Novel therapies for constipation

Thayalasekeran, Sreedhari; Ali, Hani; Tsai, Her Hsin

doi:10.3748/wjg.v19.i45.8247

Cited by 30 publications

(22 citation statements)

References 25 publications

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“…55,56 In vitro studies have clearly demonstrated that MC activation alters intestinal epithelial ion transport directly or indirectly (via intrinsic or extrinsic nerves), 57,58 through recording the transepithelial short-circuit current of the intestinal mucosal tissues or epithelial cell monolayers. In sensitized mast cell-deficient mice, secretory response to serosal antigen was reduced by 70% in comparison to normal congenic mice, but fully restored after reconstitution of intestinal mast cell population by injecting bone marrow-derived mast cell precursors.…”

Section: Mast Cells Regulate Epithelial Secretionmentioning

confidence: 99%

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

110

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Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients.

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Section: Mast Cells Regulate Epithelial Secretionmentioning

confidence: 99%

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

110

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“…While pharmacological therapies, such as prucalopride, linaclotide, and lubiprostone, are effective and relatively safe for the IBS-constipation variant [9], in general, diet and food choice are initially considered for patients with IBS in order to improve their gut symptoms [10].…”

Section: Introductionmentioning

confidence: 99%

Feasibility of Low Fermentable Oligosaccharide, Disaccharide, Monosaccharide, and Polyol Diet and Its Effects on Quality of Life in an Italian Cohort

et al. 2020

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The low Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet has demonstrated excellent results in terms of symptom control and health-related quality of life (HRQoL) in irritable bowel syndrome (IBS) sufferers, but patients have complained about unsatisfying taste, difficulty in following the diet, and time consumption. To investigate the feasibility of the low FODMAP diet in an Italian (Sardinian) cohort, sixty consecutive eligible outpatients (11 men and 49 women) with IBS were enrolled and followed a low FODMAP diet (gluten allowed, restriction phase of four weeks, reintroduction phase of four weeks). Food habits were assessed using 24-hour dietary recall, Bristol Stool Scale for stool consistency, Visual Analogue Scale for abdominal bloating, VAS (Visual Analogue Scale) for abdominal pain, IBS Severity Scoring System for perceived disease severity, and a 12-item Short Form Survey for HRQoL (psychological component summary + mental component summary) were applied at baseline (T0) and at the end of each phase (T1-four weeks and T2-eight weeks). Statistical analysis was performed by dividing the cohort into diarrhoea-dominant IBS (IBS-D) and other IBS subtypes (selected IBS-others). Comparisons between T1 and T2 vs. T0 and T2 vs. T1 were performed. The low FODMAP diet lowered VASp (VAS pain), VASb (VAS bloating), and IBS SSS (IBS Severity Scoring System), and increased PCS (Physical Component Summary) and MCS (Mental Component Summary) in both subgroups. Bristol Stool Scale (BSS) only improved in the IBS-D subgroup. The dropout mean values for MCS were higher than treated subjects and the percentage of unemployment was lower in the dropouts. According to the dropout features, the low FODMAP diet seems to show greater feasibility for patients with more time to dedicate to the diet (unemployed, homemakers, housewives, or students), more motivation, and more severe clinical features, independent of their place of residence.

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“…To overcome these limitations, novel pharmacological agents against constipation have been developed recently, such as 5-hydroxytryptamine type 4 receptor (5-HT 4 ) agonists, type 2 chloride channel agonists, and guanylate cyclase C agonists. [7][8][9][10] In particular, prucalopride (a selective 5-HT 4 agonist) stimulates intestinal motility effectively, has a good safety profile, and is well tolerated for treatment of severe functional constipation. [11][12][13] DA-9701 (Motilitone), a newly developed prokinetic agent for treating patients with functional dyspepsia, is approved for this purpose in South Korea.…”

Section: Introductionmentioning

confidence: 99%