RNA inhibitors of nuclear proteins responsible for multiple organ dysfunction syndrome.

The development of multiple organ dysfunction syndrome (MODS) following infection or tissue injury is associated with increased patient morbidity and mortality. Extensive cellular injury results in the release of nuclear proteins, of which histones are the most abundant, into the circulation. Circulating histones are implicated as essential mediators of MODS. Available anti-histone therapies have failed in clinical trials due to off-target effects such as bleeding and toxicity. Here, we describe a therapeutic strategy for MODS based on the neutralization of histones by chemically stabilized nucleic acid bio-drugs (aptamers). Systematic evolution of ligands by exponential enrichment technology identified aptamers that selectively bind those histones responsible for MODS and do not bind to serum proteins. We demonstrate the efficacy of histone-specific aptamers in human cells and in a murine model of MODS. These aptamers could have a significant therapeutic benefit in the treatment of multiple diverse clinical conditions associated with MODS.

Impact on Quality of Life in Vitiligo Patients Treated with Narrowband Ultraviolet B Phototherapy.

CONTEXT: Vitiligo is a psychosocial problem which significantly affects quality of life in Indian scenario. AIMS: The purpose of this study was to compare the changes in quality of life in patients of vitiligo before and after treatment with narrowband ultraviolet B (NBUVB) phototherapy. SUBJECTS AND METHODS: A total of 54 patients had completed the study. The age ranged between 16 and 70 years with a mean age of 26.77±14.2 years. The initial dose of NBUVB was 300 mJ/cm2 in adults and 150 mJ/cm2 in children twice weekly with 20% dose increment on subsequent visits. It was given for a maximum period of 6 months and was followed up for another 6 months to determine stability of repigmentation. RESULTS: The average number of exposure given to the patients was 45.63±12.74 while the mean irradiation cumulative dose was 39.8 J/cm2. Mean Dermatology Life Quality Index (DLQI) of the vitiligo patients was 8.64±4.32 while those patients with acrofacial vitiligo had a mean DLQI of 11.78±5.61. After treatment with NBUVB, mean DLQI of all vitiligo patients was significantly reduced to 5.86±2.15 (P<0.01). CONCLUSIONS: This study showed that phototherapy had a positive therapeutic outcome in vitiligo, especially in younger patients. Even a small, depigmented lesion in a child could be psychosocially devastating.