Sex-specifics of ECT outcome.

OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. METHODS: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). RESULTS: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. CONCLUSION: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex- specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.

Cytotoxicity of root canal irrigating solutions and photodynamic therapy using curcumin photosensitizer.

BACKGROUND: Photodynamic therapy (PDT) has shown satisfactory antibacterial effects. However, little information regarding the cytotoxicity potential of PDT using curcumin as a photosensitizer (PS) on fibroblasts are found. The aim of this in vitro study was to evaluate the cytotoxicity of root canal irrigating solutions and photodynamic therapy with curcumin PS on the L-929 cell line. METHODS: Healthy mouse skin fibroblast cells were distributed into the following 7 experimental groups: G1 - culture medium DMEM (control group); G2 - 0.9% sodium chloride; G3 - 2.5% sodium hypochlorite (NaOCl); G4 - 5% NaOCl; G5 - PDT with curcumin PS at 500 mg/L + blue LED; G6 - PDT with curcumin PS at 750 mg/L + blue LED; and G7 - PDT with curcumin PS at 1000 mg/L + blue LED. All experimental groups which underwent PDT action were submitted to blue LED for 4 min, with a wavelength of 480 nm and energy fluency of 75 J/cm². The cultures were maintained under standard cell culture conditions (37°C, 100% humidity, 5% CO2). Cell viability analysis was performed using the colorimetric method to evaluate the periods of 6, 24, and 48 h. Data were subjected to the Kruskal-Wallis test, followed by the Dunn test to compare groups and Friedman test to compare periods (α = 0.05). RESULTS: When comparing the periods, no significant differences were observed for any of the experimental groups analyzed (p > 0.05), except for the NaOCl2.5 group that exhibited higher cell viability at 6 h compared to the period of 48 h (p = 0.0489). In the comparisons of the experimental groups, there were no statistically significant differences between the control group compared to all disinfection protocols, regardless of the period evaluated (p > 0.05), except for the PDT + C1000 group that showed lower cell viability (P < 0.05). CONCLUSIONS: PDT with curcumin at 1000 mg/L was cytotoxic on L-929 fibroblast cell culture. However, laser-activated curcumin at a concentration of 500 mg/L presented no influence on L-929 fibroblast cell viability in in vitro conditions.

Inflammation induces serine protease inhibitor 3 expression in the rat pineal gland.

In the rat pineal gland, prominent expression of serine protease inhibitor 3 (SPI-3) mRNA is seen after systemic injection of lipopolysaccharide. The up-regulation of SPI-3 mRNA expression is also confirmed by northern blotting. Most SPI-3 mRNA-positive cells simultaneously express synaptophysin, a marker for pinealocytes, but not glial fibrillary acidic protein, a marker for astrocytes. This indicates that SPI-3 mRNA-positive cells are pinealocytes. Almost all SPI-3 mRNA-positive cells also showed translocation of the signal transducers and activators of transcription 3 (STAT3) into nuclei after lipopolysaccharide injection. These data support previous in vitro results that SPI-3 expression is induced in a STAT3-mediated manner. In addition, the expression of ciliary neurotrophic factor receptor (CNTFR) and leukemia inhibitory factor receptor (LIFR) mRNAs, but not of interleukin 6 receptor mRNA, was up-regulated after systemic lipopolysaccharide treatment. Because these receptors are upstream of STAT3, the present results suggest that cytokines such as LIF and/or CNTF induce SPI-3 expression via STAT3 in the pineal gland in response to inflammatory stimulus. We conclude that although the functional consequences of SPI-3 in the pineal gland during systemic inflammation are unknown, SPI-3 may have a crucial role in preventing some degenerative proteolysis induced by inflammatory stimuli.

Scotoma and fixation patterns using scanning laser ophthalmoscope microperimetry in patients with macular dystrophy.

PURPOSE: We used scanning laser ophthalmoscope microperimetry to evaluate the retinal scotoma and the fixation points in the patients with macular dystrophy. METHODS: We studied 10 eyes of five patients with macular dystrophy (three patients with cone dystrophy and two patients with Stargardt disease). The mean patient age was 37 years (range, 13 to 64 years). An estimation of scotoma and fixation points on the retina was performed using scanning laser ophthalmoscope microperimetry. RESULTS: All 10 eyes (100%) had one of two types of dense scotoma: type one was a dense ring scotoma (five eyes, 50%), and type two was a dense central scotoma (five eyes, 50%) that included the center of the fovea. In all eyes with a dense ring scotoma, the fixation points were stable and did not shift. In all eyes with a dense central scotoma, the fixation shifted. The logarithm of minimal angle of resolution of the visual acuity in the eyes with the dense central scotoma was significantly worse than that of eyes with the dense ring scotoma type (P =.005). CONCLUSIONS: Scanning laser ophthalmoscope microperimetry findings demonstrate two types of dense scotoma (dense ring scotoma and dense central scotoma) in the patients with macular dystrophy. The two types of dense scotoma affect the shifting of the fixation points and the stability of fixation and may result in the difference in visual acuity in the patients with macular dystrophy.

Expression of serine protease inhibitor 3 in ocular tissues in endotoxin-induced uveitis in rat.

PURPOSE: To ascribe the serine protease inhibitor 3 (SPI-3) as an ocular acute inflammatory molecule and to clarify its producing cells in an endotoxin-induced uveitis (EIU) model. METHODS: Male Wistar rats were injected with lipopolysaccharide (LPS), and the expression of SPI-3 mRNA in the ocular tissues was examined by in situ hybridization (ISH) and Northern blot analysis. A combination of ISH and immunohistochemistry (IHC) were performed to prove the colocalization of SPI-3 mRNA and either glial fibrillary acidic protein (GFAP) or OX-42. The expression of phosphorylated STAT3 (pSTAT3) was demonstrated by IHC and Western blot after LPS injection. The colocalization of SPI-3 mRNA and pSTAT3 was finally examined by the double labeling of ISH and IHC. RESULTS: After LPS injection, the expression of SPI-3 mRNA in ocular tissues was quickly upregulated and reached a peak between 12 and 24 hours after injection. An intense mRNA signal was observed in epithelial cells of the iris and ciliary body and the innermost retinal layer. In the retina, SPI-3 mRNA was colocalized with GFAP, demonstrating that the cells expressing SPI-3 mRNA were astrocytes. After LPS treatment, SPI-3 mRNA and pSTAT3 were colocalized in retinal astrocytes, and pSTAT3 expression appeared slightly earlier than that of SPI-3 mRNA. CONCLUSIONS: Ocular inflammation induced the transient expression of SPI-3 mRNA in retinal astrocytes and epithelial cells in the iris and ciliary body, particularly during early phase of the inflammation. Simultaneously, the activation of STAT3 (phosphorylation of STAT3) occurred slightly earlier in astrocytes. This supports the previous in vitro results that SPI-3 expression is induced in a STAT3-mediated manner. SPI-3 may have some crucial roles in preventing some degenerative proteolysis, which is induced by inflammatory stimuli.

Inhibitory effect of losartan on laser-induced choroidal neovascularization in rats.

PURPOSE: To investigate the inhibitory effects of losartan, an angiotensin receptor antagonist, on angiogenesis in a rat model of laser-induced choroidal neovascularization. METHODS: Experimental study. Fifteen Brown-Norway male rats received losartan (approximately 5 mg/kg/d) in drinking water, and 15 Brown-Norway male rats received unsupplemented drinking water 1 week before photocoagulation, and it was continued to the end of the study. Two weeks after intense laser photocoagulation, choroidal neovascularization was evaluated by fluorescein angiography and histopathologic evaluation. RESULTS: The incidence of choroidal neovascularization formation was 99.5 +/-.2% (mean +/- standard deviation) in controls and 72.5 +/- 8.8% in losartan-treated rats (P <.01). Quantitative morphometric assessment revealed mean choroidal neovascularization lesion thickness of 54 and 44.8 microm, respectively, in controls and losartan-treated rats (P <.01). CONCLUSION: Losartan seems to inhibit development of laser-induced choroidal neovascularization. Angiotensin receptor antagonists may be useful as prophylaxis against choroidal neovascularization associated with age-related macular degeneration.

Constitutive nitric oxide synthase is associated with retinal vascular permeability in early diabetic rats.

AIMS/HYPOTHESIS: We investigated the association between vascular permeability and constitutive nitric oxide synthase in rats with diabetes for a short duration (2 weeks). METHODS: Retinal vascular permeability was evaluated in rats with diabetes induced by streptozotocin using vitreous fluorophotometry and a small animal adapter. We carried out in situ hybridization and semi-quantitative reverse transcription-polymerase chain reaction to study the expression of endogenous constitutive nitric oxide synthase mRNA in diabetic retinas. We also examined changes in the protein expression of constitutive nitric oxide synthase in diabetic retinas using immunohistochemistry and Western blotting. RESULTS: Retinal vascular permeability was significantly higher in diabetic rats (median, 1.09 arbitrary unit) compared with control rats (median, 0.69 arbitrary unit) (p < 0.05). The expression of both neuronal nitric oxide synthase (NOS) and endothelial nitric oxide synthase mRNA was higher in diabetic retinas than in the retinas of control rats as determined by in situ hybridization and reverse transcription-polymerase chain reaction. Immunohistochemistry and Western blotting also showed that neuronal nitric oxide synthase increased in diabetic retinas. The immunohistochemistry of endothelial nitric oxide synthase indicated that non-vessel tissues increased in diabetic retinas while retinal vessels weakened. Western blotting showed that the amount of endothelial nitric oxide synthase increased. CONCLUSION/INTERPRETATION: These results suggest that increases in both constitutive NOSs (nNOS and eNOS) could be associated with retinal vascular permeability and that NOS is associated with clinical vascular dysfunction in the early stages of diabetes.

Injury-specific expression of activating transcription factor-3 in retinal ganglion cells and its colocalized expression with phosphorylated c-Jun.

PURPOSE: To ascribe activating transcription factor (ATF)-3 as a specifically induced transcription factor after ON injury and to describe its putative role as a modulator of c-Jun transactivation. METHODS: The adult rat optic nerve was crushed intraorbitally, and expression profiles of ATF-3, ATF-2, and phosphorylated c-Jun (p-c-Jun) were examined by immunohistochemistry and ISH. Western blot analysis for ATF-3 and -2 were also performed. Furthermore, colocalized detection of c-Jun mRNA with ATF-2 or -3 was attempted with a combined method of simultaneous immunohistochemistry and in situ hybridization. RESULTS: In response to optic nerve injury, substantial expression of ATF-3 as well as that of p-c-Jun was observed in the retinal ganglion cells, whereas no expression of ATF-3 was seen in other noninjured retinal cells. In contrast, ATF-2 was normally expressed abundantly in both retinal ganglion cells and displaced amacrine cells, but expression dropped in retinal ganglion cells after nerve injury. The expression profiles of ATF-2 and -3 after optic nerve injury were confirmed by Western blot analysis. A higher degree of colocalization was observed for ATF-3 and c-Jun than the modest codetection for ATF-2 and c-Jun. CONCLUSIONS: The transcription factor ATF-3 is specifically induced upon optic nerve injury and colocalizes with p-c-Jun in surviving ganglion cells. These findings suggest that both ATF-3 and c-Jun are crucial to trigger various transcriptional responses and may act synergistically during the survival phase of the optic nerve in the injury model.

Scanning laser ophthalmoscope correlations with biomicroscopic findings and foveal function after macular hole closure.

OBJECTIVE: To investigate the relation between foveal findings and visual function in eyes with a resolved idiopathic macular hole after vitreous surgery. METHODS: We divided 28 eyes with postoperative idiopathic macular hole resolution into 3 groups based on postoperative biomicroscopic foveal findings of complete closure, partial closure, or atrophic closure. To evaluate foveal retinal function, scanning laser ophthalmoscope (SLO) microperimetry was performed preoperatively and 6 months postoperatively. RESULTS: Postoperatively in 18 eyes (64%), the foveal images became normal or almost normal and were classified as having complete closure, 6 eyes (21%) were classified as having partial closure, and 4 eyes (14%) as having atrophic closure. The corresponding visual acuity levels 6 months postoperatively were, respectively, 0.10, 0.35, and 0.64 (P<.01) based on LogMAR analysis. Preoperative SLO microperimetry detected an absolute scotoma at the bottom of all macular holes; postoperatively, the absolute scotoma disappeared in the 18 eyes with complete hole closure, but a relative scotoma was detected in 6 eyes. Of 6 eyes with partial closure, 1 had an absolute scotoma and 5 had a relative scotoma. An absolute scotoma was detected in 4 eyes with atrophic closure. CONCLUSIONS: After macular hole closure, SLO findings correlate both with biomicroscopic findings and foveal function. Better anatomical foveal recovery in eyes after macular hole closure results in better improvement of vision than in eyes in which the foveal anatomical findings are not as good.

Oral fluorescein angiography with the confocal scanning laser ophthalmoscope.

OBJECTIVE: To evaluate the efficacy of oral fluorescein angiography with a confocal scanning laser ophthalmoscope (SLO) system. DESIGN: Comparative case series. PARTICIPANTS: The authors used a confocal SLO (Heidelberg Retina Angiograph [HRA]) to perform oral fluorescein angiography in 47 patients, 13 of whom were without any retinal disease and 34 with a variety of retinal diseases including macular holes and pucker, inflammatory diseases, retinal vascular diseases, and age-related macular degeneration. The images were also compared to images taken with a fundus camera after intravenous fluorescein injections in patients on whom both studies were done. INTERVENTION: Color fundus photographs were taken of each eye (30 degrees fundus camera) before drinking 4 ml of 25% sodium fluorescein mixed with 60 ml of orange juice. After oral fluorescein ingestion, images of each eye were taken with a fundus camera (TriX film) and the HRA (using 512- x 512-pixel resolution). The images were repeated at 0-, 2.5-, 5-, 7.5-, 10-, 12.5-, 15-, 20-, 25-, and 30-minute intervals. Twenty of the 47 patients underwent intravenous fluorescein angiography performed with the fundus camera. MAIN OUTCOME MEASURE: Images were analyzed by a masked reader, and foveal avascular zone visualization, branch retinal vessel identification, and image quality were scored. Statistical analysis was performed with a t test for paired data with a two-tailed test of significance (alpha = 0.05). RESULTS: Foveal avascular zone was 100% as seen in 16 eyes (47%) in the HRA machine versus 1 eye (2%) in the conventional fundus camera (P < 0.0001). The third-order branch retinal vessels were identified in 59% of eyes in the HRA versus 26% in the fundus camera group (P < 0.0001), and the image quality was considered comparable to an intravenous angiogram in 47% with the HRA versus 9% with the conventional fundus camera (P < 0.0001). CONCLUSIONS: Oral fluorescein angiography using the HRA produces sufficiently detailed images to diagnose, treat, and follow many types of retinal pathology.

Diurnal variation of corneal autofluorescence in normal and diabetic eyes.

PURPOSE: To examine the diurnal variations in corneal autofluorescence in normal and diabetic patients. METHODS: We measured corneal autofluorescence using a fluorophotometer fitted with an anterior segment adapter. Corneal autofluorescence was measured 10 times at 3 min intervals to evaluate the reproducibility of this instrument in 4 eyes of 4 normal subjects. The diurnal variation in corneal autofluorescence was determined by measuring the fluctuations in 10 eyes in 10 normal subjects and one unoperated eye each of 10 patients with proliferative diabetic retinopathy (PDR). We performed five consecutive measurements at 1000, 1130, 1400, 1630 and 1900 hours. The mean value of five measurements, the variation range and the coefficient of variation were analysed. RESULTS: The mean coefficient of variation in the measurement using this instrument was 8.6 +/- 1.0%. In the patients with PDR, the mean corneal autofluorescence value was significantly higher (p < 0.001), the variation range was significantly wider (p < 0.001) and the coefficient of variation was significantly greater (p < 0.01) than in the normal subjects. CONCLUSIONS: The results of this study suggest that corneal autofluorescence changes over the course of a day in patients with diabetes. This may be caused by the breakdown of the blood-aqueous barrier that we reported previously.