Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. It is characterized by the accumulation of lipids without alcohol intake and often progresses to non-alcoholic steatohepatitis (NASH), liver fibrosis, and end-stage liver diseases such as cirrhosis or cancer. Although animal models have greatly contributed to the understanding of NAFLD, studies on the disease progression in humans are still limited. In this study, we used the recently reported high-fat L-methionine-defined and choline-deficient (HFMCD) diet to rapidly induce NASH and compared the responses to HFMCD in ICR mice from three different countries: Korea (supplied by the National Institute of Food and Drug Safety Evaluation), USA, and Japan during 6 weeks. Feeding HFMCD did not cause significant differences in weight gain in comparison with mice fed control diet. Relative weight of the liver increased gradually, while the relative weight of the kidneys remained unchanged. The parameters of liver injury (serum activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) increased rapidly from 1 week and remained elevated for as long as 6 weeks. Histopathological analysis showed that the accumulation of hepatic lipids induced by HFMCD was prominent at 1 week after diet supplementation and increased further at 6 weeks. Inflammatory markers were significantly increased in a time-dependent manner by HFMCD. The mRNA levels of TNF-α and IL-6 were elevated approximately 15-fold relative to control diet and that of IL-1β was increased more than 20-folds at 6 week after the onset of HFMCD intake. In addition, mRNA expression of fibrosis markers such as α-SMA, TGFβ1, and Col1a1 were also significantly increased at 6 week. In summary, the responses of Korl:ICR mice by intake of HFMCD diet were similar to those of ICR mice from other sources, which suggests that Korl:ICR mice is also a useful resource to study the pathogenesis of diet-induced NAFLD.

BACKGROUND: The light-emitting diode (LED) curing light used is presumed to be safe. However, the scientific basis for this is unclear, and the safety of LED curing light is still controversial. The purpose of this study was to investigate the effect of LED curing light irradiation according to the conditions applied for the polymerization of composite resins in dental clinic on the cell viability and inflammatory response in Raw264.7 macrophages and to confirm the stability of LED curing light. METHODS: Cell viability and cell morphology of Raw264.7 macrophages treated with 100 ng/ml of lipopolysaccharide (LPS) or/and LED curing light with a wavelength of 440~490 nm for 20 seconds were confirmed by methylthiazolydiphenyl-tetrazolium bromide assay and microscopic observation. The production of nitric oxide (NO) and prostaglandin E2 (PGE2) was confirmed by NO assay and PGE2 enzyme-linked immunosorbent assay kit. Expression of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in total RNA and protein was confirmed by reverse transcription polymerase chain reaction and Western blot analysis. RESULTS: The LED curing light did not affect the viability and morphology of normal Raw264.7 cells but affected the cell viability and induced cytotoxicity in the inflammation-induced Raw264.7 cells by LPS. The irradiation of the LED curing light did not progress to the inflammatory state in the inflammation-induced Raw264.7 macrophage. However, LED curing light irradiation in normal Raw264.7 cells induced an increase in NO and PGE2 production and mRNA and protein expression of IL-1β and TNF-α, indicating that it is possible to induce the inflammatory state. CONCLUSION: The irradiation of LED curing light in RAW264.7 macrophage may induce an excessive inflammatory reaction and damage oral tissues. Therefore, it is necessary to limit the long-term irradiation which is inappropriate when applying LED curing light in a dental clinic.
Blotting, Western ; Cell Survival ; Composite Resins ; Dental Clinics ; Dinoprostone ; Enzyme-Linked Immunosorbent Assay ; Interleukins ; Macrophages ; Nitric Oxide ; Polymerase Chain Reaction ; Polymerization ; Polymers ; Reverse Transcription ; RNA ; RNA, Messenger ; Tumor Necrosis Factor-alpha

Acetaminophen (APAP) is the most common antipyretic analgesic worldwide. However, APAP overdose causes severe liver injury, especially centrilobular necrosis, in humans and experimental animals. At therapeutic dosage, APAP is mainly metabolized by sulfation and glucuronidation, and partly by cytochrome P450–mediated oxidation. However, APAP overdose results in production of excess reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), by cytochromes P450; NAPQI overwhelms the level of glutathione (GSH), which could otherwise detoxify it. NAPQI binds covalently to proteins, leading to cell death. A number of studies aimed at the prevention and treatment of APAP-induced toxicity are underway. Rats are more resistant than mice to APAP hepatotoxicity, and thus mouse models are mainly used. In the present study, we compared the toxic responses induced by APAP overdose in the liver of ICR mice obtained from three different sources and evaluated the usability of the Korl:ICR stock established by the National Institute of Food and Drug Safety Evaluation in Korea. Administration of APAP (300 mg/kg) by intraperitoneal injection into male ICR mice enhanced CYP2E1 protein expression and depleted hepatic GSH level 2 h after treatment accompanied with significantly increased level of hepatic malondialdehyde, a product of lipid peroxidation. Regardless of the source of the mice, hepatotoxicity, as evidenced by activity of serum alanine aminotransferase, increased from 8 h and peaked at 24 h after APAP treatment. In summary, hepatotoxicity was induced after the onset of oxidative stress by overdose of APAP, and the response was the same over time among mice of different origins.
Acetaminophen ; Alanine Transaminase ; Animals ; Cell Death ; Cytochrome P-450 CYP2E1 ; Cytochromes ; Glutathione ; Humans ; Injections, Intraperitoneal ; Korea ; Lipid Peroxidation ; Liver ; Male ; Malondialdehyde ; Mice ; Mice, Inbred ICR ; Necrosis ; Oxidative Stress ; Rats

PURPOSE: The purpose of the study is to investigate the efficacy of combined treatment with temozolomide (TMZ) and metformin for glioblastoma (GBM) in Vitro and in vivo. MATERIALS AND METHODS: We investigated the efficacy of combined treatment with TMZ and metformin using cell viability and apoptosis assays. A GBM orthotopic mice model was established by inoculation of 5×105 U87 cells and treatedwith metformin, TMZ, and the combination for 4weeks. Western blotting and immunofluorescence of tumor specimens were analyzed to investigate AMP-activated protein kinase (AMPK) and AKT pathway. RESULTS: The combination of TMZ and metformin showed higher cytotoxicity than single agents in U87, U251, and A172 cell lines. A combination of high-dose metformin and TMZ showed the highest apoptotic activity. The combination of TMZ and metformin enhanced AMPK phosphorylation and inhibited mammalian target of rapamycin phosphorylation, AKT phosphorylation, and p53 expression. The median survival of each group was 43.6, 55.2, 53.2, 65.2, and 71.3 days for control, metformin treatment (2 mg/25 g/day or 10 mg/25 g/day), TMZ treatment (15 mg/kg/day), combination treatment with low-dose metformin and TMZ, and combination treatment with high-dose metformin and TMZ, respectively. Expression of fatty acid synthase (FASN) was significantly decreased in tumor specimens treated with metformin and TMZ. CONCLUSION: The combination of metformin and TMZ was superior to monotherapy using metformin or TMZ in terms of cell viability in Vitro and survival in vivo. The combination of high-dose metformin and TMZ inhibited FASN expression in an orthotopic model. Inhibition of FASN might be a potential therapeutic target of GBM.
AMP-Activated Protein Kinases ; Animals ; Apoptosis ; Blotting, Western ; Cell Line ; Cell Survival ; Fluorescent Antibody Technique ; Glioblastoma* ; In Vitro Techniques* ; Metformin* ; Mice ; Phosphorylation ; Sirolimus

BACKGROUND: Although Escherichia coli is a common cause of bacterial enteritis in Korea, reports on community-acquired E. coli enteritis in Korean children are scarce. This study aimed to determine the clinical characteristics and pathotype distribution of community-acquired E. coli enteritis diagnosed by a multiplex polymerase chain reaction (PCR) assay in Korean children. MATERIALS AND METHODS: The medical records of children aged 18 years or less who were diagnosed with acute gastroenteritis by the attending physician between 2013 and 2016 were retrospectively reviewed. The clinical characteristics of children diagnosed with E. coli enteritis were investigated and compared with those diagnosed with Salmonella enteritis. E. coli and Salmonella infections were diagnosed by a stool PCR assay. RESULTS: Among 279 children, in whom PCR assays for E. coli and Salmonella spp. were performed, Salmonella enteritis and E. coli enteritis were diagnosed in 43 (15.4%) and 39 (14.0%) children, respectively. Among the 39 children with E. coli enteritis, enteropathogenic E. coli (n=21, 53.8%) and enteroaggregative E. coli (n=15, 38.4%) were the most common causative agents. Empirical antibiotics were administered to 33 (84.6%) children. A total of 31 (79.5%) children developed fever, and 25 (80.6%) of them had the fever for 3 days or less, which resolved a median of 1 day (range 0-3 days) after hospitalization. The most frequent gastrointestinal symptom was diarrhea (n=36, 92.3%). Significantly more children with E. coli enteritis were aged 2 years or less as compared with those with Salmonella enteritis (41.0% vs. 21.9%, P = 0.021). Children with Salmonella enteritis more frequently complained of fever (97.7% vs. 79.5%, P = 0.012), abdominal pain (90.7% vs. 64.1%, P = 0.004), and hematochezia (46.5% vs. 10.3%, P < 0.001) than those with E. coli enteritis. Erythrocyte sedimentation rate and C-reactive protein levels were significantly higher in children with Salmonella enteritis than those with E. coli enteritis (P < 0.001). CONCLUSION: Enteropathogenic E. coli was the most frequent pathotype in Korean children with E. coli enteritis that caused mild clinical symptoms. A stool PCR assay for E. coli may be useful for epidemiological purpose and for an early diagnosis of E. coli enteritis.
Abdominal Pain ; Anti-Bacterial Agents ; Blood Sedimentation ; C-Reactive Protein ; Child* ; Diarrhea ; Early Diagnosis ; Enteritis* ; Enteropathogenic Escherichia coli ; Escherichia coli* ; Escherichia* ; Fever ; Gastroenteritis ; Gastrointestinal Hemorrhage ; Hospitalization ; Humans ; Korea ; Medical Records ; Multiplex Polymerase Chain Reaction ; Polymerase Chain Reaction* ; Retrospective Studies ; Salmonella ; Salmonella Infections

OBJECTIVE: The importance of traumatic dural venous sinus injury lies in the probability of massive blood loss at the time of trauma or emergency operation resulting in a high mortality rate during the perioperative period. We considered the appropriate methods of treatment that are most essential in the overall management of traumatic dural venous sinus injuries. METHODS: We conducted a retrospective review of all cases involving patients with dural venous sinus injury who presented to our hospital between January 1999 and December 2014. RESULTS: Between January 1999 and December 2014, 20 patients with a dural venous sinus injury out of the 1,200 patients with severe head injuries who had been operated upon in our clinic were reviewed retrospectively. There were 17 male and 3 female patients. In 11 out of the 13 patients with a linear skull fracture crossing the dural venous sinus, massive blood loss from the injured sinus wall could be controlled by simple digital pressure using Gelfoam. All 5 patients with a linear skull fracture parallel to the sinus over the venous sinus developed massive sinus bleeding that could not be controlled by simple digital pressure. CONCLUSION: When there is a linear skull fracture parallel to the sinus over the dural venous sinus or a depressed skull fracture penetrating the sinus, the surgeon should be prepared for the possibility of potentially fatal venous sinus injury, even in the absence of a hematoma.
Craniocerebral Trauma ; Emergencies ; Female ; Gelatin Sponge, Absorbable ; Hematoma ; Hemorrhage ; Humans ; Male ; Mortality ; Perioperative Period ; Retrospective Studies ; Skull Fracture, Depressed ; Skull Fractures ; Superior Sagittal Sinus

PURPOSE: The complex interplay between environmental and genetic factors plays an important role in the development of asthma. Several studies have yielded conflicting results regarding the 2 asthma-related risk factors: antibiotic usage during infancy and/or a history of bronchiolitis during early life and the development of asthma. In addition to these risk factors, we also explored the effects of Toll-like receptor 4 (TLR4) polymorphism on the development of childhood asthma. METHODS: This cross-sectional study involved 7,389 middle school students who were from 8 areas of Seoul, Korea, and completed the International Study of Asthma and Allergies in Childhood questionnaire. The TLR4 polymorphism rs1927911 was genotyped in 1,395 middle school students from two areas using the TaqMan assay. RESULTS: Bronchiolitis in the first 2 years of life, antibiotic exposure during the first year of life, and parental history of asthma were independent risk factors for the development of asthma. When combined, antibiotic use and a history of bronchiolitis increased the risk of asthma (adjusted odds ratio [aOR]: 4.64, 95% confidence interval [CI]: 3.09-6.97, P value for interaction=0.02). In subjects with CC genotype of TLR4, antibiotic exposure and a history of bronchiolitis during infancy, the risk of asthma was increased, compared to subjects without these risk factors (aOR: 5.72, 95% CI: 1.74-18.87). CONCLUSIONS: Early-life antibiotic exposures and a history of bronchiolitis are risk factors for asthma in young adolescents. Polymorphisms of TLR4 modified the influence of these environmental factors. Reducing antibiotic exposure and preventing bronchiolitis during infancy may prevent the development of asthma, especially in genetically susceptible subjects.
Adolescent ; Anti-Bacterial Agents ; Asthma* ; Bronchiolitis* ; Cross-Sectional Studies ; Genotype ; Humans ; Hypersensitivity ; Korea ; Odds Ratio ; Parents ; Risk Factors ; Seoul ; Toll-Like Receptor 4 ; Surveys and Questionnaires