BACKGROUND: Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling. METHODS: BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M2 and M3 receptors were examined. RESULTS: Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M2 but decreased expression of M3 in all aged groups of OVA. CONCLUSION: Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M3 and M2 muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.
Actins ; Aged ; Airway Remodeling ; Animals ; Asthma* ; Eosinophils ; Female ; Humans ; Hydroxyproline ; Interleukin-13 ; Interleukin-5 ; Interleukins ; Mice* ; Ovalbumin ; Ovum ; Pneumonia ; Receptors, Muscarinic* ; Tiotropium Bromide*

BACKGROUND: Cognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear. We examined the role of FOXO transcription factors and the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt and apoptosis-related signaling pathways in PC-12 cells exposed to repeated glucose deprivation/reperfusion. METHODS: PC-12 cells were exposed to control (Dulbecco's Modified Eagle Medium [DMEM] containing 25 mM glucose) or glucose deprivation/reperfusion (DMEM with 0 mM glucose for 6 hours and then DMEM with 25 mM glucose for 18 hours) for 5 days. MTT assay and Western blot analysis were performed for cell viability, apoptosis, and the expression of survival signaling pathways. FOXO3/4',6-diamidino-2-phenylindole staining was done to ascertain the involvement of FOXO transcription factors in glucose deprivation/reperfusion conditions. RESULTS: Compared to PC-12 cells not exposed to hypoglycemia, cells exposed to glucose deprivation/reperfusion showed a reduction of cell viability, decreased expression of phosphorylated Akt and Bcl-2, and an increase of cleaved caspase-3 expression. Of note, FOXO3 protein was localized in the nuclei of glucose deprivation/reperfusion cells but not in the control cells. CONCLUSION: Repeated glucose deprivation/reperfusion caused the neuronal cell death. Activated FOXO3 via the PI3K/Akt pathway in repeated glucose deprivation/reperfusion was involved in genes related to apoptosis.
Apoptosis ; Blotting, Western ; Brain ; Caspase 3 ; Cell Death* ; Cell Survival ; Cognition Disorders ; Eagles ; Glucose* ; Hypoglycemia ; Neurons ; Phosphatidylinositol 3-Kinase ; Reperfusion ; Reperfusion Injury ; Transcription Factors*

BACKGROUND: In vitro experiments using only beta-cell lines instead of islets are limited because pancreatic islets are composed of four different types of endocrine cells. Several recent studies have focused on cellular interactions among these cell types, especially alpha- and beta-cells. Because islet isolation needs time and experience, we tested a simple co-culture system with alpha- and beta-cells. Their morphology and function were assessed by comparison to each single cell culture and pancreatic islets. METHODS: alpha TC-6 cells and beta TC-1 cells were maintained in Dulbecco's Minimal Essential Medium containing 5 mM glucose and 10% fetal bovine serum. Cells were mixed at a 1:1 ratio (5x10(5)) in 6-well plates and cultured for 24, 48, and 72 hours. After culture, cells were used for insulin and glucagon immunoassays and tested for glucose-stimulated insulin secretion (GSIS). RESULTS: alpha TC-6 and beta TC-1 cells became condensed by 24 hours and were more strongly compacted after 48 hours. beta TC-1 cells showed both beta-beta and beta-alpha cell contacts. GSIS increased with increasing glucose concentration in co-cultured cells, which showed lower secreted insulin levels than beta TC-1 cells alone. The increase in the secreted insulin/insulin content ratio was significantly lower for co-cultured cells than for beta-cells alone (P=0.04). Compared to islets, the alpha-/beta-cell co-culture showed a higher ratio of GSIS to insulin content, but the difference was not statistically significant (P=0.09). CONCLUSION: alpha TC-6 and beta TC-1 cells in the co-culture system showed cell-to-cell contacts and a similar stimulated insulin secretion pattern to islets. The co-culture system may be used to better mimic pancreatic islets in in vitro assessments.
Cell Culture Techniques ; Coculture Techniques* ; Endocrine Cells ; Glucagon ; Glucose ; Immunoassay ; Insulin ; Islets of Langerhans

Foreign body ingestion is a common problem in the pediatric population and the majority of such cases occur between the ages of six months and three years. Most objects pass uneventfully through the gastrointestinal tract; however, ingestion of multiple magnets can cause serious gastrointestinal complications through interaction with each other across the bowel wall. In these situations, radiologic evaluation is imperative for proper treatment. This is a case report on ingestion of 32 magnets in a 10-year-old boy. We diagnosed a small bowel fistula caused by ingestion of multiple magnets using sonography, which showed hyperechoic magnetic foreign bodies attached together penetrating the thickened neighbouring jejunum.
Child ; Eating* ; Fistula* ; Foreign Bodies ; Gastrointestinal Tract ; Humans ; Jejunum ; Male ; Ultrasonography*

OBJECTIVES: In the previous studies, it has been suggested that temperament and character may affect specialty choice in medical students. The aim of this study is to investigate the effects of temperament and character on specialty interests in medical students. METHODS: A total 132 third-year medical students initially participated in this study. Among these participants, 128 students had filled out both demographic and Temperament and Character Inventory (TCI) questionnaires. Socio-demographic data, specialty interests and Cloninger's TCI scores were obtained. The specialty interests were categorized into surgical, medical and other departments. RESULTS: Among 128 students, 88 (68.7%), 29 (22.7%) and 22 (8.6%) students chose medical, surgical and other departments, respectively. Students choosing surgery departments showed lower Harm Avoidance scores (F = 4.39, df = 1, p = 0.04) and higher Self-Directedness scores (F = 4.30, df = 1, p = 0.04) than those who chose medical departments. There was no significant differences in Novelty Seeking, Reward dependence, Persistence, Cooperativeness, Self-Transcendence scores between groups. CONCLUSIONS: To the best of our knowledge, this is the first study that has demonstrated the relationship between TCI scores and specialty interests of medical students in Korea. The current study suggests that temperament and character influence specialty interests in medical students. These findings could have implications for medical education research and career counseling.
Education, Medical ; Humans ; Korea ; Reward ; Specialties, Surgical ; Students, Medical ; Temperament ; Vocational Guidance

BACKGROUND: Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Tumor tissue produces many types of angiogenic growth factors. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumor angiogenesis. In this study, the expression of tissue VEGF and bFGF from non-small cell lung cancer (NSCLC) patients were analyzed. METHODS: We retrospectively investigated 35 patients with a histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, where the primary curative approach was surgery. An ELISA was employed to determine the expression of VEGF and bFGF in extracts prepared from 35 frozen tissue samples taken from the cancer patients. RESULTS: VEGF and bFGF concentrations were significantly increased in lung cancer tissue as compared with control (non-cancerous) tissue. The VEGF concentration was significantly increased in T2 and T3 cancers as compared with T1 cancer. Expression of VEGF was increased in node-positive lung cancer tissue as compared with node-negative lung cancer tissue (p=0.06). VEGF and bFGF expression were not directly related to the stage of lung cancer and patient survival. CONCLUSION: Expression of VEGF and bFGF were increased in lung cancer tissue, and the expression of VEGF concentration in lung cancer tissue was more likely related with tumor size and the presence of a lymph node metastasis than the expression of bFGF. However, in this study, expression of both VEGF and bFGF in tissue were not associated with patient prognosis.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Enzyme-Linked Immunosorbent Assay ; Fibroblast Growth Factor 2 ; Humans ; Intercellular Signaling Peptides and Proteins ; Lung ; Lung Neoplasms ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Vascular Endothelial Growth Factor A

PURPOSE: The incidence of multiple primary malignant tumor has ranged from 0.7% to 11% in the medical literature. Various organs in the digestive system are the sites of multiple primary cancer (MPC). MPC may be synchronous or metachronous depending on the interval between their diagnosis. To the best of our knowledge, there are only rare reports of resected cases of synchronous primary carcinomas that developed in the GB and duodenum. METHODS: We present here a patient who underwent an operation for synchronous primary carcinomas of the GB and duodenum. A 51-year-old female was admitted for postprandial abdominal discomfort. CT scan and MRI of the abdomen showed a 3 x 2 cm sized heterogenously enhancing mass in the GB and a 3.7 x 2.7 cm sized hetrogenously enhancing mass in the 2nd portion of the duodeum. The laboratory findings, including the tumor markers, were non-specific. An elective operation was done under the impression of combined GB cancer and cancer in the 2nd portion of the deuodenum. On the operative findings, there was a 3 x 2.5 cm sized mass in the GB and a 5 x 4 cm sized duodenal mass with near complete luminal obstruction 3 cm distal from the pyloric ring. Radical cholecystectomy with wedge resection of the liver bed and Whipple's operation was performed. RESULTS: On microscopic examination, the GB mass was well differentiated adenocarcinoma and the duodenal mass was moderately differentiated adenocarcinoma, and one lymph node (a lymph node along the common hepatic artery) among the 18 dissected lymph nodes was invaded by tumor cells. The microscopic findings showed that the GB mass and duodenal mass were synchronous primary carcinomas. The patient recovered uneventfully and is alive and doing well without evidence of recurrence at 21-months of follow up evaluation. CONCLUSIONS: We report here on a case of combined curative resection for synchronous primary carcinomas of the gallbladder and duodenum.
Abdomen ; Adenocarcinoma ; Cholecystectomy ; Diagnosis ; Digestive System ; Duodenum* ; Female ; Follow-Up Studies ; Gallbladder* ; Humans ; Incidence ; Liver ; Lymph Nodes ; Magnetic Resonance Imaging ; Middle Aged ; Phenobarbital ; Recurrence ; Tomography, X-Ray Computed ; Biomarkers, Tumor

Noncompaction of the ventricular myocardium is a rare congenital cardiomyopathy that is thought to be caused by arrest of normal endomyocardial embryogenesis. It is usually diagnosed via echocardiography. The three major clinical manifestations of noncompaction are heart failure, arrhythmia and embolic events. We report here on a case of isolated noncompaction of the ventricular myocardium, and the patient was admitted due to palpitation and dyspnea. Sadly, he died of intractable heart failure despite that we administered intensive medical treatment.
Aged* ; Arrhythmias, Cardiac ; Cardiomyopathies ; Dyspnea ; Echocardiography ; Embryonic Development ; Female ; Heart Failure ; Humans ; Isolated Noncompaction of the Ventricular Myocardium* ; Myocardium ; Pregnancy

BACKGROUND AND AIMS: Pre-induction of heat shock protein 70 (HSP70) is known to effectively attenuate the lipopolysaccharide (LPS)-induced inflammatory response in lung tissue. However, it is unclear if HSP70 induction after LPS exposure attenuates the subsequent LPS-induced inflammatory response in alveolar epithelial cells. This study examined the effects of HSP70 induction after LPS exposure on the IL-6 production and the cell viability after a subsequent LPS challenge in murine alveolar epithelial cells, and investigated whether or not HSP70 itself may be involved in those effects. METHODS: Murine alveolar epithelial cells were cultured and divided into two groups; the Non-Pre-LPS group without a LPS pre-treatment and the Pre-LPS group with a LPS pre-treatment. Each group was subdivided into the following four subgroups: subgroup C (control), subgroup Q (quercetin), subgroup HSP70 (HSP70 induction), and subgroup HSP70-Inh (HSP70 inhibition). HSP70 expression, which was induced by sodium arsenite and inhibited by quercetin, was analyzed by western blot analysis. The IL-6 levels in the culture supernatant were measured by ELISA, and the cell viability was measured using a simplified MTT assay. RESULTS: The IL-6 levels were lower in subgroup HSP70 than in subgroup C (p<0.01), and were higher in subgroup HSP70-Inh than in subgroup HSP70 in both the Non-Pre-LPS and Pre-LPS groups (p<0.05, p<0.01). The cell viability tended to decrease in the Pre-LPS group compared with the Non-Pre-LPS group. While the cell viability was higher in subgroups Q, HSP70, and HSP70-Inh than in subgroup C in the Non-Pre-LPS group (p<0.05, p<0.05, p<0.01), there was no difference in cell viability among the subgroups in the Pre-LPS group. CONCLUSION: HSP70 induction after a LPS pre-treatment in murine alveolar epithelial cells inhibits the subsequent LPS-induced IL-6 production without affecting the cell viability, and HSP70 by itself may play an important role in this proccess.
Acute Lung Injury ; Blotting, Western ; Cell Survival* ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells* ; Heat-Shock Proteins* ; Hot Temperature* ; HSP70 Heat-Shock Proteins* ; Interleukin-6* ; Lipopolysaccharides ; Lung ; Quercetin ; Sodium

BACKGROUND AND OBJECTIVES: We performed this study to evaluate the common carotid artery intima-media thickness (CCA IMT), and its correlation with several clinical variables, including the 10 year coronary heart disease (10 Yr CHD) risk in both healthy and hyperlipidemic hypertensive (HH) Koreans. SUBJECTS AND METHODS: This was a multi-centered prospective epidemiological study. The study population consisted of 227 healthy subjects without risk factors, with the exception of age (mean 49 years old, 114 males), and 243 HH subjects (mean 51 years old, 120 males). The carotid IMT and presence of plaques were semi automatically measured in both carotid arteries at a central reading facility. RESULTS: Linear regression analysis of all the subjects revealed that the independent factors of both CCA IMT were age, pulse pressure (PP) and HDL-cholesterol, and that of the right CCA IMT were sex and 10 Yr CHD risk. In healthy subjects, the independent factor of both CCA IMTs was age, and that of the right CCA IMT was body weight. In the HH subjects, age, sex, total cholesterol, HDL-cholesterol and PP were independent factors of both CCA IMTs, but 10 Yr CHD risk was an independent factor of only the right CCA IMT. Carotid plaques were seen in 17% of the healthy subjects and 35% of the HH subjects. An ROC curve analysis showed a right CCA IMT of 0.646 mm and left CCA IMT of 0.656 mm demonstrated 60% sensitivity and specificity in differentiating healthy from HH subjects. CONCLUSION: This result reliably demonstrates the Korean CCA IMT, as well as several other significant pieces of information.
Blood Pressure ; Body Weight ; Carotid Arteries ; Carotid Artery, Common ; Carotid Intima-Media Thickness* ; Cholesterol ; Coronary Disease ; Epidemiologic Studies* ; Humans ; Korea* ; Linear Models ; Middle Aged ; Prospective Studies ; Risk Factors* ; ROC Curve ; Sensitivity and Specificity