Disturbed gastric motility in patients with long-standing diabetes mellitus.

PURPOSE: Gastric dysmotility has been reported in patients with long-standing diabetes mellitus (DM). Some patients with DM are diagnosed as diabetes gastroparesis and have several upper gastrointestinal (GI) symptoms such as appetite loss and abdominal pain. This study aimed to identify the relationship between gastric motility and upper GI symptoms in patients with long-standing DM. METHOD: This study was conducted among 23 patients with DM and 15 healthy controls. All the patients with DM were receiving insulin treatment and had at least one history of incidence of diabetic nephropathy, retinopathy or neuropathy. Gastric motility was evaluated using electrogastrography (EGG) and gastric emptying using the 13C-acetic acid breath test. The most severe upper gastrointestinal symptoms were assessed in all patients. RESULTS: Compared to healthy controls, patients with long-standing DM showed a significantly lower percentage of normogastria at the postprandial state with a lower power ratio in EGG. Gastric emptying was significantly delayed in patients with DM in the overall analysis. Sixteen patients with DM (69.6%) demonstrated abnormalities in either gastric myoelectrical activity or gastric emptying. Among patients with abnormal EGG or delayed gastric emptying, 12 had some GI symptoms, compared with 3 patients with normal gastric motility. No significant correlation was observed between the gastric emptying parameters and HbA1c values. CONCLUSION: Patients with long-standing DM showed gastric dysmotility, including impaired gastric myoelectrical activity and delayed gastric emptying. Gastric dysmotility appears to be closely correlated with upper GI symptoms in patients with long-standing DM.

A multicenter randomized trial comparing rabeprazole and itopride in patients with functional dyspepsia in Japan: the NAGOYA study.

The aims of this study were to compare the therapeutic effects of a proton pump inhibitor (PPI), rabeprazole (RPZ), and a prokinetic agent, itopride (ITO), and to investigate the role of PPI in the treatment strategy for Japanese functional dyspepsia (FD) patients. We randomly assigned 134 patients diagnosed by Rome III criteria to 4 weeks treatment with RPZ 10 mg/day (n = 69) or ITO 150 mg/day (n = 65). Dyspeptic symptoms were evaluated using FD scores at baseline and after 1, 2 and 4 weeks of treatment. We also divided subjects into predominantly epigastric pain syndrome (EPS) or postprandial distress syndrome (PDS), and evaluated the efficacy of RPZ and ITO respectively. RPZ showed a significant decrease in the Rate of Change (RC) in FD score within 1 week, which was maintained until after 4 weeks, with RPZ a significant effect compared with ITO at all evaluation points. In addition, RPZ showed a significant decrease in FD score in subjects with both EPS and PDS, whereas a significant decrease in the RC with ITO was only shown in those with predominant PDS. Acid-suppressive therapy with RPZ is useful for PDS as well EPS in Japanese FD patients (UMIN Clinical Trials Registry number: UMIN 000013962).

Persistent reflux symptoms cause anxiety, depression, and mental health and sleep disorders in gastroesophageal reflux disease patients.

Some patients with gastroesophageal reflux disease experience persistent reflux symptoms despite proton pump inhibitor therapy. These symptoms reduce their health-related quality of life. Our aims were to evaluate the relationship between proton pump inhibitor efficacy and health-related quality of life and to evaluate predictive factors affecting treatment response in Japanese patients. Using the gastroesophageal reflux disease questionnaire, 145 gastroesophageal reflux disease patients undergoing proton pump inhibitor therapy were evaluated and classified as responders or partial-responders. Their health-related quality of life was then evaluated using the 8-item Short Form Health Survey, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale questionnaires. Sixty-nine patients (47.6%) were partial responders. These patients had significantly lower scores than responders in 5/8 subscales and in the mental health component summary of the 8-item Short Form Health Survey. Partial responders had significantly higher Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale scores, including anxiety and depression scores, than those of responders. Non-erosive reflux disease and double proton pump inhibitor doses were predictive factors of partial responders. Persistent reflux symptoms, despite proton pump inhibitor therapy, caused mental health disorders, sleep disorders, and psychological distress in Japanese gastroesophageal reflux disease patients.

Therapeutic effects of biobran, modified arabinoxylan rice bran, in improving symptoms of diarrhea predominant or mixed type irritable bowel syndrome: a pilot, randomized controlled study.

Background. Recently, it was revealed that low grade mucosal inflammation and/or immune imbalance of the lower digestive tract is one of the mechanisms involved in symptom generation in patients with irritable bowel syndrome (IBS). Biobran, arabinoxylan compound derived from rice bran, has been reported to have several biological actions such as anti-inflammatory and immune modulatory effects. So we investigated the therapeutic effects of Biobran in patients with IBS. Method. Forty patients with diarrhea predominant or mixed type IBS were randomly assigned to either a Biobran group for treatment with Biobran or a placebo group. Therapeutic efficacy and IBS symptoms were assessed subjectively by the patients after 4 weeks of administration. Results. The global assessment was effective in 63.2% of the Biobran group and in 30% of the placebo group (P < 0.05, Biobran group versus placebo group). Biobran group showed a significant decrease in the score of diarrhea and constipation and in CRP value. However, no significant changes were observed in the placebo group. Conclusion. The administration of Biobran improved IBS symptoms. It is likely that anti-inflammatory and/or immune modulatory effects of Biobran might be useful in IBS patients.

The effect of omeprazole on gastric myoelectrical activity and emptying.

Omeprazole, a proton pump inhibitor, is widely used for the treatment of patients with peptic ulcer, gastroesophageal reflux disease and functional dyspepsia (FD), although some studies have demonstrated that omeprazole delays gastric emptying. The purpose of this study was to investigate the efficacy of omeprazole on gastric motility including gastric myoelectrical activity and gastric emptying. This study was performed on 12 healthy volunteers. Gastric motility was evaluated with cutaneously recorded electrogastrography (EGG) and gastric emptying of semi-solid meals using the (13)C-acetic acid breath test. EGG and gastric emptying were measured before and after treatment with 20 mg omeprazole orally for 7 days. In the fasting state, the percentage of EGG normogastria increased significantly compared to the baseline. No significant changes were observed in other EGG parameters including the percentage of tachygastria and bradygastria in both fasting and postprandial states, and the power ratios between both before and after ingestion of omeprazole. In addition, administrated omeprazole did not show any significant differences in the gastric emptying parameters such as the half emptying time. We conclude that administration of omeprazole did not affect gastric motility but improved gastric myoelectrical activity. These effects of omeprazole may be one of the mechanisms involved in its efficacy in relieving dyspeptic symptoms in FD patients.

The TRPV4 channel is a novel regulator of intracellular Ca2+ in human esophageal epithelial cells.

The esophageal epithelium has sensory properties that enable it to sustain normal barrier function. Transient receptor potential vanilloid 4 (TRPV4) is a Ca(2+)-permeable channel that is activated by extracellular hypotonicity, polyunsaturated fatty acids, phorbol esters, and elevated temperature. We found that TRPV4 is expressed in both human esophageal tissue and in HET-1A cells, a human esophageal epithelial cell line. Specific activation of TRPV4 by the phorbol ester 4α-phorbol 12,13-didecanoate (4α-PDD) increased intracellular Ca(2+) in a subset of HET-1A cells. Elevated temperature strongly potentiated this effect at low concentrations of 4α-PDD, and all of the responses were inhibited by the TRPV antagonist ruthenium red. TRPV4 activation differentially affected cell proliferation and cell viability; HET-1A cell proliferation was increased by 1 µM 4α-PDD, whereas higher concentrations (10 µM and 30 µM) significantly decreased cell viability. Transient TRPV4 activation triggered ATP release in a concentration-dependent manner via gap-junction hemichannels, including pannexin 1 and connexin 43. Furthermore, TRPV4 activation for 24 h did not increase the production of interleukin 8 (IL-8) but reduced IL-1ß-induced IL-8 production. Small-interference RNA targeted to TRPV4 significantly attenuated all of the 4α-PDD-induced responses in HET-1A cells. Collectively, these findings suggest that TRPV4 is a novel regulator of Ca(2+)-dependent signaling pathways linked to cell proliferation, cell survival, ATP release, and IL-8 production in human esophageal epithelial cells.

Distinct expression of cold receptors (TRPM8 and TRPA1) in the rat nodose-petrosal ganglion complex.

TRPM8 and TRPA1 are cold-activated transient receptor potential (TRP) cation channels. TRPM8 is activated by moderate cooling, while TRPA1 is activated by extreme, noxious cold temperatures. These cold receptors are expressed in different subpopulations of primary afferent neurons. TRPA1 is co-expressed in a subpopulation of somatosensory neurons expressing TRPV1, which is activated by heat. However, the distribution and co-expression of these channels in the nodose-petrosal ganglion complex, which contains the jugular (JG), petrosal (PG), and nodose ganglia (NG) (mainly involved in putative somatic, chemo- and somato-sensation, and somato and visceral sensation, respectively), remain unknown. Here, we conducted in situ hybridization analysis of the rat nodose-petrosal ganglion complex using specific riboprobes for TRPM8, TRPA1, and TRPV1 to compare the features of the cranial sensory ganglia. Hybridization signals for TRPA1 were diffusely observed throughout these ganglia, whereas TRPM8 transcripts were seen in the JG and PG but not in the NG. We retrogradely labeled cranial nerve X with Fast Blue (fluorescent dye) and found TRPM8 transcripts in the jugular-vagal ganglion but not the NG neurons. TRPA1 transcripts were not detected in TRPM8-expressing neurons but were present in the subpopulation of TRPV1-expressing visceral sensory neurons. Taken together, these findings support that in the vagal system the expression of cold-activated TRP channels differs between nodose- and jugular-ganglion neurons suggesting different mechanisms of cold-transduction and that the TRPA1 distribution is consistent with its proposed function as a cold-sensing receptor in the visceral system.

Impaired gastric motility and its relationship to reflux symptoms in patients with nonerosive gastroesophageal reflux disease.

BACKGROUND: More than half of patients with refluxrelated symptoms have no endoscopic evidence of mucosal breaks. These patients are considered to have nonerosive gastroesophageal reflux disease (NERD). The pathogenesis of NERD may be multifactorial, but the role played by gastric motility in symptom generation in patients with NERD has not been examined. In this study, we elucidate gastric motility in patients with NERD and the efficacy of a prokinetic agent in the treatment of NERD. METHODS: Gastric motility was evaluated with electrogastrography (EGG) and by measurement of gastric emptying using the acetaminophen method in 26 patients with NERD and in 11 matched healthy controls. NERD patients were treated with a prokinetic agent (mosapride 15 mg, orally three times daily) for a period of 4 weeks, after which gastric motility was measured again. RESULTS: Compared with the healthy controls, the NERD patients showed a significantly lower percentage of normogastria, a lower power ratio in EGG, and delayed gastric emptying. Ten patients had normal gastric motor function (group A), and 16 showed abnormalities of either gastric myoelectrical activity or gastric emptying (group B). After treatment with mosapride, gastric motility improved significantly in both groups of patients compared with pretreatment values. The subjective assessment by the patient after the treatment was improved in 20.0% of group A versus 62.5% of group B patients (P < 0.05). CONCLUSIONS: Gastric hypomotility appears to be an important factor in reflux symptom generation in some NERD patients.

[The efficacy of probiotics in gastrointestinal disease].

Probiotics are live microbial feed supplement which beneficially affects the host animals by improving its microbial balance. Probiotics have been used in the treatment of bacterial or viral induced acute intestinal infection. In recent years, some clinical studies have shown the therapeutic effects of probiotics in the treatment of chronic inflammatory bowel disease (IBD) or prevention of allergic disease. Evidence exists for therapeutic use of probiotics in acute infectious diarrhea, Clostridium difficile colitis and antibiotic-associated diarrhea. Their exact role in IBD, irritable bowel syndrome and prevention of cancer has not to be determined. This review summarized the data about probiotics in gastrointestinal diseases and examine the mechanisms of action related to their therapeutic effects.

Improvement of gastric motility by hemodialysis in patients with chronic renal failure.

BACKGROUND: Gastrointestinal (GI) symptoms are common in patients with chronic renal failure (CRF). We have previously demonstrated that patients with predialysis end-stage renal disease showed a high prevalence of GI symptoms and gastric hypomotility, and that gastric hypomotility appears to be an important factor in generating GI symptoms. However, it is not clear whether impaired gastric motor function would improve after hemodialytic treatment. AIMS: To examine the relationship between gastric motor function and GI symptoms in CRF patients on hemodialysis. METHODS: The study was performed in 19 patients with CRF treated with hemodialysis for more than six months and in 12 matched healthy controls. GI symptom severity was quantified in all patients. Gastric motility was evaluated with cutaneously recorded electrogastrography (EGG) and gastric emptying of semi-solid meals using the (13)C-acetic acid breath test. RESULTS: Six patients had no symptoms, and 11 had slight GI symptoms with a total symptom score of less than 5. Compared with controls, CRF patients revealed no differences in gastric motility parameters, with the exception of a lower percentage of normogastria in EGG at fasting state. Eleven patients had normal gastric motor function (Group A), and eight showed abnormalities of either gastric myoelectrical activity or gastric emptying (Group B). There was no difference in symptom score between Group A and Group B. CONCLUSIONS: More than half of the patients with CRF on hemodialysis demonstrated normal gastric motility, and no or slight GI symptoms. Hemodialytic treatment may improve impaired gastric motility and reduce GI symptoms in patients with CRF.

Impaired gastric motility and its relationship to gastrointestinal symptoms in patients with chronic renal failure.

BACKGROUND: Gastrointestinal (GI) symptoms are common in patients with chronic renal failure (CRF), but the pathogenesis of these symptoms is unclear. Gastric motor function in CRF patients remains controversial, and the correlation between GI symptoms and gastric motility is also unclear. The aim of this study was to elucidate the relationship between gastric motility and GI symptoms in patients with CRF. METHODS: Gastric motility was evaluated with cutaneously recorded electrogastrographs (EGGs) and gastric emptying of a solid meal, using 13C-octanoic acid breath testing, in 21 patients with predialysis endstage CRF and in 21 matched healthy controls. GI symptom severity was quantified in all patients. RESULTS: The CRF patients had a significantly lower incidence of normogastria postprandially and a lower power ratio than did healthy controls on the EGGs, with the CRF patients showing delayed gastric emptying. Three patients with normal gastric motility had no GI symptoms, and ten patients with both abnormal EGG and delayed gastric emptying had significantly higher GI symptom scores than the patients without abnormalities. CONCLUSIONS: The patients with CRF showed gastric hypomotility, including impaired gastric myoelectrical activity and delayed gastric emptying. Gastric hypomotility appears to be an important factor in the generation of GI symptoms in patients with CRF.

Effects of oral glucose intake on gastric myoelectrical activity and gastric emptying.

To investigate the effect of oral glucose intake on gastric motility, we measured gastric myoelectrical activity and gastric emptying on two test conditions: 1) glucose intake and 2) water intake in the same 10 healthy male volunteers (20 to 29 years old). Gastric motility was evaluated with cutaneous-recorded electrogastrography (EGG) for 30 min both on fasting and after glucose or water intake, while gastric emptying was measured using acetaminophen-absorption method. There were no significant changes in EGG dominant frequency after water intake, but the frequency increased significantly after glucose intake. A postprandial dip (i.e., a transient decrease in frequency immediately after the food intake) was observed in 3 subjects after water intake and in 8 subjects following glucose intake. The EGG power ratio was significantly larger after glucose than water intake, with delayed gastric emptying in the former case. These results suggest that glucose is one of the components responsible for postprandial gastric motility.

Gastric myoelectrical activity in patients with recurrent gastric or duodenal ulcers.

The aim of this study was to characterize gastric myoelectrical activity in patients with recurrent gastric ulcer (GU) or duodenal ulcer (DU), and to compare gastric motility between these two groups of patients. Studies were performed in 59 patients with recurrent active peptic-ulcer disease as diagnosed by gastrointestinal endoscopy: 31 patients had a GU and 28 patients had a DU. Gastric myoelectrical activity was evaluated by cutaneous electro-gastrography (EGG). The following EGG parameters were assessed: the percentage of normogastria (regular 2.4-3.6 cpm slow waves); the EGG power ratio; and the occurrence of a postprandial dip (PD), which is the transient decrease in EGG frequency after a meal. In the GU group, no significant change occurred in the percentage of normogastria or in the EGG power ratio observed after treatment with a proton-pump inhibitor. During the healed stage, the occurrence of PD remained unchanged. In contrast, in the DU group, the percentage of normogastria and the EGG power ratio were significantly increased after treatment. Moreover, during the healed stage, the occurrence of PD significantly increased compared with that during the active stage. These findings suggest that abnormal gastric myoelectrical activity plays an important role in the pathophysiology of recurrent GU rather than DU.