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Proton pump inhibition

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https://www.readbyqxmd.com/read/28636554/proton-pump-inhibitors-increase-the-chemosensitivity-of-patients-with-advanced-colorectal-cancer
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28516003/mode-of-action-of-the-2-phenylquinoline-efflux-inhibitor-pqq4r-against-escherichia-coli
#12
Diana Machado, Laura Fernandes, Sofia S Costa, Rolando Cannalire, Giuseppe Manfroni, Oriana Tabarrini, Isabel Couto, Stefano Sabatini, Miguel Viveiros
Efflux pump inhibitors are of great interest since their use as adjuvants of bacterial chemotherapy can increase the intracellular concentrations of the antibiotics and assist in the battle against the rising of antibiotic-resistant bacteria. In this work, we have described the mode of action of the 2-phenylquinoline efflux inhibitor (4-(2-(piperazin-1-yl)ethoxy)-2-(4-propoxyphenyl) quinolone - PQQ4R), against Escherichia coli, by studding its efflux inhibitory ability, its synergistic activity in combination with antibiotics, and compared its effects with the inhibitors phenyl-arginine-β-naphthylamide (PAβN) and chlorpromazine (CPZ)...
2017: PeerJ
https://www.readbyqxmd.com/read/28512370/occupational-contact-allergy-to-omeprazole-and-ranitidine
#13
Inmaculada Herrera-Mozo, Pere Sanz-Gallen, Gabriel Martí-Amengual
Omeprazole is a proton pump inhibition and ranitidine is an H2 histamine receptor antagonist widely used in the treatment of gastroesophageal reflex disease, peptic ulcer disease, Zollinger-Ellison syndrome and as a protector of the gastric mucosae. We report a case of occupational contact allergy to omeprazole and ranitidine. A 48-year-old man, with no pre-existing history of atopy or lifestyle factors. He neither had any medical history of consumption of drugs such as ranitidine and omeprazole. He worked for 19 months in the pharmaceutical company that manufactured ranitidine base...
May 16, 2017: Medycyna Pracy
https://www.readbyqxmd.com/read/28512024/repurposing-of-proton-pump-inhibitors-as-first-identified-small-molecule-inhibitors-of-endo-%C3%AE-n-acetylglucosaminidase-engase-for-the-treatment-of-ngly1-deficiency-a-rare-genetic-disease
#14
Yiling Bi, Matthew Might, Hariprasad Vankayalapati, Balagurunathan Kuberan
N-Glycanase deficiency, or NGLY1 deficiency, is an extremely rare human genetic disease. N-Glycanase, encoded by the gene NGLY1, is an important enzyme involved in protein deglycosylation of misfolded proteins. Deglycosylation of misfolded proteins precedes the endoplasmic reticulum (ER)-associated degradation (ERAD) process. NGLY1 patients produce little or no N-glycanase (Ngly1), and the symptoms include global developmental delay, frequent seizures, complex hyperkinetic movement disorder, difficulty in swallowing/aspiration, liver dysfunction, and a lack of tears...
July 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28507564/management-of-the-hormonal-syndrome-of-neuroendocrine-tumors
#15
Paweł Gut, Joanna Waligórska-Stachura, Agata Czarnywojtek, Nadia Sawicka-Gutaj, Maciej Bączyk, Katarzyna Ziemnicka, Jakub Fischbach, Kosma Woliński, Jarosław Kaznowski, Elżbieta Wrotkowska, Marek Ruchała
Gastroenteropancreatic neuroendocrine tumors (GEP/NET) are unusual and rare neoplasms that present many clinical challenges. They characteristically synthesize store and secrete a variety of peptides and neuroamines which can lead to the development of distinct clinical syndrome, however many are clinically silent until late presentation with mass effects. Management strategies include surgery cure and cytoreduction with the use of somatostatin analogues. Somatostatin have a broad range of biological actions that include inhibition of exocrine and endocrine secretions, gut motility, cell proliferation, cell survival and angiogenesis...
April 1, 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28492555/acidic-ph-is-essential-for-maintaining-mast-cell-secretory-granule-homeostasis
#16
Gunnar Pejler, Jun Mei Hu Frisk, Daniel Sjöström, Aida Paivandy, Helena Öhrvik
It has been recognized for a long time that the secretory granules of mast cells are acidic, but the functional importance of maintaining an acidic pH in the mast cell granules is not fully understood. Here we addressed this issue by examining the effects of raising the pH of the mast cell secretory granules. Mast cells were incubated with bafilomycin A1, an inhibitor of the vacuolar-type ATPase proton pump. Supporting a role of vacuolar-type ATPase in mast cell granule acidification, bafilomycin A1 treatment caused a robust increase in granule pH...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28483790/effect-of-hormone-secretory-syndromes-on-neuroendocrine-tumor-prognosis
#17
Wouter T Zandee, Kimberly Kamp, R C S van Adrichem, R A Feelders, Wouter W de Herder
The treatment of hormone hypersecretory syndromes caused by neuroendocrine tumors (NETs) can be a major challenge. NETs originating from the small intestine often secrete serotonin causing flushing, diarrhea and valve fibrosis, leading to dehydration or heart failure in severe cases. NETs from the pancreas can secrete a wider variety of hormones, like insulin, glucagon and gastrin leading to distinct clinical syndromes. Historically mortality in patients with functioning NETs was high due to the complications caused by the hypersecretion of hormones...
May 8, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28475749/ineffective-esophageal-motility-clinical-manometric-and-outcome-characteristics-in-patients-with-and-without-abnormal-esophageal-acid-exposure
#18
K P Shetler, S Bikhtii, G Triadafilopoulos
The etiology and clinical impact of ineffective esophageal motility (IEM) remain poorly understood. Unless gastroesophageal acid reflux (GERD) is identified, symptomatic patients with IEM are challenging to treat. We sought to determine whether any clinical or functional characteristics could distinguish those patients with IEM and either normal or abnormal esophageal acid exposure.In this retrospective cohort study, we identified 46 consecutive patients presenting with heartburn, and other GER symptoms who underwent clinical, endoscopic, and functional evaluation that included high-resolution manometry (HRM) and ambulatory pH monitoring...
June 1, 2017: Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus
https://www.readbyqxmd.com/read/28464347/optimization-strategies-aimed-to-increase-the-efficacy-of-h-%C3%A2-pylori-eradication-therapies
#19
REVIEW
Javier P Gisbert, Adrian G McNicholl
BACKGROUND: As with any other infectious disease, we should aim for treatments offering ≥90% Helicobacter pylori eradication rates in clinical practice. AIM: To summarize optimization strategies aimed to increase the efficacy of H. pylori eradication therapies. METHODS: A systematic bibliographic search (in PubMed up to August 2016) was designed to identify studies investigating optimization strategies aimed to increase the efficacy of H...
May 2, 2017: Helicobacter
https://www.readbyqxmd.com/read/28463532/aspirin-and-omeprazole-for-secondary-prevention-of-cardiovascular-disease-in-patients-at-risk-for-aspirin-associated-gastric-ulcers
#20
Guillermo García-Rayado, Carlos Sostres, Angel Lanas
Cardiovascular disease is the most important cause of morbidity and mortality in the world and low-dose aspirin is considered the cornerstone of the cardiovascular disease prevention. However, low-dose aspirin use is associated with gastrointestinal adverse effects in the whole gastrointestinal tract. In this setting, co-therapy with a proton pump inhibitor is the most accepted strategy to reduce aspirin related upper gastrointestinal damage. In addition, some adverse effects have been described with proton pump inhibitors long term use...
June 19, 2017: Expert Review of Clinical Pharmacology
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