Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularization (CNV). We report that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in CNV endothelial cells in humans with AMD, and that, despite the expression of its ligands eotaxin-1, -2, and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation as it occurred in mice lacking eosinophils or mast cells and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor-A (VEGF-A) neutralization, which is currently in clinical use, and, unlike VEGF-A blockade, not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.

Different oxygen stresses activate NAD(P)H oxidase to varying degrees to trigger disparate pathways (angiogenesis or apoptosis). The oxygen stresses and outcomes used in this study are relevant to human ROP and may explain some of the complexity in the pathophysiology of ROP resulting from oxygen exposure.

Rac1 , a subunit of NADPH oxidase , plays an important role in directed endothelial cell motility. We reported previously that Rac1 activation was necessary for choroidal endothelial cell migration across the retinal pigment epithelium , a critical step in the development of vision-threatening neovascular age-related macular degeneration. Here we explored the roles of Rac1 and NADPH oxidase activation in response to vascular endothelial growth factor treatment in vitro and in a model of laser-induced choroidal neovascularization. We found that vascular endothelial growth factor induced the activation of Rac1 and of NADPH oxidase in cultured human choroidal endothelial cells. Further , vascular endothelial growth factor led to heightened generation of reactive oxygen species from cultured human choroidal endothelial cells, which was prevented by the NADPH oxidase inhibitors , apocynin and diphenyleneiodonium , or the antioxidant , N-acetyl-L-cysteine.

Older reports have suggested that the use of antithyroid drugs with radioactive iodine-131 (RAI) results in higher rates of persistent hyperthyroidism than treatment with RAI alone. Our objective was to determine if propylthiouracil (PTU) given prior to RAI would be associated with a higher single dose RAI failure rate than treatment with RAI alone. Patients were considered treatment failures if a second dose of RAI was required to produce euthyroidism or hypothyroidism. All study patients stopped PTU at least 4 days before RAI therapy and did not receive PTU after RAI. The overall failure rate of one course of treatment in the 86 study patients was 17% (15/86). Persistent hyperthyroidism was seen in 4% of patients (2/48) treated with only RAI and in 34% of patients (13/38) receiving RAI after pretreatment with PTU (p = 0.003). Patients were treated with PTU for a mean of 151 +/- 32 days. There were no significant differences in race, gender, thyroid size, RAI dose, or days of follow-up between patients receiving RAI alone and those receiving PTU before RAI therapy. These data suggest that pretreatment with PTU leads to a higher failure rate even if PTU is discontinued at least 4 days before RAI therapy and not restarted after RAI dosing. Consideration should be given to increasing the dose of RAI in patients pretreated with PTU to ensure adequate treatment of Graves' disease.

The objective of this investigation was to assess and compare the in vitro tribological behaviour of four commercially available self-ligating bracket systems. The frictional characteristics of the Damon3, Speed, In-Ovation R, and Time2 bracket systems were studied using a jig that mimics the three-dimensional movements that occur during sliding mechanics. Each bracket system was tested on the following stainless steel archwires: 0.016 x 0.022, 0.019 x 0.025, 0.020 round, and 0.021 x 0.021 inch Speed D-wire. An Instron testing machine with a 50 N load cell was used to measure the frictional resistance for each bracket/tooth assembly. The crosshead speed was set at a constant rate of 1 mm/minute, and each typodont tooth was moved along a fixed wire segment for a distance of 8 mm. Descriptive statistical analysis for each bracket/archwire combination with regard to frictional resistance was performed with a two-way, balanced analysis of variance for bracket type and wire size. The Damon3 bracket consistently demonstrated the lowest frictional resistance to sliding, while the Speed bracket produced significantly (P < 0.001) more frictional resistance than the other brackets tested for any given archwire. The self-ligation design (passive versus active) appears to be the primary variable responsible for the frictional resistance generated by self-ligating brackets during translation. Passively ligated brackets produce less frictional resistance; however, this decreased friction may result in decreased control compared with actively ligated systems.