Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background/Aims: Belching disorder (BD) is clinically distinct from gastroesophageal reflux disease (GERD) with belching. Supragastric belching (SGB) is closely associated with reflux episodes. This study investigates belch characteristics in association with reflux, compared between patients with BD and those who had GERD with belching. Methods: Impedance pH monitoring data from 10 patients with BD and 10 patients with GERD who exhibited belching were retrospectively analyzed. Belches were considered “isolated“ or “reflux-related” and acidicon-acidic. Belch characteristics were compared between patients with BD and those with GERD. Results: Symptomatic belches were more frequent in patients with BD than in patients with GERD (median, 160.5 vs 56.0, P < 0.05). SGB was the most common type in both groups; common subtypes comprised “isolated“ in patients with BD and “isolated during the reflux period” in patients with GERD. Reflux-related SGB was more common in patients with GERD than in BD (78.3% vs 45.2%, P < 0.005).Both “preceding belching” including the reflux period and acidic SGB were more common in patients with GERD than in BD (31.8% vs 8.6% and 38.1% vs 8.9%, both P < 0.05). Supragastric belch number positively correlated with all reflux episodes in patients with GERD (adjusted R2 = 0.572, P = 0.007). Conclusions BD is characterized by more belching, compared to GERD. SGB is more frequently associated with reflux in GERD than in BD; acidity may be related to GERD. In BD, SGB is typically non-acidic and unrelated to reflux. Distinct SGB characteristics may reflect different pathogenic mechanisms of reflux and associated symptoms.

Background/Aims: Belching disorder (BD) is clinically distinct from gastroesophageal reflux disease (GERD) with belching. Supragastric belching (SGB) is closely associated with reflux episodes. This study investigates belch characteristics in association with reflux, compared between patients with BD and those who had GERD with belching. Methods: Impedance pH monitoring data from 10 patients with BD and 10 patients with GERD who exhibited belching were retrospectively analyzed. Belches were considered “isolated“ or “reflux-related” and acidicon-acidic. Belch characteristics were compared between patients with BD and those with GERD. Results: Symptomatic belches were more frequent in patients with BD than in patients with GERD (median, 160.5 vs 56.0, P < 0.05). SGB was the most common type in both groups; common subtypes comprised “isolated“ in patients with BD and “isolated during the reflux period” in patients with GERD. Reflux-related SGB was more common in patients with GERD than in BD (78.3% vs 45.2%, P < 0.005).Both “preceding belching” including the reflux period and acidic SGB were more common in patients with GERD than in BD (31.8% vs 8.6% and 38.1% vs 8.9%, both P < 0.05). Supragastric belch number positively correlated with all reflux episodes in patients with GERD (adjusted R2 = 0.572, P = 0.007). Conclusions BD is characterized by more belching, compared to GERD. SGB is more frequently associated with reflux in GERD than in BD; acidity may be related to GERD. In BD, SGB is typically non-acidic and unrelated to reflux. Distinct SGB characteristics may reflect different pathogenic mechanisms of reflux and associated symptoms.

Background/Aims: We aimed to evaluate associations between comorbidities, peripheral neuropathy, and spontaneous internal anal sphincter relaxation (SAR) in patients with defecatory disorders. Methods: A patient was considered to exhibit SAR during high-resolution anorectal manometry (HR-ARM) when the nadir pressure is < 15 mmHg and the time from onset to relaxation was ≥ 15 seconds in the resting pressure frame. A case-control study was performed using HR-ARM data collected from 880 patients from January 2010 to May 2015. We identified 23 cases with SAR (median age 75 years; 15 females; 12 fecal incontinence and 11 constipation). We compared HR-ARM values, Charlson index comorbidity scores, neuropathy, and the prevalence of diseases that potentially cause neuropathy between controls and SAR patients. Each SAR case was compared to 3 controls. Controls were selected to match the age, gender, and examination year of each SAR case. Results: Compared to controls (26.1%), SAR patients (52.2%) exhibited a significantly higher frequency of fecal incontinence. SAR patients also had higher Charlson index scores (5 vs 4, P = 0.028). Nine of 23 SAR patients (39.1%) exhibited peripheral neuropathy— this frequency was higher than that for the control group (11.6%; P = 0.003). Diseases that potentially cause neuropathy were observed in 17 of 23 SAR cases and 32 of 69 controls (P = 0.022). Conclusions SAR develops in patients with constipation and fecal incontinence but is more common in patients with fecal incontinence. Our controlled observational study implies that SAR is associated with peripheral neuropathy and more severe comorbidities.

BACKGROUND: Atelosteogenesis type I (AO-I) is a rare lethal skeletal dysplastic disorder characterized by severe short-limbed dwarfism and dislocated hips, knees, and elbows. AO-I is caused by mutations in the filamin B (FLNB) gene; however, several other genes can cause AO-like lethal skeletal dysplasias. METHODS: In order to screen all possible genes associated with AO-like lethal skeletal dysplasias simultaneously, we performed whole-exome sequencing in a female newborn having clinical features of AO-I. RESULTS: Exome sequencing identified a novel missense variant (c.517G>A; p.Ala173Thr) in exon 2 of the FLNB gene in the patient. Sanger sequencing validated this variant, and genetic analysis of the patient's parents suggested a de novo occurrence of the variant. CONCLUSIONS: This study shows that exome sequencing can be a useful tool for the identification of causative mutations in lethal skeletal dysplasia patients.
Exome ; Female ; Filamins/chemistry/*genetics ; Gene Frequency ; Heterozygote ; Humans ; Infant, Newborn ; Mutation, Missense ; Osteochondrodysplasias/*genetics/pathology/radiography ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA

OBJECTIVE: The survival rate of very low birth weight infants (VLBWI) has increased markedly in Korea. The purpose of this study was to investigate the outcome of VLBWI in Busan area. METHODS: We retrospectively reviewed 273 VLBWI less than 1,500 g who were admitted to the neonatal intensive care units of three university hospitals in Busan between January, 2007, to December, 2008. The survival rate, distribution of infants by birth weight and gestational age, and complications were compared with previous reports in Busan. RESULTS: We enrolled 273 VLBWI, including 31.1% extremely low birth weight infants, and the overall survival rate of VLBWI was 77.3%. Mean gestational age was 29.2+/-2.9 weeks and birth weight was 1,115+/-249 g. Infants weighing <750 g, 750-999 g, 1,000-1,249 g and 1,250-1,499 g showed survival rates of 30.4%, 62.9%, 83.0%, and 92.0%, respectively. Infants at < or =24 weeks, 25-26 weeks, 27-28 weeks and > or =29 weeks had survival rates of 25.0%, 57.5%, 75.0%, and 91.0%, respectively. Survival rates by birth weight (<750 g, 750-999 g) and gestational age (< or =24 weeks, 25-26 weeks) had increased significantly compared to 2003-2005. Common morbidities of VLBWI included respiratory distress syndrome (54.9%), patent ductus arteriosus (33.3%), bronchopulmonary dysplasia (31.5%), sepsis (20.1%), necrotizing enterocolitis (7.3%), retinopathy of prematurity (> or =stage III) (6.2%) and intraventricular hemorrhage (> or =Gr III) (5.1%). CONCLUSIONS: The survival rate of VLBWI born in Busan was 77.3% over the past 2 years. Survival rates of extreme prematurity weighing less than 1,000g and gestational age of < or =26 weeks were significantly increased.
Birth Weight ; Bronchopulmonary Dysplasia ; Ductus Arteriosus, Patent ; Enterocolitis, Necrotizing ; Gestational Age ; Hemorrhage ; Hospitals, University ; Humans ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Very Low Birth Weight ; Intensive Care Units, Neonatal ; Korea ; Retinopathy of Prematurity ; Retrospective Studies ; Sepsis ; Survival Rate

We purified phytoestrogens from Pueraria root (Pueraria mirifica from Thailand and Pueraria lobata from Korea), which is used as a rejuvenating folk medicine in Thailand and China. Dried, powdered plant material was extracted with 100% ethanol and further separated by concentration, filtration, and thin layer silica gel chromatography. Using the fractions obtained during separation, we first investigated their cytotoxicity in several cancer cell lines from various tissues. The ethanol-extracted components (PE1, PE4) had significant antiproliferative effects on breast cancer cell lines, including MCF-7, ZR-75-1, MDA-MB-231, SK-BR-3, and Hs578T. Second, we compared these results with the cytotoxic effects of known flavonoids, sterols, and coumarins from Pueraria root. The known compounds were not as effective, and occurred in a different polarity region on HPLC. Third, further separation resulted in the isolation of eight different components (Sub PE-A to -H). One of these, PE-D, affected the growth of some breast cancer cell lines (MCF-7, MDA-MB-231) in a dose- and time-dependent manner, as well as the growth of ovarian (2774) and cervical cancer cells (HeLa). Finally, a transfection assay showed that this component had an estrogenic effect similar to 17beta-estradiol, which activates both estrogen receptor a (ER alpha) and ER beta. The NMR analysis determined that spinasterol (stigmasta-7, 22-dien-3beta-ol) is an active cytotoxic component of Pueraria root.
Antineoplastic Agents/isolation & purification/*pharmacology ; Chromatography, High Pressure Liquid ; Estrogen Receptor alpha/agonists ; Estrogen Receptor beta/agonists ; Female ; Humans ; Plant Preparations/therapeutic use ; Plant Roots/*chemistry ; Pueraria/*chemistry ; Research Support, Non-U.S. Gov't ; Stigmasterol/*analogs & derivatives/isolation & purification/pharmacology ; Transfection ; Tumor Cells, Cultured

Malaria is a major parasitic disease in tropical areas. Three to five hundred million people suffer from the disease and it kill a million people per year. Blood smear observation was developed for the diagnosis of malaria, but the examination needs skilled experts and exact diagnosis is time consuming. A kit based on immunochromatography can be a reliable and rapid method for clinical diagnosis, even in the hands of inexperienced personnel. However, all such currently developed kits can only diagnose P. falciparum malaria. In our previous report, the C-terminal region of P. vivax merozoite surface protein 1 (PvcMSP) was cloned and expressed in E. coli. In the present study, we developed an immunochromatographic kit using this PvcMSP for the diagnosis of specific antibody to P. vivax malaria in serum samples. The kit was used to examine sera from vivax malaria patients and non-malaria-infected person and the test showed 100% sensitivity (78/78) and 98.3% specificity (58/59). This result demonstrated that the immunochromatographic kit for P. vivax antibody detection is applicable for the rapid and precise diagnosis of P. vivax malaria.
Animals ; Antibodies, Protozoan/*analysis ; *Chromatography ; Human ; *Immunologic Techniques ; Korea ; Malaria, Vivax/*parasitology ; Plasmodium vivax/*immunology ; *Reagent Kits, Diagnostic/*standards

BACKGROUND: Metabolic syndrome, a concurrence of disturbed glucose and insulin metabolism, over- weight and abdominal fat distribution, dyslipidemia and hypertension, is associated with subsequent de- velopment of type 2 diabetes mellitus and cardiovascular disease, especially coronary heart disease. The aim of the study is to assess the relationship between metabolic syndrome and coronary heart disease in elderly greater than 65 years old. METHODS: Eighty two elderly patients greater than 65 years old who underwent coronary angiography were divided into two groups with metabolic syndrome or without metabolic syndrome, and assessed the association with coronary angiographic finding. The metabolic syndrome factors and cardiovascular risk factors of JNC 7 were investigated to assess the relationship with coronary heart disease in elderly. Coronary heart disease was defined as 50% or greater diameter in stenosis of coronary artery in coronary angiography. RESULTS: In elderly patients with metabolic syndrome, coronary angiographically abnormal findings(p<0.05) and multi vessel disease findings(p<0.05) were presented significantly higher than non metabolic syndrome patients. In elderly patients with 3 and more cardiovascular risk factors of JNC 7, coronary angiographically abnormal findings(p<0.05) and multi vessel disease findings(p=0.059) were presented more than the other patients. Diabetes mellitus was related significantly with coronary heart disease(p value 0.044). CONCLUSION: In elderly patients, metabolic syndrome was significantly related with coronary heart disease and diabetes mellitus had strong relationship with coronary heart disease. Metabolic syndrome and cardiovascular risk factors of JNC 7 should be further evaluated to assess the relationship with coronary heart disease in the future.
Abdominal Fat ; Aged* ; Cardiovascular Diseases ; Constriction, Pathologic ; Coronary Angiography ; Coronary Disease* ; Coronary Vessels ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Dyslipidemias ; Glucose ; Heart ; Humans ; Hypertension ; Insulin ; Metabolism ; Risk Factors

BACKGROUND/AIMS: Experimental studies using porcine non- heart beating donors to ameliorate graft injuries in liver transplantation has been conducted. Recently, it has been reported that cellular calcium may have an important role in ischemic injury, which consists of damage during ischemia and impairment at the time of reperfusion. therefore, it is possible that calcium channel blocker might prevent warm ischemic injury of the graft in liver transplantation when administered to the donor before harvesting and to the recipient at reperfusion. the purpose of this study was to investigate the protective effect of a calcium channel blocker diltiazem (DTZ) on hepatic ischemic injury using a porcine model. METHODS: Twenty pigs weighing 20 to 30 kg were enrolled in this study. Cardiac death was induced by direct cardiac injection of potassium chloride. The perfusion of UW (University of Wisconsin) solution started after 30 min of cardiac arrest. Orthotopic liver transplantation was perforated. Group A (experimental group) was administrated of DTZ at a dose of 70microgram/kg bolus iv injection before hepatic ischemia, perfused of 70microgram/L in UW solution and thereafter infused continuously 70microgram/L in 5% dextrose solution. RESULTS: Two ones death occurred among the ten transplant pigs. 24 hour survival rates were 80%. DTZ administrated group showed the hepatic blood flow and arterial ketone body ratio better compared with untreated controls (p<0.05). In addition, the increase of plasma lactate level was suppressed after ischemia (p<0.05). CONCLUSION: Our results suggest that DTZ has a protective effect on ischemic induced hepatic damage and might be useful in the prevention of primary graft failure caused by warm ischemia in liver transplantation.
Calcium ; Calcium Channels ; Death ; Diltiazem ; Glucose ; Heart ; Heart Arrest ; Humans ; Ischemia ; Lactic Acid ; Liver Transplantation* ; Liver* ; Perfusion ; Plasma ; Potassium Chloride ; Reperfusion ; Survival Rate ; Swine ; Tissue Donors* ; Transplants ; Warm Ischemia