Search

Abstract: Background: Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo‐controlled, double‐blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. Methods: FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single‐blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders‐Symptom Severity Index (PAGI‐SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m‐FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). Key Results: Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI‐SYM, GOS, and m‐FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI‐SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI‐SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m‐FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016). Conclusion & inferences: Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms. [ABSTRACT FROM AUTHOR]

Background Gastric accommodation is a reflex reaction related to gastric reservoir function. Psychological stress, such as anxiety, inhibits gastric accommodation in humans. Acotiamide enhances the effect of acetylcholine in the enteric nervous system, enhances gastric contractility, and accelerates delayed gastric emptying. However, the effect of acotiamide on stress-induced impaired gastric accommodation remains unclear. Therefore, we examined the effect of acotiamide on gastric accommodation and stress-induced impaired gastric accommodation using a conscious guinea pig model. Methods A polyethylene bag was inserted through the distal region of the gastric body into the proximal stomach of 5-week-old male Hartley guinea pigs. Gastric accommodation was evaluated by measuring the intrabag pressure in the proximal stomach after oral administration of a liquid meal. In the stress model, animals were subjected to water-avoidance stress. Acotiamide (Z-338) or nizatidine was administered subcutaneously. Fecal output was determined as the number of fecal pellets. Key Results Administration of the liquid meal significantly decreased intrabag pressure, indicating induction of gastric accommodation. Acotiamide treatment prolonged liquid meal-induced gastric accommodation and significantly increased the number of fecal pellets compared to controls. Water-avoidance stress significantly inhibited liquid meal-induced gastric accommodation. Pretreatment with acotiamide significantly improved stress-induced impaired gastric accommodation. The number of fecal pellets in the acotiamide group increased significantly compared to controls. Acotiamide, but not nizatidine, significantly decreased gastric emptying. Conclusions & Inferences Acotiamide prolongs gastric accommodation and improves stress-induced impaired gastric accommodation, indicating a potential role for acotiamide in the treatment of functional dyspepsia through its effects on gastric accommodation reactions. [ABSTRACT FROM AUTHOR]

Background Psychological stress has been shown to impair gastric accommodation (GA), but its mechanism has not been elucidated. This study was conducted to clarify the role of 5- HT2B receptors in a guinea pig model of stress-induced impairment of GA. Methods Gastric accommodation was evaluated by measuring the intrabag pressure in the proximal stomach after administration of a liquid meal. The guinea pigs were subjected to water-avoidance stress. The role of 5- HT2B receptors in impairment of GA was investigated by administering a 5- HT2B receptor agonist ( BW723C86) or antagonist ( SB215505), the traditional Japanese medicine rikkunshito ( RKT), a muscarinic M3 receptor antagonist (1,1-dimethyl-4-diphenylacetoxypiperidium iodide [4-DAMP]), or a nitric oxide synthase inhibitor (N ω-nitro-L-arginine [L- NNA]). Key Results In normal animals, liquid meal-induced GA was inhibited by BW723C86, but was not affected by SB215505. The inhibition of GA by BW723C86 was reversed by co-administration of 4-DAMP. Compared to normal animals, GA in stressed animals was significantly inhibited. SB215505 and RKT significantly suppressed stress-induced impairment of GA. After meal administration, the level of cyclic guanosine monophosphate in gastric fundus tissue increased by approximately twofold in normal animals, but did not change in stressed animals. The inhibition of GA by L- NNA was suppressed by SB215505 or RKT. At a dose that did not affect GA in normal animals, BW723C86 exacerbated the impairment of GA in stressed animals. Conclusions and Inferences Stress-induced impairment of GA may be mediated by an increased responsiveness of 5- HT2B receptors, and activation of the 5- HT2B receptor signaling pathway may have an inhibitory effect on nitric oxide function. [ABSTRACT FROM AUTHOR]

Background To date, few animal experiments have been conducted to examine the effects and mechanisms of buspirone in inducing the relaxation of the gastric fundus. The aim of this study is to examine the effects and mechanisms of buspirone, 5- HT1a receptor agonist, in the accommodation of gastric fundus muscle in an animal experimental model using guinea pigs. Methods In the current study, we performed an immunohistochemistry for 5- HT1a receptors in the tissue samples collected from the stomach of guinea pig, an ex vivo experiment to examine the electrical field stimulation ( EFS)-induced relaxation of the circular muscle in the gastric fundus in guinea pigs and an in vivo experiment to measure the intragastric pressure through the insertion of the balloon catheter in the fundus. Key Results Immunohistochemical stains for 5- HT1a receptor could confirm the expression of 5- HT1a receptor in guinea pig stomach. There was a significant dose-dependent inhibition of the EFS-induced relaxation of fundic muscle strips following the treatment with WAY-100635 (5- HT1a antagonist), but this was significantly improved following the treatment with buspirone. An in vivo measurement of the gastric fundic tone showed that there was a significant decrease in the intragastric pressure at same volume by pretreatment with buspirone as compared with the vehicle control, but this could be prevented with the treatment with WAY-100635. Conclusions & Inferences Based on our results, it can be concluded that buspirone is effective in relaxing the gastric fundus via 5- HT1a receptor pathway in both in vitro and in vivo experimental models using guinea pigs. [ABSTRACT FROM AUTHOR]

Objectives: The mechanism of the efficacy of long-term low-dose macrolide therapy for chronic sinusitis is not fully understood. The authors studied the inhibitory effect of erythromycin on interleukin-8 (IL-8) secretion from exudative cells in the nasal discharge of patients with chronic sinusitis.Study Design and Methods: Exudative cells in the nasal discharge were isolated from six patients with nonallergic chronic sinusitis. The cells, more than 90% of which were neutrophils, were incubated with or without erythromycin in the presence of 10 micrograms/mL of lipopolysaccharide. The IL-8 concentrations in the culture supernatants were measured by enzyme-linked immunoassay.Results: The amount of secreted IL-8 in the absence of erythromycin was 682 +/- 226 pg/10(6) cells/24 h. The IL-8 secretion was significantly reduced to 66 +/- 15% and 46 +/- 13% of the control in the presence of 10(-6) and 10(-5) M of erythromycin, respectively.Conclusion: Erythromycin may act as a biologic modulator that inhibits IL-8 secretion from exudative cells and thereby blocks the vicious circle of neutrophil recruitment and IL-8 generation in the inflammatory site in chronic sinusitis. [ABSTRACT FROM AUTHOR]

Background While there are reports that the herbal medicine rikkunshito ( RKT) relieves upper gastrointestinal disease symptoms, the effect of RKT on primary afferent neurons is unknown. Methods A model of reflux esophagitis ( RE) was implemented using male Wistar rats aged 6-7 weeks. Ten days after surgery, the total area of esophageal mucosal erosion sites was determined. Th8-10 dorsal root ganglia ( DRG) were dissected out and the expression of substance P ( SP), calcitonin gene-related peptide ( CGRP), and phosphorylated extracellular signal-regulated kinase 1/2 (p- ERK1/2) was determined in DRG using immunohistochemistry. RKT (0.6%/WV) or omeprazole ( OME) (10 mg/kg) was administered for 10 days beginning on the day after surgery. Voluntary movement was measured with an infrared sensor for 22 h each day. Key Results RE rats showed esophageal mucosal erosion and significantly increased number of SP/ CGRP- and p- ERK1/2-immunoreactive neurons in DRG. Treatment with OME improved the size of erosive lesions in the esophageal mucosa of RE rats, while RKT did not. Treatment with RKT or OME significantly reduced the expression of SP/ CGRP and p- ERK1/2 in DRG, and significantly increased voluntary movement in RE rats. Conclusions & Inferences RKT inhibited the activation of ERK1/2 and decreased the expression of SP and CGRP in DRG of RE rats, which may be associated with the observed amelioration of voluntary movement. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2012; 35: 175-182 Summary Background The mechanisms of the development of symptoms in functional dyspepsia (FD) patients have not been fully elucidated. We previously reported that acid directly infused into the stomach causes dyspeptic symptoms in asymptomatic healthy controls (HCs); however, the response to acid infusion of FD patients was not determined. Aim To investigate the severity of dyspeptic symptoms induced by direct acid infusion in FD subjects and HCs. Methods This was a multi-centre, cross-over, randomised, double-blind study in 23 FD subjects and 32 HCs. FD was defined using the Rome III criteria. All subjects were Helicobacter pylori negative. Each subject received two tests; 0.1 mol/L hydrochloric acid and water infused into the stomach. The presence and severity of 12 dyspeptic symptoms were assessed using a visual analogue scale. Results The proportion of subjects developing symptoms by acid or water infusion was significantly greater in FD subjects than HCs. All of the FD subjects experienced at least one symptom by water or acid infusion. In the FD subjects, the severity of symptoms was significantly greater with acid infusion than water infusion. The severity of symptoms in total and the scores for eight of the 12 symptoms induced by acid infusion was significantly greater in FD subjects than in HCs. Conclusions The severity of dyspeptic symptom generation induced by direct acid infusion into the stomach was significantly greater in functional dyspepsia subjects than in healthy controls, suggesting that hypersensitivity to acid is one of the important mechanisms of the development of symptoms in functional dyspepsia patients. [ABSTRACT FROM AUTHOR]

Background Proton pump inhibitors (PPIs) are less effective in non-erosive reflux disease (NERD) patients than in reflux oesophagitis patients. Whether the addition of prokinetics to PPIs improves NERD patients' symptoms remains unknown. Aim To evaluate the efficacy of mosapride in NERD patients when used with PPI. Methods A total of 200 NERD patients were randomised to one of two arms: omeprazole (10 mg once daily) plus mosapride citrate (5 mg three times a day) (treatment arm) and omeprazole plus placebo (placebo arm). The primary endpoint was the rate of responders [visual analogue scale (VAS) was zero or <1 cm] after 4 weeks of treatment. The secondary endpoints were changes in the VAS score and the safety profile. Results There was no significant difference between the rates of responders in both arms in intent-to-treat (ITT) and per-protocol (PP) analysis. The change in the VAS score in treatment arm was significantly better than placebo arm in PP analysis (-4.0 ± 0.2 and -3.3 ± 0.2, mean ± S.E.M.) (N.S. in ITT analysis). The rate of adverse events was similar in both groups. Conclusion The addition of mosapride to omeprazole was not more effective than omeprazole alone. [ABSTRACT FROM AUTHOR]

Background We previously reported that rats with reflux oesophagitis (RE) show a decrease in voluntary movement, which could be used as a measure of chronic visceral symptoms. However, what mediates these symptoms is still unknown, and pain-related neuropeptides or their receptors in oesophageal mucosa are possibly related to the symptom generation of oesophagitis. In the present study, we investigated the role of NK-1 receptor (NK-1R) as a mediator of oesophagitis symptoms. Methods Chronic RE was surgically induced using rats. The degree or severity of oesophageal symptoms was evaluated by assessing voluntary movement, which was monitored using an infrared sensor system. The NK-1R antagonist, L-732,138, was administered and changes in voluntary movement were assessed. Ten days after surgery, the rats were killed to examine the oesophagus. NK-1R and tachykinin-1 mRNA were detected by real-time RT-PCR. NK-1R protein expression was examined by Western blotting. Key Results Voluntary movement of the oesophagitis model rats was significantly lower than that of the sham-operated rats on day 10. The size of oesophageal mucosal erosion did not correlate with the amount of voluntary movement. The amount of NK-1R protein and mRNA in the oesophageal tissue was significantly higher at both the erosion and non-erosion sites. The amount of tachykinin-1 mRNA in oesophageal tissue at the non-erosion sites was significantly higher in oesophagitis rats. The voluntary movement of oesophagitis rats was significantly increased by the administration of L-732,138. Conclusions & Inferences The NK-1R and related neuropeptides are possibly involved in the decrease in voluntary movement of RE. [ABSTRACT FROM AUTHOR]

Growing interest has arisen regarding the mechanism of dyspeptic symptom generation. However, no evaluation system of these symptoms in animals has been developed. In this study, we examined whether voluntary movement of rats could be a measure to assess visceral symptoms of reflux oesophagitis. A chronic acid reflux oesophagitis model was made using rats, and the size of erosions was measured. Omeprazole was administered to the oesophagitis rats for 10 days. The amount of voluntary movement was measured by an infrared sensor. Intracellular spaces in oesophageal epithelium were also measured using a emission electron microscope. NP-40 soluble and insoluble fractions of claudins were examined by Western blot. Voluntary movement was significantly lower in the oesophagitis model rats than in the sham-operated rats ( P < 0.01). Although omeprazole reduced the size of erosions, it did not significantly affect the total amount of voluntary movement ( r = −0.033, P = 0.916). Intracellular spaces were significantly dilated in the oesophagitis model rats and claudin-3 showed a significantly lower relative quantity in the NP-40 insoluble fraction. Omeprazole significantly increased voluntary movement of oesophagitis model rats and the relative quantity of claudin-3 in the insoluble fraction ( P < 0.05). Dilated intercellular spaces and the lower level of claudin-3 may relate to the voluntary movement of oesophagitis model rats. Decreases in voluntary movement of oesophagitis model rats may reflect visceral symptoms and be able to serve as an index of chronic abdominal symptoms. [ABSTRACT FROM AUTHOR]

Nambury S. Raju (1937–2005) developed two model-based indices for differential item functioning (DIF) during his prolific career in psychometrics. Both methods, Raju's area measures ( Raju, 1988 ) and Raju's DFIT ( Raju, van der Linden, & Fleer, 1995 ), are based on quantifying the gap between item characteristic functions (ICFs). This approach provides an intuitive and flexible methodology for assessing DIF. The purpose of this tutorial is to explain DFIT and show how this methodology can be utilized in a variety of DIF applications. [ABSTRACT FROM AUTHOR]

A new item parameter replication method is proposed for assessing the statistical significance of the noncompensatory differential item functioning (NCDIF) index associated with the differential functioning of items and tests framework. In this new method, a cutoff score for each item is determined by obtaining a (1 −α) percentile rank score from a frequency distribution of NCDIF values under the no-DIF condition by generating a large number of item parameters based on the item parameter estimates and their variance-covariance structures from a computer program such as BIILOG-MG3. This cutoff for each item can be used as the basis for determining whether a given NCDIF index is significantly different from zero. This new method has definite advantages over the current method and yields cutoff values that are tailored to a particular data set and a particular item. A Monte Carlo assessment of this new method is presented and discussed. [ABSTRACT FROM AUTHOR]

: The epidemiology and pathophysiology of non-erosive gastro-oesophageal reflux disease differs from erosive gastro-oesophageal reflux disease. There is a possibility that non-erosive gastro-oesophageal reflux disease treatment requires a different regimen/approach but it is not yet acknowledged.: To investigate the efficacy of famotidine and omeprazole in the treatment of gastro-oesophageal reflux disease, especially non-erosive gastro-oesophageal reflux disease.: A randomized, open-label trial was conducted. Fifty-four gastro-oesophageal reflux disease patients were assigned to treatment with famotidine at a dosage of 20 mg twice daily; or omeprazole, 20 mg once daily, for a period of 8 weeks. The Short Form-36 Health Survey and Gastrointestinal Symptom Rating Scale administered at baseline and after 8 weeks of treatment as well as a symptom questionnaire were conducted daily.: Short Form-36 revealed that gastro-oesophageal reflux disease has severe impact on health-related quality of life. Thirty-nine subjects (77%) were endoscopically diagnosed as non-erosive gastro-oesophageal reflux disease. The mean Gastrointestinal Symptom Rating Scale abdominal pain, and indigestion score of non-erosive gastro-oesophageal reflux disease significantly improved in famotidine-treated patients (P < 0.05), but not in the omeprazole. There was no significant change regarding improved heartburn symptoms of non-erosive gastro-oesophageal reflux disease between treatments in the daytime or night-time.: Famotidine and omeprazole were both effective in improving symptoms of gastro-oesophageal reflux disease, particularly non-erosive gastro-oesophageal reflux disease. [ABSTRACT FROM AUTHOR]

: The effect of Helicobacter pylori infection on systemic disorders is not well understood. : The purpose of this study was to elucidate the systemic effects of H. pylori infection by comparing differential counts of leukocytes and platelets in peripheral blood before and after eradication of H. pylori. : A total of 164 H. pylori-positive patients underwent eradication therapy, and populations of peripheral blood leukocytes and platelets before and 0 (just after therapy), 1, 3 and 12 months after eradication were retrospectively analysed. : In the eradicated group ( n = 138), blood leukocytes, neutrophils and monocytes decreased significantly after eradication, but there was no significant change in eosinophils, basophils, lymphocytes or platelets. In the non-eradicated group ( n = 26), there was no significant change in any studied parameter. With regard to smoking status, although leukocytes and neutrophils did not decrease after eradication in the smoking group, they significantly decreased after eradication in the nonsmoking group. : These findings suggest that: (1) H. pylori infection increases neutrophil and monocyte counts in the peripheral blood, which indicates a significant role of H. pylori infection in systemic disorders; and (2) Smoking may mask the effect of H. pylori eradication on peripheral leukocytes, which would explain the controversy in previous reports concerning H. pylori infection and peripheral leukocytes. [ABSTRACT FROM AUTHOR]

Summary Background : Barrier function in gastric epithelial cells is essential for the gastric defence mechanism against acid back-diffusion into the mucosal layer. Our previous study indicated that trans-epithelial resistance (TER) of rat gastric epithelial cells was rapidly increased when the cells were exposed to acid. This response to acid was diminished by indometacin. Aim : Evaluate the effects of a mucoprotective agent, rebamipide, on the nonsteroidal anti-inflammatory drug (NSAID)-induced increase of gastric epithelial permeability. Methods : Rat gastric epithelial cells were plated on tissue culture inserts. Cells were exposed to a NSAID (indometacin, 10[sup -7] M). Trans-epithelial permeability was measured by TER and diffusion rate of [sup 14] C-mannitol. The effect of rebamipide was evaluated by measuring TER. Endogenous prostaglandin E[sub 2] (PGE[sub 2] ) production in culture medium was also measured. Results : Indometacin gradually and significantly decreased TER and increased [sup 14] C-manitol permeability. Rebamipide reversed the indometacin-induced changes in epithelial permeability and induced PGE[sub 2] synthesis. This induction was blocked by either indometacin or a Cyclooxygenase (COX)-2 specific inhibitor. Conclusions : COX inhibitors such as indometacin inhibit regulation of epithelial permeability by reducing PGE[sub 2] . COX-1 has an important role in the gastric defense mechanism. Rebamipide suppressed an indometacin-induced increase in gastric epithelial permeability by increasing PGE[sub 2] levels in a COX-2 dependent manner. [ABSTRACT FROM AUTHOR]

Focuses on the phylogenetic hypothesis for the neuronal origin of hiccough. Role of the ventilatory central pattern generator of lower vertebrates; Symptoms of hiccoughs; Description of hiccough as an expression of archaic motor patterns.

Background: Effects of propofol on human cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and blood flow-metabolism coupling have not been fully evaluated. We therefore assessed the effects of propofol on total-CBF and CMRO2 in patients without noxious stimuli and neurologic disorders.Methods: General anesthesia was induced with midazolam (0.2 mg/kg) and fentanyl (5 microg/kg) in 10 patients (ASA physical status I) undergoing knee joint endoscopic surgery. Epidural anesthesia was also performed to avoid noxious stimuli during surgery. Cerebral blood flow (CBF) and cerebral arteriovenous oxygen content difference (a-vDO2) was measured using the Kety-Schmidt method with 15% N2O as a tracer before and after propofol infusion (6 mg/kg/h for 40 min), and the CMRO2 was also calculated.Results: CBF decreased following propofol infusion from 34.4 ml/100 g/min (range 28.4-52.0) to 30.0 ml/100 g/min (range 20.2-42.4) (P=0.04). Although there was no significant change in a-vDO2, CMRO2 decreased following propofol infusion from 2.7 ml/100 g/min (range 2.2-4.3) to 2.2 ml/100 g/min (range 1.4-3.0) (P=0.04). There was a strong linear correlation between CBF and CMRO2 (r=0.90).Conclusion: Propofol proportionally decreased CBF and CMRO2 without affecting a-vDO2 in humans, suggesting that normal cerebral circulation and metabolism are maintained. [ABSTRACT FROM AUTHOR]

Background : Enhanced MAdCAM-1 (mucosal addressin cell adhesion molecule-1) expression is associated with the aetiology of inflammatory bowel disease, but little is known about MAdCAM-1: regulation, or how inflammatory bowel disease therapies modulate MAdCAM-1. Aim : To examine how agents currently used to treat inflammatory bowel disease affect MAdCAM-1: induced by tnf-α in an in vitro model of inflammatory bowel disease. Methods : Endothelial monolayers were pretreated with dexamethasone (DEX): 5-aminosalicylic acid (5-ASA), 6-mercaptopurine (6-MP), sulfasalazine or interleukin-10: (IL-10: prior to TNF-α (20 ng/mL), and MAdCAM-1: measured by Western blotting, RT-PCR, EMSA and lymphocyte adhesion assays. Results : MAdCAM-1: was induced dose- and time-dependently by TNF-α on endothelial cells. Either dexamethasone or IL-10: reduced TNF-α-induced MAdCAM-1: protein, mRNA and lymphocyte adhesion. However, neither 5-ASA, sulfasalazine nor 6-MP blocked MAdCAM-1 induction. Conclusions : Our data indicate that dexamethasone or IL-10 can exert therapeutic activity in inflammatory bowel disease through MAdCAM-1 inhibition. 5-ASA, sulfasalazine and 6-MP, while beneficial in inflammatory bowel disease, do not directly control MAdCAM-1, and are beneficial through inhibition of other inflammatory processes. [ABSTRACT FROM AUTHOR]

This paper introduces and evaluates four practical multidimensional linking procedures that are based on theoretical framework recently proposed by Davey, Oshima, and lee (1996): (a) the Direct method, (b) the Equated Function method (c) the Test Characteristic Function (TCF) method, and (d) the Item Characteristic Function (ICF) method. The evaluation was conducted using simulated data. As anticipated, the competing procedures yielded different linking parameter estimates. The TCF and ICF methods were found to be more stable and recovered the true linking parameters better than the other two methods. Further-more, all procedures were found to be acceptable under almost any of the minimication criteria and offered dramatic improvement over not linking at all. It is recommended that the choice of a linking procedure should depend on the purpose of linking. [ABSTRACT FROM AUTHOR]

Excretory/secretory (ES) antigen of Toxocara can is larvae was isolated from the culture medium of second-stage larvae by gel filtration. The antigen induced production of not only IgM or IgG but also IgE antibody. The antigen, when treated with guanidine hydrochloride and 2-mercaptoethanol, lost its allergenic activity but retained an ability to induce IgM or IgG antibody. Purified antigen was of glyco-protein nature and had a molecular weight of 35,000. The whole antigen showed a cross-reaction with the serum from Ascaris suum-infected mice. The antigen did not contain phosphorylcholine as a structural component. [ABSTRACT FROM AUTHOR]