BACKGROUND AND OBJECTIVES: When monotherapy is inadequate for blood pressure control, the next step is either to continue monotherapy in increased doses or to add another antihypertensive agent. However, direct comparison of double-dose monotherapy versus combination therapy has rarely been done. The objective of this study is to compare 10 mg of amlodipine with an amlodipine/valsartan 5/160 mg combination in patients whose blood pressure control is inadequate with amlodipine 5 mg. SUBJECTS AND METHODS: This study was conducted as a multicenter, open-label, randomized controlled trial. Men and women aged 20-80 who were diagnosed as having hypertension, who had been on amlodipine 5 mg monotherapy for at least 4 weeks, and whose daytime mean systolic blood pressure (SBP) ≥135 mmHg or diastolic blood pressure (DBP) ≥85 mmHg on 24-hour ambulatory blood pressure monitoring (ABPM) were randomized to amlodipine (A) 10 mg or amlodipine/valsartan (AV) 5/160 mg group. Follow-up 24-hour ABPM was done at 8 weeks after randomization. RESULTS: Baseline clinical characteristics did not differ between the 2 groups. Ambulatory blood pressure reduction was significantly greater in the AV group compared with the A group (daytime mean SBP change: -14±11 vs. -9±9 mmHg, p<0.001, 24-hour mean SBP change: -13±10 vs. -8±8 mmHg, p<0.0001). Drug-related adverse events also did not differ significantly (A:AV, 6.5 vs. 4.5%, p=0.56). CONCLUSION: Amlodipine/valsartan 5/160 mg combination was more efficacious than amlodipine 10 mg in hypertensive patients in whom monotherapy of amlodipine 5 mg had failed.
Amlodipine* ; Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Female ; Follow-Up Studies ; Humans ; Hypertension ; Male ; Random Allocation

PURPOSE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) and promotes degradation of the LDLR. Inhibition of PCSK9 either by reducing its expression or by blocking its activity results in the upregulation of the LDLR and subsequently lowers the plasma concentration of LDL-cholesterol. As a modality to inhibit PCSK9 action, we searched the chemical library for small molecules that block the binding of PCSK9 to the LDLR. MATERIALS AND METHODS: We selected 100 chemicals that bind to PCSK9 where the EGF-AB fragment of the LDLR binds via in silico screening of the ChemBridge chemical library, using the computational GOLD algorithm analysis. Effects of chemicals were evaluated using the PCSK9-LDLR binding assay, immunoblot analysis, and the LDL-cholesterol uptake assay in vitro, as well as the fast performance liquid chromatography assay for plasma lipoproteins in vivo. RESULTS: A set of chemicals were found that decreased the binding of PCSK9 to the EGF-AB fragment of the LDLR in a dose-dependent manner. They also increased the amount of the LDLR significantly and subsequently increased the uptake of fluorescence-labeled LDL in HepG2 cells. Additionally, one particular molecule lowered the plasma concentration of total cholesterol and LDL-cholesterol significantly in wild-type mice, while such an effect was not observed in Pcsk9 knockout mice. CONCLUSION: Our findings strongly suggest that in silico screening of small molecules that inhibit the protein-protein interaction between PCSK9 and the LDLR is a potential modality for developing hypercholesterolemia therapeutics.
Animals ; Cholesterol/*blood ; Cholesterol, LDL/blood ; Hep G2 Cells ; Humans ; Mice ; Mice, Knockout ; Proprotein Convertases/*metabolism ; Receptors, LDL/*metabolism ; Serine Endopeptidases/*metabolism ; *Small Molecule Libraries

PURPOSE: The oil spill from the Heibei Spirit in December 2007 contaminated the Yellow Coast of South Korea. We evaluated the respiratory effects of that spill on children who lived along the Yellow Coast. METHODS: Of 662 children living in the area exposed to the oil spill, 436 (65.9%) were enrolled as subjects. All subjects completed a modified International Study of Asthma and Allergies in Childhood questionnaire. A health examination, including a skin prick test, pulmonary function test, and methacholine bronchial provocation test (MBPT), was administered. The children were assigned to two groups: those who lived close to the oil spill area and those who lived far from the oil spill area. RESULTS: The children who lived close to the oil spill area showed a significantly lower forced expiratory volume in one second (FEV1), an increased prevalence of 'asthma ever' (based on a questionnaire), and 'airway hyperresponsiveness' (based on the MBPT) than those who lived far from the oil spill area (FEV1; P=0.011, prevalence of 'asthma ever' based on a questionnaire; P=0.005, prevalence of 'airway hyperresponsiveness' based on the MBPT; P=0.001). The onset of wheezing after the oil spill was significantly higher in children who lived close to the oil spill area than in those who lived far from the oil spill area among the 'wheeze ever' group (P=0.002). In a multiple logistic regression analysis, male sex, family history of asthma, and residence near the oil spill area were significant risk factors for asthma (sex [male/female]: odds ratio [OR], 2.54; 95% confidence interval [CI], 1.31-4.91; family history of asthma [No/Yes]: OR, 3.77; 95% CI, 1.83-7.75; exposure group [low/high]; OR, 2.43; 95% CI, 1.27-4.65). CONCLUSIONS: This study suggests that exposure to an oil spill is a risk factor for asthma in children.
Asthma ; Bronchial Provocation Tests ; Child ; Forced Expiratory Volume ; Humans ; Hypersensitivity ; Industrial Oils ; Korea ; Logistic Models ; Male ; Methacholine Chloride ; Odds Ratio ; Petroleum Pollution ; Prevalence ; Republic of Korea ; Respiratory Function Tests ; Respiratory Sounds ; Risk Factors ; Skin ; Surveys and Questionnaires

PURPOSE: The oil spill from the Heibei Spirit in December 2007 contaminated the Yellow Coast of South Korea. We evaluated the respiratory effects of that spill on children who lived along the Yellow Coast. METHODS: Of 662 children living in the area exposed to the oil spill, 436 (65.9%) were enrolled as subjects. All subjects completed a modified International Study of Asthma and Allergies in Childhood questionnaire. A health examination, including a skin prick test, pulmonary function test, and methacholine bronchial provocation test (MBPT), was administered. The children were assigned to two groups: those who lived close to the oil spill area and those who lived far from the oil spill area. RESULTS: The children who lived close to the oil spill area showed a significantly lower forced expiratory volume in one second (FEV1), an increased prevalence of 'asthma ever' (based on a questionnaire), and 'airway hyperresponsiveness' (based on the MBPT) than those who lived far from the oil spill area (FEV1; P=0.011, prevalence of 'asthma ever' based on a questionnaire; P=0.005, prevalence of 'airway hyperresponsiveness' based on the MBPT; P=0.001). The onset of wheezing after the oil spill was significantly higher in children who lived close to the oil spill area than in those who lived far from the oil spill area among the 'wheeze ever' group (P=0.002). In a multiple logistic regression analysis, male sex, family history of asthma, and residence near the oil spill area were significant risk factors for asthma (sex [male/female]: odds ratio [OR], 2.54; 95% confidence interval [CI], 1.31-4.91; family history of asthma [No/Yes]: OR, 3.77; 95% CI, 1.83-7.75; exposure group [low/high]; OR, 2.43; 95% CI, 1.27-4.65). CONCLUSIONS: This study suggests that exposure to an oil spill is a risk factor for asthma in children.
Asthma ; Bronchial Provocation Tests ; Child ; Forced Expiratory Volume ; Humans ; Hypersensitivity ; Industrial Oils ; Korea ; Logistic Models ; Male ; Methacholine Chloride ; Odds Ratio ; Petroleum Pollution ; Prevalence ; Republic of Korea ; Respiratory Function Tests ; Respiratory Sounds ; Risk Factors ; Skin ; Surveys and Questionnaires

A 42-year-old man was involved in a motor vehicle collision. Imaging studies revealed the presence of a post-traumatic aortic pseudo-aneurysm (about 34x26 cm) arising from the descending thoracic aorta at the level of the left subclavian artery (LSA), prone to rupture. Thoracic endovascular aneurysm repair (TEVAR) was the only feasible option due to his poor overall medical status. In this case, LSA needed to be covered in order to extend the proximal landing zone. Eventually, modified TEVAR was successfully performed by means of the chimney technique to preserve flow to the LSA and to prevent flow into the pseudoaneurysmal sac.
Accidents, Traffic ; Adult ; Aneurysm, False ; Aorta, Thoracic/radiography/*surgery ; Aortic Aneurysm, Thoracic/radiography/*surgery ; Cerebral Hemorrhage/radiography/surgery ; Endovascular Procedures/*methods ; Humans ; Male ; Subclavian Artery/radiography/surgery ; Tomography, X-Ray Computed ; Treatment Outcome ; Wounds, Nonpenetrating/radiography/surgery

A 73-year-old woman with a history of chronic hypertension and severe chronic obstructive pulmonary disease, presented to a district general hospital with thoracic pain in a profound state of shock. She was diagnosed with cardiac tamponade, severe mitral regurgitation, and Stanford type A (Debakey type I) intramural hematoma. Her ascending aorta was of a significant size and therefore emergent repair was done to replace the ascending aorta and mitral valve. After 6 months, an increased aneurysmal size of 6.0 cm was observed in a follow up contrast-enhanced computed tomography angiography. The patient was successfully treated by a staged hybrid procedure involving initial supra-aortic reconstruction.
Aged ; Aneurysm ; Angiography ; Aorta ; Aorta, Thoracic ; Aortic Aneurysm, Thoracic ; Cardiac Tamponade ; Chimera ; Endovascular Procedures ; Female ; Follow-Up Studies ; Hematoma ; Hospitals, General ; Humans ; Hypertension ; Mitral Valve ; Mitral Valve Insufficiency ; Pulmonary Disease, Chronic Obstructive ; Shock ; Vascular Grafting

A tooth is a complex biological organ and consists of multiple tissues including the enamel, dentin, cementum and pulp. Tooth loss is the most common organ failure. Can a tooth be regenerated? Can adult stem cells be orchestrated to regenerate tooth structures such as the enamel, dentin, cementum and dental pulp, or even an entire tooth? If not, what are the therapeutically viable sources of stem cells for tooth regeneration? Do stem cells necessarily need to be taken out of the body, and manipulated ex vivo before they are transplanted for tooth regeneration? How can regenerated teeth be economically competitive with dental implants? Would it be possible to make regenerated teeth affordable by a large segment of the population worldwide? This review article explores existing and visionary approaches that address some of the above-mentioned questions. Tooth regeneration represents a revolution in stomatology as a shift in the paradigm from repair to regeneration: repair is by metal or artificial materials whereas regeneration is by biological restoration. Tooth regeneration is an extension of the concepts in the broad field of regenerative medicine to restore a tissue defect to its original form and function by biological substitutes.
Adult Stem Cells ; Animals ; Humans ; Regeneration ; Regenerative Medicine ; Signal Transduction ; Stem Cell Transplantation ; Tissue Engineering ; Tissue Scaffolds ; Tooth ; physiology

Ulmus davidiana var. japonica Rehder (Urticales: Ulmaceae) (UD) is a tree widespread in northeast Asia. It is traditionally used for anticancer and anti-inflammatory therapy. The present study investigated the effect of an ethanol extract of UD on vascular tension and its underlying mechanism in rats. The dried root bark of UD was ground and extracted with 80% ethanol. The prepared UD extract was used in further analysis. The effect of UD on the cell viability, vasoreactivity and hemodynamics were investigated using propidium iodide staining in cultured cells, isometric tension recording and blood pressure analysis, respectively. Low dose of UD (10~100microg/ml) did not affect endothelial cell viability, but high dose of UD reduced cell viability. UD induced vasorelaxation in the range of 0.1~10microg/ml with an ED50 value of 2microg/ml. UD-induced vasorelaxation was completely abolished by removal of the endothelium or by pre-treatment with L-NAME, an inhibitor of nitric oxide synthase. UD inhibited calcium influx induced by phenylephrine and high K+ and also completely abolished the effect of L-NAME. Intravenous injection of UD extracts (10~100 mg/kg) decreased arterial and ventricular pressure in a dose-dependent manner. Moreover, UD extracts reduced the ventricular contractility (+dP/dt) in anesthetized rats. However, UD-induced hypotensive actions were minimized in L-NAME-treated rats. Taken together, out results showed that UD induced vasorelaxation and has antihypertensive properties, which may be due the activation of nitric oxide synthase in endothelium.
Animals ; Asia ; Blood Pressure ; Calcium ; Cell Survival ; Cells, Cultured ; Endothelial Cells ; Endothelium ; Ethanol ; Hemodynamics ; Injections, Intravenous ; NG-Nitroarginine Methyl Ester ; Nitric Oxide Synthase ; Nitric Oxide Synthase Type III ; Phenylephrine ; Propidium ; Rats ; Trees ; Ulmus ; Vasodilation ; Ventricular Pressure

Acute renal failure, acute myocardial infarction (AMI), and gastric ulcer bleeding (GUB) are associated with high rates of morbidity and mortality, especially in older patients. The development of each of these conditions can be followed by the development of another; however, it is rare for these three conditions to develop concurrently. Here, we report the case of a 92-year-old man who was admitted because of generalized weakness that developed after the ingestion of nothing but functional foods, including herbal medications containing Glycyrrhiza and Aloe, for ten days. After admission, AMI and GUB developed approximately six hours apart. Conservative treatment was chosen for the bleeding ulcer because of the high procedural risk, and the use of antiplatelet agents and heparinization for treatment of the infarction were stopped. The patient remained hemodynamically stable following the administration of a statin, diuretics, and proton pump inhibitors. A healed scar at the site of the ulcer was confirmed three weeks later; however, postinfarct angina developed after the patient's last endoscopy. Percutaneous coronary intervention was successfully performed with two stents placed in the left anterior descending artery.
Acute Kidney Injury ; Aloe ; Arteries ; Cicatrix ; Diuretics ; Eating ; Endoscopy ; Functional Food ; Glycyrrhiza ; Hemorrhage ; Heparin ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Infarction ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; Proton Pump Inhibitors ; Stents ; Stomach Ulcer ; Ulcer

Arrhythmogenic right ventricular cardiomyopathy (ARVC)/dysplasia is characterized by fibro-fatty replacement of the right ventricular myocardium. A 19-year-old soldier was admitted with sudden cardiac arrest that presented as ventricular fibrillation requiring cardiopulmonary resuscitation. His electrocardiogram (ECG) showed normal sinus rhythm with inverted T waves from leads V1 to V4 and isolated premature ventricular beats with a left bundle branch block (LBBB) pattern. Echocardiography showed that the right ventricle was enlarged with apical trabecular formation. The coronary angiogram was normal. Cardiovascular magnetic resonance imaging (MRI) showed thinning and fatty substitution of both the right and left ventricular free walls. Ventricular tachycardia (LBBB pattern) occurred frequently despite anti-arrhythmic drug treatment. His drug-resistant ventricular tachycardia was treated with an implanted cardiac defibrillator. Left ventricle involvement in ARVC is less common and more severe. Cardiac MRI is considered the best imaging technique for evaluating the right ventricle and diagnosing ARVC.
Arrhythmogenic Right Ventricular Dysplasia ; Bundle-Branch Block ; Cardiopulmonary Resuscitation ; Death, Sudden, Cardiac ; Defibrillators ; Echocardiography ; Electrocardiography ; Heart Ventricles ; Humans ; Magnetic Resonance Imaging ; Military Personnel ; Myocardium ; Tachycardia, Ventricular ; Ventricular Fibrillation ; Ventricular Premature Complexes ; Young Adult