Case report: 18F-FDG PET confirmed pupil-sparing third nerve palsy heralding aseptic cavernous sinus embolism in patient with chest malignancy.

Classical cavernous sinus embolism is a rare clinical finding, presented most commonly by complaints of headache, diplopia, visual field defects, facial pain, and progressive neurological deficits. Many patients exhibit symptoms of III, IV, and VI nerve palsies. We hereby report a rare case of aseptic cavernous sinus embolism developed in a 75-year-old male with primary lung cancer who presented with binocular diplopia due to unilateral third and sixth cranial nerve palsies with pupil-sparing. The possibility of cavernous sinus cancer embolus should be considered if the routine examination excluded metastases, infiltration, carcinomatous meningitis, or the paraneoplastic process. 18F-FDG PET imaging may provide a promising diagnostic modality for the diagnosis of cancer embolus.

Obstructive sleep apnea/hypopnea syndrome increases glaucoma risk: evidence from a meta-analysis.

Associations between Obstructive sleep apnea/hypopnea syndrome (OSAHS) and risk of glaucoma remained controversial. Therefore, we performed this meta-analysis to investigate this association. We searched Pubmed, EMBASE, and Wangfang databases for studies before Oct. 10 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association. A total of 12 studies with 36909 subjects on the association between OSAHS and glaucoma risk were included for this meta-analysis. OSAHS was associated with a significantly increased risk of glaucoma (OR = 1.65; 95% CI, 1.44-1.88; I (2) = 43%). In the race subgroup analysis, both Asians (OR = 1.78; 95% CI, 1.49-2.12; I (2) = 0%) and Caucasians (OR = 2.03; 95% CI, 1.12-3.69; I (2) = 57%) with OSAHS had increased glaucoma risk. In the subgroup analysis according to gender, both women and men were significantly associated with risk of glaucoma (OR = 1.81; 95% CI, 1.27-2.57; I (2) = 22% and OR = 1.62; 95% CI, 1.29-2.03; I (2) = 0%, respectively). In the subgroup analysis by glaucoma type, OSAHS patients showed increased primary open-angle glaucoma (POAG) risk (OR = 1.87; 95% CI, 1.54-2.33; I (2) = 0%) but not normal tension glaucoma (NTG) risk (OR = 3.57; 95% CI, 0.89-14.43; I (2) = 0%). In addition, severe OSAHS patients had an increased glaucoma risk (OR = 5.49; 95% CI, 1.04-33.83; I (2) = 0%), while mild and moderate OSAHS patients did not show significantly increased glaucoma risk. This meta-analysis suggested that the OSAHS may be a risk factor for glaucoma.

Nox2-dependent glutathionylation of endothelial NOS leads to uncoupled superoxide production and endothelial barrier dysfunction in acute lung injury.

Microvascular barrier integrity is dependent on bioavailable nitric oxide (NO) produced locally by endothelial NO synthase (eNOS). Under conditions of limited substrate or cofactor availability or by enzymatic modification, eNOS may become uncoupled, producing superoxide in lieu of NO. This study was designed to investigate how eNOS-dependent superoxide production contributes to endothelial barrier dysfunction in inflammatory lung injury and its regulation. C57BL/6J mice were challenged with intratracheal LPS. Bronchoalveolar lavage fluid was analyzed for protein accumulation, and lung tissue homogenate was assayed for endothelial NOS content and function. Human lung microvascular endothelial cell (HLMVEC) monolayers were exposed to LPS in vitro, and barrier integrity and superoxide production were measured. Biopterin species were quantified, and coimmunoprecipitation (Co-IP) assays were performed to identify protein interactions with eNOS that putatively drive uncoupling. Mice exposed to LPS demonstrated eNOS-dependent increased alveolar permeability without evidence for altered canonical NO signaling. LPS-induced superoxide production and permeability in HLMVEC were inhibited by the NOS inhibitor nitro-l-arginine methyl ester, eNOS-targeted siRNA, the eNOS cofactor tetrahydrobiopterin, and superoxide dismutase. Co-IP indicated that LPS stimulated the association of eNOS with NADPH oxidase 2 (Nox2), which correlated with augmented eNOS S-glutathionylation both in vitro and in vivo. In vitro, Nox2-specific inhibition prevented LPS-induced eNOS modification and increases in both superoxide production and permeability. These data indicate that eNOS uncoupling contributes to superoxide production and barrier dysfunction in the lung microvasculature after exposure to LPS. Furthermore, the results implicate Nox2-mediated eNOS-S-glutathionylation as a mechanism underlying LPS-induced eNOS uncoupling in the lung microvasculature.

Ascorbate in aqueous humor augments nitric oxide production by macrophages.

Immunosuppressive molecules within the aqueous humor (AqH) are thought to preserve ocular immune privilege by inhibiting proinflammatory NO production by macrophages (MΦs). Consistent with previous observations, we observed that although MΦs stimulated in the presence of AqH expressed NO synthase 2 (NOS2) protein, nitrite concentrations in culture supernatants, an indirect measure of NO production, did not increase. Interestingly, NOS2 enzymatic activity, as measured by the conversion of L-arginine (L-Arg) into L-citrulline, was augmented in lysates of MΦs stimulated in the presence of AqH. These data suggested that intracellular L-Arg may have been limited by AqH. However, we observed increased mRNA expression of the L-Arg transporter, cationic amino acid transporter 2B, and increased L-Arg uptake in MΦs stimulated in the presence of AqH. Arginases were expressed by stimulated Ms, but competition for L-Arg with NOS2 was excluded. Expression of GTP cyclohydrolase, which produces tetrahydrobiopterin (H(4)B), an essential cofactor for NOS2 homodimerization, increased after M stimulation in the presence or absence of AqH and NOS2 homodimers formed. Taken together, these data provided no evidence for inhibited NOS2 enzymatic activity by AqH, suggesting that a factor within AqH may have interfered with the measurement of nitrite. Indeed, we observed that nitrite standards were not measurable in the presence of AqH, and this effect was due to ascorbate in AqH. Controlling for interference by ascorbate revealed that AqH augmented NO production in MΦs via ascorbate, which limited degradation of H(4)B. Therefore, AqH may augment NO production in macrophages by stabilizing H(4)B and increasing intracellular L-Arg.