Comparison of intravitreal bevacizumab alone or combined with triamcinolone versus triamcinolone in diabetic macular edema: a randomized clinical trial.

PURPOSE: To compare the effect of an intravitreal injection of bevacizumab alone (IVB) or combined with triamcinolone (IVB/IVT) versus triamcinolone (IVT) in patients with diabetic macular edema (DME). METHODS: In this randomized three-arm clinical trial, eligible eyes were assigned randomly to one of the three study arms: the IVB group, 2 injections of 1.25 mg of bevacizumab with 6-week intervals; the IVB/IVT group, 1.25 mg of IVB with 2 mg of IVT, and the IVT group, 2 mg of IVT. The clinical course of best-corrected visual acuity and central macular thickness by optical coherence tomography was monitored for up to 12 months after the initial injection. RESULTS: One hundred eleven eyes of 105 patients with DME completed 12 months of follow-up. The IVB/IVT group and the IVT group showed better visual acuity and reduced central macular thickness at 6 weeks and 3 months, compared with the IVB group (p = 0.041, p = 0.02 at 6 weeks; p = 0.045, p = 0.043 at 3 months, respectively). However, no significant difference in visual acuity and central macular thickness was observed between the three groups at 12 months (p = 0.088, p = 0.132, respectively). The frequency of retreatment was lower in the IVB/IVT and IVT groups during the 12-month period (p < 0.001). No significant differences in visual acuity or central macular thickness were observed between the IVB/IVT and IVT groups during the follow-up. CONCLUSION: IVB/IVT and IVT showed more pronounced effects during the earlier postinjection period. However, levels of visual acuity or central macular thickness at 12 months were comparable in the three study groups. No beneficial effect of the combination injection was observed.

Synthesis of aurones and their inhibitory effects on nitric oxide and PGE2 productions in LPS-induced RAW 264.7 cells.

Sulfuretin is one of major constituents of Rhus verniciflua that exerts anti-inflammatory activities. Some of aurones were synthesized as sulfuretin derivatives and evaluated for their abilities to inhibit NO and PGE(2) production in LPS-induced RAW 264.7 cells in order to reveal the relationship. Of the aurones synthesized in the present study, 2h and 2i, which possess C-6 hydroxyl group in A-ring and methoxy substituents in B-ring, more potently inhibited NO and PGE(2) production and were less cytotoxic than sulfuretin.

Concentration of cytokines in the aqueous humor of patients with central serous chorioretinopathy.

PURPOSE: To evaluate the levels of aqueous humor cytokines in the eyes of patients with central serous chorioretinopathy (CSC) before an intravitreal injection of bevacizumab. METHODS: In a prospective interventional trial, 20 eyes of 20 patients with symptomatic CSC of at least 3 months duration and 20 eyes of 20 patients with cataract as control were included. Eyes with CSC received a single intravitreal injection of bevacizumab (1.25 mg/0.05 mL). Aqueous humor samples were collected from patients and controls. Multiplex bead assays were used for measurement of cytokines, including vascular endothelial growth factor and platelet-derived growth factor. RESULTS: Similar vascular endothelial growth factor levels and significantly decreased platelet-derived growth factor levels were measured in the aqueous humor of eyes from patients with CSC compared with controls (P = 0.172 and P = 0.004, respectively). There was a significant inverse correlation between the vascular endothelial growth factor and platelet-derived growth factor in patients (r = -0.555; P = 0.026). Interleukin 6, interleukin 8, and monocyte chemoattractant protein-1 were detectable, but not significantly different between the patients and controls. CONCLUSION: The results of the current study suggest that platelet-derived growth factor contributes to the pathogenesis of CSC; however, the roles of vascular endothelial growth factor in CSC are unclear and warrant further investigation.

Stenotrophomonas daejeonensis sp. nov., isolated from sewage.

A Gram-stain-negative, motile, aerobic bacterial strain, designated MJ03(T), was isolated from sewage and was characterized taxonomically by using a polyphasic approach. Comparative 16S rRNA gene sequence analysis showed that strain MJ03(T) belongs to the family Xanthomonadaceae, class Gammaproteobacteria, and was related most closely to Stenotrophomonas acidaminiphila AMX 19(T) (97.9  % sequence similarity), Stenotrophomonas humi R-32729(T) (97.1  %), Stenotrophomonas nitritireducens L2(T) (96.9  %), Stenotrophomonas maltophila ATCC 13637(T) (96.8  %) and Stenotrophomonas terrae R-32768(T) (96.7  %). The G+C content of the genomic DNA of strain MJ03(T) was 64.7 mol%. The detection of a quinone system with ubiquinone Q-8 as the predominant component and a fatty acid profile with iso-C15:0, iso-C11:0, iso-C14:0, iso-C17:1ω9c, iso-C11:0 3-OH and iso-C13:0 3-OH as major components supported the affiliation of strain MJ03(T) to the genus Stenotrophomonas. However, levels of DNA-DNA relatedness between strain MJ03(T) and the type strains of five closely related species of the genus Stenotrophomonas ranged from 11 to 34  %, showing clearly that the isolate represents a novel genospecies. Strain MJ03(T) could be differentiated clearly from its phylogenetic neighbours on the basis of several phenotypic, genotypic and chemotaxonomic features. Therefore, strain MJ03(T) is considered to represent a novel species of the genus Stenotrophomonas, for which the name Stenotrophomonas daejeonensis sp. nov. is proposed. The type strain is MJ03(T) (=KCTC 22451(T) =JCM 16244(T)).

Aqueous humor and plasma levels of vascular endothelial growth factor and interleukin-8 in patients with central serous chorioretinopathy.

PURPOSE: The purpose of this study was to determine aqueous vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) levels in patients with central serous chori-oretinopathy (CSC) before a single intravitreal bevacizumab injection. METHODS: Twelve eyes with symptomatic CSC were included. Samples from patients with cataracts served as controls. The levels of VEGF and IL-8 concentrations were measured in aqueous humor and plasma by multiplex bead assays. RESULTS: All patients with CSC showed an improvement in visual acuity and resolved neurosensory detachment after intravitreal bevacizumab injection. The aqueous humor levels of VEGF and IL-8 were not significantly increased in patients with CSC compared with the healthy control group (18.2 ± 24.8 vs. 35.3 ± 28.5 pg/mL, P > 0.05; 2.3 ± 0.4 vs. 2.8 ± 0.3 pg/mL, P > 0.05, respectively). The plasma levels of VEGF and IL-8 in patients with CSC were not different from those in the healthy control group. CONCLUSION: Vascular endothelial growth factor and IL-8 were not increased in the aqueous humor and plasma of patients with CSC. The effect of intravitreal bevacizumab injection as a treatment for CSC must be fully understood, and the true effect of anti-VEGF treatment in patients with CSC remains to be elucidated.

The effect of intravitreal bevacizumab in patients with acute central serous chorioretinopathy.

PURPOSE: To evaluate the effect of intravitreal bevacizumab injection (IVBI) in acute central serous chorioretinopathy (CSC) patients. METHODS: Patients with acute CSC received IVBI (1.25 mg/0.05 mL) or observation by randomization. Twelve eyes in each group completed 6 months of regular follow-up and were ultimately included in this study. Each patient was assessed using best corrected visual acuity measurements, fluorescein angiography, and optical coherence tomography at baseline and had regular follow-ups after treatment. RESULTS: All patients showed improvements in visual acuity and fluorescein angiographic leakage and had resolution of their neurosensory detachment following treatment. There were no significant differences in visual acuity, central retinal thickness, or remission duration between the IVBI group and the control group at baseline or after treatment (p>0.05). CONCLUSIONS: Intravitreal bevacizumab showed no positive effect in acute CSC patients compared to the observation group, and there were no adverse effects of treatment. Further investigation will be helpful to understand this therapy in patients with CSC.

Sulfuretin isolated from heartwood of Rhus verniciflua inhibits LPS-induced inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokines expression via the down-regulation of NF-kappaB in RAW 264.7 murine macrophage cells.

It has been reported that Rhusverniciflua exhibits anti-inflammatory, anti-oxidant and anti-cancer activities. However, little is known about biological activity of sulfuretin, a flavonoid isolated from R.verniciflua. In the present study, we investigated the anti-inflammatory effect and the underlying molecular mechanisms of sulfuretin in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Sulfuretin dose-dependently reduced the productions of nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) induced by LPS. Consistent with these findings, sulfuretin significantly suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-alpha, and IL-1 beta. In addition, sulfuretin attenuated LPS-induced DNA binding and the transcriptional activities of nuclear factor-kappa B (NF-kappaB), which was accompanied by a parallel reduction of degradation and phosphorylation of inhibitory kappa B-alpha (I kappaB-alpha) and consequently by decreased nuclear translocation of p65 subunit of NF-kappaB. Furthermore, pretreatment with sulfuretin significantly inhibited the LPS-stimulated activation of I kappaB kinase beta (IKK beta). Taken together, these results suggest that the anti-inflammatory effect of sulfuretin in LPS-treated RAW 264.7 macrophages is associated with the suppression of NF-kappaB transcriptional activity via the inhibitory regulation of IKKbeta phosphorylation.