Gastroprotective Effect of Cochinchina momordica Seed Extract in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Damage in a Rat Model

BACKGROUND/AIMS: The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. METHODS: The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. RESULTS: All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. CONCLUSIONS: SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.

Difficult Establishment of a Chronic Nonsteroidal Anti-inflammatory Drugs Induced Gastric Inflammation Rat Model due to Gastric Adaptation and Small Bowel Damage / 대한소화기학회지

BACKGROUND/AIMS: The prevalence of peptic ulcer disease has not decreased mainly due to an increase in the use of NSAIDs. This study was conducted in order to determine whether a chronic NSAID-induced gastric inflammation model could be established by repeated administration of NSAID. METHODS: Indomethacin (10 mg/kg) was administered once per week for six weeks in 8- and 26-week rats and animals were sacrificed every week after administration. Gross ulcer index, histologic damage index, myeloperoxidase (MPO) activity, and mucus (glucosamine) levels were measured. Small bowel damage was also evaluated. RESULTS: Gross gastric damage index showed a peak level at three weeks and then decreased slowly in the 26-week indomethacin group. Gastric mucosal glucosamine level increased in both the 8-week (p=0.038) and 26-week groups (p=0.007). In addition, gastric mucosal MPO level decreased in the 8-week group (p=0.018) but did not show a decrease in the 26-week group. Small bowel damage began to occur at three weeks during the schedule and eight of 36 rats (22.2%) died due to perforation or peritonitis of the small bowel in the 8- and 26-week indomethacin groups, respectively. CONCLUSIONS: Due to gastric adaptation and small bowel damage, repeated administration of NSAID to experimental animals may not be an adequate method for establishment of the chronic gastric inflammation model.

Difficult Establishment of a Chronic Nonsteroidal Anti-inflammatory Drugs Induced Gastric Inflammation Rat Model due to Gastric Adaptation and Small Bowel Damage / 대한소화기학회지

BACKGROUND/AIMS: The prevalence of peptic ulcer disease has not decreased mainly due to an increase in the use of NSAIDs. This study was conducted in order to determine whether a chronic NSAID-induced gastric inflammation model could be established by repeated administration of NSAID. METHODS: Indomethacin (10 mg/kg) was administered once per week for six weeks in 8- and 26-week rats and animals were sacrificed every week after administration. Gross ulcer index, histologic damage index, myeloperoxidase (MPO) activity, and mucus (glucosamine) levels were measured. Small bowel damage was also evaluated. RESULTS: Gross gastric damage index showed a peak level at three weeks and then decreased slowly in the 26-week indomethacin group. Gastric mucosal glucosamine level increased in both the 8-week (p=0.038) and 26-week groups (p=0.007). In addition, gastric mucosal MPO level decreased in the 8-week group (p=0.018) but did not show a decrease in the 26-week group. Small bowel damage began to occur at three weeks during the schedule and eight of 36 rats (22.2%) died due to perforation or peritonitis of the small bowel in the 8- and 26-week indomethacin groups, respectively. CONCLUSIONS: Due to gastric adaptation and small bowel damage, repeated administration of NSAID to experimental animals may not be an adequate method for establishment of the chronic gastric inflammation model.

The Clinical Significance of Specialized Intestinal Metaplasia in the Diagnosis of Barrett's Esophagus: Nationwide Prospective Multicenter Study

BACKGROUND/AIMS: The meaning of specialized intestinal metaplasia (SIM) in the diagnosis of Barrett's esophagus (BE) is not clear. This study was designed to determine the clinical significance of SIM in the diagnosis of Barrett's esophagus. MATERIALS AND METHODS: Biopsies were taken from 601 subjects with endoscopically suspected columnar-lined esophagus. Under light microscopy with Alcian-blue stain, SIM was identified. Demographic characteristics, gastroesophageal (GE) reflux symptoms and endoscopic findings were compared between the SIM-present group and the SIM-absent group. RESULTS: Among 601 subjects, 184 (30.6%) were confirmed by pathology to have SIM. Age over 40 years (P<0.001) and a medication history of proton pump inhibitor or H2 blocker were found more frequently in the SIM-present group (P=0.01) than in the SIM-absent group. Any of 7 GE reflux symptoms (heartburn, acid regurgitation, chest pain, hoarseness, globus sensation, cough and epigastric soreness) were more frequent in the SIM-present group than SIM-absent group (P<0.001). Specifically, heartburn, chest pain and cough were significantly more common in the SIM-present group. There was no clinically significant difference associated with endoscopic findings or other clinical characteristics. CONCLUSIONS: When subjects with endoscopically suspected BE are analyzed based on the presence or absence of SIM, the SIM-present group was significantly associated with GE reflux symptoms suggestive of frequent GE reflux. However, the presence of SIM did not correlate with endoscopic findings.

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.

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.

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.

Risk Factors for Development and Recurrence of Peptic Ulcer Disease / 대한소화기학회지

BACKGROUND/AIMS: Peptic ulcer disease (PUD) is one of the common gastrointestinal diseases, and its medical management has been developed so much that the incidence of its serious complications, such as bleeding and perforation, are declining significantly. Its prevalence in Korea is not definitely decreased, probably due to increasing proportion of elderly patients and their rising usage of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirins. This study was conducted to identify the risk factors for development and recurrence of peptic ulcer disease in Korea. METHODS: From 2003 to 2008, upper gastrointestinal endoscopy and detailed personal questionnaires were performed for patients who visited Department of Gastroenterology at Seoul National University Bundang Hospital. In total, 475 PUD patients and 335 non-ulcer dyspepsia patients were included. The results of questionnaires and repeated upper gastrointestinal endoscopy at initial diagnosis time and follow-up periods were analyzed. RESULTS: Multivariable analysis showed that male, H. pylori infection, NSAIDs use and smoking were risk factors for the development of PUD. The use of proton pump inhibitors (PPIs) and H2 receptor antagonists has significantly reduced the risk of PUD in patients who had taken NSAIDs and/or aspirins. H. pylori infection was found as the only risk factor for the recurrence of PUD. CONCLUSIONS: For the old patients who are taking drugs, such as NSAIDs and aspirins, concomitant use of PPIs or H2 receptor antagonists should be considered to protect from the development of PUD. H. pylori eradication has been confirmed again to be essential for the treatment of PUD patients infected with H. pylori.

The clinical characteristics of noncardiac chest pain and treatment response in non-erosive reflux disease (NERD) / 대한내과학회지

BACKGROUND/AIMS: Noncardiac chest pain (NCCP) is defined as recurring angina-like retrosternal chest pain of noncardiac origin. Gastroesophageal reflux disease (GERD) is by far the most common cause of NCCP. We evaluated the incidence of some esophageal abnormalities as a cause of NCCP and the treatment response to a proton pump inhibitor (PPI). METHODS: Forty seven NCCP cases were selected from 184 cases who underwent 24-hour ambulatory pH monitoring or esophageal manometry. Patients were excluded if they had a history of gastrointestinal surgery, pancreatobiliary disorder, coronary artery disease, valvular heart disease, depression or tuberculosis. In this study, all GERD patients had non-erosive reflux disease (NERD). RESULTS: Of the 47 NCCP cases, 30 (63.8%) were female and 17 (36.2%) were male. Only 7 (14.9%) cases had typical GERD symptoms such as acid regurgitation and heartburn. Of the 47 NCCP cases, 12 (25.5%) had GERD-related NCCP, and six (12.8%) had esophageal motility disorder. Of the 12 cases diagnosed as GERD-related NCCP, nine (75.0%) showed a satisfactory PPI response. The PPI was effective for GERD-related NCCP compared with non-GERD related NCCP (p=0.015). CONCLUSIONS: About 40% of NERD patients with NCCP had an esophageal disorder including GERD and esophageal motility disorder. A PPI was effective for GERD-related NCCP.

The Long-term Clinical Efficacy of Biofeedback Therapy for Patients With Constipation or Fecal Incontinence

BACKGROUND/AIMS: There has been a controversy regarding the usefulness of biofeedback therapy for functional constipation or fecal incontinence. This study was performed to investigate the long-term clinical efficacy of biofeedback therapy. METHODS: Sixty-four patients with constipation or fecal incontinence received biofeedback therapy for 4 weeks. Symptom improvements were evaluated immediately after the completion of biofeedback therapy and during the follow-up period of about 12 to 64 months. RESULTS: Twenty-five patients in the constipation group [mean age of 52.1 years, 16 men (64.0%)] received 6.2 sessions of biofeedback therapy. Improvement of constipation after the completion of biofeedback therapy was as follows: major response (or improvement) in 3 patients (12.0%), fair in 6 (24.0%), minor in 11 (44.0%) and none in 5 (20.0%). Among 9 patients who showed major or fair improvement, 8 patients (88.9%) maintained the symptom improvement through the long term follow-up periods. Thirty-nine patients in the fecal incontinence group [59.7 years old, 15 men (38.5%)] received 6.8 sessions of biofeedback therapy. Improvement of incontinence after the completion of biofeedback therapy was as follows: major improvement in 6 patients (15.4%), fair in 14 (35.9%), minor in 14 (35.9%), and none in 5 (12.8%). All 11 patients with major or fair improvement maintained the symptom improvement to the end of follow-up periods. CONCLUSIONS: Symptom improvements after biofeedback therapy were disappointing in both the constipation and incontinence group. However, when the symptom improvements were classified as major or fair, the improvements continued for at least a year.

Two Cases of Chronic Idiopathic Intestinal Pseudo-obstruction with Different Clinical Features

Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder characterized by a severe impairment of gastrointestinal propulsion in the absence of mechanical obstruction. We experienced a case of chronic pseudo-obstruction in the initial phase mimicking acute pseudo-obstruction, which was treated medically. This ongoing case was compared to another recurrent and intractable case successfully treated with surgery and diagnosed as hypoganglionosis. These two cases showed different clinical features and therapeutic approaches for CIPO; one with the first episode of CIPO mimicking Ogilvie's syndrome; the other with recurrent episodes of CIPO with typical features. In conclusion, CIPO is a difficult disorder with various clinical manifestations and different treatment modalities, therefore individualized diagnostic and therapeutic approaches are needed.

Comparison of Direct Medical Care Costs Between Erosive Reflux Disease and Non-erosive Reflux Disease in Korean Tertiary Medical Center

BACKGROUND/AIMS: Gastroesophageal reflux disease is one of the most common and frequent chronic disease requiring considerable cost. We investigated the medical care costs in the erosive reflux disease (ERD) and non-erosive reflux disease (NERD). METHODS: The risk factors and the direct medical care costs were analyzed retrospectively in the ERD (178 patients) and NERD (183 patients) groups for a follow up period of 2 years. RESULTS: Logistic regression analysis showed that the ERD was more frequent in the groups of male gender, alcohol consumption, higher body mass index (> or =25 kg/m2), hiatal hernia, and higher triglyceride levels (> or =150 mg/dL). The direct medical care costs per person for 2 years were found to be $384.8 (ERD) and $412.9 (NERD) without statistically significant differences (p = 0.364). However, 9.3% (17/183) of the NERD patients had visited the emergency room compared to 3.4% (6/178) of the ERD patients (p = 0.029). In addition, more NERD patients were hospitalized than ERD patients (p = 0.006), and because of the longer hospitalization period, the medical costs in NERD patients were higher than ERD patients (p = 0.038). CONCLUSIONS: In spite of the different risk factors for ERD and NERD, total direct medical care costs were similar between the ERD and NERD group. However, more visits to emergency room and longer hospitalization period with more hospitalization costs in NERD patients account for the differences in medical service and usage distribution between the 2 groups.

Comparison between Conventional 4 L Polyethylene Glycol and Combination of 2 L Polyethylene Glycol and Sodium Phosphate Solution as Colonoscopy Preparation / 대한소화기학회지

BACKGROUND/AIMS: Effective bowel preparation is essential for accurate diagnosis of colon disease. We investigated efficacy and safety of 2 L polyethylene glycol (PEG) solution with 90 mL sodium phosphate (NaP) solution compared with 4 L PEG method. METHODS: Between August 2009 and April 2010, 526 patients were enrolled who visited Seoul National University Bundang Hospital for colonoscopy. We allocated 249 patients to PEG 4 L group and 277 patients to PEG 2 L with NaP 90 mL group. Detailed questionnaires were performed to investigate compliance, satisfaction and preference of each method. Bowel preparation quality and segmental quality were evaluated. Success was defined as cecal intubation time less than 20 minutes without any help of supervisors. RESULTS: Both groups revealed almost the same baseline characteristics except the experience of operation. PEG 4 L group's compliance was lower than PEG 2 L with NaP 90 mL group. Success rate and cecal intubation time was not different between two groups. Overall bowel preparation quality of PEG 2 L with NaP 90 mL group was better than PEG 4 L group. Segmental bowel preparation quality of PEG 2 L with NaP 90 mL group was also better than PEG 4 L group in all segments, especially right side colon. Occurrence of hyperphosphatemia was higher in PEG 2 L with NaP 90 mL group than PEG 4 L group. However, significant adverse event was not reported. CONCLUSIONS: PEG 2 L with NaP 90 mL method seems to be more effective bowel preparation than PEG 4 L method.

Granulocyte transfusions from G-CSF- and dexamethasone-stimulated healthy donors for treatment of patients with severe neutropenia-related infections / 대한내과학회지

BACKGROUND: Granulocyte transfusions have been used to treat severe, progressive infections in neutropenic patients who fail to respond to antimicrobial agents. Although corticosteroid or granulocyte colony-stimulating factor (G-CSF) were previously used separately to increase leukocyte counts in healthy donors, increasingly G-CSF and corticosteroids are used together, requiring the need to establish the efficacy of this mobilizing regime. METHODS: This prospective study evaluated the safety and efficacy of granulocyte transfusion therapy from donors stimulated with a combination of G-CSF and dexamethasone, in 27 patients with severe neutropenia-related infections. To mobilize granulocytes, healthy volunteer donors received G-CSF, 5 micro gram/kg subcutaneously 12-14 hr before leukapheresis, and dexamethasone, 3 mg/m2 intravenously 15 min before leukapheresis. RESULTS: Donor neutrophil counts were 5,723/micro L (range: 1,500~36,420) at baseline, 22,104/micro L (range: 9,700~41,300) before the injection of dexamethasone, 23,946/micro L (range: 10,900~42,100) immediately before leukapheresis, and 19,913/micro L (range: 9,100~36,300) after leukapheresis. Ninety-two leukapheresis procedures were performed with a mean yield of 7.88 10(10) granulocytes (range: 2.2~17.9 10(10)). The mobilizing agents were well tolerated in the donors. Of the patients, 16 (59.3%) showed favorable responses, whereas 11 (40.7%) had unfavorable responses. Adverse reactions to the therapy were arrhythmia in two patients (7.4%) and pulmonary edema in one patient (3.7%). Favorable responses were seen in 83.3, 76.9, and 45.5% of the patients from whom fungal, Gram-negative, and Gram-positive organisms were isolated, respectively. CONCLUSION: This study suggests that the combination of G-CSF and dexamethasone is an effective, well-tolerated regimen for mobilizing granulocytes from healthy donors, and that granulocyte transfusion therapy is useful for neutropenic patients, especially those with fungal or Gram-negative infections that are resistant to appropriate antimicrobial agents.