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https://www.readbyqxmd.com/read/29149731/purinergic-drug-targets-for-gastrointestinal-disorders
#1
REVIEW
Geoffrey Burnstock, Kenneth A Jacobson, Fievos L Christofi
Purinergic receptors are implicated in the pathogenesis of gastrointestinal disorders and are being explored as potential therapeutic targets. Gut inflammation releases ATP that acts on neuronal, glial, epithelial and immune cells. Purinergic signalling in glia and neurons is implicated in enteric neuropathies. Inflammation activates glia to increase ATP release and alter purinergic signalling. ATP release causes neuron death and gut motor dysfunction in colitis via a P2X7-dependent neural-glial pathway and a glial purinergic-connexin-43 pathway...
November 14, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29148173/metformin-protects-against-intestinal-barrier-dysfunction-via-ampk%C3%AE-1-dependent-inhibition-of-jnk-signalling-activation
#2
Jun Deng, Lishan Zeng, Xueying Lai, Jing Li, Le Liu, Qianyun Lin, Ye Chen
Disruption of the intestinal epithelial barrier, that involves the activation of C-Jun N-terminal kinase (JNK), contributes to initiate and accelerate inflammation in inflammatory bowel disease. Metformin has unexpected beneficial effects other than glucose-lowering effects. Here, we provided evidence that metformin can protect against intestinal barrier dysfunction in colitis. We showed that metformin alleviated dextran sodium sulphate (DSS)-induced decreases in transepithelial electrical resistance, FITC-dextran hyperpermeability, loss of the tight junction (TJ) proteins occludin and ZO-1 and bacterial translocation in Caco-2 cell monolayers or in colitis mice models...
November 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29147967/association-of-inflammatory-bowel-disease-with-arthritis-evidence-from-in-silico-gene-expression-patterns-and-network-topological-analysis
#3
Anukriti Verma, Pallavi Somvanshi, Shafiul Haque, Bhawna Rathi, Shivani Sharda
Inflammatory bowel disease (IBD) is an idiopathic prolonged ailment accountable for inflammatory conditions of the intestine. Moreover, arthritis is responsible for joints' stiffness and painful inflammation. IBD shows certain articular extra-intestinal manifestations associating IBD with arthritis. IBD associated arthritis is found to be linked with ankylosing spondylitis (AS). The present study insights for the potential and putative drug targets and biomarkers of IBD associated with arthritis using in silico approaches...
November 17, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/29147880/targeted-physician-education-and-standardizing-documentation-improves-documented-reporting-with-inflammatory-bowel-disease-quality-measures-in-a-large-academic-and-private-practice
#4
Joseph D Feuerstein, Konstantinos Papamichael, Sara Popejoy, Adam Nadelson, Jeffrey J Lewandowski, Kathy Geissler, Manuel Martinez-Vazquez, Daniel A Leffler, Kim Ariyabuddhiphongs, Chandrashekhar Thukral, Adam S Cheifetz
BACKGROUND: Prior studies have shown poor compliance with quality measures for IBD at academic and private practices. We sought to provide focused interventions to improve compliance and documentation with the IBD measures. METHODS: Two centers, academic practice (AP) and private practice (PP), initially reviewed their compliance with eight established IBD quality measures in consecutive charts. A multi-faceted intervention was developed to improve awareness and documentation of these measures...
November 17, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29147824/an-integrated-qsar-modeling-approach-to-explore-the-structure-property-and-selectivity-relationships-of-n-benzoyl-l-biphenylalanines-as-integrin-antagonists
#5
Sk Abdul Amin, Nilanjan Adhikari, Sonam Bhargava, Shovanlal Gayen, Tarun Jha
Integrins [Formula: see text] and [Formula: see text] are important targets to treat different inflammatory diseases, such as multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, atherosclerosis, and asthma. Despite being valuable targets, only a few work has been reported to date regarding molecular modeling studies on these integrins. Not only that, none of these reports addressed the selectivity issue between integrins [Formula: see text] and [Formula: see text]. Therefore, a major challenge regarding the design and discovery of selective integrin antagonists remains...
November 17, 2017: Molecular Diversity
https://www.readbyqxmd.com/read/29147137/preventing-disability-in-inflammatory-bowel-disease
#6
REVIEW
Patrick B Allen, Corinne Gower-Rousseau, Silvio Danese, Laurent Peyrin-Biroulet
Disability is a common worldwide health challenge and it has been increasing over the past 3 decades. The treatment paradigm has changed dramatically in inflammatory bowel diseases (IBDs) from control of symptoms towards full control of disease (clinical and endoscopic remission) with the goal of preventing organ damage and disability. These aims are broadly similar to rheumatoid arthritis and multiple sclerosis. Since the 1990s, our attention has focused on quality of life in IBD, which is a subjective measure...
November 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29147134/the-clinical-course-after-glucocorticoid-treatment-in-patients-with-inflammatory-bowel-disease-is-linked-to-suppression-of-the-hypothalamic-pituitary-adrenal-axis-a-retrospective-observational-study
#7
Aghil Ibrahim, Per Dahlqvist, Tommy Olsson, David Lundgren, Mårten Werner, Ole B Suhr, Pontus Karling
Background: Adrenal insufficiency (AI) secondary to treatment with glucocorticoids (GCs) is common in patients with inflammatory bowel disease (IBD), but little is known about the relationship between AI and the clinical course in IBD. The aim of the study was to compare the clinical course in IBD patients with normal adrenal function versus patients with subnormal adrenal function. Methods: A retrospective observational study on 63 patients with IBD who had performed a low-dose short Synacthen test (LDSST) (1 μg) immediately (1-7 days) after a standard course of GCs...
November 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29147133/allopurinol-in-combination-with-thiopurine-induces-mucosal-healing-and-improves-clinical-and-metabolic-outcomes-in-ibd
#8
Brigitte Moreau, Pierre Clement, Yves Theoret, Ernest G Seidman
Background: Thiopurines, azathioprine (AZA) and 6-mercaptopurine (6-MP) are common maintenance medications for inflammatory bowel disease (IBD). Excessive methylation via thiopurine methyltransferase (TPMT) frequently causes therapeutic failure. Allopurinol reduces excessive 6-methyl-mercaptopurine (6-MMP) while enhancing 6-thioguanine (6-TGN) levels. The aim of this study was to evaluate clinical, metabolic and endoscopic impact of allopurinol in combination with low-dose thiopurine in IBD...
November 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29147110/colorectal-malignancy-in-a-prospective-irish-inflammatory-bowel-disease-population-15-years-since-diagnosis-comparison-with-the-ec-ibd-cohort
#9
Mary Shuhaibar, Colm O'Morain
Background and Aim: As part of the EC-IBD prospective inception cohort study, we had unique opportunity to follow up our patients since diagnosis in the early 1990s. Patients and Methods: All patients from the greater Dublin area (n = 192) were followed up from inception between 1991 and 1993 until the 30 September 2009. Patients who developed malignancies were logged electronically with verification of the site and histology. Results: Of the initial 192 patients, 133 were included in the 15-year follow-up...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/29147008/the-transcription-factor-batf3-inhibits-the-differentiation-of-regulatory-t-cells-in-the-periphery
#10
Wonyong Lee, Hyeong Su Kim, Soo Seok Hwang, Gap Ryol Lee
Naive CD4 T cells activated by antigen-presenting cells (APCs) undergo terminal differentiation in the periphery. Multiple mechanisms determine their fates, that is, whether they differentiate into conventional T (Tconv) cells or regulatory T (Treg) cells. The key event during Treg generation is expression of the transcription factor Foxp3, which is the lineage-determining regulator for Treg differentiation and function. Here we show that the transcription factor Batf3 acts as a fate-decision factor with respect to Tconv versus Tregs by restraining Treg differentiation...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29146678/cross-organ-sensitisation-between-the-colon-and-bladder-to-pee-or-not-to-pee
#11
Luke Grundy, Stuart M Brierley
Chronic abdominal and pelvic pain are common, debilitating clinical conditions experienced by millions of patients around the globe. The origin of such pain commonly arises from the intestine and bladder, which share common primary roles; the collection, storage and expulsion of waste. These visceral organs are located in close proximity to one another, and also share common innervation from spinal afferent pathways. Chronic abdominal pain, constipation or diarrhoea are primary symptoms for patients with Irritable Bowel Syndrome (IBS) or Inflammatory Bowel Disease (IBD)...
November 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29146677/functional-role-and-therapeutic-targeting-of-micrornas-in-inflammatory-bowel-disease
#12
Artin Soroosh, Marina Koutsioumpa, Charalabos Pothoulakis, Dimitrios Iliopoulos
Inflammatory Bowel Diseases (IBD) are chronic inflammatory gastrointestinal diseases, primarily consisting of Ulcerative Colitis (UC) and Crohn's Disease (CD). The complex nature of the disease, as well as the limited therapeutic options characterized by low efficiency and major side effects, shows the importance of developing novel strategies of therapeutic intervention in IBD. Susceptibility loci related to IBD are present only in a small percentage of IBD patients, implying that epigenetic modifications could influence the pathogenesis of the disease...
November 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29146080/zeroing-in-on-endoscopic-and-histologic-mucosal-healing-to-reduce-the-risk-of-colorectal-neoplasia-in-inflammatory-bowel-disease
#13
EDITORIAL
Akriti P Saxena, Jimmy K Limdi, Francis A Farraye
No abstract text is available yet for this article.
December 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/29145599/a-role-for-thiopurine-metabolites-in-the-synergism-between-thiopurines-and-infliximab-in-inflammatory-bowel-disease
#14
Ditte V Mogensen, Jørn Brynskov, Mark A Ainsworth, Jacob Nersting, Kjeld Schmiegelow, Casper Steenholdt
Background: Interactions between principal cytotoxic thiopurine metabolites, 6-thioguanine nucleotides (6-TGN), and infliximab (IFX) and anti-IFX antibodies (Abs) may contribute to higher effectiveness of IFX-thiopurine-combination therapy than monotherapies in inflammatory bowel disease. Methods: To examine if thiopurine metabolites influenced trough IFX and anti-IFX Abs, 89 patients previously assessed for anti-IFX Abs were included. To assess if IFX influenced thiopurine metabolites, 8 patients having responded to 12 weeks of intensified IFX at a constant thiopurine dosing were included...
November 14, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29145572/difference-in-clinical-course-genetics-and-the-microbiome-between-familial-and-sporadic-inflammatory-bowel-diseases
#15
Nienke Z Borren, Grace Conway, John J Garber, Hamed Khalili, Shrish Budree, Himel Mallick, Vijay Yajnik, Ramnik J Xavier, Ashwin N Ananthakrishnan
Objective: Family history is the strongest risk factor for developing Crohn's disease (CD) or ulcerative colitis (UC). We investigated whether the proximity of relationship with the affected relative and concordance for type of IBD modifies the effect of family history on phenotype and disease severity. Design: This cross-sectional study included patients with a confirmed diagnosis of IBD in a clinical registry. Family history of IBD was assessed by a questionnaire ascertaining presence of disease in a 1 st degree, 2 nd degree or a distant relative...
November 14, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29145012/the-gut-brain-interaction-in-opioid-tolerance
#16
REVIEW
Hamid I Akbarali, William L Dewey
The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms...
November 13, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29142522/drug-induced-eosinophilic-pneumonia-in-a-patient-with-crohn-s-disease-diagnosis-and-treatment-using-fraction-of-exhaled-nitric-oxide
#17
Jina Yeo, Hyun Sun Woo, Sang Min Lee, Yoon Jae Kim, Kwang An Kwon, Dong Kyun Park, Jung Ho Kim, Kyoung Oh Kim, Jun-Won Chung
Oral 5-aminosalicylic acid agents (mesalazine and sulfasalazine) and azathioprine are the mainstays of treatment for inflammatory bowel disease. Reports of pulmonary toxicity induced by oral 5-aminosalicylic acid agents or azathioprine in patients with inflammatory bowel disease are very rare; to date, only 38 cases have been reported worldwide. We, herein, report a case involving a 26-year-old man who was diagnosed with eosinophilic pneumonia after using mesalazine and azathioprine for the treatment of Crohn's disease and recovered after treatment...
October 2017: Intestinal Research
https://www.readbyqxmd.com/read/29142521/fatal-infections-in-older-patients-with-inflammatory-bowel-disease-on-anti-tumor-necrosis-factor-therapy
#18
Way-Seah Lee, Najib Azmi, Ruey-Terng Ng, Sik-Yong Ong, Sasheela Sri La Ponnampalavanar, Sanjiv Mahadeva, Ida Hilmi
Anti-tumor necrosis factor (anti-TNF) is highly effective in inflammatory bowel disease (IBD); however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years). All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy...
October 2017: Intestinal Research
https://www.readbyqxmd.com/read/29142516/outcomes-of-limited-period-of-adalimumab-treatment-in-moderate-to-severe-crohn-s-disease-patients-taiwan-society-of-inflammatory-bowel-disease-study
#19
Wei-Chen Lin, Jen-Wei Chou, Hsu-Heng Yen, Wen-Hung Hsu, Hung-Hsin Lin, Jen-Kou Lin, Chiao-Hsiung Chuang, Tien-Yu Huang, Horng-Yuan Wang, Shu-Chen Wei, Jau-Min Wong
Background/Aims: In Taiwan, due to budget limitations, the National Health Insurance only allows for a limited period of biologics use in treating moderate to severe Crohn's disease (CD). We aimed to access the outcomes of CD patients following a limited period use of biologics, specifically focusing on the relapse rate and remission duration; also the response rate to second use when applicable. Methods: This was a multicenter, retrospective, observational study and we enrolled CD patients who had been treated with adalimumab (ADA) according to the insurance guidelines from 2009 to 2015...
October 2017: Intestinal Research
https://www.readbyqxmd.com/read/29142512/non-steroidal-anti-inflammatory-drug-induced-enteropathy
#20
REVIEW
Sung Jae Shin, Choong-Kyun Noh, Sun Gyo Lim, Kee Myung Lee, Kwang Jae Lee
Non-steroidal anti-inflammatory drugs (NSAIDs) are well known to be associated with serious upper gastrointestinal complications, such as peptic ulcer, bleeding, perforation, and obstruction. Recently, attention has been mainly focused on the small bowel injuries caused by NSAIDs, and new endoscopic techniques such as capsule endoscopy and double balloon endoscopy can help in detecting such injuries. This article reviewed the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of small bowel injuries caused by NSAIDs...
October 2017: Intestinal Research
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