced the way cells age chronologically. Here we present our results demonstrating that the altered chromatin dynamics during the chronological lifespan of the yeast cells with a mutation in ARP4 (the actin-related protein 4) and without the gene HHO1 for the linker histone leads to strong alterations in the gene expression profiles of a subset of genes involved in DNA repair and autophagy. The obtained results further prove that the yeast mutants have reduced survival upon UVA/B irradiation possibly due to the accelerated decompaction of chromatin and impaired proliferation. Our hypothesis posits that the higher-order chromatin structure and the interactions among chromatin proteins are crucial for the maintenance of chromatin organization during chronological aging under optimal and UVA-B stress conditions.

Development of S-Methylmethionine Sulfonium Derivatives and Their Skin-Protective Effect against Ultraviolet Exposure.

In a previous study, we have demonstrated that S-methylmethionine sulfonium (SMMS) confers wound-healing and photoprotective effects on the skin, suggesting that SMMS can be used as a cosmetic raw material. However, it has an unpleasant odor. Therefore, in the present study, we synthesized odor-free SMMS derivatives by eliminating dimethyl sulfide, which is the cause of the unpleasant odor and identified two derivatives that exhibited skin-protective effects: one derivative comprised (2S,4S)- and (2R,4S)-2-phenylthiazolidine-4-carboxylic acid and the other comprised (2S,4R)-, (2S,4S)-, (2R,4R)-, and (2R,4S)-2-phenyl-1,3-thiazinane-4-carboxylic acid. We performed in vitro proliferation assays using human dermal fibroblasts (hDFs) and an immortalized human keratinocyte cell line (HaCaT). The two SMMS derivatives were shown to increase hDF and HaCaT cell proliferation as well as improve their survival by protecting against ultraviolet exposure. Moreover, the derivatives regulated the expression of collagen type I and MMP mRNAs against ultraviolet exposure in hDFs, suggesting that these derivatives can be developed as cosmetic raw materials.

Development of S-Methylmethionine Sulfonium Derivatives and Their Skin-Protective Effect against Ultraviolet Exposure

In a previous study, we have demonstrated that S-methylmethionine sulfonium (SMMS) confers wound-healing and photoprotective effects on the skin, suggesting that SMMS can be used as a cosmetic raw material. However, it has an unpleasant odor. Therefore, in the present study, we synthesized odor-free SMMS derivatives by eliminating dimethyl sulfide, which is the cause of the unpleasant odor and identified two derivatives that exhibited skin-protective effects: one derivative comprised (2S,4S)- and (2R,4S)-2-phenylthiazolidine-4-carboxylic acid and the other comprised (2S,4R)-, (2S,4S)-, (2R,4R)-, and (2R,4S)-2-phenyl-1,3-thiazinane-4-carboxylic acid. We performed in vitro proliferation assays using human dermal fibroblasts (hDFs) and an immortalized human keratinocyte cell line (HaCaT). The two SMMS derivatives were shown to increase hDF and HaCaT cell proliferation as well as improve their survival by protecting against ultraviolet exposure. Moreover, the derivatives regulated the expression of collagen type I and MMP mRNAs against ultraviolet exposure in hDFs, suggesting that these derivatives can be developed as cosmetic raw materials.