Treatment outcomes in the neovascular glaucoma tube versus trabeculectomy study

Graefe's Archive for Clinical and Experimental Ophthalmology - To compare surgical outcomes between patients who underwent Baerveldt glaucoma implantation versus trabeculectomy (TLE) for the...     

Calcium channel activation facilitated by nitric oxide in retinal ganglion cells

We investigated the modulation of voltage-gated Ca channels by nitric oxide (NO) in isolated salamander retinal ganglion cells with the goals of determining the type of Ca channel affected and the signaling pathway by which modulation might occur. The NO donors, S-nitroso-N-acetyl-penicillamine (SNAP, 1 mM) and S-nitroso-cysteine (1 mM) induced modest increases in the amplitude of Ca channel currents recorded with ruptured- and permeabilized-patch techniques by causing a subpopulation of the Ca channels to activate at more negative potentials. The Ca channel antagonists omega-conotoxin GVIA and nisoldipine each reduced the Ca channel current partially, but only omega-conotoxin GVIA blocked the enhancement by SNAP. The SNAP-induced increase was blocked by oxadiazolo-quinoxaline (50 microM), suggesting that the NO generated by SNAP acts via a soluble guanylyl cyclase to raise levels of cGMP. The membrane-permeant cGMP analog 8-(4-chlorophenylthio) guanosine cyclic monophosphate also enhanced Ca channel currents and 8-bromo guanosine cyclic monophosphate (1 mM) occluded enhancement by SNAP. Consistent with these results, isobutyl-methyl-xanthine (IBMX, 10 microM), which can raise cGMP levels by inhibiting phosphodiesterase activity, increased Ca channel current by the same amount as SNAP and occluded subsequent enhancement by SNAP. Neither IBMX, the cGMP analogs, nor SNAP itself, led to activation of cGMP-gated channels. N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide (2 microM), a broad spectrum inhibitor of protein kinase activity, KT5823 (1 microM), a specific protein kinase G (PKG) inhibitor, and a peptide inhibitor of PKG (200 microM) blocked SNAP enhancement, as did 5'-adenylylimidophosphate (1.5 mM), a nonhydrolyzable ATP analog that prevents protein phosphorylation. A peptide inhibitor of protein kinase A (10 nM) did not block the facilitory effects of SNAP. Okadaic acid (1 microM), a phosphatase inhibitor, had no effect by itself but increased the enhancement of Ca channel current by SNAP. These results suggest that NO modulates retinal ganglion cell N-type Ca channels by facilitating their voltage-dependent activation via a mechanism involving guanylyl cyclase/PKG-dependent phosphorylation. This effect could fine-tune neural integration in ganglion cells or play a role in ganglion cell disease by modulating intracellular calcium signaling.     

Confocal endomicroscopy for phenotypic diagnosis of gastric cancer

Background and Aim: Relationships between mucin phenotype and malignant potential in gastric cancers have attracted attention. We attempted to assess the possibility of obtaining phenotypic diagnoses by confocal endomicroscopy. Methods: Confocal images of target lesions were obtained in 29 of 40 patients with gastric cancer. Appearances of the brush border, goblet cells, and gastric foveolar epithelium were investigated with immunohistochemical staining using CD10, MUC2, and human gastric mucin to evaluate phenotypic expression in gastric carcinomas. Confocal images were compared with immunohistochemical findings for goblet cells and brush borders. Results: Both the endoscopists and the pathologist obtained high accuracy rates for differential diagnosis. Sensitivity and specificity for goblet cells were 85.7% and 92.3% (Endoscopist A), and 85.7% and 88.5% (Endoscopist B). The κ‐value for correspondence between two endoscopists for the diagnosis of goblet cells in confocal images was 0.73. Sensitivity and specificity for the brush border were 93.8% and 91.7% (Endoscopist A), and 81.3% and 91.7% (Endoscopist B). The κ‐value for correspondence between two endoscopists for diagnosis of the brush border in confocal images was 0.79. Intestinal phenotypic gastric cancers show a brush border, goblet cells, or both. Sensitivity and specificity for the intestinal phenotype in confocal endomicroscopy were 90.9% and 77.8% (Endoscopist A), and 86.4% and 83.3% (Endoscopist B). Conclusion: The confocal endomicroscopic diagnosis of the mucin phenotype in gastric cancers was limited to intestinal and mixed phenotypes, but may be useful for the diagnosis of mucin phenotype and differential diagnosis.