Betulinic acid (BA), a natural pentacyclic triterpene found in many medicinal plants is known to have various biological activity including tumor suppression and anti-inflammatory effects. In this study, the cell-death induction effect of BA was investigated in BV-2 microglia cells. BA was cytotoxic to BV-2 cells with IC50 of approximately 2.0 μM. Treatment of BA resulted in a dose-dependent chromosomal DNA degradation, suggesting that these cells underwent apoptosis. Flow cytometric analysis further confirmed that BA-treated BV-2 cells showed hypodiploid DNA content. BA treatment triggered apoptosis by decreasing Bcl-2 levels, activation of capase-3 protease and cleavage of PARP. In addition, BA treatment induced the accumulation of p62 and the increase in conversion of LC3-I to LC3-II, which are important autophagic flux monitoring markers. The increase in LC3-II indicates that BA treatment induced autophagosome formation, however, accumulation of p62 represents that the downstream autophagy pathway is blocked. It is demonstrated that BA induced cell death of BV-2 cells by inducing apoptosis and inhibiting autophagic flux. These data may provide important new information towards understanding the mechanisms by which BA induce cell death in microglia BV-2 cells.
Apoptosis* ; Autophagy ; Cell Death* ; DNA ; Inhibitory Concentration 50 ; Microglia* ; Plants, Medicinal

Background: Previous studies on the epidemiology and complications of congenital adrenal hyperplasia (CAH) were conducted in Western countries and in children/adolescents. We aimed to explore the epidemiology of CAH, as well as the risk of comorbidities and mortality, in a Korean nationwide case-control study. Methods: CAH patients (n=2,840) were included between 2002 and 2017 from the National Health Insurance Service database and the Rare Intractable Disease program. CAH patients were compared, at a 1:10 ratio, with age-, sex-, and index year-matched controls (n=28,400). Results: The point prevalence of CAH patients in Korea was 1 in 18,745 persons in 2017. The annual incidence rate declined between 2003 and 2017 from 3.25 to 0.41 per 100,000 persons. CAH patients were at elevated risk for cardiovascular disease (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.4 to 1.9), stroke (OR, 1.7; 95% CI, 1.3 to 2.0), diabetes mellitus (OR, 2.8; 95% CI, 2.6 to 3.1), dyslipidemia (OR, 2.4; 95% CI, 2.2 to 2.6), and psychiatric disorders (OR, 1.5; 95% CI, 1.3 to 1.6). Fracture risk increased in CAH patients aged over 40 years (OR, 1.4; 95% CI, 1.1 to 1.7). CAH patients were at higher risk of mortality than controls (hazard ratio, 1.6; 95% CI, 1.3 to 2.0). Conclusion Our nationwide study showed a recent decline in the incidence of CAH and an elevated risk for cardiovascular, metabolic, skeletal, and psychiatric disorders in CAH patients. Lifelong management for comorbidity risk is a crucial component of treating CAH patients.

BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors originating from chromaffin cells. PPGLs are associated with a high mortality rate and several complications. To date, no epidemiological studies have been conducted on PPGLs in Asia. This study aimed to investigate the epidemiology and prognosis of PPGLs in Korea using nationwide data. METHODS: Using the National Health Insurance Service Database, subjects with a principal diagnosis of PPGLs on two or more occasions between 2003 and 2014 who satisfied the operational definition of PPGLs were included. Incidence, prevalence, complications, metastasis, and mortality were investigated. RESULTS: In total, 1048 subjects with a mean age of 47.6±16.1 years were included. There was no sex preponderance. The overall prevalence of PPGLs was 2.13 per 100,000 persons, and the overall age-standardized incidence rate was 0.18 per 100,000 person-years. Malignant PPGLs accounted for 17.7% (185 of 1,048) of cases, and 94 subjects exhibited metastasis at the time of diagnosis. Among initially non-metastatic PPGLs, 9.5% (nine of 954) eventually metastasized after a mean duration of 78.1±41.4 months. The 5-year survival rates for non-metastatic and metastatic PPGLs at diagnosis were 97% and 84%, respectively. Multivariable Cox regression models adjusted for covariates showed that metastatic PPGLs were associated with a 2.40-fold higher risk of mortality than non-metastatic PPGLs (95% confidence interval, 1.38 to 4.17; P=0.002). CONCLUSION PPGLs are rare in Korea, and the prognosis of these endocrine tumors varies depending on whether they are benign or malignant. This epidemiological study paves the way for further research on PPGLs.

BACKGROUND: Intracranial cerebral atherosclerosis (ICAS) is an important cause of stroke, but it is not well-known whether and how much it contributes to the long-term prognosis of stroke patients. The purpose of this study was to elucidate the impact of ICAS on the long-term mortality of patients with acute ischemic stroke. METHODS: From November 1998 to December 2002, a consecutive series of 1306 patients who were hospitalized due to acute ischemic stroke were listed in the stroke registry. Among them, 946 patients who underwent brain MRI and MRA were selected and their vital status was identified by the National Death certificates. RESULTS: Among 946 subjects, 624 (65.9%) had ICAS, while 106 (11.2%) had extracranial carotid atherosclerosis (ECAS). During a period of 59 months (27+/-16 months), 220 patients died. The 30-day, 1-year, 2-year, 3-year, and 4-year mortalities were 2.8%, 14.5%, 22.9%, 27.8% and 35.1% for those with ICAS (N=624); whereas 2.2%, 7.7%, 13.2%, 15.4% and 19.2% for those without ICAS (N=322) (p=0.0001 on log rank test). Crude hazard ratio (HR) of ICAS was 1.9 (95% confidence interval, 1.39 to 2.62), but adjusted HR of ICAS was 1.16 (0.82 to 1.62). The number of intracranial arteries with atherosclerosis and the existence of symptomatic ICAS were also considered. Both of them were significant predictors of the long-term mortality in crude analyses, but lost their significance after adjustments. CONCLUSIONS: This study failed to prove the independent contribution of ICAS to the mortality of patients with acute ischemic stroke.
Arteries ; Atherosclerosis ; Brain ; Carotid Artery Diseases ; Death Certificates ; Humans ; Intracranial Arteriosclerosis* ; Magnetic Resonance Imaging ; Mortality* ; Prognosis ; Stroke*

BACKGROUND AND PURPOSE: Health-related quality of life (HRQoL) is a multidimensional concept that signifies a subjective evaluation of perceived health; hence, it has gained wide acceptance in geriatrics. However, its application has not been tested in patients with post-stroke cognitive impairment with no dementia (PSCIND). We investigated whether PSCIND interferes with HRQoL measured by EQ-5D, compared the findings to those of healthy people with normal cognition, and evaluated the influence of each cognitive domain on this score. METHODS: In total, 1,528 subjects were identified who had undergone neuropsychological assessment using the 60-min protocol of the Korean version of Vascular Cognitive Impairment Harmonization Standards, EQ-5D, and magnetic resonance imaging at the stroke prevention clinic. Fifty PSCIND patients were matched to 50 post-stroke dementia (PSD) patients and 50 normal age- (+/-3 years) and sex-matched controls. The effects of PSCIND, PSD, and control groups upon the EQ-5Dindex score were tested by generalized estimating equation modeling. RESULTS: Estimated means+/-standard errors of EQ-5Dindex scores were as follows: 0.94+/-0.06 (control group), 0.86+/-0.08 (PSCIND group), and 0.61+/-0.32 (PSD group); and the difference among the three groups was statistically significant (P<0.0001). Pairwise comparisons showed that EQ-5Dindex scores in the PSCIND group differed from those in the PSD and control groups (both P<0.01). No cognitive domain was specifically associated with EQ-5Dindex scores after adjusting for functional status. CONCLUSIONS: This study shows that PSCIND may interfere with the quality of life in stroke victims.
Cognition ; Dementia ; Geriatrics ; Humans ; Magnetic Resonance Imaging ; Quality of Life ; Stroke

BACKGROUND: This study examined the prevalence of the major risk factors of ischemic stroke in a Korean population. METHODS: Two investigators conducted an independent literature search of previously published reports on the prevalence of hypertension, diabetes, hypercholesterolemia, smoking, atrial fibrillation, obesity, ischemic heart disease, and history of stroke in Koreans. A study was considered eligible for inclusion if it was a population-based cross-sectional survey published between January 1996 and June 2007. RESULTS: The inclusion criteria were satisfied by 14 publications on hypertension, 7 on diabetes, 4 on hypercholesterolemia, 3 on smoking, 3 on obesity, 2 on atrial fibrillation, 3 on ischemic heart disease, and 3 on stroke. The prevalence of risk factors varied between studies, but it increased with age in most studies. Applying the estimates to the projected population in 2030 revealed a large increase in the prevalence of risk factors. CONCLUSIONS: Considering the rapid increase in the elderly population, in which major risk factors for ischemic stroke are prevalent, there is an urgent need to develop strategies for preventing this condition among Koreans.
Aged ; Atrial Fibrillation ; Cross-Sectional Studies ; Humans ; Hypercholesterolemia ; Hypertension ; Myocardial Ischemia ; Obesity ; Prevalence ; Research Personnel ; Risk Factors ; Smoke ; Smoking ; Stroke

BACKGROUND: Thrombolysis becomes an emerging therapeutic option for acute ischemic stroke. However, few reports exist on its use in the very elderly. We investigated whether there is a difference in the effectiveness and safety of intravenous (IV) and/or intra-arterial (IA) thrombolysis between patients aged > or =80 years and those aged <80 years. METHODS: A consecutive series of patients hospitalized within 12 hours from stroke onset were selected. We evaluated the effectiveness of thrombolysis with modified Rankin scale (mRS) at 3 months, and the safety with symptomatic hemorrhagic transformation (sHT). The odds ratio (OR) of thrombolysis on the favorable mRS (0-2) was calculated using multivariable logistic regression analysis with adjustments for potential confounders. Whether the effectiveness of thrombolysis is age-dependent or not was analyzed by introducing an interaction term (thrombolysisxage group) into multivariable models. RESULTS: Among 219 patients > or =80 years, 21% of patients received IV or IA or combined thrombolysis while 23% of 980 patients <80 years received thrombolysis (P=0.51). With respect to the favorable mRS, the adjusted ORs of thrombolysis were 1.70 (95% confidence interval, 1.08-2.68) in all subjects, 1.61 (0.58-4.49) in those > or =80 years, and 1.71 (1.05-2.78) in those <80 years. There was no significant interaction between age group and thrombolysis (P=0.91). With respect to sHT, the adjusted OR was 4.72 (1.94-11.45) in all subjects with no significant interaction (P=0.86). CONCLUSION: This study suggests that thrombolysis may be equally safe and effective in stroke patients aged > or =80 years versus <80 years.
Aged ; Electrolytes ; Humans ; Logistic Models ; Odds Ratio ; Stroke ; Treatment Outcome

Background: and Purpose Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke. Methods: This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from baseline at 90 days. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events. Results: Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The baseline LDL-C level was 130.2±34.7 mg/dL in the ROS10/EZT10 group and 131.0±33.9 mg/dL in the ROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1.944 [1.352–2.795]; P= 0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 groups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group and 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups. Conclusion Moderate-intensity rosuvastatin plus ezetimibe was superior to high-intensity rosuvastatin alone for intensive LDL-C reduction in patients with recent ischemic stroke. With the combination therapy, more than 70% of patients achieved LDL-C reduction ≥50% and 80% had an LDL-C <70 mg/dL at 90 days.

The gradual loss of telomeric DNA can contribute to replicative senescence and thus, having longer telomeric DNA is generally considered to provide a longer lifespan. Maintenance and stabilization of telomeric DNA is assisted by binding of multiple DNA-binding proteins, including those involved in double strand break (DSB) repair. We reasoned that declining DSB repair capacity and increased telomere shortening in aged individuals may be associated with decreased expression of DSB repair proteins capable of telomere binding. Our data presented here show that among the DSB repair proteins tested, only the expression of Ku70 and Mre11 showed statistically significant age-dependent changes in human lymphocytes. Furthermore, we found that expressions of Ku70 and Mre11 are statistically correlated, which indicate that the function of Ku70 and Mre11 may be related. All the other DSB repair proteins tested, Sir2, TRF1 and Ku80, did not show any significant differences upon aging. In line with these data, people who live in the regional community (longevity group), which was found to have statistically longer average life span than the rest area, shows higher level of Ku70 expression than those living in the neighboring control community. Taken together, our data show, for the first time, that Ku70 and Mre11 may represent new biomarkers for aging and further suggest that maintenance of higher expression of Ku70 and Mre11 may be responsible for keeping longer life span observed in the longevity group.
Telomere/genetics ; Middle Aged ; Longevity ; Humans ; DNA-Binding Proteins/*metabolism ; DNA Repair/*genetics ; DNA/genetics ; Cell Aging/*physiology ; CD4-Positive T-Lymphocytes/metabolism ; Antigens, Nuclear/*metabolism ; Aging/*physiology ; Aged, 80 and over ; Aged ; Adult

There are many studies on the prevalence, clinical characteristics, and economic burden of diabetes across the past four decades in Korea. Nonetheless, there is a dearth of nationwide study regarding diabetes encompassing all age group. Eight years ago, the Committee on the Epidemiology of Diabetes Mellitus of Korean Diabetes Association collaborated with Health Insurance Review & Assessment Service to evaluate the status of diabetes care and characteristics in diabetic patients in Korea. In 2007, the collaborative task force team published a comprehensive survey titled "Diabetes in Korea 2007." In this review, we reappraise the diabetic epidemics from the joint report and suggest further studies that are needed to be investigated in the future.
Advisory Committees ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Humans ; Insurance, Health ; Joints ; Korea ; Prevalence