BACKGROUND AND OBJECTIVES: Metabolic syndrome (MetS) increases the risk of heart failure (HF). The purpose of this study was to identify the prevalence of MetS in patients with HF and determine the syndrome's association with HF in clinical and laboratory parameters. SUBJECTS AND METHODS: A total of 3200 HF patients (67.6+/-14.5 years) enrolled in a nationwide prospective Korea HF Registry between Jan. 2005 and Oct. 2009. Patients were divided into two groups according to the presence or absence of MetS at admission: group I (presence, n=1141) and group II (absence, n=2059). RESULTS: The prevalence of MetS was 35.7% across all subjects and was higher in females (56.0%). The levels of white blood cells, platelets, creatinine, glucose, and cholesterol were significantly higher in group I than in group II. Left ventricular dimension and volume was smaller and ejection fraction was higher in group I than in group II. An ischemic cause of HF was more frequent in group I. The rates of valvular and idiopathic cause were lower in group I than in group II. The rate of mortality was lower in group I than in group II (4.9% vs. 8.3%, p<0.001). CONCLUSION: Despite the increased cardiovascular risks in MetS, MetS was found to be associated with decreased mortality in HF.
Blood Platelets ; Cholesterol ; Creatinine ; Female ; Glucose ; Heart ; Heart Failure ; Humans ; Korea ; Leukocytes ; Prevalence ; Prospective Studies

BACKGROUND AND OBJECTIVES: Acute heart failure (AHF) is associated with a poor prognosis and it requires repeated hospitalizations. However, there are few studies on the characteristics, treatment and prognostic factors of AHF. The aims of this study were to describe the clinical characteristics, management and outcomes of the patients hospitalized for AHF in Korea. SUBJECTS AND METHODS: We analyzed the clinical data of 3,200 hospitalization episodes that were recorded between June 2004 and April 2009 from the Korean Heart Failure (KorHF) Registry database. The mean age was 67.6+/-14.3 years and 50% of the patients were female. RESULTS: Twenty-nine point six percent (29.6%) of the patients had a history of previous HF and 52.3% of the patients had ischemic heart disease. Left ventricular ejection fraction (LVEF) was reported for 89% of the patients. The mean LVEF was 38.5+/-15.7% and 26.1% of the patients had preserved systolic function (LVEF > or =50%), which was more prevalent in the females (34.0% vs. 18.4%, respectively, p<0.001). At discharge, 58.6% of the patients received beta-blockers (BB), 53.7% received either angiotensin converting enzyme-inhibitors or angiotensin receptor blockers (ACEi/ARB), and 58.4% received both BB and ACEi/ARB. The 1-, 2-, 3- and 4-year mortality rates were 15%, 21%, 26% and 30%, respectively. Multivariate analysis revealed that advanced age {hazard ratio: 1.023 (95% confidence interval: 1.004-1.042); p=0.020}, a previous history of heart failure {1.735 (1.150-2.618); p=0.009}, anemia {1.973 (1.271-3.063); p=0.002}, hyponatremia {1.861 (1.184-2.926); p=0.007}, a high level of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) {3.152 (1.450-6.849); p=0.004} and the use of BB at discharge {0.599 (0.360-0.997); p=0.490} were significantly associated with total death. CONCLUSION: We present here the characteristics and prognosis of an unselected population of AHF patients in Korea. The long-term mortality rate was comparable to that reported in other countries. The independent clinical risk factors included age, a previous history of heart failure, anemia, hyponatremia, a high NT-proBNP level and taking BB at discharge.
Anemia ; Angiotensin Receptor Antagonists ; Angiotensins ; Female ; Heart ; Heart Failure ; Hospitalization ; Humans ; Hyponatremia ; Korea ; Multivariate Analysis ; Myocardial Ischemia ; Natriuretic Peptide, Brain ; Peptide Fragments ; Prognosis ; Registries ; Risk Factors ; Stroke Volume

In light of the anti-inflammatory properties of histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), we examined a new HDAC inhibitor KBH-A42 for its anti-inflammatory activities. KBH-A42 showed noteworthy anti-inflammatory properties in vitro via suppression of the production of TNF-alpha, a proinflammatory cytokine, and nitric oxide (NO), a proinflammatory effector molecule, in LPS-stimulated RAW264.7 cells and peritoneal macrophages. It also inhibited TNF-alpha production in vivo as demonstrated in a LPS-induced mouse endotoxemia model. The levels of TNF-alpha, IL-1beta, IL-6 and iNOS mRNAs determined by RT-PCR propose that the inhibition of these pro-inflammatory mediators by KBH-A42 resulted from inhibiting expression of these genes. However, the EMSA study to see the effect of KBH-A42 on the binding of NF-kappaB, a transcription factor, to a specific DNA sequence showed that the binding of NF-kappaB to DNA was not changed regardless of increasing the concentration of KBH-A42 in the presence and absence of LPS stimulation. Interestingly, DNA binding of another transcription factor AP-1 dose-dependently increased by KBH-A42. KBH-A42 differentially regulated the phosphorylation of MAP kinases. While the phosphprylation of ERK1/2 and SAPK/JNK was not affected by KBH-A42, the phosphorylation of p38 decreased by KBH-A42. These results showed that KBH-A42 inhibits production of proinflammatory cytokines in macrophages by decreasing their mRNA levels, and p38 kinase is involved in the KBH-A42-mediated inhibition.
Animals ; Blotting, Western ; Cell Line ; Cell Survival/drug effects ; Cytokines/blood/genetics/*metabolism ; Electrophoretic Mobility Shift Assay ; Endotoxemia/blood/metabolism/pathology ; Enzyme Inhibitors/chemistry/*pharmacology ; Histone Deacetylases/*antagonists & inhibitors ; Hydroxamic Acids/chemistry/*pharmacology ; Interleukin-1beta/genetics/metabolism ; Interleukin-6/genetics/metabolism ; Macrophages/cytology/*drug effects/metabolism ; Mice ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Molecular Structure ; NF-kappa B/metabolism ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type II/genetics/metabolism ; Phosphorylation/drug effects ; Piperidones/chemistry/*pharmacology ; Protein Binding/drug effects ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factor AP-1/metabolism ; Tumor Necrosis Factor-alpha/blood/genetics/metabolism

This study was designed to identify and characterize Na+ -activated K+ current (I(K(Na))) in guinea pig gastric myocytes under whole-cell patch clamp. After whole-cell configuration was established under 110 mM intracellular Na+ concentration ([Na+]i) at holding potential of -60 mV, a large inward current was produced by external 60 mM K+([K+] degree). This inward current was not affected by removal of external Ca2+. K+ channel blockers had little effects on the current (p>0.05). Only TEA (5 mM) inhibited steady-state current to 68+/-2.7% of the control (p<0.05). In the presence of K+ channel blocker cocktail (mixture of Ba2+, glibenclamide, 4-AP, apamin, quinidine and TEA), a large inward current was activated. However, the amplitude of the steadystate current produced under [K+]degree (140 mM) was significantly smaller when Na+ in pipette solution was replaced with K+ - and Li+ in the presence of K+ channel blocker cocktail than under 110 mM [Na+]i. In the presence of K+ channel blocker cocktail under low Cl- pipette solution, this current was still activated and seemed K+ -selective, since reversal potentials (E(rev)) of various concentrations of [K+]degree-induced current in current/voltage (I/V) relationship were nearly identical to expected values. R-56865 (10-20 microgram), a blocker of IK(Na), completely and reversibly inhibited this current. The characteristics of the current coincide with those of IK(Na) of other cells. Our results indicate the presence of IK(Na) in guinea pig gastric myocytes.
Tetraethylammonium Compounds/pharmacology ; Stomach/*physiology ; Sodium/metabolism/*pharmacology ; Potassium Channels/*physiology ; Potassium Channel Blockers/pharmacology ; Myocytes, Smooth Muscle/*physiology ; Membrane Potentials ; Male ; Guinea Pigs ; Female ; Chlorides/pharmacology ; Calcium/metabolism ; Animals

BACKGROUND AND OBJECTIVES: Aortic stiffness is believed to be an important risk factor of coronary artery atherosclerosis (CAA), as it directly affects coronary perfusion. The following aspects of the invasively measured aortic pulse wave velocity (PWV) were assessed in relation to CAA: The effect of cardiovascular risk factors on PWV, the effect of PWV on the severity of CAA and on the development of the restenosis after drug-eluting stent (DES) implantation. SUBJECTS AND METHODS: 371 subjects who had undergone coronary angiography were enrolled, with all undergoing an invasive aortic PWV measurement also. 112 patients, who had undergone a DES implantation, were prospectively investigated for the effect of PWV in relation to the subsequent risk of major adverse cardiac events (MACE). RESULTS: Among the conventional cardiovascular risk factors, an age >60 (10.79+/-4.92 vs. 8.35+/-4.02, p=0.0006), diabetes (10.97+/-4.66 vs. 9.26+/-4.70 m/sec, p=0.0118) and dyslipidemia (10.38+/-4.97 vs. 9.47+/-4.55m/sec, p=0.0421) were significantly associated with an increased PWV, but sex, smoking and hypertension were not associated with an increased PWV. The PWV was shown to be significantly associated with the severity of CAD. The odds ratio (OR) of 1m/sec increment in the PWV for an increased vessel score was 1.08 (95% confidence interval (CI): 1.03-1.13, p=0.0017). There were no differences in the incidence of MACE and the changes in the angiographic parameters between the high (>10 m/sec) and low PWV groups. CONCLUSION: The invasively measured aortic PWV was affected by age (>60), diabetes and dyslipidemia, and also showed a strong association with the severity of CAD. The aortic PWV was not a significant risk factor for restenosis following a DES implantation.
Atherosclerosis ; Coronary Angiography ; Coronary Artery Disease* ; Coronary Restenosis ; Coronary Vessels* ; Drug-Eluting Stents ; Dyslipidemias ; Humans ; Hypertension ; Incidence ; Odds Ratio ; Perfusion ; Prospective Studies ; Pulse Wave Analysis ; Risk Factors ; Smoke ; Smoking ; Vascular Stiffness*

By using differential display, we identified one of the genes encoding the multi-subunit complex protein V-ATPase, c subunit gene (ATP6L), and showed alterations of the gene expression by oxidative stresses. Expression of the ATP6L gene in Neuro-2A cells was increased by the treatment with H2O2 and incubation in hypoxic chamber, implying that the expression of the ATP6L gene is regulated by oxidative stresses. To examine mechanisms involved in the regulation of the gene expression by oxidative stresses, the transcriptional activity of the rat ATP6L promoter was studied. Transcription initiation site was determined by primer extension analysis and DNA sequencing, and promoter of the rat ATP6L and its deletion clones were constructed in reporter assay vector. Significant changes of the promoter activities in Neuro-2A cells were observed in two regions within the proximal 1 kbp promoter, and one containing a suppressor was in -195 to -220, which contains GC box that is activated by binding of Sp1 protein. The suppression of promoter activity was lost in mutants of the GC box. We confirmed by electrophoretic mobility shift and supershift assays that Sp1 protein specifically binds to the GC box. The promoter activity was not changed by the H2O2 treatment and incubation in hypoxic chamber, however, H2O2 increased the stability of ATP6L mRNA. These data suggest that the expression of the ATP6L gene by oxidative stresses is regulated at posttranscriptional level, whereas the GC box is important in basal activities of the promoter.
Animals ; Clone Cells ; Gene Expression* ; Hydrogen Peroxide ; Oxidative Stress* ; Rats ; RNA, Messenger ; Sequence Analysis, DNA ; Transcription Initiation Site ; Vacuolar Proton-Translocating ATPases*

To study the direct effect of somatostatin (SS) on calcium channel current (IBa) in guinea-pig gastric myocytes, IBa was recorded by using whole-cell patch clamp technique in single smooth muscle cells. Nicardipine (1microM), a L-type Ca2+ channel blocker, inhibited IBa by 98+/-1.9% (n=5), however IBa was decreased in a reversible manner by application of SS. The peak IBa at 0 mV were decreased to 95+/-1.1, 92+/-1.9, 82+/-4.0, 66+/-5.8, 10+/-2.9% at 10-10, 10-9, 10-8, 10-7, 10-5 M of SS, respectively (n=3~6; mean+/-SEM). The steady-state activation and inactivation curves of IBa as a function of membrane potentials were well fitted by a Boltzmann equation. Voltage of half-activation (V0.5) was -12+/-0.5 mV in control and -11+/-1.9 mV in SS treated groups (respectively, n=5). The same values of half-inactivation were -35+/-1.4 mV and -35+/-1.9 mV (respectively, n=5). There was no significant difference in activation and inactivation kinetics of IBa by SS. Inhibitory effect of SS on IBa was significantly reduced by either dialysis of intracellular solution with GDPbetaS, a non-hydrolysable G protein inhibitor, or pretreatment with pertussis toxin (PTX). SS also decreased contraction of guinea-pig gastric antral smooth muscle. In conclusion, SS decreases voltage-dependent L-type calcium channel current (VDCCL) via PTX- sensitive signaling pathways in guinea-pig antral circular myocytes.
Calcium Channels ; Calcium Channels, L-Type* ; Dialysis ; GTP-Binding Proteins ; Kinetics ; Membrane Potentials ; Muscle Cells* ; Muscle, Smooth ; Myocytes, Smooth Muscle ; Nicardipine ; Pertussis Toxin ; Somatostatin*

BACKGROUND AND OBJECTIVES: Cellular cardiomyoplasty (CCM) is considered to be a novel therapeutic approach for post-myocardial infarction (MI) heart failure. In this study, the functional effects of cultured mesenchymal stem cells (MSCs) transplantation and the associated histopathologic changes were evaluated in a rat model of MI. MATERIALS AND METHODS: Rats were subjected to 5 hours of coronary ligation followed by reperfusion, and 10 days after MI, animals were randomized into either the MSCs transplantation (MI-MSC, n=8) group or the control (n=8) group. Allogeneic MSCs (3x10(6) cells) or media were epicardially injected into the center and the border area of the infarct scar. RESULTS: Four weeks after the MSCs transplantation, the echocardiogram showed preserved anterior regional wall motion and increases in fractional shortening in the MI-MSC heart relative to the control heart. Left ventricular (LV) end diastolic pressure was smaller in the MI-MSC than in the control group. Implanted MSCs formed islands of cell clusters on the border of the infarct scar, and the cells were positively immunostained by sarcomeric alpha-actinin and cardiac troponin T. In addition, the number of microvessels on the border area of the infarct scar was greater in the MI-MSC than in the control group. CONCLUSION: Allogeneic MSCs transplanted into the MI scar formed clusters of cell grafts on the border of the infarct, expressed cardiac muscle proteins, increased microvessel formation, and improved regional and global LV function. Our data indicate that CCM using MSCs may have a significant role in the treatment of post-MI heart failure.
Actinin ; Animals ; Blood Pressure ; Bone Marrow* ; Cardiomyoplasty* ; Cicatrix ; Heart Failure* ; Heart* ; Infarction ; Islands ; Ligation ; Mesenchymal Stromal Cells* ; Microvessels ; Models, Animal ; Myocardial Infarction* ; Myocardium ; Rats ; Reperfusion ; Stem Cells ; Transplantation ; Transplants ; Troponin T

PURPOSE: Wilms tumor is the most common malignant renal tumor in children. We investigated the epidemiology, clinical features and treatment outcome of the children with Wilms tumor in Korea during the recent 10 years. METHODS: Two hundred forty six patients were enrolled between January 1991 and December 2000 from 26 major hospitals in Korea. The data regarding the clinical features including sex, age, pathologic type, prognostic factor and treatment outcome of patients were analyzed retrospectively by review of patient's medical records. Kaplan-Meier survival curves were constructed, The differences between groups were analyzed by log-rank test. RESULTS: There were 130 males and 116 females. The incidence between the age of 1~4 years was the highest with 66.2%. The annual incidence rate per 1, 000, 000 population varied from 1.9 to 2.1. The 10 years overall survival rate according to sex, clinical stage, pathologic type and relapse were as follows: 88.6% in male, 90.9% in female, 100% in stage I, 94.7% in stage II, 92.1% in stage III, 63.4% in stage IV, 85.7% in stage V, 95.3% in favorable histology, 64.1% in unfavorable histology, 94.8% in non-relapse, and 40.9% in relapse. The relapse rate was 12%. The 10 years overall survival rate of 246 patients were 89.1%. CONCLUSION: Our results could provide the most recent and important clinical information on Wilms tumor of children in Korea.
Child ; Epidemiology* ; Female ; Humans ; Incidence ; Kaplan-Meier Estimate ; Korea* ; Male ; Medical Records ; Recurrence ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Wilms Tumor*

BACKGROUND AND OBJECTIVES: An intracoronary brachytherapy is the only approved treatment for in-stent restenosis. However, a considerable rate of restenosis occurs after a brachytherapy. Up to now, there was no long term outcome for repeated brachytherapy for these lesions. SUBJECTS AND METHODS: Eleven patients were admitted due to angina, with significant ischemic evidence in the stress test after the intracoronary brachytherapy. These patients were re-treated with a beta-emitting 188 rhenium-DTPA (diethylene triamine penta-acetic acid) filled balloon catheter system, using an identical method and radiation dose (17.6 Gy) to the initial radiation treatment. The long term angiographic and clinical outcomes of repeated brachytherapy in these patients were evaluated. RESULTS: The angiographic and clinical data of ten patients were evaluated, as 1 was lost. The follow-up period was 37.4+/-16.2 months (range, 8 to 53 months). There was no angiographic restenosis or target lesion revascularization (TLR) during the short term follow-up period (mean 6 months). but 2 restenosis (25%) occurred in the 2 year follow-up period and one other was added during the long term clinical follow-up period. All these restenosis lesions needed revascularization. These three TLRs occurred at 15, 24 and 43 months after the repeated brachytherapy. There was no death or nonfatal MI. No vascular perforation, aneurysm or late thrombosis was observed. CONCLUSION: A repeated brachytherapy for the treatment of a failed intracoronary brachytherapy lesion is safe and acceptably effective during the long term follow-up period. This modality might be considered as a therapeutic option for failed intracoronary brachytherapy lesions.
Aneurysm ; Brachytherapy* ; Catheters ; Coronary Disease ; Exercise Test ; Follow-Up Studies ; Humans ; Thrombosis