BACKGROUND/AIMS: Despite numerous studies on the relation of genetic polymorphisms with irritable bowel syndrome (IBS), the results still remain inconclusive. The aim of this study was to assess the possible association between SLC6A4 serotonin transporter gene linked polymorphic region (5-HTTLPR), ADRA2A -1291C>G, GNB3 825C>T, CCK1R intron 779T>C and TRPV1 945G>C polymorphisms and IBS based on Rome III criteria in Korea. METHODS: Study subjects were prospectively recruited from visitors to Seoul National University Bundang Hospital between July 2009 and January 2014. Ninety-nine IBS patients and 171 healthy controls were enrolled. Polymorphisms of above-mentioned 5 genes were genotyped. Serum serotonin from 101 participants was measured by ELISA and compared according to SLC6A4 5-HTTLPR polymorphisms and IBS subtypes. RESULTS: Regarding SLC6A4 5-HTTLPR polymorphism, L/L genotype was significantly associated with the total IBS, constipation predominant IBS (IBS-C) and mixture of diarrhea and constipation IBS (IBS-M) (adjusted OR: 4.35, 95% CI: 1.04-16.67; adjusted OR: 11.11, 95% CI: 1.69-50.00 and adjusted OR: 5.56, 95% CI: 1.05-33.33, respectively). Carrying ADRA2A -1291G allele was significantly associated with total IBS and diarrhea predominant IBS (adjusted OR: 3.37, 95% CI: 1.16-9.77 and adjusted OR: 5.64, 95% CI: 1.18-27.01, respectively). IBS-C patients showed reduced level of serum serotonin compared to controls and patients with diarrhea predominant IBS (50.2 ng/mL vs. 69.0 ng/mL and 92.9 ng/mL, P = 0.017 and P = 0.001, respectively). CONCLUSIONS: Genetic polymorphisms of SLC6A4 5-HTTLPR and ADRA2A -1291C>G could be one of the pathophysiological factors of IBS in Korea. Reduced serum serotonin shown in the IBS-C group suggested a role of serotonin in IBS, but large study is needed for confirming genotypic difference in serum serotonin level.
Alleles ; Constipation ; Diarrhea ; Enzyme-Linked Immunosorbent Assay ; Genotype ; Humans ; Introns ; Irritable Bowel Syndrome* ; Korea ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Prospective Studies ; Receptors, Adrenergic ; Seoul ; Serotonin ; Serotonin Plasma Membrane Transport Proteins*

BACKGROUND/AIMS: Development of antibiotic resistance is a significant clinical problem in the eradication of H. pylori. To select an appropriate regimen, systematic information on antibiotic resistance is mandatory. Thus, we investigated the distribution of minimal inhibitory concentration (MIC) and evaluated the antibiotic resistance of H. pylori isolates from Korean patients in 2003. METHODS: The susceptibility of 65 isolates obtained in 2003 to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, and ciprofloxacin were determined by agar dilution method. RESULTS: Resistance rates of H. pylori to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, and ciprofloxacin were 18.5%, 13.8%, 66.2%, 12.3%, 32.3%, and 33.8%, respectively. Multi-drug resistance rate of H. pylori was 47.7%. Especially, 6.2% of the H. pylori isolates were resistant to both amoxicillin and clarithromycin. In addition, resistance to amoxicillin and clarithromycin resulted in decreasing tendency of the eradication efficacy for H. pylori. CONCLUSIONS: These results indicate that the antibiotics used for H. pylori eradication show high resistance rates in Korea. Furthermore, continuous surveillance of antibiotic susceptibilities should be needed and further increases in antibiotic resistance would require susceptibility testing before treatment to maximize the efficacy of H. pylori treatment.
Aged ; *Drug Resistance, Bacterial ; Drug Resistance, Multiple, Bacterial ; English Abstract ; Female ; Helicobacter Infections/microbiology ; Helicobacter pylori/*drug effects ; Humans ; Korea ; Male ; Middle Aged

OBJECTIVE: The aim of this study was to evaluate pregnancy outcomes and the live birth rate at 1-year age increments in women aged ≥40 years undergoing fresh non-donor in vitro fertilization (IVF) and embryo transfer (ET), and to identify predictors of success in these patients. METHODS: This retrospective study was performed among women ≥40 years of age between 2004 and 2011. Of the 2,362 cycles that were conducted, ET was performed in 1,532 (73.1%). RESULTS: The clinical pregnancy rate and live birth rate in women ≥40 years significantly decreased with each year of increased age (p<0.001). Maternal age (odds ratio [OR], 0.644; 95% confidence interval [CI], 0.540–0.769; p<0.001), basal follicle-stimulating hormone (FSH) levels (OR, 0.950; 95% CI, 0.903–0.999; p=0.047), the number of high-quality embryos (OR, 1.258; 95% CI, 1.005 –1.575; p=0.045), and the number of transferred embryos (OR, 1.291; 95% CI, 1.064 –1.566; p=0.009) were significant predictors of live birth. A statistically significant increase in live birth rates was seen when ≥3 embryos were transferred in patients 40 to 41 years of age, whereas poor pregnancy outcomes were seen in patients ≥43 years of age, regardless of the number of transferred embryos. Moreover, the cumulative live birth rate increased in patients 40 to 42 years of age with repeated IVF cycles, but the follicle-stimulating hormone in those ≥43 years of age rarely showed an increase. CONCLUSION: IVF-ET has acceptable outcomes in those <43 years of age when a patient's own oocytes are used. Maternal age, basal FSH levels, and the number of high-quality embryos and transferred embryos are useful predictors of live birth.
Embryo Transfer ; Embryonic Structures ; Female ; Fertilization in Vitro* ; Follicle Stimulating Hormone ; Humans ; In Vitro Techniques* ; Infertility ; Live Birth* ; Maternal Age ; Oocytes ; Pregnancy Outcome ; Pregnancy Rate ; Pregnancy* ; Retrospective Studies

Clusterin (CLU) is a multifunctional glycoprotein that has secretory and nuclear isoforms. The two isoforms are known to play opposite roles in cell survival/death. In this review, we summarize recent progress on the pro-apoptotic function of nuclear CLU in vitro and in vivo and discuss previous reports on the role of CLU in brain damage and neurodegeneration.
Apoptosis ; Brain ; Clusterin ; Glycoproteins ; Protein Isoforms

Background/Aims: This study aimed to characterize the changes in the gut microbiota of irritable bowel syndrome (IBS) patients and to investigate the consequent alterations in bacterial functions. Methods: We performed 16S rRNA metagenomic sequencing and a phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analyses using fecal samples from control (n=12) and diarrhea-dominant IBS patients (n=7). Results: The samples were clustered by the principal coordinates analysis depending on the presence of IBS (p=0.003). In the IBS patients, the abundances of Acidaminococcaceae, Sutterellaceae, and Desulfovibrionaceae were significantly increased, while those of Enterococcaceae, Leuconostocaceae, Clostridiaceae, Peptostreptococcaceae, and Lachnospiraceae were significantly decreased. The PICRUSt results indicated that two orthologues involved in secondary bile acid biosynthesis were significantly decreased in IBS patients. Modules involved in multidrug resistance, lipopolysaccharide biosynthesis, the reductive citrate cycle, and the citrate cycle were significantly increased in the IBS patients. In contrast, modules involved in cationic antimicrobial peptide resistance, and some transport systems were more abundant in controls than in IBS patients. Conclusions Changes in the gut microbiota composition in IBS patients lead to alterations in bacterial functions, such as bile acid transformation and the induction of inflammation, which is a known pathophysiological mechanism of IBS.

Background: Postoperative pain occurring after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is difficult to control because of extensive surgical injuries and long incisions. We assessed whether the addition of a four-quadrant transabdominal plane (4Q-TAP) block could help in analgesic control. Methods: Seventy-two patients scheduled to undergo elective CRS with HIPEC and intravenous patient-controlled analgesia (IV PCA) were enrolled. The patients received 4Q-TAP blocks in a 10 ml mixture of 2% lidocaine and 0.75% ropivacaine per site (4Q-TAP group, n = 36) or normal saline (control group, n = 33). Oxycodone in the post-anesthesia care unit (PACU) and pethidine or tramadol in the ward were used as rescue analgesics. The primary outcome was less than 3 times of rescue analgesic administration (%) in the ward for 5 postoperative days. Secondary endpoints included oxycodone requirement in PACU, fentanyl doses of IV PCA, morphine milligram equivalent (MME) of total opioid use, hospital stay, and postoperative complications. Results: During 5 postoperative days, there was no difference in pain scores and total rescue analgesic administration between two groups. However, the use of oxycodone in PACU (P = 0.011), fentanyl requirement in IV PCA (P = 0.029), and MME/kg of total opioid use (median, 2.35 vs. 3.21 mg/kg, P = 0.009) were significantly smaller in the 4Q-TAP group. Hospital stay and incidence of postoperative morbidity were similar in both groups. Conclusions The 4Q-TAP block enhanced multimodal analgesia and decreased opioid requirements in patients with CRS with HIPEC, but did not change postoperative recovery outcomes.

Background/Aims: A high-fat diet (HFD) causes dysbiosis and promotes inflammatory responses in the colon. This study aims to evaluate the effects of Clostridium butyricum on HFD-induced gut microbial changes in rats. Methods: Six-week-old Fischer-344 rats with both sexes were given a control or HFD during 8 weeks, and 1-to-100-fold diluted Clostridium butyricum were administered by gavage. Fecal microbiota analyses were conducted using 16S ribosomal RNA metagenomic sequencing and predictive functional profiling of microbial communities in metabolism. Results: A significant increase in Ruminococcaceae and Lachnospiraceae, which are butyric acid-producing bacterial families, was observed in the probiotics groups depending on sex. In contrast, Akkermansia muciniphila, which increased through a HFD regardless of sex, and decreased in the probiotics groups. A. muciniphila positively correlated with Claudin-1 expression in males (P < 0.001) and negatively correlated with the expression of Claudin-2 (P = 0.042), IL-1β (P = 0.037), and IL-6 (P = 0.044) in females. In terms of functional analyses, a HFD decreased the relative abundances of M00131 (carbohydrate metabolism module), M00579, and M00608 (energy metabolism), and increased those of M00307 (carbohydrate metabolism), regardless of sex. However, these changes recovered especially in male C. butyricum groups. Furthermore, M00131, M00579, and M00608 showed a positive correlation and M00307 showed a negative correlation with the relative abundance of A. muciniphila (P < 0.001). Conclusion The beneficial effects of C. butyricum on HFD-induced gut dysbiosis in young male rats originate from the functional profiles of carbohydrate and energy metabolism.

BACKGROUND/AIMS: Failure rates of Helicobacter pylori eradication treatment turned out to be exceeding 10%, causing recurrence of peptic ulcers. In the case of eradication failure, the Korean College of Helicobacter Research and Practice recommends quadruple therapy consisting of proton pump inhibitor, bismuth, tetracycline and metronidazole. Many reports regarding the eradication rates of quadruple therapy have been reported. However, most were limited by short follow-up periods. Hence, we evaluated the efficacy of the metronidazole containing quadruple therapy as a second line treatment from April, 1996 through July, 2004. METHODS: Sixty-three patients were enrolled. Treatment consisted of aforementioned quadruple therapy for 1 week. Four to six weeks after completion of treatment, biopsies and CLO tests were performed to detect the presence of H. pylori. The patients were then followed-up with upper endoscopy once every year. RESULTS: The efficacy of the quadruple therapy was 74.6% in intention-to-treat analysis and 83.9% in per protocol analysis. Eradication rates of the years 1996, 1999-2000, 2001, and 2002-2004 were 75.0%, 93.8%, 100%, and 72.7%, respectively. CONCLUSIONS: Our data can not reveal the evidence of decreasing trend for eradication rate quadruple therapy of H. pylori in 8 years. However, eradication rate of 72.7% in recent 2 years necessitates the development of more efficient eradication regimen.
Adult ; Antacids/administration & dosage ; Anti-Infective Agents/*administration & dosage ; Bismuth/administration & dosage ; Drug Therapy, Combination ; English Abstract ; Female ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Male ; Metronidazole/*administration & dosage ; Middle Aged ; Peptic Ulcer/microbiology ; Proton Pumps/antagonists & inhibitors ; Recurrence ; Tetracycline/administration & dosage

Helicobacter pylori-infected gastric mucosa is characterized by infiltration of various inflammatory cells such as neutrophils and eosinophils. Although several mechanisms for neutrophil infiltration are well known, there has been little known the role of eotaxin, which is a potent chemoattractant for eosinophils, on the inflammatory process of H. pylori infection. The present study was to investigate the mechanisms of eotaxin expression in gastric epithelial cells stimulated with H. pylori vacuolating cytotoxin (VacA). Stimulation with VacA purified from VacA+ H. pylori slightly increased eotaxin expression in MKN-45 gastric epithelial cells. In contrast, the combined stimulation with VacA and IL-4 synergistically increased the eotaxin expression as determined by quantitative RT-PCR and ELISA. In MKN-45 cells transfected with an eotaxin promoter-luciferase reporter plasmid, costimulation with VacA and IL-4 induced more luciferase activity than either VacA or IL-4 alone did. However, such up-regulation was significantly decreased in the cells transfected with luciferase reporter plasmid bearing an eotaxin promoter which has a mutation at STAT6 binding site. These results suggest that the up-regulation of eotaxin in VacA-stimulated gastric epithelial cells may be synergistically facilitated by IL-4 via a STAT6-dependent mechanism.
Binding Sites ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; Epithelial Cells* ; Gastric Mucosa ; Helicobacter pylori* ; Helicobacter* ; Interleukin-4 ; Luciferases ; Neutrophil Infiltration ; Neutrophils ; Plasmids ; Up-Regulation

Helicobacter pylori-infected gastric mucosa is characterized by infiltration of various inflammatory cells such as neutrophils and eosinophils. Although several mechanisms for neutrophil infiltration are well known, there has been little known the role of eotaxin, which is a potent chemoattractant for eosinophils, on the inflammatory process of H. pylori infection. The present study was to investigate the mechanisms of eotaxin expression in gastric epithelial cells stimulated with H. pylori vacuolating cytotoxin (VacA). Stimulation with VacA purified from VacA+ H. pylori slightly increased eotaxin expression in MKN-45 gastric epithelial cells. In contrast, the combined stimulation with VacA and IL-4 synergistically increased the eotaxin expression as determined by quantitative RT-PCR and ELISA. In MKN-45 cells transfected with an eotaxin promoter-luciferase reporter plasmid, costimulation with VacA and IL-4 induced more luciferase activity than either VacA or IL-4 alone did. However, such up-regulation was significantly decreased in the cells transfected with luciferase reporter plasmid bearing an eotaxin promoter which has a mutation at STAT6 binding site. These results suggest that the up-regulation of eotaxin in VacA-stimulated gastric epithelial cells may be synergistically facilitated by IL-4 via a STAT6-dependent mechanism.
Binding Sites ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; Epithelial Cells* ; Gastric Mucosa ; Helicobacter pylori* ; Helicobacter* ; Interleukin-4 ; Luciferases ; Neutrophil Infiltration ; Neutrophils ; Plasmids ; Up-Regulation