NecroX-5 protects mitochondrial oxidative phosphorylation capacity and preserves PGC1alpha expression levels during hypoxia/reoxygenation injury

Although the antioxidant and cardioprotective effects of NecroX-5 on various in vitro and in vivo models have been demonstrated, the action of this compound on the mitochondrial oxidative phosphorylation system remains unclear. Here we verify the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity during hypoxia-reoxygenation (HR). Necrox-5 treatment (10 microM) and non-treatment were employed on isolated rat hearts during hypoxia/reoxygenation treatment using an ex vivo Langendorff system. Proteomic analysis was performed using liquid chromatography-mass spectrometry (LC-MS) and non-labeling peptide count protein quantification. Real-time PCR, western blot, citrate synthases and mitochondrial complex activity assays were then performed to assess heart function. Treatment with NecroX-5 during hypoxia significantly preserved electron transport chain proteins involved in oxidative phosphorylation and metabolic functions. NecroX-5 also improved mitochondrial complex I, II, and V function. Additionally, markedly higher peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1alpha) expression levels were observed in NecroX-5-treated rat hearts. These novel results provide convincing evidence for the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity and in preserving PGC1alpha during cardiac HR injuries.

Mitochondrial pyruvate dehydrogenase phosphatase 1 regulates the early differentiation of cardiomyocytes from mouse embryonic stem cells

Mitochondria are crucial for maintaining the properties of embryonic stem cells (ESCs) and for regulating their subsequent differentiation into diverse cell lineages, including cardiomyocytes. However, mitochondrial regulators that manage the rate of differentiation or cell fate have been rarely identified. This study aimed to determine the potential mitochondrial factor that controls the differentiation of ESCs into cardiac myocytes. We induced cardiomyocyte differentiation from mouse ESCs (mESCs) and performed microarray assays to assess messenger RNA (mRNA) expression changes at differentiation day 8 (D8) compared with undifferentiated mESCs (D0). Among the differentially expressed genes, Pdp1 expression was significantly decreased (27-fold) on D8 compared to D0, which was accompanied by suppressed mitochondrial indices, including ATP levels, membrane potential, ROS and mitochondrial Ca²⁺. Notably, Pdp1 overexpression significantly enhanced the mitochondrial indices and pyruvate dehydrogenase activity and reduced the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate compared to a mock control. In confirmation of this, a knockdown of the Pdp1 gene promoted the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate. In conclusion, our results suggest that mitochondrial PDP1 is a potential regulator that controls cardiac differentiation at an early differentiation stage in ESCs.

The Critical Roles of Zinc: Beyond Impact on Myocardial Signaling

Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc (Zn2+) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of Zn2+ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular Zn2+ levels are largely regulated by metallothioneins (MTs), Zn2+ importers (ZIPs), and Zn2+ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of Zn2+. However, these regulatory actions of Zn2+ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular Zn2+ levels, Zn2+-mediated signal transduction, impacts of Zn2+ on ion channels and mitochondrial metabolism, and finally, the implications of Zn2+ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of Zn2+.

Efficacy of 7-Day and 14-Day Bismuth-Containing Quadruple Therapy and 7-Day and 14-Day Moxifloxacin-Based Triple Therapy as Second-Line Eradication for Helicobacter pylori Infection

BACKGROUND/AIMS: Bismuth-containing quadruple and moxifloxacin-based triple regimens are recommended as second-line therapy for Helicobacter pylori infection. The aim of this study was to compare the efficacy of each regimen. METHODS: From August 2004 to October 2012, a total of 949 patients (mean age, 54.32+/-12.08 years; male, 49.4%) who failed H. pylori eradication with a standard triple regimen were included. Patients treated with a bismuth-containing quadruple regimen for 7 and 14 days were designated as 7-BMT and 14-BMT, respectively, and those treated with a moxifloxacin-based triple regimen for 7 and 14 days were designated as 7-MA and 14-MA, respectively. H. pylori eradication was confirmed using the 13C-urea breath test, rapid urease test or histology. RESULTS: The eradication rates by 7-BMT, 14-BMT, 7-MA, and 14-MA were 66.4% (290/437), 71.1% (113/159), 53.1% (51/96), and 73.5% (189/257), respectively, by intention-to-treat analysis (ITT) and 76.5% (284/371), 83.8% (109/130), 55.6% (50/90), and 80.6% (187/232), respectively, by per-protocol analysis (PP). The eradication rates were higher in 14-BMT than 7-BMT by the ITT and PP analyses (p=0.277 and p=0.082, respectively). The 14-BMT and 14-MA treatments showed similar efficacies by ITT and PP (p=0.583 and p=0.443, respectively). CONCLUSIONS: The 7-BMT, 14-BMT, and 14-MA treatments showed similar and suboptimal efficacies. In both regimens, extending the duration of treatment may be reasonable considering the high level of antibiotic resistance in Korea.

Effects of aged garlic extract and endurance exercise on skeletal muscle FNDC-5 and circulating irisin in high-fat-diet rat models

BACKGROUND/OBJECTIVES: Irisin, a newly identified hormone, is associated with energy homeostasis. We investigated whether aged garlic extract (AGE) and exercise training intervention could improve body weight, insulin sensitivity, skeletal muscle fibronectin domain containing protein 5 (FNDC-5) levels, and plasma irisin in high-fat diet (HFD). MATERIALS/METHODS: Male Sprague Dawley rats were fed a ND (normal diet, n = 5) or HFD (n = 28) for 6 weeks. After 6 weeks, all rats were divided into 5 groups for the next 4 weeks: ND, (normal diet, n = 5), HFD (high-fat diet, n = 7), HFDA (high-fat diet + aged garlic extract, n = 7), HFDE (high-fat diet + exercise, n = 7), and HFDEA (high-fat diet + exercise + aged garlic extract, n = 7). Exercise groups performed treadmill exercises for 15-60 min, 5 days/week, and AGE groups received AGE (2.86 g/kg, orally injected) for 4 weeks. RESULTS: Significant decreases in body weight were observed in the ND, HFDE, and HFDEA groups, as compared with the HFD group. Neither intervention affected the masses of the gastrocnemius muscle or liver. There were no significant differences in glucose levels across the groups. The homeostatic model assessments of insulin resistance were significantly higher in the HFD group, as compared with the ND, HFDA, HFDE, and HFDEA groups. However, skeletal muscle FNDC-5 levels and plasma irisin concentrations were unaffected by AGE or exercise in obese rats. AGE supplementation and exercise training did not affect skeletal muscle FNDC-5 or plasma irisin, which are associated with insulin sensitivity in obese rats. CONCLUSION: Our results suggest that the protection against HFD-induced increases in body fat/weight and insulin resistance that are provided by AGE supplementation and exercise training may not be mediated by the regulation of FNDC-5 or irisin.

Clinicopathological Features and Surgical Safety of Gastric Cancer in Elderly Patients

Gastric cancer is one of the most common cancers, especially among the elderly. However little is known about gastric cancer in elderly patients. This study was designed to evaluate the specific features of gastric cancer in elderly patients. Medical records of 1,107 patients who had radical gastrectomy for gastric cancer between June 2005 and December 2009 were reviewed. They were divided into young ( or =75 yr, n=99). Increased CA 19-9 (5.6%, 13.4%, 14.6%, P=0.001), advanced diseases (42.5%, 47.0%, and 57.6, P=0.014), and node metastasis (37.6%, 38.9%, 51.5%, P=0.029) were more common in the young-old and old-old age groups. There were no significant differences in Helicobacter pylori status (63.6%, 56.7%, 61.2%, P=0.324) between the three groups. Surgery-related complication rates were similar in the three groups (5.3%, 5.1%, 8.1%, P=0.497). Microsatellite instability (P<0.001) and p53 overexpression (P<0.001) were more common among the elderly. The elderly group had more synchronous tumors (7.5%, 10.2%, 17.2%; P=0.006). Surgery can be applied to elderly gastric cancer without significant risk of complications. However, considering the more advanced disease and synchronous tumors among the elderly, care should be taken while deciding the extent of surgery for elderly gastric cancer.

Kinesin Spindle Protein Inhibition in Translational Research

The kinesin superfamily is a class of motor proteins moving along microtubule filaments and playing essential roles in mitosis of eukaryotic cells. In the cancer biology, mitotic activity is an essential factor for development and metastasis of various cancers. Therefore, the inhibition of kinesin activity is suggested as an alternative cancer therapy. Accumulated clinical evidences have proved the potency of kinesin inhibitors in cancer treatments. In this review, we provided an overview of kinesins that play a critical role in the pathophysiology of various cancers and described the beneficial vs. side effects of their inhibitors that have been tested in both basic science and clinical studies.

Combination treatment with 2-methoxyestradiol overcomes bortezomib resistance of multiple myeloma cells

Bortezomib is a proteasome inhibitor used for the treatment of relapsed/refractory multiple myeloma (MM). However, intrinsic and acquired resistance to bortezomib has already been observed in MM patients. In a previous report, we demonstrated that changes in the expression of mitochondrial genes lead to changes in mitochondrial activity and bortezomib susceptibility or resistance, and their combined effects contribute to the differential sensitivity or resistance of MM cells to bortezomib. Here we report that the combination treatment of bortezomib and 2-methoxyestradiol (2ME), a natural estrogen metabolite, induces mitochondria-mediated apoptotic cell death of bortezomib-resistant MM KMS20 cells via mitochondrial reactive oxygen species (ROS) overproduction. Bortezomib plus 2ME treatment induces a higher level of cell death compared with treatment with bortezomib alone and increases mitochondrial ROS and Ca2+ levels in KMS20 cells. Pretreatment with the antioxidant N-acetyl-L-cysteine scavenges mitochondrial ROS and decreases cell death after treatment with bortezomib plus 2ME in KMS20 cells. Moreover, we observed that treatment with bortezomib plus 2ME maintains the activation of c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase kinase kinase 4/7 (MKK4/7). Collectively, combination treatment with bortezomib and 2ME induces cell death via JNK-MKK4/7 activation by overproduction of mitochondrial ROS. Therefore, combination therapy with specific mitochondrial-targeting drugs may prove useful to the development of novel strategies for the treatment of bortezomib-resistant MM patients.

Prediction of Risk of Malignancy of Gastrointestinal Stromal Tumors by Endoscopic Ultrasonography

BACKGROUND/AIMS: The accurate preoperative prediction of the risk of malignancy of gastrointestinal stromal tumors (GISTs) is difficult. The aim of this study was to determine whether tumor size and endoscopic ultrasonography (EUS) features can preoperatively predict the risk of malignancy of medium-sized gastric GISTs. METHODS: Surgically resected, 2 to 5 cm gastric GIST patients were enrolled and retrospectively reviewed. EUS features, such as heterogeneity, hyperechoic foci, calcification, cystic change, hypoechoic foci, lobulation, and ulceration, were evaluated. Tumors were grouped in 1 cm intervals. The correlations of tumor size or EUS features with the risk of malignancy were evaluated. RESULTS: A total of 75 patients were enrolled. The mean tumor size was 3.43+/-0.92 cm. Regarding the risk of malignancy, 51 tumors (68%) had a very low risk, and 24 tumors (32%) had a moderate risk. When the tumors were divided into three groups in 1 cm intervals, the proportions of tumors with a moderate risk were not different between the groups. The preoperative EUS features also did not differ between the very low risk and the moderate risk groups. CONCLUSIONS: Tumor size and EUS features cannot be used to preoperatively predict the risk of malignancy of medium-sized gastric GISTs. A preoperative diagnostic modality for predicting risk of malignancy is necessary to prevent the overtreatment of GISTs with a low risk of malignancy.

Localized Gastrocnemius Myositis in Crohn's Disease

We describe a case of localized gastrocnemius myositis which developed with flare-up of Crohn's disease. A 21-year old male patient with an 8-year history of Crohn's disease presented with pain and tenderness in both calves without recent abdominal symptoms. Electromyography and gastrocnemius muscle biopsy revealed evidence of inflammatory myositis. Magnetic resonance imaging (MRI) showed bilateral symmetrical diffuse increased signal intensity in T2 weighted images in both gastrocnemius muscles and patchy contrast enhancement. Subsequent gastrointestinal investigation revealed active inflammation of colon with multiple pseudopolyps and enteroenteric fistula on which we commenced oral prednisolone of 30 mg daily. His pain on both calves was improved and muscle enzymes became normal. Following dose reduction of prednisolone, azathioprine 50 mg daily was started considering the patient's active Crohn's disease on endoscopic findings prior to the development of overt abdominal symptoms. This is the first case report of localized gastrocnemius myositis associated with Crohn's disease described in Korea. Calf myositis responded to corticosteroid well and did not recur with maintenance therapy using azathioprine and mesalazine.

High Recurrence Rate of Idiopathic Peptic Ulcers in Long-Term Follow-up

BACKGROUND/AIMS: Our aim was to compare the long-term clinical outcomes of idiopathic peptic ulcer disease (IPUD) with those of Helicobacter pylori-positive and nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcer disease (PUD). METHODS: Patients with endoscopically diagnosed PUD were retrospectively reviewed. According to their H. pylori-infection status and history of NSAIDs use, patients were categorized into three groups: H. pylori-positive PUD, NSAID-induced PUD, and IPUD. Clinical outcomes were analyzed, and the recurrence rate of PUD was compared among the three groups. RESULTS: A total of 238 patients were enrolled. Those with IPUD, NSAID-induced PUD, and H. pylori-positive PUD comprised of 56, 60, and 122 patients, respectively. The 5-year cumulative incidences of recurrent ulcers were 24.3% (95% confidence interval [CI], 11.6% to 37.0%) in IPUD, 10.9% (95% CI, 2.6% to 19.2%) in NSAID-induced PUD, and 3.8% (95% CI, 0.1% to 7.5%) in H. pylori-positive PUD (IPUD vs NSAID-induced PUD/H. pylori-positive PUD, p=0.43/p<0.001 by log-rank test). In the Cox-proportional hazards model, only IPUD remained as an independent risk factor associated with recurrent ulcers (hazard ratio, 5.97; 95% CI, 1.94 to 18.34; p=0.002). CONCLUSIONS: IPUD exhibited a higher recurrence rate than H. pylori-positive and NSAID-induced PUD in long-term follow-up and was an independent risk factor for ulcer recurrence.

Effect of Helicobacter pylori Eradication According to the IL-8-251 Polymorphism in Koreans

Previous studies suggested that polymorphisms of proinflammatory cytokine genes are important host genetic factors in Helicobacter pylori infection. The present study evaluated whether IL-8-251 polymorphism affected H. pylori eradication rate and to investigate the effect of H. pylori eradication on angiogenesis and the inflammatory process according to the IL-8-251 polymorphism. A total of 250 H. pylori-positive patients treated by endoscopic resection of the gastric neoplasm were classified into 3 groups (134 H. pylori-eradicated group, 19 H. pylori-eradication failure group, and 97 H. pylori-infected group). H. pylori status, histology, and angiogenic factor levels were evaluated at baseline, 6 months, and 18 months. H. pylori eradication rate was 92.9% in AA genotype, 85.7% in AT genotype and 88.4% in TT genotype (P value = 0.731). Elevated IL-8 and matrix metalloproteinase-9 concentrations in H. pylori-infected gastric mucosa were reversible by successful eradication of H. pylori, independent of the IL-8-251 polymorphism. It is suggested that elevated IL-8 and MMP-9 concentrations in H. pylori-infected gastric mucosa are altered significantly after successful eradication and these conditions continue for 18 months. However, IL-8-251 polymorphism does not affect H. pylori eradication rate and the sequential changes of related angiogenic factors after H. pylori eradication in Koreans.

Clinical Characteristics of Patients Diagnosed as Peptic Ulcer Disease in the Third Referral Center in 2007 / 대한소화기학회지

BACKGROUND/AIMS: In spite of the improvement of medical treatment for the peptic ulcer disease (PUD), PUD is still one of the common upper gastrointestinal diseases. The purpose of this study was to evaluate the risk factors and general characteristics of Korean patients diagnosed as PUD at a single third referral center. METHODS: A total of 310 patients, diagnosed as PUD through endoscopy during one year of 2007 at Seoul National University Bundang Hospital were, retrospectively, evaluated regarding age, gender, Helicobacter pylori (H. pylori) positivity, clinical manifestations, comorbidities and medications. In addition, PUD was analyzed in the aspect of ulcer location, type of visit, gastrointestinal bleeding, and age. RESULTS: The mean age was 61.5 years old (48.1% over 65) and 208 (66.7%) patients were men. The rate of H. pylori infection was 47.8%, and any ulcerogenic medication history such as antiplatelet agents and NSAIDs was found to be 21.0% (65 patients). The rate of idiopathic peptic ulcer without evidence of H. pylori and NSAIDs was found to be 40.6% (126 patients). Among 310 PUD patients, bleeding symptoms such as melena, hematemesis and hematochezia occurred in 110 patients (35.5%). CONCLUSIONS: PUD was more prevalent in the elderly patients and frequently associated with bleeding. Substantial proportion of PUD patients had neither H. pylori infection nor history of ulcerogenic medications, suggesting of increasing prevalence of idiopathic PUD.

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.

The Risk Factors for Colonic Diverticular Bleeding / 대한소화기학회지

BACKGROUND/AIMS: Colonic diverticular bleeding cases account for 30-40% of the lower gastrointestinal bleeding, among which, 3-5% appear to be massive bleeding. The purpose of this study was to evaluate the risk factors for colonic diverticular bleeding diagnosed by colonoscopic examination. METHODS: Among the 1,003 patients, who were identified to have colonic diverticulosis including sleeding by diverticulitis and diverticular bleeding coding search, 216 patients had diverculosis, and they were divided into two groups: one with diverticular bleeding, and the other without bleeding. We evaluated the potential risk factors for diverticular bleeding, based on age, gender, location of diverticulum, comorbidities related to atherosclerosis, smoking, alcohol and medications, and compared them between both groups. RESULTS: Among the 216 patients, we observed colonic diverticular bleeding in 35 patients (16.2%). The mean age of the bleeding group was significantly older than that of non-bleeding group. No difference was observed regarding gender ratio. Right colonic diverticula were common in both groups, but there were higher proportion of patients with bleeding in bilateral diverticuosis. Old age, bilateral diverticulosis, presence of atherosclerosis related diseases (hypertension, diabetes mellitus, ischemic heart disease, obesity), use of aspirin, NSAIDs and calcium channel blocker, increased the risk of bleeding. In a multivariate analysis, use of aspirin and bilateral diverticulosis were identified as independent risk factors for colonic diverticular bleeding. CONCLUSIONS: Since the patients who took aspirin and/or had bilateral colonic diverticulosis increased the risk of bleeding from divertuculi. As such, caution and education of patients are required.

The Role of CDX2 in Intestinal Metaplasia Evaluated Using Immunohistochemistry

BACKGROUND/AIMS: Intestinal metaplasia (IM) has been regarded as a premalignant condition. This study evaluated the role of the transforming factor CDX2 according to the severity and type of IM. METHODS: This analysis was performed on 383 subjects with IM in the antrum and/or body, with diagnoses that were categorized as controls, dysplasias, and gastric cancers. The IM grades were classified into four groups as negative, mild, moderate or severe using the updated Sydney scoring system. The IM subtypes were categorized as type I, type II, and type III using high iron diamine and alcian blue (pH 2.5) staining. The CDX2 expression in the IM foci was evaluated using immunohistochemistry in specimens from the antrum and/or body. RESULTS: CDX2 expression increased according to IM severity (p=0.001) but was not associated with the IM subtype (p=0.881) in the antrum specimens. Similarly, CDX2 expression increased according to the IM grade (p=0.001) but was not associated with the IM subtype (p=0.755) in the body specimens. CDX2 expression was also increased according to baseline disease in the antrum, especially dysplastic and GC group (p=0.003), but not in the body (p=0.582). However, status of Helicobacter pylori infection was not associated with CDX2 expression in the antrum (p=0.692) and body (p=0.271). CONCLUSIONS: These results show that CDX2 expression is associated with the IM grade regardless of the IM subtype and that it was more frequent in the dysplasia group. These results suggest that CDX2 expression might play an important role in the progression of IM in various environments that can affect neoplastic change.

Primary Antibiotic Resistance of Helicobacter pylori Strains and Eradication Rate according to Gastroduodenal Disease in Korea / 대한소화기학회지

BACKGROUND/AIMS: This study was performed to evaluate whether the prevalence rates of primary antibiotic resistance in Helicobacter pylori (H. pylori) isolates and the eradication rate of H. pylori could be different between cancer and non-cancer patients. METHODS: H. pylori were isolated from gastric mucosal biopsy specimens obtained from 269 Koreans, who did not have any eradication therapy history and were diagnosed as one of the following diseases; chronic gastritis, benign gastric ulcer, duodenal ulcer or gastric cancer. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin were examined with the agar dilution method. In addition, eradication rate of H. pylori was evaluated. RESULTS: There was no significant difference in the primary antibiotic resistance to above eight antibiotics among chronic gastritis, peptic ulcer disease and gastric cancer. Furthermore there was no difference of antibiotic resistance between cancer and non-cancer patients, and there was no difference of eradication rate of H. pylori according to disease. CONCLUSIONS: Primary antibiotic resistance and H. pylori eradication rate were not different between cancer and non-cancer patients.

Effects of Proton Pump Inhibitors in Asthmatics with Gastroesophageal Reflux Disease / 대한소화기학회지

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) is common in asthma patients. Proton pump inhibitor (PPI) therapy improves symptoms of asthma in some patients. The objective of this study was to investigate endoscopic findings of GERD in asthma patients and to assess the effect of gastric acid suppression with the PPIs on symptom improvement and pulmonary function. METHODS: From 105 consecutive patients with GERD symptoms during follow up for asthma, 45 patients were enrolled. Patients enrolled to this study were asked about GERD symptoms before and after treating with PPI. Endoscopic findings were described according to Los Angeles classification. The improvement of asthma symptoms and follow-up pulmonary function test were investigated after administration of PPIs. RESULTS: Esophageal symptoms such as heartburn and acid reflux were present in 25 patients (55.6%), and patients without esophageal symptoms were 20 (44.4%). The degree of endoscopic abnormality was not significantly different between groups with or without esophageal symptoms. The improvement of symptoms was seen in 44 patients (97.8%) except 1 patient after administration of PPIs. The number of patients classified to the low-dose group was 7 patients (15.6%) and that of patients classified to the standard-dose group was 38 patients (84.4%). The follow-up pulmonary function test, peak expiratory flow rate (L/sec) was improved in 3 patients (3 of 7, 42.9%) of the low-dose group, and in 24 patients (24 of 38, 63.2%) of the standard-dose group. The improvement of ventilatory function was not significantly different according to dose of PPIs. CONCLUSIONS: Treatment with PPIs is expected to improve subjective symptoms and ventilatory function in asthma patients.

CDX1 and CDX2 Expression in Intestinal Metaplasia, Dysplasia and Gastric Cancer

Intestinal metaplasia (IM) has been regarded as a premalignant condition. However, the pathogenesis of IM is not fully understood. The aim of this study was to evaluate the role of CDX1 and CDX2 in the formation of IM and the progression to dysplasia and gastric cancer (GC). A total of 270 subjects included 90 with GC, dysplasia and age- and sex-matched controls. Real-time PCR (RT-PCR) was performed with body specimens for CDX1 and CDX2. The expression of CDX2 was significantly higher in H. pylori positive group than H. pylori negative group (P = 0.045). CDX1 and CDX2 expression increased proportional to the IM grade of the body (P < 0.001). CDX2 expression was significantly higher in incomplete type of IM than in complete type (P = 0.045). The expression of CDX1 in dysplasia group was significantly higher than in the control group (P = 0.001); in addition, CDX1 and CDX2 in cancer group was significantly higher than control group (P < 0.001, and P < 0.001, respectively). Aberrant expression of CDX1 and CDX2 correlated with H. pylori infection and grade of IM in the body. Furthermore, the results suggest that CDX1 and CDX2 play a role in the progression to GC and dysplasia.

Helicobacter pylori Serology Inversely Correlated With the Risk and Severity of Reflux Esophagitis in Helicobacter pylori Endemic Area: A Matched Case-Control Study of 5,616 Health Check-Up Koreans

BACKGROUND/AIMS: The role of Helicobacter pylori in gastroesophageal reflux disease remains still controversial and the effect of the organism on severity of reflux esophagitis have been rarely issued. The aim of this study was to investigate the relationship between H. pylori infection and reflux esophagitis, and especially the severity of reflux esophagitis. METHODS: We performed a cross-sectional case-control study of 5,616 subjects undergoing both upper endoscopy and H. pylori serology during health Check-up (2,808 cases vs age- and sex-matched controls). Smoking, alcohol, body mass index and waist circum - ference were added to a multiple regression model. RESULTS: Prevalence of H. pylori infection was lower in cases with reflux esophagitis than in controls (38.4% vs 58.2%, P < 0.001) and negative associations with H. pylori infection continued across the grade of esophagitis (46.7% in Los Angeles classification M [LA-M], 34.3% in LA-A or LA-B and 22.4% in LA-C or LA-D, P < 0.001). Positive serology for H. pylori independently reduced the risk of reflux esophagitis (adjusted OR, 0.44; 95% CI, 0.39-0.49). Notably, the negative associations continued across the grade of esophagitis with adjusted ORs of 0.63 in LA-M, 0.36 in LA-A or LA-B and 0.20 in LA-C or LA-D (P < 0.001). CONCLUSIONS: In a age-sex matched Korean, H. pylori seropositivity was independently and inversely associated with the risk and severity of reflux esophagitis, suggesting the organism may have a protective role against gastroesophageal reflux disease.