[show abstract][hide abstract] ABSTRACT: Antispasmodics such as octylonium are widely used to manage irritable bowel syndrome (IBS) symptoms. However, the efficacy and safety of another antispasmodic, tiropramide, remain uncertain. We aimed to evaluate the efficacy and safety of tiropramide compared with octylonium in patients with IBS.
In this multicenter, randomized, non-inferiority trial, 287 patients with IBS (143 receiving tiropramide and 144 octylonium) were randomly allocated to either tiropramide 100 mg or octylonium 20 mg t.i.d (means 3 times a day) for 4 weeks. Primary endpoint was the mean change of abdominal pain from baseline assessed by visual analogue scales (VAS) score after 4 weeks of treatment. Secondary endpoints were the changes in abdominal pain from baseline at week 2 and in abdominal discomfort at weeks 2 and 4, using VAS scores, patient-reported symptom improvement including stool frequency and consistency, using symptom diaries, IBS-quality of life (IBS-QoL), and depression and anxiety, at week 4.
The VAS scores of abdominal pain at week 4, were significantly decreased in both tiropramide and octylonium groups, but the change from baseline did not differ between the 2 groups (difference,-0.26 mm; 95% CI,-4.33-3.82; P = 0.901). Abdominal pain and discomfort assessed using VAS scores, diaries, and IBS-QoL were also improved by both treatments, and the changes from baseline did not differ. The incidence of adverse events was similar in the 2 groups, and no severe adverse events involving either drug were observed.
Tiropramide is as effective as octylonium in managing abdominal pain in IBS, with a similar safety profile.
Journal of neurogastroenterology and motility 01/2014; 20(1):113-21.
[show abstract][hide abstract] ABSTRACT: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n=38), early gastric cancer (EGC) (n=38), and advanced gastric cancer (AGC) (n=38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways.
Biochemical and Biophysical Research Communications 01/2014; · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Many patients with gastroesophageal reflux disease (GERD) also present with extraesophageal symptoms (EESs). This study sought to determine the prevalence of concomitant EESs and to evaluate quality of life (QOL) impairment in a Korean population with GERD.
This questionnaire-based study was carried out from 64 hospitals in Korea between October 2008 and March 2009. Patients with typical GERD symptoms of heartburn or acid regurgitation were recruited for study. Participants filled out questionnaire consisting of GerdQ questions and EES questions. All participants underwent endoscopy and were divided into patients with erosive reflux disease (ERD) and with non-erosive reflux disease (NERD).
A total of 1,712 patients were included in this study. Of these, 697 (40.7%) patients had ERD and 1,015 (59.3%) NERD. The prevalence of EES was 90.3%. The most prevalent EES was epigastric burning (73.2%), followed by globus (51.8%), chest pain (48.4%), cough (32.0%), hoarseness (24.2%) and wheezing (17.3%). Individual EES was more prevalent in patients with ERD than in those with NERD. Regarding QOL, 701 patients (41.0%) had sleep disturbance and 676 (37.7%) had taken additional over-the-counter medication for heartburn and/or regurgitation, which were more prevalent in patients with ERD than in those with NERD (49.5% vs. 35.1% and 45.8% vs. 32.2%, respectively; all P < 0.001).
The prevalence of EES is high in Korean patients with symptomatic GERD. Individual EES is more prevalent in patients with ERD than in those with NERD. QOL impairment is observed less frequently than previous studies.
Journal of neurogastroenterology and motility 01/2014; 20(1):87-93.
[show abstract][hide abstract] ABSTRACT: Abstract Background. Recent studies have shown that mast cells play an important role in irritable bowel syndrome (IBS). We investigated the relationship between mast cells and the gut hormones substance P and vasoactive intestinal peptide (VIP) in irritable bowel syndrome with diarrhea (IBS-D). Methods. Colonoscopic biopsies were performed on the rectal mucosa of 43 subjects (IBS-D patients: 22, healthy volunteers: 21) diagnosed according to the Rome III criteria. Mast cells, and substance P & VIP were evaluated by quantitative immunohistology and image analysis. Mast cells were counted as tryptase-positive cells in the lamina propria, and substance P and VIP levels were expressed as percentages of total areas of staining. Results. Mast cell counts were higher in IBS-D patients than healthy volunteers (9.6 ± 3.3 vs. 5.7 ± 2.5/high power field (HPF), p < 0.01). Substance P was also elevated (0.11 ± 0.08% vs. 0.03 ± 0.02 %, p < 0.01) while VIP was only high in women with IBS-D. Mast cell counts were positively correlated with levels of substance P & VIP in women but not men (women: r = 0.625, p < 0.01 for substance P and r = 0.651, p < 0.01 for VIP). However, mast cell counts were not correlated with IBS symptoms including abdominal pain. Conclusion. Mast cells are activated leading to the raised levels of substance P & VIP in IBS-D patients. However, the correlation between mast cells and levels of substance P & VIP differs according to gender.
Scandinavian journal of gastroenterology 11/2013; · 2.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Percutaneous endoscopic gastrostomy (PEG) is a commonly performed procedure for patients with severe dysphagia leading to malnutrition. Improved knowledge of risk factors for PEG-related complications might decrease patient discomfort and healthcare costs.
The aim of the present study was to investigate factors associated with complications after PEG.
A retrospective review was performed for all patients referred for PEG placement from December 2002 to December 2012 in single-tertiary care center. PEG-related complications and risk factors were evaluated through chart reviews, endoscopic reports, and endoscopic and radiologic images.
Among a total of 245 consecutive individuals (146 male, mean age 59.2 ± 12.6 years) enrolled, 43 major complications had developed. Multivariate analysis revealed that patients with an internal bolster of a PEG tube in the upper body of stomach were at significant risk for early [OR 6.127 (95 % CI 1.447-26.046)] and late complications [OR 6.710 (95 % CI 1.692-26.603)]. Abnormal leukocyte counts [OR 3.198 (95 % CI 1.174-8.716)], stroke as an indication for PEG [OR 3.047 (95 % CI 1.174-8.882)], and PEG tube placement by an inexperienced endoscopist [OR 3.401 (95 % CI 1.073-10.779)] were significantly associated with early complications.
A PEG tube should not be inserted into the upper body of stomach to reduce complication risk, and PEG procedures should be performed by skilled endoscopists to prevent early complications. An abnormal leukocyte count can be a predictor of early complication, and care is needed when PEG is performed for patients with stroke.
Digestive Diseases and Sciences 10/2013; · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: We investigated the efficacy of treatment with multi-species probiotics on IBS symptoms and the alterations of gut microbiota in patients who have taken probiotics.
This randomized, double-blind, placebo-controlled trial involved 49 IBS patients (probiotics: 25, placebo: 24) diagnosed according to the Rome III criteria. Patients were randomly assigned to two groups: either to receive multi-species probiotics (a mixture of Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Streptococcus thermophilus) twice a day for four weeks, or to receive a placebo twice a day for four weeks. The primary efficacy endpoint was the proportion of participants whose IBS symptoms were substantially relieved at week 4. Secondary endpoints were the intensity of abdominal pain/discomfort, bloating, stool frequency/consistency, alterations in fecal microflora over the four weeks. Fecal microflora were analyzed in 34 patients (probiotics: 17, placebo: 17) by quantitative real-time PCR assays.
The proportion of patients whose IBS symptoms were substantially relieved at week 4 was significantly higher in the probiotics group than in the placebo group: 68.0% (17/25) vs. 37.5% (9/24) (p<0.05). Secondary endpoints such as improvement in abdominal pain/discomfort and bloating occurred in the probiotics group but not in the placebo group. Fecal analysis revealed that B. lactis, L. rhamnosus and S. thermophilus had increased significantly in the probiotics group after four weeks, and that B. lactis had increased in the placebo group.
Multi-species probiotics are effective in IBS patients, and induced the alterations in the composition of intestinal microbiota.
Journal of Gastroenterology and Hepatology 07/2013; · 3.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: A 73-year-old woman presented with intermittent abdominal pain and weight loss of 15 kg for 2 years. Colonoscopy revealed an erythematous polypoid tumor with a long and wide stalk in the cecum, but with air inflation, it abruptly went away through the ileocecal valve (ICV). An abdominal computed tomography showed a well-demarcated pedunculated subepithelial mass of 2.6×2.7 cm size with fat attenuation in the terminal ileum. It was an intussusceptum of the ileal lipoma through the ICV. This ileal lipoma was causing her symptoms because repeated ileocolic intussusceptions resulted in intermittent intestinal obstructions. In order to avoid surgical sequelae of ileal resection, snare polypectomy using cap-assisted colonoscopy technique was performed within the ileum without complications. The histopathology report confirmed it as a subepithelial lipoma. After endoscopic resection of the ileal lipoma, the patient has been free of symptoms and was restored to the original weight.
[show abstract][hide abstract] ABSTRACT: Several epidemiological studies have shown that coffee intake attenuates the progression of liver fibrosis; however, the mechanism is unclear.
We investigated the direct effects of caffeine on hepatic stellate cells (HSCs), and assessed whether caffeine attenuated intrahepatic fibrosis in rat model of liver cirrhosis.
LX-2, an immortalized human HSCs line, was used in in vitro assay system. Cell migration and proliferation were assessed in presence of various caffeine concentrations (0, 1, 5, and 10 mM), and levels of procollagen type IC and α-SMA were measured by Western blot. Severity of liver inflammation and fibrosis were compared between thioacetamide treated rats with and without caffeine supplementation.
Caffeine increased HSCs apoptosis and intracellular F-actin and cAMP expression. Caffeine also inhibited procollagen type IC and α-SMA expression in a dose- and time-dependent manner. In rat model, caffeine decreased periportal inflammation, levels of inflammatory cells (1.4±0.52 vs. 2.6±0.46, p<0.05) and fibrosis (2.1±0.35 vs. 2.9±0.84, p<0.05).TGF-β and α-SMA expressions were also reduced by caffeine.
Caffeine attenuates the progression of liver fibrosis by inhibiting HSCs adhesion and activation.
Journal of Gastroenterology and Hepatology 06/2013; · 3.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Whether hydrogen and methane gas produced during lactulose breath test (LBT) are associated with symptoms of irritable bowel syndrome (IBS) is not determined. We aimed to investigate whether hydrogen and methane on LBT are associated with IBS symptoms. Sixty-eight IBS patients meeting the Rome III criteria for IBS, and 55 healthy controls, underwent LBT. The IBS subjects recorded their customary gastrointestinal symptoms on a questionnaire using visual analogue scales. LBT positivity was defined to be above 20 ppm rise of hydrogen or 10 ppm rise of methane within 90 min. Gas amounts produced during LBT were determined by calculating area under the curve of hydrogen and methane excretion. Symptom severity scores were not different between the LBT (+) IBS and LBT (-) IBS subjects and also between methane producers and non-methane producers. Gas amounts produced during LBT were not associated with IBS symptoms, except a weak correlation between total gas amounts and a few IBS symptoms such as bloating (r = 0.324, P = 0.039), flatulence (r = 0.314, P = 0.046) and abdominal pain (r = 0.364, P = 0.018) only in LBT (+) IBS. In conclusion, hydrogen and methane gas on LBT are not useful for predicting the customary symptoms and subtypes of IBS.
Journal of Korean medical science 06/2013; 28(6):901-7. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUNDAIMS: It is suggested that the hepatic lipid composition is more important than lipid quantity in the pathogenesis of non-alcoholic steatohepatitis. We examined whether lipoic acid (LA) could alter intrahepatic lipid composition and free cholesterol distribution.
HepG2 cells were cultured with palmitic acid (PA) with and without LA. Apoptosis, changes of the mitochondrial structure, intracellular lipid partitioning, and reactive oxygen species (ROS) activity were measured.
Free fatty acid (FA) increased apoptosis, and LA co-treatment prevented this lipotoxicity (apoptosis in controls vs PA vs PA+LA, 0.5% vs 19.5% vs 1.6%, p<0.05). LA also restored the intracellular mitochondrial DNA copy number (553±33.8 copies vs 291±14.55 copies vs 421±21.05 copies, p<0.05) and reversed the morphological changes induced by PA. In addition, ROS was increased in response to PA and was decreased in response to LA co-treatment (41,382 relative fluorescence unit [RFU] vs 43,646 RFU vs 41,935 RFU, p<0.05). LA co-treatment increased the monounsaturated and polyunsaturated FA concentrations and decreased the total saturated FA fraction. It also prevented the movement of intracellular free cholesterol from the cell membrane to the cytoplasm.
LA opposes free FA-generated lipotoxicity by altering the intracellular lipid composition and free cholesterol distribution.
Gut and liver 03/2013; 7(2):221-7. · 1.31 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: 5-hydroxytryptamine (5-HT) receptors are upregulated in activated hepatic stellate cells (HSCs), and are therefore thought to play an important role in their activation. AIM: The aim of this study was to determine whether 5-HT(2A) receptor antagonists affect the activation or apoptosis of HSCs in vitro and/or in vivo. METHODS: For the in vitro experiments, the viability, apoptosis and wound healing ability of LX-2 cells were examined after treatment with various 5-HT(2A) receptor antagonists. Levels of HSC activation markers (procollagen type I, α-SMA, TGF-β and Smad 2/3) were measured. For in vivo experiments, rats were divided into three groups: (i) a control group, (ii) a disease group, in which cirrhosis was induced by thioacetamide (iii) a treatment group, in which cirrhosis was induced and a 5-HT(2A) receptor antagonist (sarpogrelate, 30 mg/kg) was administered. RESULTS: 5-HT(2A) , but not 5-HT(2B) receptor mRNA increased with time upon HSC activation. 5-HT(2A) receptor antagonists (ketanserin and sarpogrelate) inhibited viability and wound healing in LX-2 cells and induced apoptosis. Expression of α-SMA and procollagen type I was also inhibited. In the in vivo study, lobular inflammation was reduced in the sarpogrelate-treated group, but there was only slight and statistically insignificant attenuation of periportal fibrosis. Expression of α-SMA, TGF-β and Smad 2/3 was also reduced in the treatment group. CONCLUSIONS: 5-HT(2A) receptor antagonists can reduce inflammation and the activation of HSCs in this cirrhotic model.
Liver international: official journal of the International Association for the Study of the Liver 01/2013; · 3.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: In Asian countries including Korea, the prevalence of gastroesophageal reflux disease (GERD) is on the rise and its clinical impact has been emphasized. The purpose of this study was to investigate the clinical characteristics of esophagitis patients with or without symptoms, and their association with psychological factors.
Subjects diagnosed as erosive esophagitis of Los Angeles-A or more in screening by upper gastrointestinal endoscopy were enrolled. Questionnaires regarding GERD symptoms and Symptom Checklist-90-Revision were used to identify the presence of psychological symptoms.
There was no difference between the subjects' general characteristics (gender, age, body mass index, smoking and alcohol intake) according to the existence of typical symptoms in these patients with erosive esophagitis. Patients with typical GERD symptoms were more likely to have atypical symptoms, dyspepsia and higher scores on psychological symptoms (somatization, obsessive-compulsiveness and phobic anxiety) than those without.
Psychological symptoms and other gastrointestinal symptoms should be considered in the patients with erosive esophagitis.
Journal of neurogastroenterology and motility 07/2012; 18(3):284-90.
[show abstract][hide abstract] ABSTRACT: Tricyclic antidepressants have good efficacy in irritable bowel syndrome with diarrhea (IBS-D), but their clinical use is limited by considerations of tolerability. Tianeptine, another antidepressant, acts as a selective serotonin reuptake enhancer. We compared tianeptine with amitriptyline for the treatment of patients with IBS-D.
We undertook a multicenter, randomized, open-label, non-inferiority clinical study that compared tianeptine with amitriptyline, each in combination with probiotics, for the treatment of IBS-D. Subjects were randomized to receive tianeptine (37.5 mg)/probiotics (Bacillus subtilis + Streptococcus faecium) or amitriptyline (10 mg)/probiotics (Bacillus subtilis + Streptococcus faecium) for 4 weeks. A total of 228 patients were analyzed by the intention-to-treat approach. The primary efficacy endpoint was the proportion of patients who had global relief of IBS symptoms at week 4. The secondary efficacy endpoints were intensity of abdominal pain/discomfort, stool frequency/consistency, quality of life, and overall satisfaction with treatment.
At week 4, non-inferiority of the tianeptine group to the amitriptyline group (treatment difference -15.1%; 95% CI -26.6% to -3.8%) was shown, with 81.1% (99 of 122 patients) of the patients in the tianeptine group and 66.0% (70 of 106 patients) in the amitriptyline group reporting global relief of IBS symptoms. The secondary endpoints also demonstrated non-inferiority of the tianeptine group to the amitriptyline group. Adverse events such as dry mouth and constipation were significantly lower in the tianeptine group than the amitriptyline group (P<0.05).
Tianeptine is not inferior to amitriptyline for treating IBS-D in terms of both efficacy and tolerability.
Neurogastroenterology and Motility 06/2012; 24(9):860-e398. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Recently, many studies reported that high carbohydrate and simple sugar intake increase a risk of obesity and metabolic syndrome significantly. AIM: To investigate the effect of carbohydrate on aminotransferase levels in Korea, where the proportion of carbohydrate in meals is extremely high but fat is low. METHODS: We used the data of Korean National Health and Nutrition Examination Surveys (KNHANES). A total of 19 749 people were included. Amounts and types of consumed foods were examined by the 24 h recall method. RESULTS: Mean carbohydrate and fat proportions in total energy intake were 67.7% and 17.4%, respectively. Aminotransferase activity increased according to the rise of the proportion of carbohydrate in the energy intake. A high carbohydrate intake (>70% of energy) was associated with abnormal aminotransferase activity and metabolic syndrome. After adjusting for covariates, such as age, energy intake and body mass index, abnormal aminotransferase activity was significantly associated with carbohydrate proportion. There was a negative correlation between fat proportion in the total energy intake and aminotransferase activity (P < 0.01). The relation between aminotransferase activity and carbohydrate composition showed a J-shaped curve. The lowest point (the J point) was located at 50-60% carbohydrate. CONCLUSIONS: The proportion of carbohydrate in energy intake but not fat is positively correlated with abnormal aminotransferase activity in Koreans. This finding may be useful in planning a strategy of nutrition education for NAFLD in countries where the proportion of carbohydrate in most meals is extremely high.
[show abstract][hide abstract] ABSTRACT: Mosapride citrate is known to affect gastric motility. However, whether mosapride citrate has any effect on visceral pain in the colon or rectum is not certain. The aim of this study was to assess the effects of mosapride citrate on visceral pain in a rat visceral hypersensitivity model.
The perception of visceral pain was evaluated by the visceromotor response to colorectal distension observed on electromyographs of the abdominal musculature in urethane-anesthetized rats. Visceral hypersensitivity was induced by the intrarectal instillation of 4% acetic acid or 1.5% zymosan. Mosapride citrate was administered intraperitoneally 3 h later. VMRs to CRD were recorded prior to the instillation of acetic acid or zymosan and before and after mosapride citrate treatment.
The intracolonic instillation of acetic acid resulted in a significant increase in VMRs of the abdominal muscles to CRD, compared with the pretreatment state (174 ± 24%, P < 0.05). The intracolonic instillation of zymosan resulted in a significant increase in VMRs of the abdominal muscles to CRD, compared with the pretreatment state (144 ± 9%, P < 0.05). Intraperitoneal injection of mosapride citrate resulted in a significant reduction in the VMRs to CRD in an acetic acid-induced visceral hypersensitivity rat model (61 ± 9%, P < 0.05). The intraperitoneal injection of mosapride citrate also resulted in a significant reduction in the VMRs to CRD in a zymosan-induced visceral hypersensitivity rat model (67 ± 9%, P < 0.05).
Mosapride citrate diminished visceral pain in rats.
Digestive Diseases and Sciences 03/2012; 57(6):1517-24. · 2.26 Impact Factor