Ryoung Hee Nam

Prevalence of Primary and Secondary Antimicrobial Resistance of Helicobacter pylori in Korea from 2003 through 2012

Antimicrobial resistance of Helicobacter pylori (H. pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H. pylori isolates to antibiotics and to characterize the risk factors associated with antimicrobial resistance in Korea.

Change in antibiotic resistance of Helicobacter pylori strains and the effect of A2143G point mutation of 23S rRNA on the eradication of H. pylori in a single center of Korea.

Background The current prevalence of primary antibiotic resistance of H. pylori is not known in Korea. This study was done to evaluate the prevalence of primary antibiotic resistance of H. pylori, and to evaluate the effect of point mutations of 23S rRNA on the rate of eradication of H. pylori. Methods H. pylori were isolated from gastric mucosal biopsy specimens obtained from 222 Koreans. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin were examined using the agar dilution method. DNA sequencing was carried out to detect H. pylori 23S rRNA mutations. Results The resistance to clarithromycin, tetracycline, ciprofloxacin, and levofloxacin increased during the period of 2007 to 2009 compared with 2003 to 2005 (P<0.05). However, amoxicillin and metronidazole resistance slightly decreased. The rates of eradication were 95.5% for the clarithromycin-sensitive strains, which was higher than the 67.9% for the clarithromycin-resistant strains (P=0.001). By contrast, the eradication rate was 100% in patients with amoxicillin-resistant H. pylori. Among 26 clarithromyin-resistant strains, 6 (23%) had A2143G mutations, and all of the cases in which these mutations were present were not eradicated by proton pump inhibitor-based triple therapy (P=0.0004). By contrast, none of the 26 clarithromyin-sensitive strains had A2143G mutations. The T2183C and A2223G mutations were frequently found in the sensitive strains and in the resistant strains. Conclusions Clarithromycin resistance of H. pylori, which determined the efficacy of H. pylori eradication of proton pump inhibitor triple regimen, was found to be increased in a single center study. A2143G was an important 23S rRNA mutation associated with clarithromycin resistance and affected the H. pylori eradication efficacy.

Moxifloxacin-Containing Triple Therapy as Second-Line Treatment for Helicobacter pylori Infection: Effect of Treatment Duration and Antibiotic Resistance on the Eradication Rate

Background and Aim:  The aim of this study was to evaluate the efficacy of a moxifloxacin‐containing triple therapy as second‐line treatment for Helicobacter pylori infection. We also investigated the effect of treatment duration and antibiotic resistance on the eradication rate of this therapy.

Effect of aging on gastric mucosal defense mechanisms: ROS, apoptosis, angiogenesis, and sensory neurons.

Aging changes in the stomach lead to a decreased capacity for tissue repair in response to gastric acid. The aim of this study was to determine the mechanism associated with the increased susceptibility to injury of aging mucosa including reactive oxygen species (5), apoptosis, angiogenesis, and sensory neuron activity. Fischer 344 rats at four different ages (6, 31, 74 wk, and 2 yr of age) were studied. The connective tissue indicators [salt-soluble collagen and sulfated glycosaminoglycan (sGAG)], lipid hydroperoxide (LPO), myeloperoxidase (MPO), and hexosamine were assessed. We also evaluated the expression of early growth response-1 (Egr-1), phosphatase and tension homologue deleted on chromosome 10 (PTEN), caspase-9 (index of apoptosis), VEGF (index of angiogenesis), calcitonin gene-related peptide (CGRP, index of sensory neurons), and neuronal nitric oxide synthase (nNOS). The histological connective tissue area in the lower part of rat gastric mucosa increased with aging, with increase of salt-soluble collagen and sGAG. LPO and MPO in old rats were significantly greater than in the young rats, whereas hexosamine was significantly reduced. The old gastric mucosa had increased expression of Egr-1, PTEN, and caspase-9, whereas the VEGF, CGRP, and nNOS expression were significantly reduced. These results indicate that the lower part of rat gastric mucosa was found to be replaced by connective tissue with accumulation of oxidative products with aging. In addition, impairment of apoptosis, angiogenesis, and sensory neuron activity via the activation of Egr-1 and PTEN might increase the susceptibility of gastric mucosa to injury during aging.

Comparison of Indomethacin, Diclofenac and Aspirin-Induced Gastric Damage according to Age in Rats

Background/Aims Aging gastric mucosa is known to have decreased mucosal defenses and increased susceptibility to injury by nonsteroidal anti-inflammatory drugs. Depending on the type of nonsteroidal anti-inflammatory drug (NSAID), the underlying mechanisms and the extent of damage to the stomach or intestine may differ. This study was performed to evaluate the acute gastric damage caused by different doses of indomethacin, diclofenac and aspirin in rats of various ages. Methods For the acute models, indomethacin (10, 20 or 40 mg/kg), diclofenac (40 or 80 mg/kg) or aspirin (100 mg/kg) was given to 7- and 25-week-old and 1-year-old Sprague-Dawley rats by intragastric gavage. The gross ulcer index, damage area as assessed by imaging, histological index, myeloperoxidase (MPO) activity, and cytosolic phospholipase A2 (cPLA2) levels were measured after 24 hours. Results The gross ulcer index and damage area increased with age in the presence of three NSAIDs (p<0.05). The increases in MPO levels induced by diclofenac and aspirin were significantly higher in 1-year-old than 7-week-old rats (p<0.05). cPLA2 expression induced by indomethacin (10 and 40 mg/kg) was greater in the 1-year-old rats, compared with 7-week-old rats (p<0.05). Conclusions NSAID-induced acute gastric damage increased in a dose- and age-dependent manner.

GenoType HelicoDR test in the determination of antimicrobial resistance of Helicobacter pylori in Korea

Abstract Objective. Antimicrobial resistance of Helicobacter pylori is most important factor in eradication success. GenoType HelicoDR test has been developed for rapid detection of antimicrobial resistance. The present study evaluated the clinical usefulness of GenoType HelicoDR test in Korea. Materials and methods. To detect 23S rRNA for clarithromycin resistance and gyrA mutations for fluoroquinolone resistance, both DNA sequencing after minimal inhibitory test (MIC) and GenoType HelicoDR test were performed in H. pylori isolates from the gastric mucosa of 101 patients. The eradication results of clarithromycin and moxifloxacin-containing triple therapy were evaluated by the 23S rRNA and gyrA mutations. Results. For 42 isolates with A2143G mutation by GenoType HelicoDR, 83.3% (35/42) of concordance rate was estimated with DNA sequencing method and 85.7% (36/42) for MIC test. For 43 isolates with N87K mutation by GenoType HelicoDR, 71.1% (31/43) of concordance rate was estimated with DNA sequencing and 88.4% (38/43) for MIC test. The sensitivity and specificity of GenoType HelicoDR test in determination of 23S rRNA mutation were 94.9% and 87.1%, and those of gyrA 98.2% and 80.0%. The sensitivity and specificity of GenoType HelicoDR test in determination of clarithromycin resistance based on MIC test were 55.0% and 80.0%, for fluoroquinolone 74.4% and 70.0%. Conclusion. GenoType HelicoDR test is useful to determine mutations responsible for clarithromycin or fluoroquinolone-containing eradication failure but has a limitation for the clinical applicability in determination of resistance.

Different MicroRNA Expression Levels in Gastric Cancer Depending on Helicobacter pylori Infection

Background/Aims This study was conducted to identify microRNAs (miRNAs) that are differentially expressed in Helicobacter pylori-infected patients with an intestinal type of gastric cancer using miRNA microarray and to confirm the candidate miRNA expression levels. Methods Total RNA was extracted from the cancerous and noncancerous regions of formalin-fixed, paraffin-embedded tissues of H. pylori-positive (n=8) or H. pylori-negative (n=8) patients with an intestinal type of gastric cancer. RNA expression was analyzed using a 3,523 miRNA profiling microarray based on the Sanger miRBase. Validation analysis was performed using TaqMan miRNA assays. Results A total of 219 miRNAs in the aberrant miRNA profiles across the miRNA microarray showed at least a 2-fold change differential expression in H. pylori-positive and H. pylori-negative cancer tissues. After candidate miRNAs were selected using online miRNA databases, TaqMan miRNA assays confirmed that three miRNAs (miR-99b-3p, miR-564, and miR-638) were significantly increased in three H. pylori-positive cancer tissues compared to the H. pylori-negative cancer tissues. Additionally, four miRNAs (miR-204-5p, miR-338-5p, miR-375, and miR-548c-3p) were significantly increased in H. pylori-negative cancer tissues compared to H. pylori-positive cancer tissues. Conclusions miRNA expression in the intestinal type of H. pylori infection-dependent gastric cancer suggests that different gastric cancer pathogenesis mechanisms could exist between H. pylori-positive and H. pylori-negative gastric cancer. Additional functional studies are required.

Mutations of Helicobacter pylori Associated with Fluoroquinolone Resistance in Korea

Background and Aim:  Fluoroquinolone resistance of Helicobacter pylori is known to be dependent on mutations in the QRDR of gyrA. This study was performed to investigate the distribution of gyrA point mutations and to evaluate the impact of the mutations on second‐line H. pylori eradication therapy.

Analysis of Gastric Microbiota by Pyrosequencing: Minor Role of Bacteria Other Than Helicobacter pylori in the Gastric Carcinogenesis.

Little is known about the role of gastric microbiota except for Helicobacter pylori (HP) in human health and disease. We compared the differences of human gastric microbiota according to gastric cancer or control and HP infection status and assessed the role of bacteria other than HP.

A comparison between 15-day sequential, 10-day sequential and proton pump inhibitor-based triple therapy for Helicobacter pylori infection in Korea

Abstract Objective. The eradication rate of 10-day sequential therapy for Helicobacter pylori (H. pylori) infection was not satisfactory in Korea, probably due to antibiotic resistance. To compare the treatment efficacy of 15-day and 10-day sequential therapy of conventional 7-day proton pump inhibitor (PPI) triple therapy for the treatment of H. pylori infection. Methods. A total of 332 patients with H. pylori infection were randomly assigned to receive either 7-day PPI triple therapy, 10-day sequential therapy or 15-day sequential therapy. Eradication rate, drug compliance, and adverse events were compared among the three regimens. Results. The eradication rates by intention-to-treat analysis were 64.3% (95% CI: 55.5–73.2; 74 of 115 patients), 72.1% (95% CI: 63.6–80.5; 80 of 111 patients), and 80.2% (95% CI: 72.5–87.9; 85 of 106 patients) in the 7-day PPI triple, 10-day and 15-day sequential therapy groups, respectively (p = 0.032). The eradication rates by per-protocol analysis were 68.5% (95% CI: 59.6–77.4; 74 of 108 patients), 78.4% (95% CI: 70.3–86.5; 80 of 102 patients), and 89.5% (95% CI: 83.2–95.8; 85 of 95 patients) in the 7-day PPI triple, 10-day and 15-day sequential therapy groups, respectively (p = 0.001). There were no statistically significant differences between the three eradication therapy groups in regard to drug compliance and adverse events. Conclusion. The 15-day sequential therapy demonstrated improved eradication efficacy compared with 7-day PPI triple and 10-day sequential therapy in Korea.