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Proton pump inhibition

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https://www.readbyqxmd.com/read/28728310/the-effect-of-h2-receptor-antagonist-in-acid-inhibition-and-its-clinical-efficacy
#1
REVIEW
Young Kwang Shim, Nayoung Kim
The first histamine H2 receptor antagonists (H2RAs) were developed in the early 1970s. They played a dominant role in treating peptic ulcer disease and gastroesophageal reflux disease (GERD). H2RAs block the production of acid by H(+), K(+)-ATPase at the parietal cells and produce gastric luminal anacidity for varying periods. H2RAs are highly selective, and they do not affect H1 receptors. Moreover, they are not anticholinergic agents. Sequential development of H2RAs, proton pump inhibitors (PPIs), and discovery of Helicobacter pylori infection changed the paradigm of peptic ulcer disease with marked decrease of morbidity and mortality...
July 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28720734/lack-of-acrb-efflux-function-confers-loss-of-virulence-on-salmonella-enterica-serovar-typhimurium
#2
Xuan Wang-Kan, Jessica M A Blair, Barbara Chirullo, Jonathan Betts, Roberto M La Ragione, Alasdair Ivens, Vito Ricci, Timothy J Opperman, Laura J V Piddock
AcrAB-TolC is the paradigm resistance-nodulation-division (RND) multidrug resistance efflux system in Gram-negative bacteria, with AcrB being the pump protein in this complex. We constructed a nonfunctional AcrB mutant by replacing D408, a highly conserved residue essential for proton translocation. Western blotting confirmed that the AcrB D408A mutant had the same native level of expression of AcrB as the parental strain. The mutant had no growth deficiencies in rich or minimal medium. However, compared with wild-type SL1344, the mutant had increased accumulation of Hoechst 33342 dye and decreased efflux of ethidium bromide and was multidrug hypersusceptible...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28711545/antiulcer-properties-of-fruits-and-vegetables-a-mechanism-based-perspective
#3
REVIEW
Choudhary Harsha, Kishore Banik, Devivasha Bordoloi, Ajaikumar B Kunnumakkara
Gastric ulcer is the damage caused to mucosal layer of the stomach under the action of various factors like high levels of acid and pepsin, invasion by Helicobacter pylori, etc. Although most cases have been controlled and the rate of ulcer occurrence has reduced over the last few decades, gastric ulcer still holds a prime concern today. A range of palliative medicines comprising proton pump inhibitors, H2 receptor antagonists, COX-2 inhibitors (coxibs) is widely in use and patients have also been administered with acid suppression therapies...
July 12, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28707966/targeted-molecular-ablation-of-cancer-stem-cells-for-curing-gastrointestinal-cancers
#4
Yong Seok Kim, Ho Jae Lee, Jong-Min Park, Young-Min Han, Napapan Kangwan, Ji Young Oh, Dong Yoon Lee, Ki Baik Hahm
Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis...
July 14, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28705331/a-non-interventional-retrospective-cohort-study-of-the-interaction-between-methotrexate-and-proton-pump-inhibitors-or-aspirin
#5
E Boerrigter, M Crul
INTRODUCTION: Methotrexate (MTX) is an antifolate drug, which is frequently used in the treatment of cancer. Proton pump inhibitors (PPIs) could delay the elimination of plasma MTX in high-dose MTX therapy by inhibition of tubular secretion, which could lead to MTX toxicity. However, the evidence of the clinical relevance of this drug-drug interaction is inconsistent. No previous studies into the effect of low dose aspirin on the elimination of MTX in high-dose therapy have been performed...
July 10, 2017: Annales Pharmaceutiques Françaises
https://www.readbyqxmd.com/read/28700346/restoring-microenvironmental-redox-and-ph-homeostasis-inhibits-neoplastic-cell-growth-and-migration-therapeutic-efficacy-of-esomeprazole-plus-sulfasalazine-on-3-mca-induced-sarcoma
#6
Enrica Balza, Patrizia Castellani, Paola Sanchez Moreno, Patrizia Piccioli, Iria Medraño-Fernandez, Claudia Semino, Anna Rubartelli
Neoplastic cells live in a stressful context and survive thanks to their ability to overcome stress. Thus, tumor cell responses to stress are potential therapeutic targets. We selected two such responses in melanoma and sarcoma cells: the xc- antioxidant system, that opposes oxidative stress, and surface v-ATPases that counteract the low pHi by extruding protons, and targeted them with the xc- blocker sulfasalazine and the proton pump inhibitor esomeprazole. Sulfasalazine inhibited the cystine/cysteine redox cycle and esomeprazole decreased pHi while increasing pHe in tumor cell lines...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698674/insight-into-synergetic-mechanisms-of-tetracycline-and-the-selective-serotonin-reuptake-inhibitor-sertraline-in-a-tetracycline-resistant-strain-of-escherichia-coli
#7
Lili Li, Sofie Kromann, John Elmerdahl Olsen, Søren Wedel Svenningsen, Rikke Heidemann Olsen
Sertraline, an antidepressive drug, has been reported to inhibit general bacterial efflux pumps. In the present study, we report for the first time a synergistic effect of sertraline and tetracycline in a TetA-encoded tetracycline-resistant strain of Escherichia coli. Synergy between sertraline and tetracycline in an E. coli strain with TetA-mediated tetracycline resistance (E. coli APEC_O2) was assessed by the MIC and checkerboard assays. The global transcriptome of E. coli APEC_O2 exposed to ½ MIC concentrations of sertraline and/or tetracycline was analyzed to elucidate the interaction mechanism between sertraline and tetracycline...
July 12, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28657473/vonoprazan-fumarate-for-the-management-of-acid-related-diseases
#8
Irene Martinucci, Corrado Blandizzi, Giorgia Bodini, Elisa Marabotto, Vincenzo Savarino, Santino Marchi, Nicola de Bortoli, Edoardo Savarino
Proton pump inhibitors (PPIs) display a number of limitations and unmet clinical needs that have prompted the development of novel drugs to improve the outcomes of acid-related diseases, including the eradication of H. pylori. In this context, a new synthesized potassium-competitive acid blocker (P-CAB), vonoprazan, showed higher suppression of gastric acid secretion. Areas covered: This review discusses the current knowledge regarding the efficacy of vonoprazan in the treatment of acid-related diseases, with a particular focus on its use in Helicobacter pylori eradication...
August 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28648501/depolarized-gabaergic-signaling-in-subicular-microcircuits-mediates-generalized-seizure-in-temporal-lobe-epilepsy
#9
Yi Wang, Cenglin Xu, Zhenghao Xu, Caihong Ji, Jiao Liang, Ying Wang, Bin Chen, Xiaohua Wu, Feng Gao, Shuang Wang, Yi Guo, Xiaoming Li, Jianhong Luo, Shumin Duan, Zhong Chen
Secondary generalized seizure (sGS) is a major source of disability in temporal lobe epilepsy (TLE) with unclear cellular/circuit mechanisms. Here we found that clinical TLE patients with sGS showed reduced volume specifically in the subiculum compared with those without sGS. Further, using optogenetics and extracellular electrophysiological recording in mouse models, we found that photoactivation of subicular GABAergic neurons retarded sGS acquisition by inhibiting the firing of pyramidal neurons. Once sGS had been stably acquired, photoactivation of GABAergic neurons aggravated sGS expression via depolarized GABAergic signaling...
July 5, 2017: Neuron
https://www.readbyqxmd.com/read/28636554/proton-pump-inhibitors-increase-the-chemosensitivity-of-patients-with-advanced-colorectal-cancer
#10
Xiaoyu Wang, Chun Liu, Jiaqi Wang, Yue Fan, Zhenghua Wang, Yuanyuan Wang
Changes in pH can alter the uptake of chemotherapy drugs. Proton pump inhibitors (PPIs) may therefore increase the chemosensitivity of cancer cells and cytotoxicity of chemotherapeutic drugs by increasing their uptake. We investigated the chemosensitizing potential of PPIs in colorectal cancer (CRC). Our in vitro data show that the PPI pantoprazole increases the chemosensitivity of CRC HT29 and RKO cells to fluorouracil (5-FU). Our in vivo data demonstrate that pantoprazole also increases the ability of 5-FU to inhibit CRC tumor growth in mice...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28629736/kfp-h008-blocks-gastric-acid-secretion-through-inhibiting-h-k-atpase
#11
Cheng-Yuan Li, Mei Su, Yun-Yi Yan, Lin Zhou, Lu-Yao Ao, Wei-Rong Fang, Yun-Man Li
1-(5-(1H-indol-5-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine (KFP-H008),a novel and potent potassium-competitive acid blocker for the treatment of acid secretion related diseases, has not been reported previously. In this study, we demonstrated that KFP-H008 inhibits basal acid secretion, 2-deoxy-D-glucose- (2DG-) stimulated gastric acid secretion in rats. KFP-H008 blocked histamine-stimulated acid secretion in rats and heidenhain pouch dogs and reversed acid output in isolated gastric perfusion under histamine stimulation...
June 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28615015/the-gastroprotective-effect-of-ethyl-acetate-fraction-of-hot-water-extract-of-trichosanthes-cucumerina-linn-and-its-underlying-mechanisms
#12
Ramani Karunakaran, M Ira Thabrew, G Mayuri Thammitiyagodage, B Prasanna Galhena, L D A Menuka Arawwawala
BACKGROUND: Antacids, anticholinergic drugs, histamine H2- receptor antagonists and irreversible proton pump inhibitors have been used for the treatment of gastric ulcers. However, prolonged use of these drugs may lead to series of adverse effects such as diarrhea, headache, rash, hypertension, muscular and joint pain. Therefore, there is an urgent need of more effective and safer treatments with fewer side effects. The aim of the present study was to scientifically evaluate the gastroprotective activity of fractions of the hot water extract of Trichosanthes cucumerina Linn (Family: Cucurbitaceae) aerial parts with a view to identifying the fraction with the best gastroprotective activity and the possible mechanism/s by which this fraction exert gastroprotection...
June 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28592812/activity-independent-targeting-of-mtor-to-lysosomes-in-primary-osteoclasts
#13
Andrew Wang, Luciene R Carraro-Lacroix, Celeste Owen, Bowen Gao, Paul N Corey, Pascal Tyrrell, John H Brumell, Irina Voronov
Mammalian target of rapamycin (mTOR) is activated by numerous stimuli, including amino acids and growth factors. This kinase is part of the mTOR complex 1 (mTORC1) which regulates cell proliferation, differentiation, and autophagy. Active mTORC1 is located on lysosomes and has been reported to disassociate from the lysosomal surface in the absence of amino acids. Furthermore, mTORC1 activity has been linked to the vacuolar H(+)-ATPases (V-ATPases), the proton pumps responsible for lysosomal acidification; however, the exact role of the V-ATPases in mTORC1 signaling is not known...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588208/human-dimethylarginine-dimethylaminohydrolase-1-inhibition-by-proton-pump-inhibitors-and-the-cardiovascular-risk-marker-asymmetric-dimethylarginine-in-vitro-and-in-vivo-significance
#14
S Tommasi, D J Elliot, J A Hulin, B C Lewis, M McEvoy, A A Mangoni
Proton pump inhibitor (PPI)-induced inhibition of dimethylarginine dimethylaminohydrolase 1 (DDAH1), with consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA), might explain the increased cardiovascular risk with PPI use. However, uncertainty exists regarding whether clinical PPI concentrations significantly inhibit DDAH1 under linear initial rate conditions, and whether PPI-induced DDAH1 inhibition significantly increases ADMA in humans. DDAH1 inhibition by esomeprazole, omeprazole, pantoprazole, lansoprazole and rabeprazole was determined by quantifying DDAH1-mediated L-citrulline formation in vitro...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28570695/molecular-basis-for-the-binding-and-modulation-of-v-atpase-by-a-bacterial-effector-protein
#15
Jianhua Zhao, Ksenia Beyrakhova, Yao Liu, Claudia P Alvarez, Stephanie A Bueler, Li Xu, Caishuang Xu, Michal T Boniecki, Voula Kanelis, Zhao-Qing Luo, Miroslaw Cygler, John L Rubinstein
Intracellular pathogenic bacteria evade the immune response by replicating within host cells. Legionella pneumophila, the causative agent of Legionnaires' Disease, makes use of numerous effector proteins to construct a niche supportive of its replication within phagocytic cells. The L. pneumophila effector SidK was identified in a screen for proteins that reduce the activity of the proton pumping vacuolar-type ATPases (V-ATPases) when expressed in the yeast Saccharomyces cerevisae. SidK is secreted by L. pneumophila in the early stages of infection and by binding to and inhibiting the V-ATPase, SidK reduces phagosomal acidification and promotes survival of the bacterium inside macrophages...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28567114/a-randomized-double-blind-study-to-evaluate-the-acid-inhibitory-effect-of-vonoprazan-20-mg-and-40-mg-in-patients-with-proton-pump-inhibitor-resistant-erosive-esophagitis
#16
Katsuhiko Iwakiri, Yuuichi Sakurai, Madoka Shiino, Hiroyuki Okamoto, Kentaro Kudou, Akira Nishimura, Naoki Hiramatsu, Eiji Umegaki, Kiyoshi Ashida
BACKGROUND: Standard treatment for patients with erosive esophagitis (EE) is proton-pump inhibitors (PPIs), but some patients are resistant to PPIs. We aimed to evaluate the acid-inhibitory effects and efficacy of a novel potassium-competitive acid blocker (vonoprazan) in patients with PPI-resistant EE. METHODS: This randomized, double-blind, multicenter study of vonoprazan evaluated gastric and esophageal pH over a 24-hour period as the primary endpoint and EE healing rate as the secondary endpoint...
June 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28560128/identification-of-aqueous-access-residues-of-the-sodium-half-channel-in-transmembrane-helix-5-of-the-fo-a-subunit-of-propionigenium-modestum-atp-synthase
#17
Noriyo Mitome, Hiroki Sato, Taishi Tomiyama, Katsuya Shimabukuro, Takuya Matsunishi, Kohei Hamada, Toshiharu Suzuki
The Fo-a subunit of the Na(+)-transporting FoF1 ATP synthase from Propionigenium modestum plays a key role in Na(+) transport. It forms half channels that allow Na(+) to enter and leave the buried carboxyl group on Fo-c subunits. The essential Arg residue R226, which faces the carboxyl group of Fo-c subunits in the middle of transmembrane helix 5 of the Fo-a subunit, separates the cytoplasmic side and periplasmic half-channels. To elucidate contributions of other amino acid residues of transmembrane helix 5 using hybrid FoF1 (Fo from P...
2017: Biophysics and Physicobiology
https://www.readbyqxmd.com/read/28536198/understanding-the-essential-proton-pumping-kinetic-gates-and-decoupling-mutations-in-cytochrome-c-oxidase
#18
Ruibin Liang, Jessica M J Swanson, Mårten Wikström, Gregory A Voth
Cytochrome c oxidase (CcO) catalyzes the reduction of oxygen to water and uses the released free energy to pump protons against the transmembrane proton gradient. To better understand the proton-pumping mechanism of the wild-type (WT) CcO, much attention has been given to the mutation of amino acid residues along the proton translocating D-channel that impair, and sometimes decouple, proton pumping from the chemical catalysis. Although their influence has been clearly demonstrated experimentally, the underlying molecular mechanisms of these mutants remain unknown...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533674/impact-of-gastroesophageal-reflux-control-through-tailored-proton-pump-inhibition-therapy-or-fundoplication-in-patients-with-barrett-s-esophagus
#19
Francisco Baldaque-Silva, Michael Vieth, Mumen Debel, Bengt Håkanson, Anders Thorell, Nuno Lunet, Huan Song, Miguel Mascarenhas-Saraiva, Gisela Pereira, Lars Lundell, Hanns-Ulrich Marschall
AIM: To determine the impact of upwards titration of proton pump inhibition (PPI) on acid reflux, symptom scores and histology, compared to clinically successful fundoplication. METHODS: Two cohorts of long-segment Barrett's esophagus (BE) patients were studied. In group 1 (n = 24), increasing doses of PPI were administered in 8-wk intervals until acid reflux normalization. At each assessment, ambulatory 24 h pH recording, endoscopy with biopsies and symptom scoring (by a gastroesophageal reflux disease health related quality of life questionnaire, GERD/HRLQ) were performed...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28533185/the-small-molecule-iitr08027-restores-the-antibacterial-activity-of-fluoroquinolones-against-multidrug-resistant-acinetobacter-baumannii-by-efflux-inhibition
#20
Tapas Bhattacharyya, Atin Sharma, Jawed Akhter, Ranjana Pathania
Efflux pumps are one of the major determinants of multiple drug resistance. In this study, AbeM, a multidrug efflux pump in Acinetobacter baumannii, was cloned into a multicopy plasmid (pUC18) and was transformed into an efflux-deficient mutant of Escherichia coli (KAM32). The elevated resistance profile of the recombinant E. coli for ciprofloxacin was utilised to screen a small-molecule library of 8000 molecules to identify IITR08027, a small molecule that is not inhibitory on its own but that could potentiate the activity of ciprofloxacin...
May 19, 2017: International Journal of Antimicrobial Agents
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