Silver Sulfadiazine Cream Treatment Results in More Wound Contraction and More Itch in a Standardized Porcine Scald Model.

A variety of dressings is available for the treatment of partial-thickness wounds, but none has strong evidence supporting their beneficial effect on healing. This may be due to variation in the type and depth of wounds in clinical studies. The aim of this study was to use a standardized porcine wound model to compare three dressings commonly used in burn centers for partial-thickness burns. Partial-thickness scalds were made on the flanks of pigs. Wounds were treated with silver sulfadiazine (SSD, flammazine), a hydrofiber dressing, or glycerol-preserved allogeneic (pig) skin. The healing process was monitored for 8 weeks. Macroscopic parameters were the itching behavior, the cosmetic appearance of the scars, and contraction. Microscopic parameters were the inflammatory response, myofibroblast influx, and the numbers of nerves. All wounds were closed on day 14 and wound infection did not occur. Treatment with SSD resulted in significantly more wound contraction compared to treatment with glycerol-preserved pig skin. Animals treated with SSD suffered more from itching (scratching) during the first 2 weeks after wounding. The number of nerves in healing wounds of these animals was significantly higher compared to wounds treated with hydrofiber dressing or allogeneic skin. In our standardized porcine partial-thickness wound model, treatment with SSD resulted in less favorable wound healing. Compared to treatment with glycerol-preserved allogeneic skin, SSD resulted in more contraction.

Homocysteine-induced apoptosis in endothelial cells coincides with nuclear NOX2 and peri-nuclear NOX4 activity.

Apoptosis of endothelial cells related to homocysteine (Hcy) has been reported in several studies. In this study, we evaluated whether reactive oxygen species (ROS)-producing signaling pathways contribute to Hcy-induced apoptosis induction, with specific emphasis on NADPH oxidases. Human umbilical vein endothelial cells were incubated with 0.01-2.5 mM Hcy. We determined the effect of Hcy on caspase-3 activity, annexin V positivity, intracellular NOX1, NOX2, NOX4, and p47(phox) expression and localization, nuclear nitrotyrosine accumulation, and mitochondrial membrane potential (ΔΨ m). Hcy induced caspase-3 activity and apoptosis; this effect was concentration dependent and maximal after 6-h exposure to 2.5 mM Hcy. It was accompanied by a significant increase in ΔΨ m. Cysteine was inactive on these parameters excluding a reactive thiol group effect. Hcy induced an increase in cellular NOX2, p47(phox), and NOX4, but not that of NOX1. 3D digital imaging microscopy followed by image deconvolution analysis showed nuclear accumulation of NOX2 and p47(phox) in endothelial cells exposed to Hcy, but not in control cells, which coincided with accumulation of nuclear nitrotyrosine residues. Furthermore, Hcy enhanced peri-nuclear localization of NOX4 coinciding with accumulation of peri-nuclear nitrotyrosine residues, a reflection of local ROS production. p47(phox) was also increased in the peri-nuclear region. The Hcy-induced increase in caspase-3 activity was prevented by DPI and apocynin, suggesting involvement of NOX activity. The data presented in this article reveal accumulation of nuclear NOX2 and peri-nuclear NOX4 accumulation as potential source of ROS production in Hcy-induced apoptosis in endothelial cells.