Treatment Of Functional Gastrointestinal Disorders Research Articles

Mo2102 Gastric Emptying Rate and CCK and GLP-1 Release After a Solid Test Meal Are Dependent on Body Mass Index

G A A b st ra ct s both transcriptional levels through stimulating its classical nuclear receptors: ER α and ERβ. On the other hand, a G protein coupled receptor, GPR30 responds to estrogen with rapid signaling. Whether estrogen has a direct physiologic role in the exacerbation of GI symptoms by altering GI motility or visceral sensation has not been sufficiently explored. We designed this study to see if: a) estrogen alters GI motility and pain sensation and b) its effects are mediated by GPR30. Methods: CD1 female mice (4-5 weeks old) were used in this study. The effects of cumulative concentrations (100 nM-3μM) of β-Estradiol and a potent and selective GPR30 agonist, G-1 on the contractility of the longitudinal colonic preparations induced by electrical field stimulation (EFS; 4Hz, 10Sec, 24V, 50Sec intervals) or, at the highest concentration (3μM), on the muscarinic agonist bethanechol (10μM) induced contractions were studied in vitro. Colonic propulsion of a glass bead after administration of β-Estradiol or G-1 was studied in vivo. The effects of either compound on visceral pain, induced by intracolonic mustard oil (MO) were characterized by recording spontaneous behaviors. Results: G-1 and β-Estradiol inhibited colonic EFS and bethanechol induced contractilities. G-15, a selective GPR30 antagonist, blocked the effects of G-1 but not βEstradiol on the colonic contractility. MPP dihydrochloride, a highly selective ERα antagonist partially reversed the effects of G-1 and β-Estradiol; however, PHTPP, an ERβ antagonist, did not alter the effects of either G-1 or β-Estradiol on the colonic contractility. In vivo, βEstradiol and G-1, both at the dose of 10-20 mg. i.v., prolonged colonic propulsion. The effects of β-Estradiol on colonic propulsion were significantly reversed by G-15 (5 mg, i.v.) or MPP dihydrochloride (5 mg, i.v.). The effects of G-1 were significantly reversed by G15 and partially by the ER antagonists. The number of MO induced pain related behaviors was decreased by G-1 or β-Estradiol (20 mg, i.v.). G-15 and MPP dihydrochloride, but not PHTPP (5 mg, i.v.) reversed the effects of G-1 on visceral pain. The antinociceptive effect of β-Estradiol was only blocked by G-15 and not by ER antagonists. Conclusion: GPR30 is involved in the regulation of GI motility and visceral sensation. Our data suggests that GPR30 may be a promising target for the treatment of functional GI disorders with impaired GI motility or visceral sensation.

Functional gastrointestinal diseases in children: Facing the rising tide

However, looking at the overall picture, this study suggests that use of romiplostim is safe and effective as it raised platelet count in 33/35 of the patients, with the majority peaking platelet count between two to three weeks since the first peptide injection. This may help raise platelet counts in CHC patients undergoing antiviral treatment. Currently, most of adverse effects of antiviral therapy with pegylated interferon, ribavirin, and protease inhibitors, such as anemia, leucopenia, fever, body ache, etc can be managed with supportive treatment such as erythropoietin, G-CSF injection, paracetamol, and nonsteroidal anti-inflammatory drugs. Yet no good treatment exists for thrombcyopenia. This study brings hope for CHC patients with thrombocytopenia who are in need of antiviral treatment. Understandingly, this is a phase II study, and the authors rightly caution in the concluding paragraph that further studies in larger group of patients over a longer period of time are warranted in defining the optimal treatment schedule and dosage of romiplostim. Nevertheless, studies on romiplostim will be closely watched by hepatologists like me, as this may bring hope to many patients with advanced fibrosis or cirrhosis from CHC who are excluded from current antiviral treatment due to pre-existing thrombocytopenia.

Effects on gastrointestinal functions and symptoms of serotonergic psychoactive agents used in functional gastrointestinal diseases

The effects of antidepressants on the gastrointestinal tract may contribute to their potential efficacy in functional dyspepsia and irritable bowel syndrome; buspirone, a prototype 5-HT1A agonist, enhances gastric accommodation and reduces postprandial symptoms in response to a challenge meal. Paroxetine, a selective serotonin reuptake inhibitor, accelerates small bowel but not colonic transit, and this property may not be relevant to improve gut function in functional gastrointestinal disorders. Venlafaxine, a prototype serotonin norepinephrine reuptake inhibitor, enhances gastric accommodation, increases colonic compliance and reduces sensations to distension; however, it is associated with adverse effects that reduce its applicability in treatment of functional gastrointestinal disorders. Tricyclic antidepressants reduce sensations in response to food, including nausea, and delay gastric emptying, especially in females. Buspirone appears efficacious in functional dyspepsia; amitriptyline was not efficacious in a large trial of children with functional gastrointestinal disorders. Clinical trials of antidepressants for treatment of irritable bowel syndrome are generally small. The recommendations of efficacy and number needed to treat from meta-analyses are suspect, and more prospective trials are needed in patients without diagnosed psychiatric diseases. Antidepressants appear to be more effective in the treatment of patients with anxiety or depression, but larger prospective trials assessing both clinical and pharmacodynamic effects on gut sensorimotor function are needed.

STW 5 (Iberogast®)—a safe and effective standard in the treatment of functional gastrointestinal disorders

SummaryFunctional dyspepsia (FD) and irritable bowel syndrome (IBS) are frequent disorders affecting quality of life. They often require long-term treatment. Abdominal symptoms of both disorders can overlap, making differential diagnosis and treatment challenging. The extracts of the herbal combination preparation STW 5 (Iberogast®) exert pharmacological effects in different gastrointestinal regions and can address symptoms of both FD and IBS. This review summarizes safety and efficacy data of 12 clinical trials using STW 5 in FD and IBS since 1990. Double-blind and randomized studies versus placebo or active control found statistically significant effects of STW 5 on patients’ symptoms with a comparable efficacy to a standard prokinetic. Non-interventional and retrospective studies confirmed these effects. Various studies evaluated the tolerability profile of STW 5: the incidence of adverse drug reactions was 0.04 %. The worldwide spontaneous reporting system confirmed this profile. STW 5 has a favorable tolerability which is relevant for long-term treatment.

Cochrane Review: Antidepressants for the treatment of abdominal pain‐related functional gastrointestinal disorders in children and adolescents

Cochrane Review: Antidepressants for the treatment of abdominal pain‐related functional gastrointestinal disorders in children and adolescents

Clarification of trial end points presented in a recent review of linaclotide

Response to: Roque MV, Camilleri M. Linaclotide, a synthetic guanylate cyclase C agonist, for the treatment of functional gastrointestinal disorders associated with constipation. Expert Rev. Gastroenterol. Hepatol. 5(3), 301–310 (2011).

Practical Treatments for Constipation in Korea

Constipation is a digestive symptom that is frequently seen in clinical practice. Its prevalence has been reported to be 2% to 20%, depending on geographical region. Despite the rapid development of medical science, systematic studies on constipation have been rarely conducted in Korea. Recently, guidelines on the diagnosis and treatment of functional gastrointestinal disorders, including constipation, were proposed by The Korean Society of Neurogastroenterology and Motility. These guidelines are expected to reflect the current situation regarding treatment of constipation in Korea. In this paper, practical constipation treatment methods that are in current use will be reviewed with reference to these recent guidelines.

Inhibitory effects of desvenlafaxine on gastric slow waves, antral contractions, and gastric accommodation mediated via the sympathetic mechanism in dogs

Desvenlafaxine succinate (DVS; Pristiq) is a new antidepressant, serotonin-norepinephrine reuptake inhibitor. Antidepressants have been widely used for the treatment of functional gastrointestinal disorders. Possible roles of DVS on gastrointestinal motility have not been studied. The aim of this study was to investigate the effects of DVS on gastric slow waves (GSW), antral contractions, and gastric accommodation in dogs. Fifteen healthy dogs implanted with gastric serosal electrodes and a gastric cannula were studied in four separate sessions: control, DVS (50 mg), propranolol (1 mg·kg(-1)·h(-1)), and propranolol + DVS. GSW were measured via the gastric serosal electrodes. Antral contractions were assessed via an intraluminal manometric catheter inserted via the gastric cannula. The sympathovagal activity was assessed from the spectral analysis of the heart rate variability signal. Gastric tone was measured by barostat via an intragastric balloon inserted into the fundus via the gastric cannula. In the postprandial period, in comparison with the control, DVS reduced the percentage of normal GSW (P=0.001) and increased the percentage of tachygastria (P=0.005) and bradygastria (P=0.002). Simultaneously, DVS increased the sympathetic activity (P=0.006) and the sympathovagal ratio (low frequency/high frequency; P=0.044). These effects were blocked by propranolol. DVS attenuated postprandial antral contractions and gastric accommodation. The postprandial antral contractile index (area under the curve) was decreased by 26% with DVS (P=0.013), and gastric accommodation was decreased by about 50% with DVS (P < 0.001). The inhibitory effect of DVS on gastric accommodation was blocked by propranolol. DVS inhibits gastric contractions, slow waves, and accommodation in the fed state. These inhibitory effects are associated with an increased sympathetic modulation in the gastrointestinal system. Cautions should be made when DVS is used for treating patients with depression and gastric motility disorders.

Pharmacological characterization of tegaserod at the wild type and 124Cys variant of the human 5-HT1B receptor

Sumatriptan, an antimigraine drug, causes contraction of human coronary arteries through activation of 5-HT1B receptors which couple to Gi/Go inducing inhibition of adenylate cyclase. At a rare, naturally occurring human receptor variant (124Cys-h5-HT1B), sumatriptan has previously been shown to act as a more potent agonist than at wild-type receptor. Tegaserod, a 5-HT4-receptor agonist, developed for the treatment of functional gastrointestinal disorders, has been suspected to be involved in very rare cardiac ischemic events in patients with cardiovascular risk factors. In this study, we examined the potential agonist-like effects of tegaserod in comparison with sumatriptan at heterologously expressed human wild type and 124Cys-variant 5-HT1B receptors, using assays addressing G-protein coupling and inhibition of forskolin-stimulated cyclic AMP accumulation. Sumatriptan exhibited agonist effects as previously reported, whereas tegaserod acted as partial agonist at both wild type and 124Cys-variant h5-HT1B receptors (expressed in rat C6 glioma cells). Sumatriptan and tegaserod were more potent at the 124Cys-variant h5-HT1B receptor. It remains to be shown whether the very rare cardiovascular side effects reported with these drugs are predominantly observed in patients homozygously expressing the variant receptor.

Patient-Reported Outcomes for Irritable Bowel Syndrome Are Associated With Patients' Severity Ratings of Gastrointestinal Symptoms and Psychological Factors

Patient-reported outcomes (PROs) are used to gauge the benefit of treatments for functional gastrointestinal disorders, including irritable bowel syndrome (IBS). Commonly used end points derived from scales of symptom severity differ in their structure, format, and the extent to which they are based on established psychometric fundamentals. We evaluated the overlap between 2 measures of IBS symptom severity, documented their association with different symptoms (pain, bloating, altered defecation), and identified psychological factors that might bias PRO ratings, by affecting how patients interpret IBS symptom severity. Ninety-eight patients diagnosed with IBS, based on Rome III criteria, completed the multicomponent IBS Symptom Severity Scale and the single-item, UCLA Symptom Severity Scale. Data were collected on pain, bloating, and bowel habits, as well as somatization, sensitivity to arousal symptoms (anxiety sensitivity), and a negative thinking style called pain catastrophizing. The 2 global scales were correlated with one another (r = 0.56); each scale was associated most strongly with variation in abdominal pain. Data were consistent with a model in which pain catastrophizing and somatization influenced 1 or more of patients' judgments of pain, bloating, and/or bowel habits, which then affected the PROs. Depending on their structure and format, PROs can have different levels of sensitivity to core IBS symptoms and be influenced by psychological and somatic complaints that are beyond the aim of therapy and labeling claim. PROs that rely on patients' perspectives to index symptom severity can be improved by consideration of psychometric principles that influence self-report.

Linaclotide, a synthetic guanylate cyclase C agonist, for the treatment of functional gastrointestinal disorders associated with constipation

Chronic constipation (CC) and irritable bowel syndrome with constipation (IBS-C) are two functional gastrointestinal disorders that are associated with constipation. CC and IBS-C affect approximately 20% of the general population including the elderly, impairing quality of life. Patients not responding to over-the-counter treatments require effective and safe long-term therapies. Some treatments introduced in the last decade have been associated with side effects that led to withdrawal from the US market (e.g., tegaserod) or intolerance to treatment (e.g., nausea in patients treated with lubiprostone). Linaclotide is a novel drug, with a unique mechanism of action, low bioavailability and local action in the intestinal epithelial cells. It is currently being developed for patients with CC and IBS-C. From animal studies to human pharmacodynamic Phase Ib trials, and a comprehensive program of Phase IIb and III trials in health and disease, linaclotide demonstrates long-term efficacy and safety in CC and IBS-C.

Cytokine Modulation of Visceral Afferents via Cation Channels is Switched in Chronic Visceral Hypersensitivity

Introduction: Increasing evidence suggests that chronic stress alters behavior and modifies epigenetic regulation of genes in the central nervous system. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), is an important epigenetic mechanism of transcriptional control of gene expression. We reported previously that chronic psychological stress induced visceral hyperalgesia and differential alterations in the expression of several genes in DRG neurons innervating the colon in the rat. A potential role for epigenetic regulation in peripheral sensory pathways has not been investigated. Objectives: We examined the hypothesis that DNMTs play an important role in the regulation of chronic stress-induced visceral hyperalgesia. Methods: Male rats were exposed to 1-hour water avoidance (WA) stress daily for 10 consecutive days as a chronic stress paradigm. SiRNA for DNMT1 was administrated in situ to L6-S2 DRGs every other day during the stress procedure. The visceromotor response (VMR) to colorectal distension was measured. Retrograde labeling with cholera toxin B (CTB)-FITCwas employed to identify colonDRG neurons. Immunofluorescence andWestern blot analysis were used to assess protein expression. In Vitro studies were performed in isolated control DRGs in the presence or absence of corticosterone (CORT; 10 μM) and RU-486 (corticoid receptor antagonist, 500 nM). Results: WA stress rats demonstrated significant increases in the level of DNMT1 and DNMT3b but not DNMT3a in L6-S2 DRGs compared with the controls. Enzyme activity assessment showed a 42% increase in DNMT1 activity in L6-S2 DRGs in stressed rats. Immunofluorescence studies revealed a significant increase in DNMT1 in small-sized, C-fiber neurons in WA stressed rats (52.3±2.2%) compared with the control (31.7±1.6%). Retrograde labeling demonstrated that 72.0±2.1% of the CTB-FITC labeled colonic DRG neurons were positive for DNMT1 in stressed rats compared to 40.0±6.5% in controls (P<0.05; n=4). The VMR in WA stressed rats was increased 68% and 92% above control responses at pressures of 40 and 60 mm Hg, respectively. Treatment of stressed rats with siRNA for DNMT1 prevented the VMR enhancement and changes in DNMT1 proteins levels in L6-S2 DRGs. In addition, treatment of control L6-S2 DRGs In Vitro with CORT (10 μM) increased DNMT1 expression level that was prevented by RU-486 (500 nM) (P<0.05). Conclusions: These data support the novel and provocative interpretation that: 1. Chronic stress induces epigenetic regulation of genes in primary nociceptive neurons; 2. DNA methyltransferase 1 (DNMT1) plays an important role in modulation of chronic stress-induced visceral hyperalgesia; and 3. DNA methyltransferases represent a potential target for treatment of functional GI disorders associated with visceral hyperalgesia.

Identification of Colonic Afferent Central Terminals and Changes Following Colonic Inflammation

Introduction: Increasing evidence suggests that chronic stress alters behavior and modifies epigenetic regulation of genes in the central nervous system. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), is an important epigenetic mechanism of transcriptional control of gene expression. We reported previously that chronic psychological stress induced visceral hyperalgesia and differential alterations in the expression of several genes in DRG neurons innervating the colon in the rat. A potential role for epigenetic regulation in peripheral sensory pathways has not been investigated. Objectives: We examined the hypothesis that DNMTs play an important role in the regulation of chronic stress-induced visceral hyperalgesia. Methods: Male rats were exposed to 1-hour water avoidance (WA) stress daily for 10 consecutive days as a chronic stress paradigm. SiRNA for DNMT1 was administrated in situ to L6-S2 DRGs every other day during the stress procedure. The visceromotor response (VMR) to colorectal distension was measured. Retrograde labeling with cholera toxin B (CTB)-FITCwas employed to identify colonDRG neurons. Immunofluorescence andWestern blot analysis were used to assess protein expression. In Vitro studies were performed in isolated control DRGs in the presence or absence of corticosterone (CORT; 10 μM) and RU-486 (corticoid receptor antagonist, 500 nM). Results: WA stress rats demonstrated significant increases in the level of DNMT1 and DNMT3b but not DNMT3a in L6-S2 DRGs compared with the controls. Enzyme activity assessment showed a 42% increase in DNMT1 activity in L6-S2 DRGs in stressed rats. Immunofluorescence studies revealed a significant increase in DNMT1 in small-sized, C-fiber neurons in WA stressed rats (52.3±2.2%) compared with the control (31.7±1.6%). Retrograde labeling demonstrated that 72.0±2.1% of the CTB-FITC labeled colonic DRG neurons were positive for DNMT1 in stressed rats compared to 40.0±6.5% in controls (P<0.05; n=4). The VMR in WA stressed rats was increased 68% and 92% above control responses at pressures of 40 and 60 mm Hg, respectively. Treatment of stressed rats with siRNA for DNMT1 prevented the VMR enhancement and changes in DNMT1 proteins levels in L6-S2 DRGs. In addition, treatment of control L6-S2 DRGs In Vitro with CORT (10 μM) increased DNMT1 expression level that was prevented by RU-486 (500 nM) (P<0.05). Conclusions: These data support the novel and provocative interpretation that: 1. Chronic stress induces epigenetic regulation of genes in primary nociceptive neurons; 2. DNA methyltransferase 1 (DNMT1) plays an important role in modulation of chronic stress-induced visceral hyperalgesia; and 3. DNA methyltransferases represent a potential target for treatment of functional GI disorders associated with visceral hyperalgesia.

Chronic Stress-Induced Visceral Hyperalgesia: Evidence for Epigenetic Regulation of DNA Methyltransferase I (Dnmt1) in Dorsal Root Ganglion (DRG) Neurons Innervating the Colon in the Rat

Introduction: Increasing evidence suggests that chronic stress alters behavior and modifies epigenetic regulation of genes in the central nervous system. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), is an important epigenetic mechanism of transcriptional control of gene expression. We reported previously that chronic psychological stress induced visceral hyperalgesia and differential alterations in the expression of several genes in DRG neurons innervating the colon in the rat. A potential role for epigenetic regulation in peripheral sensory pathways has not been investigated. Objectives: We examined the hypothesis that DNMTs play an important role in the regulation of chronic stress-induced visceral hyperalgesia. Methods: Male rats were exposed to 1-hour water avoidance (WA) stress daily for 10 consecutive days as a chronic stress paradigm. SiRNA for DNMT1 was administrated in situ to L6-S2 DRGs every other day during the stress procedure. The visceromotor response (VMR) to colorectal distension was measured. Retrograde labeling with cholera toxin B (CTB)-FITCwas employed to identify colonDRG neurons. Immunofluorescence andWestern blot analysis were used to assess protein expression. In Vitro studies were performed in isolated control DRGs in the presence or absence of corticosterone (CORT; 10 μM) and RU-486 (corticoid receptor antagonist, 500 nM). Results: WA stress rats demonstrated significant increases in the level of DNMT1 and DNMT3b but not DNMT3a in L6-S2 DRGs compared with the controls. Enzyme activity assessment showed a 42% increase in DNMT1 activity in L6-S2 DRGs in stressed rats. Immunofluorescence studies revealed a significant increase in DNMT1 in small-sized, C-fiber neurons in WA stressed rats (52.3±2.2%) compared with the control (31.7±1.6%). Retrograde labeling demonstrated that 72.0±2.1% of the CTB-FITC labeled colonic DRG neurons were positive for DNMT1 in stressed rats compared to 40.0±6.5% in controls (P<0.05; n=4). The VMR in WA stressed rats was increased 68% and 92% above control responses at pressures of 40 and 60 mm Hg, respectively. Treatment of stressed rats with siRNA for DNMT1 prevented the VMR enhancement and changes in DNMT1 proteins levels in L6-S2 DRGs. In addition, treatment of control L6-S2 DRGs In Vitro with CORT (10 μM) increased DNMT1 expression level that was prevented by RU-486 (500 nM) (P<0.05). Conclusions: These data support the novel and provocative interpretation that: 1. Chronic stress induces epigenetic regulation of genes in primary nociceptive neurons; 2. DNA methyltransferase 1 (DNMT1) plays an important role in modulation of chronic stress-induced visceral hyperalgesia; and 3. DNA methyltransferases represent a potential target for treatment of functional GI disorders associated with visceral hyperalgesia.

Functional gastrointestinal disorders in New Zealand

Functional gastrointestinal disorders are common worldwide. To review functional gastrointestinal disorder prevalence, diagnosis and treatment in New Zealand. A Medline search was performed to identify all published studies relating to prevalence, diagnosis and treatment of functional gastrointestinal disorders in New Zealand. Reflux prevalence is 30% and non-reflux dyspepsia is 34.2%. Helicobacter pylori prevalence varies considerably in NZ by geographical area and ethnicity and overall prevalence of infection is 24% in adults. 50% of patients with dyspepsia presenting for endoscopy in NZ will have no mucosal abnormality identified. National Dyspepsia Guidelines assist in management of patients. Guidelines exist for undifferentiated dyspepsia, Gastro-oesophageal Reflux Disease (GORD), H. pylori, peptic ulcer, NSAID's and gastrointestinal complications. Irritable Bowel Syndrome (IBS) is reported by 21% of adults. Symptoms were more than twice as frequent and severe in females than males. Access to colonoscopy for investigation of bowel symptoms is limited in NZ and priority is given to patients with "alarm features". Non-invasive markers of inflammation, such as faecal calprotectin, are being used to differentiate the patient with functional diarrhoea from inflammatory bowel disease. Treatment for irritable bowel symptoms is targeted to the predominant symptom. Functional gastrointestinal disorders are common in New Zealand. There is increasing awareness of dietary management for functional bowel symptoms.

Diagnosis and treatment of functional gastrointestinal disorders in the Asia‐Pacific region: A survey of current practices

Functional gastrointestinal disorders (FGIDs), namely functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common disorders important to public health in the Asia-Pacific region. Our objectives were to determine the current practices in diagnosis and management of these disorders in the Asia-Pacific region. Forty-three physicians and researchers in FGID who attended the first Asian Pacific Topic Conference at Tokyo in November 2010 were invited to answer a questionnaire. Twenty-three Japanese doctors and twenty doctors from other Asia-Pacific Societies answered the questionnaire, which consisted of 60 multiple-choice questions concerning physician's preferences in diagnosis and management of FGIDs. Overall, there were similarities in diagnostic approach, such as differential diagnosis, exclusion of organic diseases, psychophysiological assessment, medical advice or medication with psychological drugs, not only among different Asia-Pacific region but also between FD and IBS. Several notable differences were seen. For example, general practitioners did not commonly use the term FD or diagnose FD by themselves, while the term IBS was widely used and frequently diagnosed. Sub-categorization was more common in IBS than FD. There was also a difference between Japan and other Asia-Pacific region; upper GI endoscopy and blood examination were more common in Japan, while eradication of Helicobacter pylori was more frequently done in other countries. Anti-secretory drugs for FD and mild laxatives or anti-diarrheal drug for IBS were frequently used, and prokinetics were used for all patients with FD or IBS. Interestingly, drugs developed in Japan and Chinese herbal medicines were more frequently prescribed in Japan. Information obtained in this survey is useful for understanding the most common clinical approaches for FGIDs in the Asia-Pacific region.

Is Bifidobacterium breveeffective in the treatment of childhood constipation? Results from a pilot study

BackgroundProbiotics are increasingly used in the treatment of functional gastrointestinal disorders. Studies in constipated adults with a Bifidus yoghurt (containing Bifidobacterium breve, Bifidobacterium bifidum and Lactobacillus acidophilus) showed a significant increase in defecation frequency. The aim of this pilot study was to determine if Bifidobacterium breve is effective in the treatment of childhood constipation.MethodsChildren, 3 to 16 years of age, with functional constipation according to the Rome III criteria were eligible for this study. During 4 weeks, children received one sachet of powder daily, containing 108- 1010 CFU Bifidobacterium breve. Furthermore, children were instructed to try to defecate on the toilet for 5-10 minutes after each meal and to complete a standardized bowel diary daily. The primary outcome measure was change in defecation frequency. Secondary outcome measures were stool consistency using the Bristol stool scale frequency of episodes of faecal incontinence, pain during defecation, frequency of abdominal pain, frequency of adverse effects (nausea, diarrhoea and bad taste), and frequency of intake of bisacodyl.ResultsTwenty children (75% male, mean age 7.4) were included in this pilot study. The defecation frequency per week significantly increased from 0.9 (0-2) at baseline to 4.9 (0-21) in week 4 (p < 0.01). The mean stool consistency score increased from 2.6 (2-4) at baseline to 3.5 (1-6) in week 4 (p = 0.03). The number of faecal incontinence episodes per week significantly decreased from 9.0 (0-35) at baseline to 1.5 (0-7) in week 4 (p < 0.01). Abdominal pain episodes per week significantly decreased from 4.2 (0-7) at baseline to 1.9 (0-7) in week 4 (p = 0.01). No side effects occurred.ConclusionBifidobacterium breve is effective in increasing stool frequency in children with functional constipation. Furthermore it has a positive effect with respect to stool consistency, decreasing the number of faecal incontinence episodes and in diminishing abdominal pain. A randomized placebo controlled trial is required to confirm these data.

Inhibitory effect ofSuaeda asparagoides(Miq.) extract on the motility of rat gastric antrum is mediated by β-adrenoceptor

Suaeda asparagoides (Miq.) has long been used as a Korean folk herbal medicine for the treatment of functional gastrointestinal disorders. However, reports on its pharmacological activity on gastrointestinal motility are scarce. The present study investigated the effects of Suaeda asparagoides water fraction of the extract (SAWF) on antral motility in vitro. Muscle strips from rat gastric antrum were set up in an organ bath in a circular orientation. SAWF (100 µg/mL) inhibited the spontaneous contraction of antral circular muscle strips. These inhibitory effects were not significantly affected by tetrodotoxin (1 µM), Nω-Nitro-L-arginine methyl ester hydrochloride (100 µM), 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (10 µM), ryanodine (10 µM) and phentolamine (10 µM). SAWF-induced inhibition was mostly restored by cyclopiazonic acid (10 µM). Furthermore, the β-adrenergic receptor antagonist, propranolol (10 µM), abolished SAWF-induced inhibition. These results suggest that SAWF may exert its activity on gastrointestinal smooth muscle via â-adrenergic receptors and sarcoplasmic reticulum Ca2+ ATPase.

Approaching patients with irritable bowel syndrome

Treatment of functional gastrointestinal disorders remains difficult with many very different approaches showing similar response rates, regardless of whether they target luminal contents (e.g., presumed bacterial overgrowth), signaling within the gut wall (e.g., serotonin agonists or antagonists) or processing in the brain (e.g., cognitive behavioral therapy). Discrepancies between recent clinical trials and a meta-analysis have forced us to re-examine the use of antidepressants. Other studies have looked beyond the traditional drug therapies and have suggested other options such as dietary interventions and communication strategies that address relevant disease mechanisms and enable us to understand patient concerns, with the ultimate goal being to individualize and thus improve treatment outcomes.

Multimodale Therapie funktioneller Erkrankungen des Verdauungstraktes

A multimodal approach is state-of-the art for effective treatment of functional gastrointestinal disorders (FGD) like irritable bowel syndrome and functional dyspepsia. Based on the now established view that the pathogenesis of FGD is multicausal, evidence-based therapeutic options comprise education about the nature of the disorder, dietary modifications, relaxation techniques, behavioral changes, and pharmacological treatments. These therapies are variously combined depending on the severity of the FGD and the individual needs of the patient. Our overview portrays the options for the therapy of FGD and proposes that these are best provided by an interdisciplinary team of primary care physicians, gastroenterologists, and psychosomatic medicine specialists.