The anticonvulsant carbamazepine (CBZ) frequently causes cutaneous adverse drug reactions (cADRs), including maculopapular eruption (MPE), hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We reported that SJS/TEN caused by CBZ is strongly associated with the HLA-B*1502 gene in Han Chinese. Here, we extended our genetic study to different types of CBZ-cADRs (91 patients, including 60 patients with SJS/TEN, 13 patients with hypersensitivity syndrome and 18 with maculopapular exanthema versus 144 tolerant controls). We used MALDI-TOF mass spectrometry to screen the genetic association of 278 single nucleotide polymorphisms (SNPs), which cover the major histocompatibility complex (MHC) region, tumor necrosis factor-alpha, heat shock protein and CBZ-metabolic enzymes, including CYP3A4, 2B6, 2C8, 2C9, 1A2 and epoxide hydrolase 1. In addition, we genotyped 20 microsatellites in the MHC region and performed HLA-typing to construct the recombinant map. We narrowed the susceptibility locus for CBZ-SJS/TEN to within 86 kb flanking the HLA-B gene on the extended B*1502 haplotype, and confirmed the association of B*1502 with SJS/TEN [Pc=1.6x10, odds ratio (OR)=1357; 95% confidence interval (CI)=193.4-8838.3]. By contrast to CBZ-SJS/TEN, HLA-B*1502 association was not observed in the MPE or HSS groups: MPE was associated with SNPs in the HLA-E region and a nearby allele, HLA-A*3101 (Pc=2.2x10, OR=17.5; 95% CI=4.6-66.5), and HSS with SNPs in the motilin gene (Pc=0.0064, OR=7.11; 95% CI=3.1-16.5) located terminal to the MHC class II genes. No SNPs in genes involved in CBZ metabolism were associated with CBZ-induced cADRs. Our data suggest that HLA-B*1502 could contribute to the pathogenesis of CBZ-SJS/TEN, and that genetic susceptibility to CBZ-induced cADRs is phenotype-specific.

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Daylight photodynamic therapy (dPDT) uses sunlight as a light source to treat superficial skin cancer. Using sunlight as a therapeutic device has been present for centuries, forming the basis of photodynamic therapy in the 20th century. Compared to conventional PDT, dPDT can be a less painful, more convenient and an effective alternative. The first clinical uses of dPDT on skin cancers began in Copenhagen in 2008. Currently, aminolevulinic acid-mediated dPDT has been approved to treat actinic keratosis patients in Europe. In this review article, we introduce the history and mechanism of dPDT and focus on the pros and cons of dPDT in treating superficial skin cancers. The future applications of dPDT on other skin diseases are expected to expand as conventional PDT evolves.

Catalytic DNA molecules that target the transcription factor c- jun inhibit skin cancer growth in mice.

Catechin is a flavan-3-ol, a derivative of flavans, with four phenolic hydroxyl groups, which exhibits a wide range of physiological properties. Chromatographic analyses were employed to examine the effects of blue light irradiation on the changes of catechin hydrate in an alkaline condition. In particular, the detection of a superoxide anion radical (O2•−), a reactive oxygen species (ROS), and the inactivation of Acinetobacter baumannii (A. baumannii)—including a carbapenem-resistant A. baumannii (CRAB)—was investigated during the photoreaction of catechin hydrate. Following basification with blue light irradiation, the transparent solution of catechin hydrate turned yellowish, and a chromogenic catechin dimer was separated and identified as a proanthocyanidin. Adding ascorbic acid during the photolytic treatment of catechin hydrate decreased the dimer formation, suggesting that ascorbic acid can suppress the photosensitive oxidation of catechin. When catechin hydrate was irradiated by blue light in an alkaline solution, O2•− was produced via photosensitized oxidation, enhancing the inactivation of A. baumannii and CRAB. The present findings on the photon-induced oxidation of catechin hydrate provides a safe practice for the inactivation of environmental microorganisms.

Vibrio vulnificus is a gram-negative, highly invasive bacterium responsible for human opportunistic infections. We studied the antibacterial effects of toluidine blue O (TBO)-mediated photodynamic therapy (PDT) for V. vulnificus wound infections in mice. Fifty-three percent (10 of 19) of mice treated with 100 g of TBO per ml and exposed to broad-spectrum red light (150 J/cm 2 at 80 mW/cm 2 ) survived, even though systemic septicemia had been established with a bacterial inoculum 100 times the 50% lethal dose. In vitro, the bacteria were killed after exposure to a lower light dose (100 J/cm 2 at 80 mW/cm 2 ) in the presence of low-dose TBO (0.1 g/ml). PDT severely damaged the cell wall and reduced cell motility and virulence. Cell-killing effects were dependent on the TBO concentration and light doses and were mediated partly through the reactive oxygen species generated during the photodynamic reaction. Our study has demonstrated that PDT can cure mice with otherwise fatal V. vulnificus wound infections. These promising results suggest the potential of this regimen as a possible alternative to antibiotics in future clinical applications.Photodynamic therapy (PDT) is an experimental treatment which shows great potential for the treatment of neoplastic and nonneoplastic diseases (11,12). PDT involves a light-sensitive photosensitizer, light, and molecular oxygen (14). After excitation with visible light, highly cytotoxic singlet oxygen and other reactive oxygen species (ROS) are generated by either energy or electron transfer (14,30,32). The use of photosensitizers for microbial eradication can be traced back to before the age of chemotherapy (16,38). The antimicrobial effects of PDT are increasingly recognized. The technique has been shown to have effects against a range of oral pathogens and also against drug-resistant bacteria. More importantly, there have been reports of the use of PDT to treat infections in selected animal models (13,15,17) and some clinical trials (16), with encouraging results. The activities of the virulence factors of gram-negative bacteria were also reduced with PDT (24). Among the many photosensitizers, toluidine blue O (TBO), a cationic phenothiazinium photosensitizer (16,38), has been shown to be phototoxic to gram-negative bacilli with red-light irradiation (39). However, in vivo antimicrobial studies of TBO-PDT were mainly limited to oral infections (39).Vibrio vulnificus is a gram-negative, motile, curved bacillus of the family Vibrionaceae (22). Most Vibrio species are free-living in marine or brackish water (6). Many cases of V. vulnificus infection have been reported from the coastal areas of the United States (4), Asia (6), and Europe (10). V. vulnificus causes primary sepsis, wound infection, and gastrointestinal illness in humans (6,22). This organism is extremely virulent, and infections with this organism typically occur in patients with underlying liver disease 1 to 2 days after exposure. The mortality rate is up to 55% in septic patients and 25% in those with wound infect...

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Traditional wound care methods include wound infection control, adequate nutritional supplements, education of changing position every 2-3 h to avoid tissue hypoxia, vacuum assistant closure, debridement, skin graft, and tissue flap. Electric current stimulation, ultrasound, laser, and hydrotherapy have emerged as adjuvant therapies. However, most, if not all, of these therapies are expensive, and the treatment results are variable. The development of the active methods to improve wound healing is mandatory. CO administration has been known to improve microcirculation and local oxygen supply that are beneficial to wound healing. Here, the metal ion-ligand coordination nanoarchitecture was designed to reveal NIR light-induced CO generation for wound healing. The administration simply topically dropped the colloidal solution on the incisional wound, followed by exposure of near-infrared (NIR) lamp to yield CO, resulting in the observation of the accelerated wound healing.