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https://www.readbyqxmd.com/read/29095765/new-therapies-in-irritable-bowel-syndrome-what-works-and-when
#1
Orla Craig
PURPOSE OF REVIEW: The purpose of this review is to examine the evidence supporting the use of recently developed pharmacological treatments for IBS together with new evidence supporting more traditional therapies in order to understand where the new agents are best used in the treatment pathway. RECENT FINDINGS: There is evidence to support the use of traditional treatments such as antispasmodics, antidepressants and dietary alteration in IBS. New therapeutic agents such as Linaclotide, Lubiprostone, Plecanatide, Rifaxamin and Eluxadoline are all more effective than placebo in treating symptoms of IBS with Tenapanor being a promising new agent...
November 1, 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/29091082/low-dose-linaclotide-72%C3%A2-%C3%AE-g-for-chronic-idiopathic-constipation-a-12-week-randomized-double-blind-placebo-controlled-trial
#2
Philip Schoenfeld, Brian E Lacy, William D Chey, Anthony J Lembo, Caroline B Kurtz, David S Reasner, Wieslaw Bochenek, Kenneth Tripp, Mark G Currie, Susan M Fox, Rick E Blakesley, Christopher R O'Dea, Nicholas D Omniewski, Michael L Hall
OBJECTIVES: Linaclotide is a guanylate cyclase-C agonist approved in the United States, Canada, and Mexico at a once-daily 145-μg dose for the treatment of chronic idiopathic constipation (CIC); a once-daily 72-μg dose for CIC recently received FDA approval. The trial objective was to evaluate the efficacy and safety of a 72-μg linaclotide dose in CIC patients. METHODS: This double-blind, placebo-controlled trial randomized patients with CIC (Rome III criteria) to once-daily linaclotide 72 μg or 145 μg, or placebo for 12 weeks...
August 22, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28970722/pharmacological-evaluation-of-nsaid-induced-gastropathy-as-a-translatable-model-of-referred-visceral-hypersensitivity
#3
Michele Hummel, Terri Knappenberger, Meghan Reilly, Garth T Whiteside
AIM: To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. METHODS: Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice (n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated...
September 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28830131/-pharmacotherapy-in-patients-with-chronic-constipation
#4
REVIEW
Sang Jin Kim, Kyung Sik Park
Chronic constipation is one of the most common digestive diseases frequently observed in a clinical setting. It has been known to cause considerable damage to the quality of life of patients. Despite recent developments, there are considerable limitations in the use of constipation-modulating agents in Korea. Chloride channel inhibitors, such as lubiprostone and linaclotide, have not been introduced in Korea yet, and prucalopride and several kinds of polyethylene glycol are not covered under medical insurance...
August 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28711731/insulin-chains-as-efficient-fusion-tags-for-prokaryotic-expression-of-short-peptides
#5
Ligang Deng, Xiaoying Xue, Cangjie Shen, Xiaohan Song, Chunyang Wang, Nan Wang
Insulin chains are usually expressed in Escherichia coli as fusion proteins with different tags, including various low molecular weight peptide tags. The objective of this study was to determine if insulin chains could facilitate the recombinant expression of other target proteins, with an emphasis on low molecular weight peptides. A series of short peptides were fused to mini-proinsulin, chain B or chain A, and induced for expression in Escherichia coli. All the tested peptides including glucagon-like peptide 1 (GLP-1), a C-terminal extended GLP-1, oxyntomodulin, enfuvirtide, linaclotide, and an unstructured artificial peptide were expressed with reasonable yields, identified by Tricine-SDS-PAGE and immunoblotting...
October 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28592587/linaclotide-activates-guanylate-cyclase-c-cgmp-protein-kinase-ii-dependent-trafficking-of-cftr-in-the-intestine
#6
Md Kaimul Ahsan, Boris Tchernychev, Marco M Kessler, Robert M Solinga, David Arthur, Cristina I Linde, Inmaculada Silos-Santiago, Gerhard Hannig, Nadia A Ameen
The transmembrane receptor guanylyl cyclase-C (GC-C), expressed on enterocytes along the intestine, is the molecular target of the GC-C agonist peptide linaclotide, an FDA-approved drug for treatment of adult patients with Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation. Polarized human colonic intestinal cells (T84, CaCo-2BBe) rat and human intestinal tissues were employed to examine cellular signaling and cystic fibrosis transmembrane conductance regulator (CFTR)-trafficking pathways activated by linaclotide using confocal microscopy, in vivo surface biotinylation, and protein kinase-II (PKG-II) activity assays...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28448580/sildenafil-normalizes-bowel-transit-in-preclinical-models-of-constipation
#7
Sarah K Sharman, Bianca N Islam, Yali Hou, Margaux Usry, Allison Bridges, Nagendra Singh, Subbaramiah Sridhar, Satish Rao, Darren D Browning
Guanylyl cyclase-C (GC-C) agonists increase cGMP levels in the intestinal epithelium to promote secretion. This process underlies the utility of exogenous GC-C agonists such as linaclotide for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Because GC-C agonists have limited use in pediatric patients, there is a need for alternative cGMP-elevating agents that are effective in the intestine. The present study aimed to determine whether the PDE-5 inhibitor sildenafil has similar effects as linaclotide on preclinical models of constipation...
2017: PloS One
https://www.readbyqxmd.com/read/28423917/management-of-opioid-induced-constipation-in-hospice-patients
#8
Leah Sera, Mary Lynn McPherson
BACKGROUND: Constipation is a common symptom in patients with advanced disease taking opioids. Opioid-induced constipation (OIC) is commonly treated with laxatives and stool softeners. Recently, newer agents have come to market which broaden options for patients in whom first-line therapies are not effective. OBJECTIVE: To determine what pharmacologic regimens are currently used in hospice programs to prevent and treat OIC, whether those regimens have changed with the introduction of newer agents and evidence discouraging the use of docusate, and whether hospice programs are standardizing the management of OIC...
January 1, 2017: American Journal of Hospice & Palliative Care
https://www.readbyqxmd.com/read/28396341/bioactivity-of-oral-linaclotide-in-human-colorectum-for-cancer-chemoprevention
#9
David S Weinberg, Jieru E Lin, Nathan R Foster, Gary Della'Zanna, Asad Umar, Drew Seisler, Walter K Kraft, David M Kastenberg, Leo C Katz, Paul J Limburg, Scott A Waldman
Guanylate cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of its luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Linaclotide is an FDA-approved oral GUCY2C agonist formulated for gastric release, inducing fluid secretion into the small bowel to treat chronic idiopathic constipation. The ability of oral linaclotide to induce a pharmacodynamic response in epithelial cells of the colorectum in humans remains undefined...
June 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28357122/therapeutically-targeting-guanylate-cyclase-c-computational-modeling-of-plecanatide-a-uroguanylin-analog
#10
Andrea Brancale, Kunwar Shailubhai, Salvatore Ferla, Antonio Ricci, Marcella Bassetto, Gary S Jacob
Plecanatide is a recently developed guanylate cyclase-C (GC-C) agonist and the first uroguanylin analog designed to treat chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). GC-C receptors are found across the length of the intestines and are thought to play a key role in fluid regulation and electrolyte balance. Ligands of the GC-C receptor include endogenous agonists, uroguanylin and guanylin, as well as diarrheagenic, Escherichia coli heat-stable enterotoxins (ST)...
April 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28238460/-irritable-bowel-syndrome-with-constipation-and-functional-constipation-in-adults-treatment-part-2-of-2
#11
F Mearin, C Ciriza, M Mínguez, E Rey, J J Mascort, E Peña, P Cañones, J Júdez
In this Clinical practice guide we examine the diagnostic and therapeutic management of adult patients with constipation and abdominal discomfort, at the confluence of the spectrum of irritable bowel syndrome and functional constipation. Both fall within the framework of functional intestinal disorders and have major personal, health and social impact, altering the quality of life of the patients affected. The former is a subtype of irritable bowel syndrome in which constipation and altered bowel habit predominate, often along with recurring abdominal pain, bloating and abdominal distension...
March 2017: Atencion Primaria
https://www.readbyqxmd.com/read/28236087/gastrointestinal-pharmacology
#12
REVIEW
Miguel Saps, Adrian Miranda
There is little evidence for most of the medications currently used to treat functional abdominal pain disorders (FAPDs) in children. Not only are there very few clinical trials, but also most have significant variability in the methods used and outcomes measured. Thus, the decision on the most appropriate pharmacological treatment is frequently based on adult studies or empirical data. In children, peppermint oil, trimebutine, and drotaverine have shown significant benefit compared with placebo, each of them in a single randomized clinical trial...
2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28162021/guanylate-cyclase-c-as-a-target-for-prevention-detection-and-therapy-in-colorectal-cancer
#13
REVIEW
Allison A Aka, Jeff A Rappaport, Amanda M Pattison, Takami Sato, Adam E Snook, Scott A Waldman
Colorectal cancer remains the second leading cause of cancer death in the United States, and new strategies to prevent, detect, and treat the disease are needed. The receptor, guanylate cyclase C (GUCY2C), a tumor suppressor expressed by the intestinal epithelium, has emerged as a promising target. Areas covered: This review outlines the role of GUCY2C in tumorigenesis, and steps to translate GUCY2C-targeting schemes to the clinic. Endogenous GUCY2C-activating ligands disappear early in tumorigenesis, silencing its signaling axis and enabling transformation...
May 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28116777/pharmacological-treatment-for-antipsychotic-related-constipation
#14
REVIEW
Susanna Every-Palmer, Giles Newton-Howes, Mike J Clarke
BACKGROUND: Antipsychotic-related constipation is a common and serious adverse effect, especially for people taking clozapine. Clozapine has been shown to impede gastrointestinal motility, leading to constipation, and has been reported in up to 60% of patients receiving clozapine. In rare cases, complications can be fatal. Appropriate laxatives should be prescribed to treat constipation in people taking antipsychotics, but there is a lack of guidance on the comparative effectiveness and harms of different agents in this population...
January 24, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28116695/update-on-the-management-of-chronic-constipation
#15
REVIEW
Jenna Koliani-Pace, Brian E Lacy
Chronic constipation (CC) is a highly prevalent disorder encountered by health care providers of all specialties. The diagnosis can be confidently made by taking a careful history, evaluating for warning signs and symptoms, performing an examination, including a digital rectal exam, and using the Rome IV criteria. Treatment should begin at the first visit; most patients require few diagnostic tests to make, or confirm, the diagnosis of CC. Assuming that the patient has persistent symptoms of constipation, despite using traditional therapy (fiber, osmotic agents), then patients should be offered one of the newer treatments, rather than repeating prior treatments, which is a common practice...
March 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28070176/advances-in-ibs-2016-a-review-of-current-and-emerging-data
#16
Philip S Schoenfeld
Irritable bowel syndrome (IBS) is characterized by chronic intermittent abdominal pain and associated diarrhea (IBS-D), constipation (IBS-C), or both. IBS can significantly impact patient function and quality of life. The diagnosis of IBS is based on the presence of characteristic symptoms, the exclusion of concerning features, and selected tests to exclude organic diseases that can mimic IBS. The pathophysiology of IBS remains incompletely understood, and new contributing factors have been identified over the past decade...
August 2016: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27888862/functional-and-motor-gastrointestinal-disorders
#17
Fermín Mearin, Enrique Rey, Agustín Balboa
This article discusses the most interesting presentations at Digestive Disease Week, held in San Diego, in the field of functional and motor gastrointestinal disorders. One of the most important contributions was undoubtedly the presentation of the new Rome IV diagnostic criteria for functional gastrointestinal disorders. We therefore devote some space in this article to explaining these new criteria in the most common functional disorders. In fact, there has already been discussion of data comparing Rome IV and Rome III criteria in the diagnosis of irritable bowel syndrome, confirming that the new criteria are somewhat more restrictive...
September 2016: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/27815136/phenylquinoxalinone-cftr-activator-as-potential-prosecretory-therapy-for-constipation
#18
Onur Cil, Puay-Wah Phuan, Jung-Ho Son, Jie S Zhu, Colton K Ku, Niloufar Akhavan Tabib, Andrew P Teuthorn, Loretta Ferrera, Nicholas C Zachos, Ruxian Lin, Luis J V Galietta, Mark Donowitz, Mark J Kurth, Alan S Verkman
Constipation is a common condition for which current treatments can have limited efficacy. By high-throughput screening, we recently identified a phenylquinoxalinone activator of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel that stimulated intestinal fluid secretion and normalized stool output in a mouse model of opioid-induced constipation. Here, we report phenylquinoxalinone structure-activity analysis, mechanism of action, animal efficacy data in acute and chronic models of constipation, and functional data in ex vivo primary cultured human enterocytes...
April 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27688649/guanylyl-cyclase-c-signaling-axis-and-colon-cancer-prevention
#19
REVIEW
Amanda M Pattison, Dante J Merlino, Erik S Blomain, Scott A Waldman
Colorectal cancer (CRC) is a major cause of cancer-related mortality and morbidity worldwide. While improved treatments have enhanced overall patient outcome, disease burden encompassing quality of life, cost of care, and patient survival has seen little benefit. Consequently, additional advances in CRC treatments remain important, with an emphasis on preventative measures. Guanylyl cyclase C (GUCY2C), a transmembrane receptor expressed on intestinal epithelial cells, plays an important role in orchestrating intestinal homeostatic mechanisms...
September 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27633684/peptide-therapeutics-and-the-pharmaceutical-industry-barriers-encountered-translating-from-the-laboratory-to-patients
#20
REVIEW
John Rafferty, Hema Nagaraj, Alice P McCloskey, Rawan Huwaitat, Simon Porter, Alyaa Albadr, Garry Laverty
Peptides are receiving increasing interest as clinical therapeutics. These highly tunable molecules can be tailored to achieve desirable biocompatibility and biodegradability with simultaneously selective and potent therapeutic effects. Despite challenges regarding up-scaling and licensing of peptide products, their vast clinical potential is reflected in the 60 plus peptide-based therapeutics already on the market, and the further 500 derivatives currently in developmental stages. Peptides are proving effective for a multitude of disease states including: type 2 diabetes (controlled using the licensed glucagon-like peptide-1 receptor liraglutide); irritable bowel syndrome managed with linaclotide (currently at approval stages); acromegaly (treated with octapeptide somatostatin analogues lanreotide and octreotide); selective or broad spectrum microbicidal agents such as the Gram-positive selective PTP-7 and antifungal heliomicin; anticancer agents including goserelin used as either adjuvant or monotherapy for prostate and breast cancer, and the first marketed peptide derived vaccine against prostate cancer, sipuleucel-T...
2016: Current Medicinal Chemistry
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