Jan Tack

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..EXPERT OPINION: Compared to placebo, no adverse events have been reported in the current short-term studies, while acotiamide seems efficacious for treating postprandial distress syndrome symptoms in FD patients...

..Further randomized controlled trials testing treatment response by subgroup are urgently needed...

..The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs)...

..Y(2) receptor antagonists were not able to decrease gastric tone without exogenous administration of PYY(3-36), indicating that Y(2) receptors do not play a crucial role in the determination of gastric tone in physiological conditions...

..Finally, an overview on the therapeutic agents used in clinical practice is provided...

..They also have a number of side-effects. Constipation is thought to be common, and a potential serious side-effect, which has received little attention in recent literature...

..To determine the efficacy, impact on quality of life (QOL) and safety of prucalopride, a selective, high-affinity 5-HT(4) receptor agonist, in patients with chronic constipation...

..The involved mechanism could at least in part depend on an effect on meal-induced accommodation. 100 mg Acotiamide exhibited the potential to improve FD symptoms and QOL. Further studies are indicated...

..We aimed to investigate the association between body mass index (BMI) and abdominal circumference on the incidence and proximal extent of reflux...

..EXPERT OPINION: While many new prokinetic drugs are in the early stages of evaluation, acotiamide emerges as the drug with a promising efficacy profile. Convincing evidence for the efficacy of psychotropics is lacking...

..New agents under evaluation include the 5-HT4 agonists velusetrag and naronapride, the guanylate cyclase-C receptor agonist linaclotide and the peripherally acting mu opioid receptor antagonist alvimopan...

..It is now well-recognised that rumination syndrome occurs in patients of all ages and cognitive abilities...

..Our current knowledge of visceral chemosensitivity of the human gastrointestinal tract in health and in disease is reviewed, with a specific focus on the interaction between mechano- and chemosensitive pathways...

..Areas of major advances are the role of infection and genetic predisposition and studies on the role of abnormalities in gastric motility and sensitivity...

..Irritable bowel syndrome (IBS) is a common, chronic disorder, characterized by abdominal pain/discomfort, bloating and altered bowel habit...

..The actions of sumatriptan on gastric motility seem to be attributable to a direct action on enteric neurones...

..The therapeutic options for the non-acid component of the refluxate, including acid suppression, prokinetics, baclofen, surgery and mucosal protective agents like alginates, are discussed...

..Rarely, in case of debilitating refractory symptoms, experimental or invasive therapies can be tried such as injection of botulinum toxin, enteral feeding tube insertion, gastric electrical stimulation or surgery...

..However, a direct relationship between duodenal acid exposure and symptom severity is lacking...

..Our aim was to investigate regional cerebral blood flow during painful proximal gastric distention in hypersensitive FD...

..ATD alters gastric postprandial motor function and distension-induced nausea. These findings confirm involvement of 5-HT in the control of gastric accommodation and sensitivity...

..Experimentally induced anxiety in healthy volunteers is associated with changes in sensorimotor function of the proximal stomach...

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..Fosamprenavir, a phosphate ester prodrug of the poorly water-soluble HIV-inhibitor amprenavir, was selected as model compound...

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..The aim of the study was to examine postprandial phasic contractility in functional dyspepsia in relation to pathophysiological, clinical, and demographic variables...

..Therefore, we aimed to determine the influence of gastric sensitivity and abuse history on gastric sensation scores and brain activity in homeostatic-afferent, emotional-arousal, and cortical-modulatory brain regions in FD...

..Blocking passage to the duodenum significantly decreases the amplitude of the accommodation reflex and induces early satiety...

..The aims of this study were to study the long-term evolution of symptoms in a clinical FD population and to identify factors associated with outcome...

..We compared the efficacy of subcutaneous octreotide with that of the long-acting repeatable (LAR) octreotide formulation, which is administered monthly, in patients with dumping syndrome...

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..Psychosocial factors and altered response to duodenal lipids or acid have also been identified as pathophysiologic mechanisms...

..In conclusion, age-dependent permeability of intestinal tissue (rather than age-dependent luminal drug solubility) may contribute to altered intestinal drug absorption in older patients compared to young adults...

..The effect of sildenafil on gastric fundus suggests a therapeutic potential for phosphodiesterase inhibitors in patients with impaired gastric accommodation...

..In conclusion, FaSSIF(c) and FeSSIF(c) can be considered biorelevant media for intestinal solubility estimation. A simpler TPGS-based system may be a valuable alternative with improved stability and lower cost...

..The current study reports on supersaturation, precipitation and excipient mediated precipitation inhibition of five poorly soluble drugs (loviride, glibenclamide, itraconazole, danazol, and etravirine) in human and simulated gastric fluids...

..This study sought to determine the association of abuse history, psychiatric comorbidity, and somatization with gastric sensorimotor function...

..However, excipients showing no effect in simple aqueous buffer or FaSSIF/FeSSIF also proved to be ineffective in HIF, indicating the value of these simulation media in the elimination of excipients during formulation development...

..CONCLUSIONS: Experimentally induced anxiety alters gastric sensorimotor function, suggesting that psychological factors may play a causal role in the pathogenesis of some dyspeptic symptoms and mechanisms...

..Until now, neuronal activity recordings from a more accessible human tissue source have remained a true challenge...

..FD + IBS is more prevalent in female patients and is associated with a higher weight loss, with greater overall symptom severity, and with hypersensitivity to distention...

..To determine the role of duodenogastro-esophageal reflux (DGER) in the pathogenesis of refractory gastro-esophageal reflux disease (GERD) in children...

..Through these mechanisms, increased duodenal acid exposure may be involved in the pathogenesis of dyspeptic symptoms...

..Delayed gastric emptying of solids was constantly associated with postprandial fullness and with vomiting. Delayed emptying for liquids was also associated with postprandial fullness and with severe early satiety...

..The effect of motilin is atropine-resistant and involves a direct muscular pathway or a non-cholinergic neural pathway...

..4-1 mM) and another buffering compound such as 2-morpholinoethanesulfonic acid (MES)...

..The present study illustrates, for the first time, that supersaturation can be created and maintained in HIF, even in the absence of excipients...

..Buspirone, a 5-hydroxytryptamine 1A receptor agonist, relaxes the proximal stomach in healthy individuals. We studied the effects of buspirone on symptoms and mechanisms of FD...

..We investigated whether the gustatory G-protein, α-gustducin, and the free fatty acid receptors GPR40 and GPR120 are involved in the fatty acid sensing mechanisms of the ghrelin cell...

..We investigated risk factors for esophageal perforation after PD and evaluated safety and long-term outcome of nonsurgical management strategies...

..To explore the effect of the nutritional state on the solubilizing properties of human intestinal fluids (HIF) on a time-after-food administration basis...

..CONCLUSION: The findings of the present article do not support routine proximal esophageal pH monitoring as a clinical tool: PR does not differentiate patients with typical or atypical GERD manifestations and depends mainly on DR...

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..A 4-week placebo-controlled Phase III study in PDS patients in Japan confirmed efficacy of acotiamide in relieving postprandial fullness, early satiation and upper abdominal bloating...

..Drugs targeting esophageal motility and sensitivity to be used as add-onc therapy in PPI insufficient responders have not reached Phase III trials to date, due to difficulties with patient selection, tolerability and end points...

..The present article provides an overview of pathogenetic factors, pathophysiologic mechanisms and their potential roles in FD...

..In patients with reflux-related ENT symptoms, initial findings on upper GI endoscopy and 24-hr pH-metry help to predict the need for maintenance therapy...

..This review summarizes recent progress in our understanding of gastroduodenal motility and sensitivity in health and in disease...

..Finally, the inhibitory effect of galanin on electrical stimulation, but not on DMPP- and carbachol-induced responses, suggests that, at least for the cholinergic component, galanin acts at the presynaptic level...

..In conclusion, in patients with functional dyspepsia the presence of HP infection does not seem to affect significantly the overall prevalence of symptoms or the gastric sensory-motor functions...

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..We found no evidence for a functional neuroanatomic divergence in the processing of noxious and innocuous gastric stimuli...

..Severe erosive oesophagitis is associated with low impedance baseline. We hypothesised that impedance baseline measurements could be used to evaluate changes in oesophageal mucosa integrity in man...

..In contrast to previously published studies, in which only plasma concentrations were determined, we also explored the gastric and intestinal behaviour of posaconazole after a single oral dose...

..The objective of this study was to test the hypothesis that Stretta alters GEJ resistance...

..Recently studied drugs include drugs under investigation including nitrates, serotonin reuptake blockers, 5-HT(1A) receptor agonists (buspirone and R137696), and muscarinc M1/M2 receptor antagonists (acotiamide or Z-338)...

..This study investigated the effects of colitis on the contractile effects of motilin, an important endocrine regulator of gastric motility, in the antrum...

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..This review summarizes recent progress in our understanding of the pathophysiology and treatment of gastroesophageal reflux disease...

..This study illustrates the importance of the evaluation of intraluminal conditions after drug intake and their integration in permeability estimation in vitro...

..CONCLUSIONS: In a tertiary care population, functional dyspepsia is a heterogeneous condition characterized by 4 major dimensions differentially associated with psychopathological and physiopathological mechanisms...

..This review summarizes the current understanding of the role of visceral hypersensitivity in the pathogenesis of NERD symptoms and the mechanisms implicated in the pathogenesis of esophageal hypersensitivity...

..Whether the sumatriptan-induced gastric relaxation in cats is due to interaction with 5-HT(1F) receptors could not be proven absolutely in view of the lack of selective 5-HT(1F) receptor antagonists...

..The Phase III studies mainly recruited patients with insufficient response to laxatives, and showed consistent efficacy and excellent tolerability for prucalopride...

..It has been proposed that treatments for irritable bowel syndrome with constipation (IBS-C) should provide rapid symptomatic relief, be intermittent, and effective upon repeated use...

..This review summarizes recent progress in our understanding of normal and pathologic gastric sensory and motor function...

..CONCLUSIONS: Subdividing FD patient groups according to the predominant symptom does not reliably identify subgroups with a homogeneous underlying pathophysiological mechanism...

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..In patients with treatment-refractory dumping syndrome, surgical reintervention or continuous enteral feeding can be considered, but the outcomes of such approaches are variable...

..Phase II studies indicated potential beneficial effects on symptoms and bowel habits in patients with constipation-predominant IBS and mixed-type IBS. The outcome of Phase III studies is currently under evaluation...

..Thus, efforts to further elucidate underlying pathophysiologic mechanisms and identify the appropriate patient population using some type of pathophysiologic testing will be required...

..In addition, knowledge of luminal drug concentrations may assist in the selection of drug concentrations applied in in-vitro permeability assays...

..Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, is released from the stomach. Animal studies suggest that ghrelin stimulates gastrointestinal motor activity...

..Impaired gastric accommodation is a major pathophysiological mechanism in functional dyspepsia. The aim of the present work was to assess a satiety drinking test in the evaluation of accommodation in health and dyspepsia...

..This study has established proof of concept and supports further investigation of renzapride in patients with constipation-predominant irritable bowel syndrome...

..This study examined the effects of hypnosis on autonomic cardiac control. We hypothesized a modification of autonomic modulation of the heart rate with an enhanced vagal tone during hypnosis compared to baseline...

..Many experts consider laparoscopic Heller's myotomy (LHM) to be superior to pneumatic dilation for the treatment of achalasia, and LHM is increasingly considered to be the treatment of choice for this disorder...

..It usually occurs in otherwise healthy patients and was first described as We report the case of a patient with chronic dysphagia due to chronic oesophagitis dissecans...

..This provides further support for an integrative, multidisciplinary biopsychosocial approach to FGID...

..It is unclear whether endogenous serotonin release is involved in the regulation of gastric motility and food intake...

..The therapeutic options for the non-acid component of the refluxate, including acid suppression, prokinetics, baclofen and surgery, are discussed...

..Whether this represents task-independent suspension of 'default mode' activity (as described in various cognitive tasks) or an visceral pain/interoception-specific process remains to be elucidated...

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..Methodological differences between the brain imaging studies on gastric distension may account for these somewhat discrepant findings...

..The influence of patient characteristics on HRQoL in functional dyspepsia is poorly understood...

..Besides its role in neuronal growth and differentiation, brain-derived neurotrophic factor (BDNF) has been implicated in the control of peristalsis where it serves to enhance gastrointestinal motility...