Background/Aims: Previous studies have reported the protective effects of tauroursodeoxycholic acid (TUDCA) on gastric epithelial cells in some animal models, but the precise mechanisms are unclear. This study examined the effects of TUDCA on NF-κB signaling in gastric epithelial cells. Moreover, the protective effects of TUDCA in experimental gastritis models induced by ethanol and NSAID were evaluated and compared with ursodeoxycholic acid (UDCA). Methods: After a pretreatment with TUDCA or UDCA, human gastric epithelial MKN-45 cells were stimulated with tumor necrosis factor (TNF)-α to activate NF-κB signaling. A real-time PCR (RT-PCR) for human interleukin (IL)-1 mRNA was performed. An electrophoretic mobility shift assay (EMSA) and immunoblot analyses were carried out. In murine models, after a pretreatment with TUDCA or UDCA, ethanol and indomethacin were administered via oral gavage. Macroscopic and microscopic assessments were performed to evaluate the preventive effects of TUDCA and UDCA on murine gastritis. Results: A pretreatment with TUDCA downregulated the IL-1α mRNA levels in MKN-45 cells stimulated with TNF-α, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-α-induced NF-κB DNA binding activity. A pretreatment with TUDCA inhibited IκBα phosphorylation induced by TNF-α, as assessed by immunoblot analysis. TUDCA attenuated the ethanol-induced and NSAID-induced gastritis in murine models, as determined macroscopically and microscopically. Conclusions TUDCA inhibited NF-κB signaling in gastric epithelial cells and ameliorated ethanol- and NSAID-induced gastritis in murine models. These results support the potential of TUDCA for the prevention of gastritis in humans.

Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl3 solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl3 aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction via the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref-1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM-1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.

Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl3 solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl3 aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction via the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref-1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM-1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.

PURPOSE: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. METHODS: Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. RESULTS: All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from −0.39 at baseline to −0.87 after 36 months (p<0.001). CONCLUSION: QoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.
Aromatase ; Asian Continental Ancestry Group ; Bone Density ; Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Cholesterol ; Consent Forms ; Female ; Humans ; Observational Study ; Quality of Life*

PURPOSE: To report a case of toxic optic neuropathy caused by chlorfenapyr ingestion accompanied by central nervous system involvement. CASE SUMMARY: A 44-year-old female visited our clinic complaining of reduced visual acuity in both eyes for 7 days. She had ingested a mouthful of chlorfenapyr for a suicide attempt 2 weeks prior to the visit. Gastric lavage was performed immediately after ingestion at the other hospital. Her best-corrected visual acuity was finger count 30 cm in the right eye and hand motion in the left eye. Both pupils were dilated by 5.0 mm and the response to light was sluggish in both eyes. A relative afferent pupillary defect was detected in her left eye. Funduscopy revealed optic disc swelling in both eyes. Magnetic resonance imaging of the brain showed a symmetric hyper-intense signal in the white matter tract including the internal capsule, corpus callosum, middle cerebellar peduncle, and brainstem. The patient was diagnosed with toxic optic neuropathy induced by chlorfenapyr ingestion, and underwent high-dose intravenous corticosteroid pulse therapy. Three days later, the best-corrected visual acuity was no light perception in both eyes. Three months later, optic atrophy was observed in both eyes. Optical coherence tomography revealed a reduction in the thicknesses of the retinal nerve fiber layer and ganglion cell and inner plexiform layer in the macular area. CONCLUSIONS: Ingestion of even a small amount of chlorfenapyr can cause severe optic nerve damage through the latent period, despite prompt lavage and high-dose steroid treatment.
Adult ; Brain ; Brain Stem ; Central Nervous System ; Corpus Callosum ; Eating ; Female ; Fingers ; Ganglion Cysts ; Gastric Lavage ; Hand ; Humans ; Internal Capsule ; Magnetic Resonance Imaging ; Middle Cerebellar Peduncle ; Mouth ; Nerve Fibers ; Optic Atrophy ; Optic Nerve ; Optic Nerve Diseases ; Poisoning ; Pupil ; Pupil Disorders ; Retinaldehyde ; Suicide ; Therapeutic Irrigation ; Tomography, Optical Coherence ; Visual Acuity ; White Matter

OBJECTIVES: This study aimed to develop a high-risk drinking scorecard using cross-sectional data from the 2014 Korea Community Health Survey. METHODS: Data were collected from records for 149,592 subjects who had participated in the Korea Community Health Survey conducted from 2014. The scorecard model was developed using data mining, a scorecard and points to double the odds approach for weighted multiple logistic regression. RESULTS: This study found that there were many major influencing factors for high-risk drinkers which included gender, age, educational level, occupation, whether they received health check-ups, depressive symptoms, over-moderate physical activity, mental stress, smoking status, obese status, and regular breakfast. Men in their thirties to fifties had a high risk of being a drinker and the risks in office workers and sales workers were high. Those individuals who were current smokers had a higher risk of drinking. In the scorecard results, the highest score range was observed for gender, age, educational level, and smoking status, suggesting that these were the most important risk factors. CONCLUSION: A credit risk scorecard system can be applied to quantify the scoring method, not only to help the medical service provider to understand the meaning, but also to help the general public to understand the danger of high-risk drinking more easily.
Breakfast ; Commerce ; Data Mining ; Depression ; Drinking* ; Health Surveys ; Humans ; Korea* ; Logistic Models ; Male ; Motor Activity ; Occupations ; Research Design ; Risk Factors ; Smoke ; Smoking

PURPOSE: MicroRNAs (miRNAs) regulate various cellular functions, including development, cell proliferation, apoptosis, and tumorigenesis. Different signatures associated with various tissue types, diagnosis, progression, prognosis, staging, and treatment response have been identified by miRNA expression profiling of human tumors. miRNAs function as oncogenes or as tumor suppressors. The relationship between gastric cancer and miRNA garnered attention due to the high incidence of gastric cancer in Asian countries. miR-222/221 expression increases in gastric tumor tissues. The oncogenic effect of miR-222/221 was previously determined in functional studies and xenograft models. In this study, transgenic mice over-expressing miR-222/221 were generated to confirm the effect of miR-222/221 on gastric carcinogenesis. MATERIALS AND METHODS: At 6 weeks of age, 65 transgenic mice and 53 wild-type mice were given drinking water containing N-nitroso-N-methylurea (MNU) for 5 alternating weeks to induce gastric cancer. The mice were euthanized at 36 weeks of age and histologic analysis was performed. RESULTS: Hyperplasia was observed in 3.77% of the wild-type mice and in 18.46% of the transgenic mice (p=0.020). Adenoma was observed in 20.75% of the wild-type mice and 26.15% of the transgenic mice (p=0.522). Carcinoma was observed in 32.08% of the wild-type mice and 41.54% of the transgenic mice (p=0.341). The frequency of hyperplasia, adenoma, and carcinoma was higher in transgenic mice, but the difference was statistically significant only in hyperplasia. CONCLUSION: These results suggest that hyperplasia, a gastric pre-cancerous lesion, is associated with miR-222/221 expression but miR-222/221 expression does not affect tumorigenesis itself.
Adenoma ; Animals ; Apoptosis ; Asian Continental Ancestry Group ; Carcinogenesis* ; Cell Proliferation ; Diagnosis ; Drinking Water ; Heterografts ; Humans ; Hyperplasia ; Incidence ; Mice ; Mice, Transgenic* ; MicroRNAs ; Oncogenes ; Prognosis ; Stomach Neoplasms

Somatic cell nuclear transfer (SCNT) is a cost-effective technique for producing transgenic pigs. However, abnormalities in the cloned pigs might prevent use these animals for clinical applications or disease modeling. In the present study, we generated several cloned pigs. One of the pigs was found to have intrapancreatic ectopic splenic tissue during histopathology analysis although this animal was grossly normal and genetically identical to the other cloned pigs. Ectopic splenic tissue in the pancreas is very rare, especially in animals. To the best of our knowledge, this is the first such report for cloned pigs.
Animals ; Animals, Genetically Modified ; Choristoma/pathology/*veterinary ; Cloning, Organism ; Nuclear Transfer Techniques/*veterinary ; *Pancreas ; Splenic Diseases/pathology/*veterinary ; Swine ; Swine Diseases/*pathology ; Swine, Miniature

The level of P4 at the time of embryo transfer (ET) is important. P4 concentrations and numbers of corpora lutea for 126 recipients were evaluated. Nuclear transfer embryos were transferred into 126 surrogates. 11 maintained their pregnancy until full-term delivery, 17 miscarried, and implantation failed in 98 animals. P4 levels in the full-term group were significantly different from those of the pigs that aborted or in which implantation failed (p < 0.05). However, the numbers of corpora lutea were not significantly different. These findings indicate that the concentration of progesterone can be an important factor for successful ET in pigs.
Animals ; Corpus Luteum/*physiology ; Embryo Transfer/*veterinary ; Embryo, Mammalian/*physiology ; Female ; Nuclear Transfer Techniques ; Pregnancy ; *Pregnancy Rate ; Progesterone/*blood ; Retrospective Studies ; Sus scrofa/*physiology

PURPOSE: This study was conducted in order to describe how intern physicians in the emergency department (ED) spent their time, and the frequency of tasks performed by them. METHODS: This was an observational, time-motion study for 15 intern physicians in 15 emergency centers. Observers in each hospital shadowed interns for a 60-minute period, two times, both day and night shift. They recorded time spent on various activities, type and number of activities. The proportion of activity that can be replaced by other staff members was calculated. RESULTS: Average number of duty hours of interns was 80.9 hours (63~87.8) per week. A total of 662 activities were observed during 30 hours. Interns' activities were classified as direct patient care 28.2%, personal time 24.2%, documentation 17.0%, procedures 16.7%, communication 8.1%, transportation 2.6%, indirect patient care 2.0%, learning activity 0.8%, and administrative work 0.4%. The proportion of procedural task showed negative correlation with the number of emergency medical technicians (r=-0.710, p=0.003). The proportion of activity that can be replaced by staff members other than doctors was 24.3% (0~47%) of time, except personal or learning activity. CONCLUSION: Results of this study showed that only 24.3% of interns' activity in the emergency department could be replaced by staff members other than doctors. Because the proportion of activities that could be replaced was variable among hospitals, each hospital should perform task analysis of interns' activity in order to forecast alternative manpower.
Cross-Sectional Studies* ; Emergencies ; Emergency Medical Technicians ; Emergency Service, Hospital* ; Humans ; Internship and Residency ; Learning ; Patient Care ; Time and Motion Studies ; Transportation