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Pubmed-Engineering of an Anti-Inflammatory Peptide Based on the Disulfide-Rich Linaclotide Scaffold.
Related Articles Engineering of an Anti-Inflammatory Peptide Based on the Disulfide-Rich Linaclotide Scaffold. Biomedicines. 2018 Oct 06;6(4): Authors: Cobos C, Bansal PS, Jones L, Wangchuk P, Wilson D, Loukas A, Daly NL Abstract Inflammatory bowel diseases are a set of complex and debilitating diseases, for which there is no satisfactory treatment. Peptides as small as three amino acids have been shown to have anti-inflammatory activity in mouse models of colitis, but they are likely to be unstable, limiting their development as drug leads. Here, we have grafted a tripeptide from the annexin A1 protein into linaclotide, a 14-amino-acid peptide with three disulfide bonds, which is currently in clinical use for patients with chronic constipation or irritable bowel syndrome. This engineered disulfide-rich peptide maintained the overall fold of the original synthetic guanylate cyclase C agonist peptide, and reduced inflammation in a mouse model of acute colitis. This is the first study to show that this disulfide-rich peptide can be used as a scaffold to confer a new bioactivity. PMID: 30301200 [PubMed] View the full article
Pubmed-UK clinical experience up to 52 weeks with linaclotide for irritable bowel syndrome with constipation.
Related Articles UK clinical experience up to 52 weeks with linaclotide for irritable bowel syndrome with constipation. Therap Adv Gastroenterol. 2018;11:1756284818798791 Authors: Yiannakou Y, Agrawal A, Allen PB, Arebi N, Brown SR, Eugenicos MP, Farmer AD, McLain-Smith S, McLaughlin J, Sanders DS, Lawrance D, Emmanuel A Abstract Background: Linaclotide, a guanylate cyclase C agonist, has been shown in clinical trials to improve symptoms of irritable bowel syndrome with constipation (IBS-C). Here we report data from a real-world study of linaclotide in the UK. Methods: This 1-year, multicentre, prospective, observational study in the UK enrolled patients aged 18 years and over initiating linaclotide for IBS-C. The primary assessment was change from baseline in IBS Symptom Severity Scale (IBS-SSS) score at 12 weeks, assessed in patients with paired baseline and 12-week data. Change from baseline in IBS-SSS score at 52 weeks was a secondary assessment. Adverse events were recorded. Results: In total, 202 patients were enrolled: 185 (91.6%) were female, median age was 44.9 years (range 18.1-77.2) and 84 (41.6%) reported baseline laxative use. Mean (standard deviation) baseline IBS-SSS score was 339 (92), with most patients (n = 129; 66.8%) classified as having severe disease (score ⩾300). In patients with paired data, there was a significant mean (95% confidence interval) decrease in IBS-SSS score from baseline to 12 weeks [-77.0 (-96.3, -57.7); p < 0.001; n = 124] and baseline to 52 weeks [-70.7 (-95.0, -46.5); p < 0.001; n = 76]. Overall, 174 adverse events were reported in 77 (38.1%) patients, most commonly diarrhoea (n = 54; 26.7%), abdominal pain (n = 21; 10.4%) and abdominal distension (n = 13; 6.4%). Conclusion: Linaclotide significantly improved IBS-SSS score at 12 and 52 weeks. These results provide insights into outcomes with linaclotide treatment over 1 year in patients with IBS-C in real-world clinical practice. PMID: 30302125 [PubMed] View the full article
Google-Woman told she had IBS for a year actually had bowel cancer at 34 – now UK doctors say there is no more they can do ...
Woman told she had IBS for a year actually had bowel cancer at 34 – now UK doctors say there is no more they can do ... inews.co.uk Full coverage View the full article
Pubmed-Oral treatment with plecanatide or dolcanatide attenuates visceral hypersensitivity via activation of guanylate cyclase-C in rat models.
Related Articles Oral treatment with plecanatide or dolcanatide attenuates visceral hypersensitivity via activation of guanylate cyclase-C in rat models. World J Gastroenterol. 2018 May 07;24(17):1888-1900 Authors: Boulete IM, Thadi A, Beaufrand C, Patwa V, Joshi A, Foss JA, Eddy EP, Eutamene H, Palejwala VA, Theodorou V, Shailubhai K Abstract AIM: To investigate the effects of plecanatide and dolcanatide on maintenance of paracellular permeability, integrity of tight junctions and on suppression of visceral hypersensitivity. METHODS: Transport of fluorescein isothiocyanate (FITC)-dextran was measured to assess permeability across cell monolayers and rat colon tissues. Effects of plecanatide and dolcanatide on the integrity of tight junctions in Caco-2 and T84 monolayers and on the expression and localization of occludin and zonula occludens-1 (ZO-1) were examined by immunofluorescence microscopy. Anti-nociceptive activity of these agonists was evaluated in trinitrobenzene sulfonic acid (TNBS)-induced inflammatory as well as in non-inflammatory partial restraint stress (PRS) rat models. Statistical significance between the treatment groups in the permeability studies were evaluated using unpaired t-tests. RESULTS: Treatment of T84 and Caco-2 monolayers with lipopolysaccharide (LPS) rapidly increased permeability, which was effectively suppressed when monolayers were also treated with plecanatide or dolcanatide. Similarly, when T84 and Caco-2 monolayers were treated with LPS, cell surface localization of tight junction proteins occludin and ZO-1 was severely disrupted. When cell monolayers were treated with LPS in the presence of plecanatide or dolcanatide, occludin and ZO-1 were localized at the cell surface of adjoining cells, similar to that observed for vehicle treated cells. Treatment of cell monolayers with plecanatide or dolcanatide without LPS did not alter permeability, integrity of tight junctions and cell surface localization of either of the tight junction proteins. In rat visceral hypersensitivity models, both agonists suppressed the TNBS-induced increase in abdominal contractions in response to colorectal distension without affecting the colonic wall elasticity, and both agonists also reduced colonic hypersensitivity in the PRS model. CONCLUSION: Our results suggest that activation of GC-C signaling might be involved in maintenance of barrier function, possibly through regulating normal localization of tight junction proteins. Consistent with these findings, plecanatide and dolcanatide showed potent anti-nociceptive activity in rat visceral hypersensitivity models. These results imply that activation of GC-C signaling may be an attractive therapeutic approach to treat functional constipation disorders and inflammatory gastrointestinal conditions. PMID: 29740204 [PubMed - indexed for MEDLINE] View the full article
Use of dietary interventions for functional gastrointestinal disorders. Curr Opin Pharmacol. 2018 Oct 08;43:132-138 Authors: Manning LP, Biesiekierski JR Abstract The role of food in the development of symptoms experienced within functional gastrointestinal disorders (FGIDs) is well recognised. This review aims to describe the evidence base for dietary interventions in the different functional esophageal, duodenal and bowel disorders. Randomised controlled trials are lacking for many of the FGIDs, with the exception of irritable bowel syndrome (IBS). Restricting rapidly fermentable, short-chain carbohydrates (FODMAPs) provides an evidence based dietary approach for the management of symptoms of IBS. Recent evidence shows the upper GI motility response varies between carbohydrates, which gives promise for the potential application of the low FODMAP diet in upper GI disorders. In addition to fine-tuning our FODMAP understanding, other observational data and smaller sized studies create an exciting and optimistic future for dietary management of all FGIDs. PMID: 30308416 [PubMed - as supplied by publisher] View the full article
Twitter-Maternal #lowFODMAP diet reduces crying and fussing duration in breast-fed infants with colic – veryexciting results from Monash research led by our very own, Dr Marina Iacovou! Read the full paper here: https://t.co/dwtLlEIbFu https://t.co/nALdEe
Maternal #lowFODMAP diet reduces crying and fussing duration in breast-fed infants with colic – veryexciting results from Monash research led by our very own, Dr Marina Iacovou! Read the full paper here: http://bit.ly/2ywmoIN (RSS generated with FetchRss) View the full article
Twitter-RT @marinaiacovou: Hot off the press by @APandT. Results of my randomised clinical trial, a feeding study that was double-blinded and a cro…
RT @marinaiacovou: Hot off the press by @APandT. Results of my randomised clinical trial, a feeding study that was double-blinded and a cro… (RSS generated with FetchRss) View the full article
Twitter-Stacy Menees receiving award for best FBD abstract #acg2018 LFD improves FI in pts with loose stools. https://t.co/aNdjye5wAs
Stacy Menees receiving award for best FBD abstract #acg2018 LFD improves FI in pts with loose stools. (RSS generated with FetchRss) View the full article
Twitter-Have #IBS? Looking to apply the low #FODMAP diet? Join me & @Toni_Fiori_RD on Oct. 19th for a educational workshop in #Medway, MA! Only a few spots left. Register here >> https://t.co/ID3fZuSTPD
Have #IBS? Looking to apply the low #FODMAP diet? Join me & @Toni_Fiori_RD on Oct. 19th for a educational workshop in #Medway, MA! Only a few spots left. Register here >> https://tinyurl.com/y939ggsq (RSS generated with FetchRss) View the full article
Twitter-Yummy Low FODMAP gravy. This is a comment I received about the gravy from a follower of my blog: “This evening I decided to give your low FODMAP gravy recipe a try and I must say, it far succeeded my expectations...... It was... https://t.co/FQJWN
Yummy Low FODMAP gravy. This is a comment I received about the gravy from a follower of my blog: “This evening I decided to give your low FODMAP gravy recipe a try and I must say, it far succeeded my expectations...... It was... https://www.lowfodmapdiets.com/low-fodmap-gravy/ (RSS generated with FetchRss) View the full article
Can Eating Too Much Cheese Give Your Kids Constipation? Health Essentials from Cleveland Clinic (blog) Full coverage View the full article
U of Guelph researcher develops possible vaccine against traveller's diarrhea GuelphMercury.com Full coverage View the full article
Severe Constipation Tied to Faster Progression in Parkinson's Medscape Full coverage View the full article
Google-Launch of ibs-smart™, an advancement in blood testing for Irritable Bowel Syndrome (IBS) announced by Gemelli ...
Launch of ibs-smart™, an advancement in blood testing for Irritable Bowel Syndrome (IBS) announced by Gemelli ... PR Newswire (press release) Full coverage View the full article
Best medications for treating diarrhea in Crohn's disease Medical News Today Full coverage View the full article
University of Guelph researcher develops 3-in-1 vaccine against traveller's diarrhea EurekAlert (press release) Full coverage View the full article
Pubmed-Is the genetic variability of Cathepsin B important in the pathogenesis of Blastocystis spp.?
Related Articles Is the genetic variability of Cathepsin B important in the pathogenesis of Blastocystis spp.? Parasitol Res. 2018 Oct 08;: Authors: Gonzalez-Arenas NR, Villalobos G, Vargas-Sanchez GB, Avalos-Galarza CA, Marquez-Valdelamar LM, Ramirez-Miranda ME, Olivo-Diaz A, Romero-Valdovinos M, Martinez-Hernandez F, Maravilla P Abstract The potential role of Blastocystis as a pathogen is controversial because it is found in both symptomatic and asymptomatic carriers. Since Cathepsin B has been identified as a main virulence factor that contributes to the pathogenesis of this parasite, the purpose of this study was to analyze the genetic polymorphisms of cathepsin B from Blastocystis from patients with irritable bowel syndrome and from asymptomatic carriers. DNA from fecal samples of both groups, which were previously genotyped by 18S sequencing, was used to amplify a fragment of the cathepsin B gene. Phylogenetic reconstructions were performed and some genetic population indexes were obtained. Amplicons of 27 samples (15 cases, 10 controls, and two commercial ATCC strains) were obtained and analyzed. Phylogenetic reconstructions using nucleotides or inferred amino acid sequences did not separate between cases or controls or among subtypes. Regarding the values of genetic variability, we found that the haplotype and nucleotide diversity indexes of cathepsin B from cases and controls were similar to the values of 18S from controls. By contrast, 18S from cases showed low variability, suggesting that the genetic variability of cathepsin B was not related to the symptomatology of Blastocystis carriers. However, since no polymorphisms related to cases or controls were found, it is logical to assume that the potential damage caused by Blastocystis in situ may be due to unclear mechanisms of Cathepsin B regulation and expression that should be studied in future studies. PMID: 30298236 [PubMed - as supplied by publisher] View the full article
Pubmed-Evidence of increased fecal granins in children with irritable bowel syndrome and correlates with symptoms.
Evidence of increased fecal granins in children with irritable bowel syndrome and correlates with symptoms. Neurogastroenterol Motil. 2018 Oct 09;:e13486 Authors: Shulman RJ, Öhman L, Stridsberg M, Cain K, Simrén M, Heitkemper M Abstract BACKGROUND: Granins have been implicated in the pathophysiology of irritable bowel syndrome (IBS) in adults. We sought to determine whether fecal granins are altered in children with IBS and associated with symptoms. METHODS: Children (7-12 years of age) with IBS and healthy controls (HC) kept daily pain and stool diaries for 2 weeks. Stool samples were analyzed for chromogranins A and B (CgA, CgB) and secretogranins II and III (SgII, SgIII). Children also completed psychological measures to assess anxiety, depression, somatization, and internalizing symptoms. KEY RESULTS: Fecal CgB and SgIII concentrations were higher in all the boys (IBS plus HC, n = 48) than in all the girls (IBS plus HC, n = 75) (P = 0.02 and P = 0.046, respectively). CgA and SgIII were greater in children with IBS (n = 52) vs HC (n = 69) (P = 0.01, P = 0.017, respectively). CgB and SgII did not differ between groups. In children with IBS, the number of pain episodes per week and mean daily pain rating correlated positively with all four granins. The number of stools per day correlated positively with CgB and SgII, and the percent of diarrheal stools (6 or 7 on the Bristol Scale) correlated inversely with all four granins in boys but not in girls. Fecal granins did not correlate with psychological measures. CONCLUSIONS AND INFERENCES: As measured by fecal granins, there is evidence of neuroimmune activation in children with IBS. Granins are related to abdominal pain symptoms, stooling frequency, and stool form in children with IBS. Sex influences the fecal concentration of CgB and SgIII. PMID: 30298961 [PubMed - as supplied by publisher] View the full article
Pubmed-The Relationship Between Daytime Salivary Melatonin and Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care.
The Relationship Between Daytime Salivary Melatonin and Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care. Psychosom Med. 2018 Oct 06;: Authors: Söderquist F, Sundberg I, Ramklint M, Widerström R, Hellström PM, Cunningham JL Abstract OBJECTIVE: The pathophysiology of irritable bowel syndrome (IBS) is not completely understood, although we do know that patients with IBS have a high prevalence of psychiatric comorbidity (mainly depression and anxiety disorders). Melatonin, produced in the gastrointestinal tract, influences gut motility. Psychiatric conditions are associated with circadian disturbances in peripheral melatonin levels. This study aimed to investigate associations between daytime salivary melatonin and gastrointestinal symptoms in young adult psychiatric patients. METHODS: Ninety-six patients (86% women), age 18-25 years (mean 21, SD=2), seeking psychiatric care with primarily anxiety disorders, affective disorders, or both were included in the study. Total scores from The Gastrointestinal Symptoms Rating Scale - IBS (GSRS-IBS) were compared with salivary melatonin measured at three time points (30 minutes after waking up, at 11:00 hours and 30 minutes after lunch) during the waking hours of one day. RESULTS: When controlling for potential confounders, melatonin levels in saliva 30 minutes after lunch remained significantly correlated to the total GSRS-IBS score after correction for multiple testing (B=0.016, SE=0.006, p=0.015, q=0.045). In a post hoc analysis, symptoms of gastrointestinal pain and bloating contributed most to this association. CONCLUSIONS: In young adult psychiatric patients salivary melatonin levels after lunch are associated with gastrointestinal symptoms, which is consistent with the proposed effect of elevated levels of gastrointestinal melatonin on gut motility. This result suggests a link between IBS symptoms and regulation of melatonin in patients with psychiatric disorders.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. PMID: 30299401 [PubMed - as supplied by publisher] View the full article
Evaluation of Escherichia coli pathotypes associated with Irritable Bowel Syndrome. FEMS Microbiol Lett. 2018 Oct 08;: Authors: Dogan B, Belcher-Timme HF, Dogan EI, Jiang ZD, DuPont HL, Synder N, Yang S, Chandler B, Scherl EJ, Simpson KW Abstract Irritable Bowel Syndrome (IBS) affects 10-20% of people. Increased numbers of Escherichia coli (E. coli) correlate with symptoms, and patients respond to antimicrobials targeting E. coli. We examined whether specific E. coli strains, phylogroups and pathotypes are associated with IBS. We evaluated 218 E. coli isolates from 33 IBS patients and 23 healthy controls. RAPD analysis revealed 89 E. coli strains (29 controls, 60 IBS), spanning the A, B1, B2, D phylogroups. Strains were similarly enriched in virulence genes associated with extraintestinal pathogenic E.coli (ExPEC) and/or adherent-invasive E.coli (AIEC). Three strains harbored a diarrheagenic virulence gene (2 IBS, 1 control). E. coli capable of invading epithelial cells or replicating in macrophages were detected in 53% of IBS and 50% controls, and 67% IBS and 45% controls respectively (P>0.05). AIEC were identified in 33% of IBS patients vs. 20% of controls (P=0.35). Virulence genes ibeA, ColV and pduC were associated with intramacrophage persistence; ibeA and ColV were associated with epithelial invasion and AIEC pathotype (P<0.05). IBS patients and controls are commonly colonized by E. coli that resemble ExPEC and display pathogen-like behavior in vitro, similar to CD-associated AIEC. The relationship of these resident pathosymbiont E. coli to IBS warrants further investigation. PMID: 30299475 [PubMed - as supplied by publisher] View the full article