Therapeutic Effect of Curcumin, a Plant Polyphenol Extracted From Curcuma longae, in Fibroblasts From Patients With Graves' Orbitopathy.

Purpose: We examined the therapeutic effect of nontoxic concentrations of curcumin, a plant polyphenol extracted from Curcuma longae, in primary cultures of orbital fibroblasts from Graves' orbitopathy (GO). Methods: The effect of curcumin on interleukin (IL)-1ß induced-proinflammatory cytokine production was determined using quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis. Adipogenic differentiation was identified using Oil-Red O staining, and levels of peroxisome proliferator activator γ (PPARγ) and CCAAT-enhancer-binding proteins (C/EBP) α/ß were determined by Western blot analyses. Antioxidant activity was measured using an oxidant-sensitive fluorescent probe to detect intracellular reactive oxygen species (ROS) generated in response to hydrogen peroxide (H2O2) and cigarette smoke extract (CSE). Results: Treatment with curcumin resulted in a dose- and time-dependent decrease in IL-1ß-induced synthesis of inflammatory cytokines, including IL-6, IL-8, MCP-1, and ICAM-1 at both mRNA and protein levels. Decrease in lipid droplets and expression of PPARγ and c/EBPα/ß were noted in fibroblasts treated with curcumin during adipose differentiation. CSE- or H2O2-induced ROS synthesis was significantly lower in curcumin-treated fibroblasts in comparison with the control. Curcumin significantly suppressed IL-1ß-induced phosphorylated extracellular signal-regulated kinase, Akt, c-Jun NH(2)-terminal kinase, and nuclear factor κ-light-chain-enhancer of activated B cells, p65 proteins and stimulated ß-catenin translocation into nucleus during adipogenesis. Conclusions: Curcumin inhibits proinflammatory cytokine production, ROS synthesis, and adipogenesis in orbital fibroblasts of GO patients in vitro possibly related to multiple proinflammatory signaling molecules and ß-catenin pathway. The results of the study support potential use of the curcumin in the treatment of GO.

Association of Corticosteroid Use With Incidence of Central Serous Chorioretinopathy in South Korea.

Importance: Information on the incidence of central serous chorioretinopathy (CSC) in individuals who receive corticosteroids is scarce but clinically important because these agents are useful and widely used. Objective: To estimate the annual and 5-year incidence of CSC in South Korea in the overall population and in those who have used corticosteroid medications. Design, Setting, and Participants: A cohort study of a population-based random sample included East Asian adults for whom records are held in the Korean National Health Insurance Service database for calendar years 2011 through 2015. The data analysis was performed from July 1, 2017 to January 5, 2018. Exposures: Any type of corticosteroid use from 2002 through 2015. Main Outcomes and Measures: Incidence of CSC. Results: The data set contained data from 868 939 adults (4 117 768 person-years). From 2011 through 2015, 1423 individuals (among whom the mean [SD] age was 46.8 [16.4] years and 1091 [76.7%] were male) with newly diagnosed CSC were identified. From 2002 to 2015, 783 099 individuals in the data set (90.1%) had ever used corticosteroids. The incidence of CSC per 10 000 person-years was 3.5 (5.4 in men; 1.6 in women) among the total population, 2.5 (3.0 in men; 1.2 in women) in those who had never used corticosteroids, and 3.6 (5.7 in men; 1.6 in women) among those who had ever used corticosteroids. The risk of CSCR with individuals who had ever used corticosteroids was estimated as an adjusted hazard ratio of 1.81 (95% CI, 1.47-2.23) compared with those who have never used these drugs. Current or recent corticosteroid use showed a positive association with the incidence of CSC (depending on duration of use, adjusted hazard ratio ranged from 1.54 to 2.15). Corticosteroid use in 2006 through 2009 was associated with an increased incidence of CSC after 2011 (adjusted hazard ratio 1.57 [95% CI, 1.13-2.18]). Conclusions and Relevance: In 2002 through 2015, 90.1% of adults in Korea received corticosteroids at least once. Although there was a clear difference in relative risk, this data analysis could not replicate the more than 30-fold increase in the risk ratio of CSC that has been reported previously. The incidence of CSC in the most vulnerable group, middle-aged men, was estimated to be approximately 1 case per 1000 corticosteroid users in the year following medication use. The overall incidence among those who had ever used corticosteroids and those who had never used these drugs was 2.5 and 3.6 per 10 000 person-years, respectively. This study provides additional evidence to support the potential role of corticosteroids in CSC.

Left ventricular diastolic function is closely associated with mechanical function of the left atrium in patients with paroxysmal atrial fibrillation.

BACKGROUND: Left ventricular (LV) diastolic dysfunction may be a mechanism of left atrial (LA) electroanatomical remodeling in atrial fibrillation (AF). We evaluated the association between LV diastolic function and LA mechanical function in non-valvular paroxysmal AF (PAF). METHODS AND RESULTS: In 286 patients with PAF (males 73%, 57 ± 11 years), LA size, indexed LA volume, LV diastolic function, and LA appendage flow velocity (LAA-FV) in sinus rhythm were measured using transthoracic echocardiography, transesophageal echocardiography and cardiac computed tomography. The LA voltage map was obtained using NavX contact mapping. Patients with impaired LA mechanical function (LAA-FV <58 cm/s, n=142) showed a higher E/Em ratio (10.3 vs. 9.2, P=0.034) and lower Em velocity (6.8 vs. 7.7 cm/s, P=0.004) than those with preserved function (LAA-FV ≥ 58 cm/s, n=144). The patient population displayed weak correlations of E/Em with LAA-FV (r=-0.19, P=0.003) and LA voltage (r=-0.23, P=0.004), but more significant association of E/Em and LAA-FV (r=-0.39, P<0.001) for age ≥ 55 years and LA diameter ≥ 40 mm. E/Em was an independent predictor of LAA mechanical function (ß=-0.20, P=0.013) even after age, sex, LA size and comorbidities were controlled for. CONCLUSIONS: In patients with non-valvular PAF, LA mechanical function is closely related to the degree of LA remodeling and LV diastolic function. Impaired LV diastolic function significantly contributes to LA electoanatomical remodeling in older patients with a larger LA.

Significant reduction of atrial defibrillation threshold and inducibility by catheter ablation of atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) has antiarrhythmic effects by multiple mechanisms. We hypothesized that RFCA curtails atrial defibrillation threshold (A-DFT) and postablation induction pacing cycle length (iPCL), making critical mass reduction one potential mechanism by which antiarrhythmic effect is achieved. METHODS: We included 289 patients with AF (male 77.9%, 55.7 ± 10.8 years old; 197 paroxysmal AF: 92 persistent AF) who underwent RFCA. A-DFT (serial internal cardioversion 2, 3, 5, 7, and 10 J) and iPCL (serial 10 mA 10-second atrial pacing with pacing cycle length 250, 200, 190, 180, 170, 160, and 150 ms) were evaluated before and after RFCA. RESULTS: (1) RFCA of AF reduced the A-DFT from 6.7 ± 3.7 J to 3.0 ± 3.0 J (P < 0.001). (2) AF ablation reduced AF inducibility from 95.4% before the procedure to 56.3% after the procedure (P < 0.001), and the iPCL from 194.8 ± 32.6 to 160.9 ± 26.2 ms (P < 0.001). (3) In patients who underwent a greater number of ablation lines, the post-RFCA A-DFT (P < 0.001) was lower, and %ΔA-DFT (P = 0.003) and proportion of atrial tachycardia (P = 0.022) were higher than those with a lower number of ablation lines. CONCLUSION: AF ablation significantly reduced A-DFT, AF inducibility, and iPCL, and the degree of their reduction was related to the number of ablation lines. (PACE 2012;35:1428-1435).