BACKGROUND/OBJECTIVES: Although several recent studies have reported the anti-cancer effects of extracts or components of Citrus unshiu peel, which has been used for various purposes in traditional medicine, the molecular mechanisms for their effects remain unclear. In the present study, the anti-cancer activity of a water-soluble extract of C. unshiu peel (WECU) in MDA-MB-231 human breast carcinoma cells at the level of apoptosis induction was investigated. MATERIALS/METHODS: Cytotoxicity was evaluated using the MTT assay. Apoptosis was detected using DAPI staining and flow cytometry analyses. Mitochondrial membrane potential, reactive oxygen species (ROS) assay, caspase activity and Western blotting were used to confirm the basis of apoptosis. RESULTS: The results indicated that WECU-induced apoptosis was related to the activation of caspase-8, and -9, representative initiator caspases of extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3 accompanied by proteolytic degradation of poly(ADP-ribose) polymerase and down-regulation of the inhibitors of apoptosis protein family members. WECU also increased the pro-apoptotic BAX to anti-apoptotic BCL-2 ratio, loss of mitochondrial membrane potential and cytochrome c release from mitochondria to cytoplasm. Furthermore, WECU provoked the generation of ROS, but the reduction of cell viability and induction of apoptosis by WECU were prevented when ROS production was blocked by antioxidant N-acetyl cysteine. CONCLUSIONS: These results suggest that WECU suppressed proliferation of MDA-MB-231 cells by activating extrinsic and intrinsic apoptosis pathways in a ROS-dependent manner.
Apoptosis* ; Blotting, Western ; Breast Neoplasms* ; Breast* ; Caspase 3 ; Caspase 8 ; Caspases, Initiator ; Cell Survival ; Citrus* ; Cysteine ; Cytochromes c ; Cytoplasm ; Down-Regulation ; Flow Cytometry ; Humans* ; Medicine, Traditional ; Membrane Potential, Mitochondrial ; Mitochondria ; Oxygen* ; Poly(ADP-ribose) Polymerases ; Reactive Oxygen Species ; Water*

BACKGROUND/OBJECTIVES: Benign prostatic hypertrophy (BPH) is a major cause of abnormal overgrowth of the prostate mainly in the elderly. Corni Fructus has been reported to be effective in the prevention and treatment of various diseases because of its strong antioxidant effect, but its efficacy against BPH is not yet known. This study was designed to evaluate the therapeutic efficacy of Corni Fructus water extract (CF) in testosterone-induced BPH rats. MATERIALS/METHODS: To induce BPH, rats were intraperitoneal injected with testosterone propionate (TP). Rats in the treatment group were orally administered with CF with TP injection, and finasteride, which is a selective inhibitor of 5α-reductase type 2, was used as a positive control. RESULTS: Our results showed that the increased prostate weight and histopathological changes in BPH model rats were suppressed by CF treatment. CF, similar to the finasteride-treated group, decreased the levels of testosterone and dihydrotestosterone by TP treatment in the serum, and it also reduced 5α-reductase expression and concentration in prostate tissue and serum, respectively. In addition, CF significantly blocked the expression of the androgen receptor (AR), AR co-activators, and proliferating cell nuclear antigen in BPH rats, and this blocking was associated with a decrease in prostate-specific antigen levels in serum and prostate tissue. CONCLUSIONS: These results suggest that CF may weaken the BPH status through the inactivation of at least 5α-reductase and AR activity and may be useful for the clinical treatment of BPH.
Aged ; Animals ; Antioxidants ; Cornus* ; Dihydrotestosterone ; Finasteride ; Humans ; Proliferating Cell Nuclear Antigen ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia* ; Rats* ; Receptors, Androgen* ; Testosterone ; Testosterone Propionate ; Water

BACKGROUND: Although transfusion in neonates needs to be strictly regulated due to the vulnerability of neonates, there is lack of systematic studies and the working process is not well-established. This study was aimed to point out the problems of current status and to improve the efficiency of systems used in blood aliquots for neonatal transfusions. METHODS: Total red blood cell (RBC) aliquots were analyzed between May 2009 and January 2016 in the neonate intensive care unit. We investigated the aliquot number, issued day interval from the first issued aliquot among the post-aliquots, patients' blood type, and discarded RBC units among the requested RBC units. RESULTS: Of the 472 RBC aliquots, 95.4% (450/472) were divided into two units. The distribution of patients' blood type was similar to that of the Korean population, in decreasing order: A blood group (34.3%), B group (28.2%), and O group (27.5%). The second, third, and forth units of post-aliquots were taken after an average of 49.9 (0∼617.9) hours. Among the post-aliquots, the number of units discarded without use was 22.5%. CONCLUSION: According to the evaluation of current status for neonatal transfusions, we should use aliquot RBC properly and reduce unnecessary requests for aliquot RBC. In addition, in order to reduce the number of near misses, we propose a new label to be attached on the aliquotted blood bags and suggest a development of electronic blood issuing system.
Erythrocytes* ; Humans ; Infant, Newborn ; Intensive Care Units

Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes.
Cardiovascular Diseases ; Cause of Death ; Cell Survival ; Cyclin E ; Cyclins ; Diabetic Cardiomyopathies ; Down-Regulation ; Glucose* ; Humans* ; Hyperglycemia ; Mitochondria ; Mitochondrial Dynamics* ; Stem Cells*

OBJECTIVES: We retrospectively investigated the efficacy and tolerability of risperidone monotherapy in subjects with autism spectrum disorder (ASD). In addition, we did mixed effect model analysis of the effects of risperidone in patients with ASDs naturalistically treated in a routine clinical setting to determine whether the clinical effects were maintained and the side effects were tolerable. METHODS: This retrospective study assessed children and adolescents with ASD, who were on risperidone monotherapy from July 2010 to July 2011 at the Child and Adolescent ASD Clinic at Seoul National Hospital. Outcome measures included the Clinical Global Impression-Severity of Illness (CGI-S) and the CGI-Improvement (CGI-I) scales along with other clinical indices: dosage, target symptoms, and side effects. RESULTS: The mean dose of risperidone in 47 children and adolescents with ASD (40 males, 7 females; age range 5-19 years) who were on risperidone monotherapy was 1.6+/-0.8 mg/day, and the mean duration of the treatment period was 20.2+/-17.3 months. Aggressive behavior, stereotypic behavior, irritability, and self-injurious behavior were the most frequent target symptoms of risperidone. The most common side effects were weight gain followed by somnolence and extrapyramidal symptoms. In a mixed effects model analysis of CGI-I scores, the mean CGI-I score at the 1 month follow-up was significantly different from the mean CGI-I score of the 3-month follow-up (p=.046), and the CGI-I scores were equally maintained over 3 to 48 months [F(6, 28.9)=4.393, p=.003]. Of the 47 patients, 33 patients (70.2%) were identified as the response group, showing an end point CGI-I rating of 3 or under and having continued risperidone treatment for at least 6 months. The baseline CGI-S score showed significant association with clinical response to risperidone (p=.005), the mean baseline CGI-S was higher in the response group compared to the non-response group. CONCLUSION: In this study, clinical improvement of risperidone stabilized around 3 months and was equally maintained up to 48 months with tolerable side effects, supporting maintenance of risperidone treatment in children and adolescents with ASDs.
Adolescent* ; Autistic Disorder* ; Autism Spectrum Disorder* ; Child* ; Female ; Follow-Up Studies ; Humans ; Male ; Outcome Assessment (Health Care) ; Retrospective Studies ; Risperidone* ; Self-Injurious Behavior ; Seoul ; Weight Gain ; Weights and Measures

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are characterized by abnormal deposition of alpha-synuclein aggregates in many regions of the central and peripheral nervous systems. Accumulating evidence suggests that the alpha-synuclein pathology initiates in a few discrete regions and spreads to larger areas in the nervous system. Recent pathological studies of PD patients have raised the possibility that the enteric nervous system is one of the initial sites of alpha-synuclein aggregation and propagation. Here, we evaluated the induction and propagation of alpha-synuclein aggregates in the enteric nervous system of the A53T alpha-synuclein transgenic mice after injection of human brain tissue extracts into the gastric walls of the mice. Western analysis of the brain extracts showed that the DLB extract contained detergent-stable alpha-synuclein aggregates, but the normal brain extract did not. Injection of the DLB extract resulted in an increased deposition of alpha-synuclein in the myenteric neurons, in which alpha-synuclein formed punctate aggregates over time up to 4 months. In these mice, inflammatory responses were increased transiently at early time points. None of these changes were observed in the A53T mice injected with saline or the normal brain extract, nor were these found in the wild type mice injected with the DLB extract. These results demonstrate that pathological alpha-synuclein aggregates present in the brain of DLB patient can induce the aggregation of endogenous alpha-synuclein in the myenteric neurons in A53T mice, suggesting the transmission of synucleinopathy lesions in the enteric nervous system.
alpha-Synuclein ; Animals ; Brain ; Dementia ; Enteric Nervous System ; Humans ; Inflammation ; Lewy Bodies ; Mice ; Mice, Transgenic ; Nervous System ; Neurons ; Parkinson Disease ; Peripheral Nervous System ; Tissue Extracts

PURPOSE: Mitochondrial disorders are a clinical entity characterized by diverse symptoms and signs of involvement of various systems. Furthermore, the disorders are known to show ophthalmologic manifestations as well as neurological findings. Visually evoked potential is a sensitive measure to check the integrity of the visual pathway. In this study, we have investigated the value of visually evoked potential in mitochondrial disorders with respiratory chain defects. METHODS: Nineteen patients diagnosed with mitochondrial respiratory chain complex I defect as confirmed by spectrophotometric enzyme assay in muscle samples were enrolled for this study. The patients underwent a visually evoked potential study. We classified the results into four groups and compared these with clinical ophthalmologic findings. RESULTS: Among the 19 patients, 14 showed abnormal visually evoked potential findings. Seven patients showed abnormal clinical ophthalmologic findings. All patients with abnormal ophthalmologic findings showed abnormal visually evoked potential findings. Among the 12 patients with normal ophthalmologic findings, seven showed abnormal results in visually evoked potential. CONCLUSION: Visually evoked potential study could be used as an effective screening tool for mitochondrial disorders to detect ophthalmologic and neurological abnormalities.
Child ; Electron Transport ; Enzyme Assays ; Evoked Potentials ; Eye ; Humans ; Mass Screening ; Mitochondria ; Mitochondrial Diseases ; Muscles ; Visual Pathways

PURPOSE: Inflammation plays a potential role in the pathogenesis of bronchopulmonary dysplasia (BPD). Strategies for preventing BPD include respiratory management, antioxidants, nutritional treatment, and others such as anti-inflammatory agents. We aimed to assess the safety, tolerability, and efficacy of montelukast (MK), a cysteinyl leukotriene 1 receptor antagonist, as an add-on therapy in BPD. METHODS: In addition to currently available standard measures such as oxygen supplementation, bronchodilators, nutritional support, and/or diuretics, montelukast was administered to 15 preterm infants with BPD. MK was given orally (1 mg/kg/d) for a mean period of 12 weeks. We compared safety and efficacy parameters with historical controls. RESULTS: All 15 patients survived, and no differences were found in the incidence of adverse reactions between the 2 groups. The ventilation index was significantly improved after 2 weeks in MK group compared with historical controls. There were no significant differences in other respiratory parameters (MAP, oxygen dependency, and ventilator dependency) between the groups, but the MK group showed trends of greater improvement. CONCLUSION: Administration of MK 1 mg/kg/d was well tolerated in preterm BPD patients as an add-on therapy. We demonstrated that after 2 weeks of MK administration of 1 mg/kg/d, MK had beneficial therapeutic effects on BPD patients as an add-on to the standard therapy. Further multicenter randomized controlled clinical trials are needed to confirm the efficacy and safety of MK as a useful supplement to standard therapy for BPD patients.
Acetates ; Anti-Inflammatory Agents ; Antioxidants ; Bronchodilator Agents ; Bronchopulmonary Dysplasia ; Dependency (Psychology) ; Diuretics ; Humans ; Incidence ; Infant, Newborn ; Infant, Premature ; Inflammation ; Nutritional Support ; Oxygen ; Quinolines ; Ventilation ; Ventilators, Mechanical

PURPOSE: The surfactant dysfunction may play an important role in meconium aspiration syndrome (MAS). We aim to evaluate the effect of surfactant lavage in the treatment of term infants with MAS. METHODS: The medical records of 15 neonates with severe MAS admitted at Yongdong Severance Hospital from 2005 to 2007 were reviewed and analyzed. Seven infants with severe MAS necessitating mechanical ventilation underwent tracheobronchial lavage with 20 mL/kg of diluted (5.3 mg phospholipid/mL) surfactant saline suspension (Newfactan(R)). Data regarding clinical outcomes was assessed by comparison with 8 control infants with equally severe MAS retrospectively. RESULTS: In the lavage group, radiological improvement was evident after 6 hours of treatment. The duration of artificial ventilation and duration of hospital day were also significantly shorten in the lavage group compared with the control group. The mean oxygen index, mean ventilation index improved significantly within the first 6 hours after treatment. No differences were found in the incidence of major complications and mortality between the two groups. CONCLUSION: The surfactant lavage seems to be an effective and safe method for treatment of severe MAS. A multicenter, large scaled randomized controlled trial is needed for further study.
Bronchoalveolar Lavage ; Humans ; Incidence ; Infant ; Infant, Newborn ; Meconium ; Meconium Aspiration Syndrome ; Medical Records ; Oxygen ; Pulmonary Surfactants ; Respiration, Artificial ; Therapeutic Irrigation ; Ventilation

BACKGROUND: Childhood obesity is becoming more prevalent, associated with a variety of adverse consequences which leads to adulthood obesity. Although diagnosis is usually made by body mass index, there is neither a cutoff point for the percentage body fat nor abdominal circumference. The aim of this study was to identify each cutoff point for both measures. METHODS: The measurement of height, weight, abdominal circumference and percentage body fat was performed through manual assessment and bioelectrical impedance analysis for 4,242 subjects aged 11 in Gunpo City, South Korea. The cutoff point for body fat percentage and abdominal circumference is set to maximize the sum of sensitivity and specificity for detecting obesity and overweight using the Receiver Operating Characteristics (ROC) curve. RESULTS: The mean percentage body fat was 13.6+/-6.9% for boys and 19.4+/-5.3% for girls. The mean abdominal circumference of boys was 68.0+/-9.1 cm, and that of girls was 64.3+/-7.7 cm. The cutoff point of percentage body fat for obesity was 21.8% in boys and 24.5% in girls. The prevalence of obesity was 15.2%, 16.7% for males and females, respectively. The abdominal circumference cutoff for obesity was 76.9 cm in boys and 70.7cm in girls. Based on that, the prevalence of obesity was 19.7% for boys and 20.0% for girls, which was higher than what was identified by body mass index, as in the case of body fat percentage. CONCLUSION: The cutoffs of body fat percentage and abdominal circumference in one city of Gyeonggi Province were lower than those suggested in the previous studies.
Adipose Tissue ; Aged ; Body Mass Index ; Electric Impedance ; Female ; Humans ; Male ; Obesity ; Overweight ; Prevalence ; Republic of Korea ; ROC Curve ; Sensitivity and Specificity