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Janghyun Yoo, Tae-Sun Lee, Byungsan Choi, Min Ju Shon, Tae-Young Yoon
Extremely weak protein-protein interactions (PPIs), signified by micromolar or even millimolar dissociation constants, are one of the keys to understanding the rapid responses of cellular systems. Although single-molecule methods are particularly useful in determining kinetics of biological processes, their application is largely limited to rather strong interactions because of the diffraction-limited observation volume. In this study, we report a single-molecule method that allows the characterization of PPIs using a prey concentration four orders of magnitude lower than the dissociation constant...
October 19, 2016: Journal of the American Chemical Society
Shuitu Feng, Zhigao Zheng, Lihua Feng, Lihong Yang, Zuhong Chen, Yubiao Lin, Yingqin Gao, Yide Chen
The cancer stem cell (CSC) model suggests that a small subset of cancer cells possess stem cell properties and plays a crucial role in tumor initiation, metastasis and resistance to anticancer therapy. Exploration of the specific therapies targeting at CSCs has been a crucial issue in antitumor research. Gastric cancer (GC) cells often exist in an ischemic microenvironment with acidic conditions in vivo, thus maintenance of cellular pH homeostasis is important for the survival and function of GC cells. Proton pump inhibitors (PPIs) may prevent intracellular proton extrusions which consequently reduce cancer cell survival under acidic conditions...
October 7, 2016: Oncology Reports
Zaheer Nabi, D Nageshwar Reddy
Gastroesophageal reflux disease (GERD) is defined by the presence of troublesome symptoms resulting from the reflux of gastric contents. The prevalence of GERD is increasing globally. An incompetent lower esophageal sphincter underlies the pathogenesis of GERD. Proton pump inhibitors (PPIs) form the core of GERD management. However, a substantial number of patients do not respond well to PPIs. The next option is anti-reflux surgery, which is efficacious, but it has its own limitations, such as gas bloating, inability to belch or vomit, and dysphagia...
September 2016: Clinical Endoscopy
Blaz Skrlj, Tanja Kunej
BACKGROUND: Protein-protein interactions (PPI) play an important role in function of all organisms and enable understanding of underlying metabolic processes. Computational predictions of PPIs are an important aspect in proteomics, as experimental methods may result in high degree of false positive results and are more expensive. Although there are many databases collecting predicted PPIs, exploration of genetics information underlying PPI interactions has not been investigated thoroughly...
October 4, 2016: Computers in Biology and Medicine
Nicole A Huijgen, Maria A J de Ridder, Katia M Verhamme, Gert R Dohle, Ann M Vanrolleghem, Miriam C J M Sturkenboom, Joop S E Laven, Régine P M Steegers-Theunissen
OBJECTIVE: To determine associations between proton-pump inhibitor (PPI) use and semen parameters in young men of couples who are planning pregnancy. DESIGN: Case-control study of a population-based registry. SETTING: Not applicable. PATIENT(S): General practitioner patients comprising 2,473 men from couples planning pregnancy with a recorded semen analysis: 241 with a low total motile sperm count (TMSC ≤1) and 714 with TMSC >1 as matched controls...
October 12, 2016: Fertility and Sterility
Mario Iannaccone, Fabrizio D Ascenzo, Ovidio De Filippo, Marco Gagliardi, Danielle A Southern, Sergio Raposeiras-Roubín, Emad Abu-Assi, Jose Paulo Simao Henriques, Jorge Saucedo, José Ramón González-Juanatey, Stephen B Wilton, Wouter J Kikkert, Iván Nuñez-Gil, Albert Ariza-Sole, Xiantao Song, Dimitrios Alexopoulos, Christoph Liebetrau, Tetsuma Kawaji, Zenon Huczek, Shao-Ping Nie, Toshiharu Fujii, Luis Correia, Masa-Aki Kawashiri, José María García-Acuña, Emilio Alfonso, Belén Terol, Alberto Garay, Dongfeng Zhang, Yalei Chen, Ioanna Xanthopoulou, Neriman Osman, Helge Möllmann, Hiroki Shiomi, Michal Kowara, Krzysztof Filipiak, Xiao Wang, Yan Yan, Jing-Yao Fan, Yuji Ikari, Takuya Nakahashi, Kenji Sakata, Masakazu Yamagishi, Claudio Moretti, Fiorenzo Gaita, Oliver Kalpak, Sasko Kedev
OBJECTIVE: Our objective was to define the most appropriate treatment for acute coronary syndrome (ACS) in patients with malignancy. METHODS AND RESULTS: The BleeMACS project is a worldwide multicenter observational prospective registry in 16 hospitals enrolling patients with ACS undergoing percutaneous coronary intervention. Primary endpoints were death, re-infarction, and major adverse cardiac events (MACE; composite of death and re-infarction) after 1 year of follow-up...
October 13, 2016: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Michael P Chu, J Randolph Hecht, Dennis Slamon, Zev A Wainberg, Yung-Jue Bang, Paulo M Hoff, Alberto Sobrero, Shukui Qin, Karen Afenjar, Vincent Houe, Karen King, Sheryl Koski, Karen Mulder, Julie Price Hiller, Andrew Scarfe, Jennifer Spratlin, Yingjie J Huang, Saba Khan-Wasti, Neil Chua, Michael B Sawyer
Importance: Capecitabine is an oral cytotoxic chemotherapeutic commonly used across cancer subtypes. As with other oral medications though, it may suffer from drug interactions that could impair its absorption. Objective: To determine if gastric acid suppressants such as proton pump inhibitors (PPIs) may impair capecitabine efficacy. Design, Setting, and Participants: This secondary analysis of TRIO-013, a phase III randomized trial, compares capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer (GEC); patients were randomized 1:1 between CapeOx with or without lapatinib...
October 13, 2016: JAMA Oncology
Ernest H Law, Melissa Badowski, Yu-Ting Hung, Kimberly Weems, Angelica Sanchez, Todd A Lee
OBJECTIVE: Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is characterized by chronic, watery, nonbloody diarrhea. Concern regarding a potential association between proton-pump inhibitors (PPIs) and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association between PPIs and MC. DATA SOURCES: We systematically searched EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Google Scholar using the terms proton-pump inhibitors (omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, or esomeprazole), microscopic colitis, collagenous colitis, and lymphocytic colitis STUDY SELECTION: Full-text, English-language reports of case reports/series, observational studies, experimental studies, and systematic reviews/meta-analyses published between January 2000 to August 2016 were included...
October 12, 2016: Annals of Pharmacotherapy
Sihuai Sun, Xiaobing Yang, Yao Wang, Xihui Shen
Proteins are the elementary machinery of life, and their functions are carried out mostly by molecular interactions. Among those interactions, protein-protein interactions (PPIs) are the most important as they participate in or mediate all essential biological processes. However, many common methods for PPI investigations are slightly unreliable and suffer from various limitations, especially in the studies of dynamic PPIs. To solve this problem, a method called Bioluminescence Resonance Energy Transfer (BRET) was developed about seventeen years ago...
October 11, 2016: International Journal of Molecular Sciences
Tommaso Moschetti, Timothy Sharpe, Gerhard Fischer, May E Marsh, HongKin Ng, Matthew Morgan, Duncan Scott, Tom L Blundell, Ashok Venkitaraman, John Skidmore, Chris Abell, Marko Hyvönen
Protein-protein interactions (PPIs) are increasingly important targets for drug discovery. Efficient fragment-based drug discovery approaches to tackle PPIs are often stymied by difficulties in the production of stable, unliganded target proteins. Here, we report an approach that exploits protein engineering to 'humanise' thermophilic archeal surrogate proteins as targets for small molecule inhibitor discovery, and exemplify this approach in the development of inhibitors against the PPI between the recombinase RAD51 and tumour suppressor BRCA2...
October 7, 2016: Journal of Molecular Biology
H M Steffen
The S2k-Guideline "Helicobacter pylori and gastroduodenal ulcer disease" offers a statement and comment on the subject of stress ulcer prophylaxis that need a critical response.
October 2016: Zeitschrift Für Gastroenterologie
Jin-Young Min, Christopher J Ocampo, Whitney W Stevens, Caroline P E Price, Christopher F Thompson, Tetsuya Homma, Julia H Huang, James E Norton, Lydia A Suh, Kathryn L Pothoven, David B Conley, Kevin C Welch, Stephanie Shintani-Smith, Anju T Peters, Leslie C Grammer, Kathleen E Harris, Kathryn E Hulse, Atsushi Kato, Nikolai N Modyanov, Robert C Kern, Robert P Schleimer, Bruce K Tan
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by tissue eosinophilia that is associated with poor prognosis. Recent findings that proton pump inhibitors (PPIs) directly modulate the expression of eotaxin-3, an eosinophil chemoattractant, in patients with eosinophilic diseases suggest therapeutic potential for PPIs in those with CRSwNP. OBJECTIVE: We assessed the effect of type 2 mediators, particularly IL-13 and eotaxin-3, on tissue eosinophilia and disease severity in patients with chronic rhinosinusitis (CRS)...
October 4, 2016: Journal of Allergy and Clinical Immunology
S Barel, D Elad, O Cuneah, J A Shimshoni
The Israeli feed safety legislation, which came to prominence in the early 1970's, has undergone a major change from simple feed safety and quality regulations to a more holistic concept of control of feed safety and quality throughout the whole feed production chain, from farm to the end user table. In February 2014 a new law was approved by the Israeli parliament, namely the Control of Animal Feed Law, which is expected to enter into effect in 2017. The law is intended to regulate the production and marketing of animal feed, guaranteeing the safety and quality of animal products throughout the production chain...
October 4, 2016: Journal of the Science of Food and Agriculture
Jill J Hall, Monika Bolina, Trish Chatterley, Fakhreddin Jamali
OBJECTIVE: To review the potential drug interactions between low-dose methotrexate (LD-MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs), penicillins, and proton-pump inhibitors (PPIs) given the disparity between interactions reported for high-dose and low-dose MTX to help guide clinicians. DATA SOURCES: A literature search was performed in MEDLINE (1946 to September 2016), EMBASE (1974 to September 2016), and International Pharmaceutical Abstracts (1970 to January 2015) to identify reports describing potential drug interactions between LD-MTX and NSAIDS, penicillins, or PPIs...
October 3, 2016: Annals of Pharmacotherapy
Guo-Hua Jin, Wei Xu, Yang Shi, Li-Bo Wang
Gastric cancer (GC) is a prevalent cancer, which remains incurable, and therefore requires an alternative treatment method. Celecoxib is a nonsteroidal anti-inflammatory drug that targets cyclooxygenase-2, and exhibits anticancer effects. The present study aimed to investigate the anti-GC mechanism of celecoxib using bioinformatics methods. Gene expression datasets GSE56807 (GC tissues and normal gastric tissues) and GSE54657 (celecoxib-treated and non-treated human GC epithelial AGS cells) were downloaded from the Gene Expression Omnibus database...
October 2016: Oncology Letters
Kathryn Peterson, David J Bjorkman
During their lifetime, about 10% of the population will develop a peptic ulcer. Despite major advancements in the approach to peptic ulcer bleeding over the last 10-20 years including newer endoscopic hemostatic techniques and the advent of proton pump inhibitors (PPIs), upper gastrointestinal bleeding due to peptic ulcers results in substantial morbidity, mortality, and cost. Both oral and intravenous PPIs have proven to be effective in preventing recurrent bleeding from peptic ulcers. However, the dosing and administration of PPIs have been a source of ongoing debate, specifically in relation to cost...
October 2016: American Journal of Gastroenterology
Xiaofang Huo, Agoston T Agoston, Kerry B Dunbar, Daisha J Cipher, Xi Zhang, Chunhua Yu, Edaire Cheng, Qiuyang Zhang, Thai H Pham, Uttam K Tambar, Richard K Bruick, David H Wang, Robert D Odze, Stuart J Spechler, Rhonda F Souza
OBJECTIVE: In an earlier study wherein we induced acute reflux by interrupting proton pump inhibitor (PPI) therapy in patients with reflux oesophagitis (RO) healed by PPIs, we refuted the traditional concept that RO develops as an acid burn. The present study explored our alternative hypothesis that RO results from reflux-stimulated production of pro-inflammatory molecules mediated by hypoxia-inducible factors (HIFs). DESIGN: Using oesophageal biopsies taken from patients in our earlier study at baseline and at 1 and 2 weeks off PPIs, we immunostained for HIF-1α, HIF-2α and phospho-p65, and measured pro-inflammatory molecule mRNAs...
September 30, 2016: Gut
Erica M Elliott
: The use of medications that block gastric acid secretion, such as proton pump inhibitors, has rapidly escalated in the United States. Although originally intended for short-term treatment of specific conditions, PPIs have expanded to long-term use with unanticipated consequences, including mineral deficiencies related to lack of sufficient stomach acid needed for extraction of minerals from the foods and supplements ingested. Herein, the author reports on a case of a patient with tachycardia and other arrhythmias that had been resistant to the medications prescribed by a series of cardiologists...
August 26, 2016: Explore: the Journal of Science and Healing
Brenda Hartman, Mary Donnelly-VanderLoo, Tiffany Watson, Colleen O'Connor, Janet Madill
The risk for impaired vitamin B12 status increases with age, as does the use of proton pump inhibitors (PPI). Long-term use of PPIs is associated with several nutritional deficiencies including B12. Currently, there are no recommendations for B12 screening among patients taking PPIs. Data were abstracted on B12 concentrations, B12-containing supplement use, medications, and select hematological values from a retrospective chart review of 658 adults, 391 with serum B12 concentrations, admitted to 6 different medical units at 2 regional hospitals in Southwestern Ontario between 2010 and 2012...
June 23, 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Zhi-Cheng Yang, Feng Yu, Yong-Qing Wang, Ji-Fu Wei
BACKGROUND: Proton pump inhibitors (PPIs) are a group of gastric acid suppressing drugs, they work by irreversibly blocking the H+/K+ ATPase. The structure of PPIs is similar. They all have a similar core with a sulphur atom chiral center combined with different substituent groups. In relation to the sulphur atom chiral center, the pharmacodynamics, pharmacokinetics are diverse between the racemates and their stereoisomers. But there are no reviews outlining the stereoselective pharmacodynamics and pharmacokinetics in PPIs...
2016: Current Drug Metabolism
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