[show abstract][hide abstract] ABSTRACT: Kahweol, a coffee-specific diterpene, found in the beans of Coffea arabica, has potent anti-carcinogenic, anti-tumor, and anti-inflammatory properties. TRAIL is a potential anti-cancer compound that induces apoptosis in a wide variety of cancer cells, but not in most normal human cell types. In the present study, we show that kahweol sensitizes human renal cancer cells, but not normal human mesangial cells, to TRAIL-mediated apoptosis. Moreover, treatment with a combination of kahweol and TRAIL induces significant apoptosis in various cancer cell types, thus presenting an attractive novel strategy for cancer treatment. Our experiments show that treatment with a combination of kahweol and TRAIL-induced apoptosis, and stimulated of DEVDase activity, DNA fragmentation, and cleavage of PARP, which was prevented by pretreatment with z-VAD, indicative of cell death via a caspase-dependent pathway. Kahweol-induced down-regulation of Bcl-2 and ectopic expression of Bcl-2 led to attenuation of kahweol plus TRAIL-mediated apoptosis, indicative of Bcl-2 involvement in the apoptotic process. In addition, the c-FLIP and caspase signal pathways seem to play a crucial role in apoptosis triggered by the combination of kahweol and TRAIL in Caki cells. Our results collectively demonstrate that down-regulation of Bcl-2 and c-FLIP contributes to the sensitizing effect of kahweol on TRAIL-mediated apoptosis in cancer cells.
[show abstract][hide abstract] ABSTRACT: This multicenter, open-labeled, randomized trial was performed to compare the effects of rosuvastatin 10 mg and atorvastatin 10 mg on lipid and glycemic control in Korean patients with nondiabetic metabolic syndrome.
In total, 351 patients who met the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria for metabolic syndrome with low-density lipoprotein cholesterol (LDL-C) levels > or = 130 mg/dL were randomized to receive either rosuvastatin 10 mg (n = 173) or atorvastatin 10 mg (n = 178) for over 6 weeks.
After 6 weeks of treatment, greater reductions in total cholesterol (- 35.94 +/- 11.38 vs. - 30.07 +/- 10.46%, p < 0.001), LDL-C (48.04 +/- 14.45 vs. 39.52 +/- 14.42%, p < 0.001), non-high-density lipoprotein cholesterol (- 42.93 +/- 13.15 vs. - 35.52 +/- 11.76%, p < 0.001), and apolipoprotein-B (- 38.7 +/- 18.85 vs. - 32.57 +/- 17.56%, p = 0.002) levels were observed in the rosuvastatin group as compared to the atorvastatin group. Overall, the percentage of patients attaining the NCEP ATP III goal was higher with rosuvastatin as compared to atorvastatin (87.64 vs. 69.88%, p < 0.001). Changes in glucose and insulin levels, and homeostasis model assessment of insulin resistance index were not significantly different between the two groups. The safety and tolerability of the two agents were similar.
Rosuvastatin 10 mg was more effective than atorvastatin 10 mg in achieving NCEP ATP III LDL-C goals in patients with nondiabetic metabolic syndrome, especially in those with lower NCEP ATP III target level goals.
The Korean Journal of Internal Medicine 03/2010; 25(1):27-35.
[show abstract][hide abstract] ABSTRACT: Although uric acid (UA) level has been associated with an increased risk of cardiovascular events, it is unclear whether UA can provide greater prognostic information than N-terminal pro B-type natriuretic peptide (NT-proBNP) in advanced heart failure with nonischemic dilated cardiomyopathy (DCM). UA and NT-proBNP values were obtained from a total of 122 DCM patients. Development of clinical events during follow-up was defined as the composite of cardiac death and readmission for heart failure. During follow-up, there were 18 cardiac events. UA and NT-proBNP values were significantly higher in patients with events. The receiver operating characteristics curve showed the area under the curve for UA was greater than that for NT-proBNP. On multivariate analysis, UA remained the only independent predictor of prognosis. UA concentrations > or =8.7 mg/dL rather than NT-proBNP > or =3800 pg/mL were associated with significantly decreased event-free survival. The authors' findings demonstrated that UA value could be an informative predictor in nonischemic DCM.
[show abstract][hide abstract] ABSTRACT: Late-acquired incomplete stent apposition (ISA) is frequently observed after drug-eluting stent (DES) implantation. Most incidences of late-acquired ISA induced by positive vascular remodeling were of the focal type and occurred in a single vessel. We present an unusual case of a 45-year-old male subject diagnosed with late-acquired ISA that occurred in multiple vessels.
[show abstract][hide abstract] ABSTRACT: A scheme for designing a hierarchical fuzzy classification system with a different number of fuzzy partitions based on statistical characteristics of the data is proposed. To minimize the number of misclassified patterns in intermediate layers, a method of fuzzy partitioning from the defuzzified outputs of previous layers is also presented. The effectiveness of the proposed scheme is demonstrated by comparing the results from five datasets in the UCI Machine Learning Repository.
IEICE Transactions on Information and Systems 01/2010; 93-D:2319-2323. · 0.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent intravascular ultrasound (IVUS) studies of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) have demonstrated a significant reduction in neointimal hyperplasia (NIH) based on simple coronary lesions. In this study, we evaluated the efficacy of SES and PES using IVUS in complex coronary lesions.
Eighty-seven patients in whom 95 drug-eluting stents (66 SES and 29 PES) were implanted in complex coronary lesions were enrolled in this study. Case selection was based on the availability of IVUS and quantitative coronary angiographic (QCA) examinations at the index procedure and at follow-up. The neointimal volume index (volume/length: NIVI) and percent neointimal volume (% NIV) were calculated. The longitudinal length of stented segments without IVUS-detectable NIH was also evaluated.
The baseline patient demographics were similar between the SES and PES groups. At follow-up, no significant differences were observed in the vessel, plaque, or stent volume indices between the two groups. However, the NIVI and % NIV were significantly lower in the SES group (p<0.01). The longitudinal length of stented segments without IVUS-detectable NIH was significantly higher in the SES group (p<0.01). The net gain was significantly larger in the SES group (2.3+/-0.7 vs. 2.0x0.6 mm, p=0.025), while the rate of major adverse cardiac events was similar between the two groups.
Although SES showed significantly greater suppression of NIH at follow-up, both stents were highly effective at inhibiting NIH in complex coronary lesions.
The Korean Journal of Internal Medicine 12/2009; 24(4):323-9.
[show abstract][hide abstract] ABSTRACT: Coronary angiography (CAG) is an invasive diagnostic procedure, which could lead to procedure related complications. One of the well known post-procedural complications is cerebral embolic infarction with or without symptoms. Silent embolic cerebral infarction (SECI) has clinical significance because it can progress to a decline in cognitive function and increase the risk of dementia in the long term. The aim of this study was to detect the incidence and predictors of SECI after diagnostic CAG using diffusion-weighted magnetic resonance imaging (DW-MRI).
A total of 197 patients with coronary artery disease who underwent DW-MRI for evaluation of intracranial vasculopathy before coronary artery bypass graft surgery were retrospectively enrolled in the present study. DW-MRI was performed within 48 h after diagnostic CAG. SECI was diagnosed as presence of focal bright high signal intensity in DW-MRI. Patients were divided into groups according to presence/absence of SECI (+ SECI vs. - SECI, respectively). The clinical and angiographic characteristics were analyzed and independent predictors were evaluated.
Of the 197 patients, SECI occurred in 20 patients (10.2%) after diagnostic CAG. Age, female gender, frequency of underlying atrial fibrillation, extent of coronary disease, and fluoroscopic time during diagnostic CAG were not different between the + SECI and - SECI groups. Left ventricular ejection fraction was significantly lower in the + SECI group than in the - SECI group (45.9 ± 8.5% vs. 51.4 ± 13.1%, p=0.014) and performance rate of internal mammary artery (IMA) angiography was significantly higher in the + SECI group compared with the - SECI group (85% vs. 37.2%, p<0.001). By multivariate analysis, performing IMA angiography was the only predictor of SECI (OR=14.642; 95% CI=3.201 to 66.980, p=0.001).
The incidence of SECI after diagnostic CAG was not infrequent. Diagnostic CAG with IMA angiography may increase the risk of SECI.
International journal of cardiology 11/2009; 148(2):179-82. · 7.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Angiotensin II is a major effector molecule in the development of cardiovascular disease. In vascular smooth muscle cells (VSMCs), angiotensin II promotes cellular proliferation and extracellular matrix accumulation through the upregulation of plasminogen activator inhibitor-1 (PAI-1) expression. Previously, we demonstrated that small heterodimer partner (SHP) represses PAI-1 expression in the liver through the inhibition of TGF-β signaling pathways. Here, we investigated whether SHP inhibited angiotensin II-stimulated PAI-1 expression in VSMCs. Adenovirus-mediated overexpression of SHP (Ad-SHP) in VSMCs inhibited angiotensin II- and TGF-β-stimulated PAI-1 expression. Ad-SHP also inhibited angiotensin II-, TGF-β- and Smad3-stimulated PAI-1 promoter activity, and angiotensin II-stimulated AP-1 activity. The level of PAI-1 expression was significantly higher in VSMCs of SHP-/- mice than wild type mice. Moreover, loss of SHP increased PAI-1 mRNA expression after angiotensin II treatment. These results suggest that SHP inhibits PAI-1 expression in VSMCs through the suppression of TGF-β/Smad3 and AP-1 activity. Thus, agents that target the induction of SHP expression in VSMCs might help prevent the development and progression of atherosclerosis.
Experimental and Molecular Medicine 11/2009; · 2.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although previously reported studies on coronary calcification mainly focused on its presence or absence in discrete focal target lesions, calcified coronary lesions (CCL) angiographically present as diffuse long lesions in some patients. The aim of our study was to evaluate the long-term efficacy of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) on long CCL.
A total of 122 patients with 134 lesions (77 patients with 88 lesions for SES and 45 patients with 46 lesions for PES) were enrolled from 3 centers. Long CCL was defined visually as a culprit lesion with type B or C that was mainly due to coronary calcification with > 20 mm in total length by coronary angiography. Clinical follow-up was performed at 1 year and angiographic follow-up at 6 to 9 months after procedure. Major adverse coronary events (MACE) were defined as all-cause death, myocardial infarction (MI), and repeat target-lesion revascularization (TLR).
There were no statistically significant differences in baseline, procedural, or angiographic characteristics and in 1-year rates of all-cause death, MI, and TLR between the 2 groups (all P = NS [not significant]). Likewise, the cumulative incidence of MACE at 1 year was similar between the 2 groups (7.8% of patients in the SES group vs 4.4% of patients in the PES group, respectively, P = NS). In patients who underwent follow-up angiography, the angiographic binary restenosis rate was 6.2% in the SES group vs 12.1% in the PES group, respectively (P = NS).
In patients with long CCL, both SES and PES were comparably effective in either angiographic or clinical long-term outcomes.
[show abstract][hide abstract] ABSTRACT: The data of long-term outcomes of sirolimus-eluting stent (SES) according to lesion location of unprotected left main coronary artery (LMCA) is scarce.
The purpose of this study was to evaluate the long-term outcomes after implantation of the SES in LMCA.
A total of 84 patients (51 males) who had undergone SES implantation for the treatment of native LMCA stenosis were enrolled. The patients were divided into 2 groups based on angiographic lesion location: those with significant stenosis in the ostium and/or body (group 1; n = 39) and those involving bifurcation (group 2; n = 45).
All of the group 1 patients were treated with simple lesion coverage while different stenting techniques were used in group 2 (cross-over: 44.8%, T: 6.7%, kissing: 37.8%, and crush techniques: 11.1%). The 8-month quantitative angiographic findings and in-hospital and 2 year rates of major adverse cardiac events (MACE) were compared between the 2 groups. Although angiographic success and in-hospital MACE rates were similar in both groups with 1 cardiac death due to acute stent thrombosis in group 2, at 2-year follow-up, the MACE rate was significantly higher in group 2 than in group 1 at 2 years (22.2% vs 2.6%, respectively, P = 0.008). Coronary angiography revealed a significantly higher binary restenosis rate in group 2 compared with group 1 (20% vs 0%, respectively, P = 0.003).
Interventional treatment using SES in left main lesions showed favorable short-term and long-term outcomes in selected patients with lesion location being an important determinant of clinical and angiographic outcomes.
[show abstract][hide abstract] ABSTRACT: Patients with heart failure with a preserved ejection fraction (HFPEF) have high N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) level and a high ratio of early transmitral inflow to diastolic velocity of the mitral annulus (E/E') derived from tissue Doppler imaging (TDI). Because left atrial volume indexed to body surface area (LAVI) is believed to reflect chronic diastolic dysfunction, we assessed the ability of LAVI and E/E' ratio to predict NT-pro-BNP level in patients with HFPEF.
One hundred forty-eight patients with HFPEF (ejection fraction >or= 50%, NT-pro-BNP >or= 100 pg/ml) underwent conventional echocardiography including LAVI and E/E' ratio, which were compared with NT-pro-BNP level.
In the overall patient population, modest correlations were found between NT-pro-BNP level and peak systolic TDI (S') (P = 0.009), LAVI (P = 0.009), and E/E' ratio (P = 0.017). However, in patients with E/E' ratio >or=13, LAVI was the most important predictor of NT-pro-BNP level (P < 0.001), whereas in those with E/E' ratio <13 it was S' (P < 0.001) in multivariate analysis.
In patients with HFPEF evidenced by high NT-pro-BNP level, LAVI correlates with NT-pro-BNP level in the setting of elevated E/E' ratio. However, in the setting of low E/E' ratio, LAVI does not seem to be associated with NT-pro-BNP level.
[show abstract][hide abstract] ABSTRACT: The ratio of peak early diastolic mitral inflow to annular velocity (E/E') and left atrial size could provide prognosis on congestive heart failure (CHF). N-terminal Pro B-type natriuretic peptide (NT-ProBNP) has also been useful for predicting adverse cardiac events. However, it is not clear how these parameters compare with conventional risk factors. Thus, we investigated whether E/E', left atrial dimension index (LADI) and NT-ProBNP would predict adverse events and add incremental value to conventional risk factors, even in non-ischemic advanced dilated cardiomyopathy (DCM).
Both NT-ProBNP and echocardiography were evaluated in 105 patients. The cardiac events were defined as the composite of cardiac death and re-admission for CHF. At follow up, cardiac events occurred in 24 patients who had high NT-ProBNP and showed higher LADI and E/E'. In multivariate analysis, both NT-ProBNP and LADI, but not E/E', remained as independent predictors; patients with both increased LADI and NT-ProBNP had a 27-fold higher risk of cardiac events than those without any risk factors (p = 0.003). Moreover, LADI and NT-ProBNP showed a better incremental prognostic value over conventional risk factors (global chi-square increase from 7 to 17 to 49, p = 0.003, p < 0.001, respectively).
Both NT-ProBNP and LADI might have the most predictable power, particularly in non-ischemic advanced DCM.
[show abstract][hide abstract] ABSTRACT: Hypertension is an important contributor to different left ventricular (LV) geometric patterns with resultant myocardial dysfunction. Strain rate image (SRI) has been suggested as a useful tool for the evaluation of myocardial function. The aim of this study was to assess whether SRI correlates with LV geometric patterns in hypertensive subjects. Fifty-one hypertensive subjects and 21 healthy controls were enrolled and examined with conventional echocardiography including LV mass index (LVMI). Moreover, tissue Doppler imaging (TDI) and strain or SRI were obtained in all subjects. The hypertensives were subanalyzed according to geometric patterns. The hypertensive subjects were more likely to have enlarged left atrial dimensions, prolonged decelerating time and isovolumic relaxation time, and showed a lower TDI of early diastolic mitral annulus and SRI of early diastolic component (SR-e). Among hypertensive subjects, there was a significant trend toward a lower value of SR-e in those with hypertrophy and SR-e was the lowest in the concentric hypertrophy than other geometric patterns. In addition, SR-e was associated most strongly with LVMI of LV other than echoparameters. The hypertrophic hypertensive subjects showed altered systolic and/or diastolic function. Moreover, SR-e appeared to be correlated most with geometric patterns according to LVMI.
Heart and Vessels 07/2008; 23(4):271-8. · 2.13 Impact Factor