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Proton pump inhibition

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https://www.readbyqxmd.com/read/28088584/proton-pump-inhibition-and-cancer-therapeutics-a-specific-tumor-targeting-or-it-is-a-phenomenon-secondary-to-a-systemic-buffering
#1
REVIEW
Enrico Spugnini, Stefano Fais
One of the unsolved mysteries in oncology includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to the development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. In the last decades a primordial role for proton exchangers has been supported as a key tumor advantage in facing off the acidic milieu...
January 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28024166/an-east-asian-perspective-on-the-interaction-between-proton-pump-inhibitors-and-clopidogrel
#2
Duowu Zou, Khean-Lee Goh
Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for ARDs (Acid Related Disorders) including gastroesophageal reflux disease (GERD). They are also co-prescribed with oral anticoagulant agents (OAAs)and with dual-antiplatelet therapy (DAPT) for the treatment and prevention of gastrointestinal (GI) bleeding. Clopidogrel belongs to the drug class of thienopyridines, and is currently the most widely prescribed OAA either alone or in combination with aspirin...
December 26, 2016: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27992223/revealing-the-mechanistic-pathway-of-acid-activation-of-proton-pump-inhibitors-to-inhibit-the-gastric-proton-pump-a-dft-study
#3
Kalyanashis Jana, Tusar Bandyopadhyay, Bishwajit Ganguly
Acid-related gastric diseases are associated with disorder of digestive tract acidification due to the acid secretion by gastric proton pump, H(+),K(+)-ATPase. Omeprazole is one of the persuasive irreversible inhibitor of the proton pump H(+),K(+)-ATPase. However, the reports on the mechanistic pathway of irreversible proton pump inhibitors (PPIs) on the acid activation and formation of disulfide complex are scarce in the literature. We have examined the acid activation PPIs, i.e., timoprazole, S-omeprazole and R-omeprazole using M062X/6-31++G(d,p) in aqueous phase with SMD solvation model...
December 29, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27991853/influences-of-proton-pump-inhibitor-on-helicobacter-pylori-adherence-to-the-gastrointestinal-cell-lines
#4
Marhanis Salihah Omar, Noor Safwah Damanhuri, Endang Kumolosasi
BACKGROUND/AIMS: Helicobacter pylori is a carcinogenic bacterium that could induce P-glycoprotein expression in the human gastrointestinal tract. Bacterial adherence to the gastrointestinal cell lines could be influenced by the level of P-glycoprotein. This study aimed to determine the influence of proton pump inhibitors that exhibit an inhibitory effect on P-glycoprotein in gastrointestinal carcinoma cell lines, namely Caco-2 and LS174T, in relation to H. pylori adherence. MATERIALS AND METHODS: Caco-2 and LS174T cells lines treated with omeprazole and esomeprazole were used in this study to assess the bacterial attachment of H...
December 19, 2016: Turkish Journal of Gastroenterology: the Official Journal of Turkish Society of Gastroenterology
https://www.readbyqxmd.com/read/27981489/influence-of-low-dose-proton-pump-inhibitors-administered-concomitantly-or-separately-on-the-anti-platelet-function-of-clopidogrel
#5
Takahisa Furuta, Mitsushige Sugimoto, Chise Kodaira, Masafumi Nishino, Mihoko Yamade, Takahiro Uotani, Shu Sahara, Hitomi Ichikawa, Takuma Kagami, Moriya Iwaizumi, Yasushi Hamaya, Satoshi Osawa, Ken Sugimoto, Kazuo Umemura
Proton pump inhibitors (PPIs) at low doses can effectively prevent gastrointestinal bleeding due to aspirin and are widely used in Japan for gastroprotection in patients taking anti-platelet agents. We examined the influence of different PPIs at low doses administered concomitantly or separately on anti-platelet functions of clopidogrel. In 41 healthy Japanese volunteers with different CYP2C19 genotypes who took clopidogrel 75 mg in the morning alone, or with omeprazole 10 mg, esomeprazole 10 mg, lansoprazole 15 mg, or rabeprazole 10 mg, either concomitantly in the morning or separately in the evening, we measured the inhibition of platelet aggregation (IPA, %) using VerifyNow P2Y12 assay at 4 h after the last clopidogrel dose on Day 7 of each regimen...
December 15, 2016: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/27932981/proton-pump-inhibitors-display-antitumor-effects-in-barrett-s-adenocarcinoma-cells
#6
Eduardo Chueca, Nadezda Apostolova, Juan V Esplugues, María A García-González, Ángel Lanas, Elena Piazuelo
Recent evidence has reported that proton pump inhibitors (PPIs) can exert antineoplastic effects through the disruption of pH homeostasis by inhibiting vacuolar ATPase (H(+)-VATPase), a proton pump overexpressed in several tumor cells, but this aspect has not been deeply investigated in EAC yet. In the present study, the expression of H(+)-VATPase was assessed through the metaplasia-dysplasia-adenocarcinoma sequence in Barrett's esophagus (BE) and the antineoplastic effects of PPIs and cellular mechanisms involved were evaluated in vitro...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27932475/intercalated-cell-depletion-and-vacuolar-h-atpase-mistargeting-in-an-ae1-r607h-knockin-model
#7
Rizwan Mumtaz, Francesco Trepiccione, J Christopher Hennings, Antje K Huebner, Bettina Serbin, Nicolas Picard, A K M Shahid Ullah, Teodor G Păunescu, Diane E Capen, Rawad M Lashhab, Isabelle Mouro-Chanteloup, Seth L Alper, Carsten A Wagner, Emmanuelle Cordat, Dennis Brown, Dominique Eladari, Christian A Hübner
Distal nephron acid secretion is mediated by highly specialized type A intercalated cells (A-ICs), which contain vacuolar H(+)-ATPase (V-type ATPase)-rich vesicles that fuse with the apical plasma membrane on demand. Intracellular bicarbonate generated by luminal H(+) secretion is removed by the basolateral anion-exchanger AE1. Chronically reduced renal acid excretion in distal renal tubular acidosis (dRTA) may lead to nephrocalcinosis and renal failure. Studies in MDCK monolayers led to the proposal of a dominant-negative trafficking mechanism to explain AE1-associated dominant dRTA...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27929705/snapin-is-critical-for-lysosomal-acidification-and-autophagosome-maturation-in-macrophages
#8
Bo Shi, Qi-Quan Huang, Robert Birkett, Renee Doyle, Andrea Dorfleutner, Christian Stehlik, Congcong He, Richard M Pope
We previously observed that SNAPIN, which is an adaptor protein in the SNARE core complex, was highly expressed in rheumatoid arthritis synovial tissue macrophages, but its role in macrophages and autoimmunity is unknown. To identify SNAPIN's role in these cells, we employed siRNA to silence the expression of SNAPIN in primary human macrophages. Silencing SNAPIN resulted in swollen lysosomes with impaired CTSD (cathepsin D) activation, although total CTSD was not reduced. Neither endosome cargo delivery nor lysosomal fusion with endosomes or autophagosomes was inhibited following the forced silencing of SNAPIN...
December 8, 2016: Autophagy
https://www.readbyqxmd.com/read/27922734/population-pharmacokinetics-of-ceritinib-in-adult-patients-with-tumors-characterized-by-genetic-abnormalities-in-anaplastic-lymphoma-kinase
#9
Ying Hong, Vanessa Q Passos, Pai-Hsi Huang, Yvonne Y Lau
Ceritinib is a second-generation selective and potent oral anaplastic lymphoma kinase (ALK) inhibitor approved for ALK-positive advanced non-small cell lung cancer previously treated with crizotinib. Population pharmacokinetic (PK) analysis was performed to describe the PK of ceritinib and was used to evaluate the covariate effects on systemic exposure at its label dose (750 mg orally once daily). Ceritinib concentration-time data from 4 clinical studies were described by a 1-compartment model with delayed first-order absorption and time-dependent elimination...
December 6, 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27920416/re-evaluating-the-inhibition-of-stress-erosions-revise-a-protocol-for-pilot-randomized-controlled-trial
#10
Waleed Alhazzani, Gordon Guyatt, John C Marshall, Richard Hall, John Muscedere, Francois Lauzier, Lehana Thabane, Mohammed Alshahrani, Shane W English, Yaseen M Arabi, Adam M Deane, Tim Karachi, Bram Rochwerg, Simon Finfer, Nick Daneman, Nicole Zytaruk, Diane Heel-Ansdell, Deborah Cook, On Behalf Of
INTRODUCTION: Clinicians routinely administer stress ulcer prophylaxis to mechanically ventilated patients in the intensive care unit (ICU), most commonly prescribing proton pump inhibitors (PPIs). However, the incidence of gastrointestinal (GI) bleeding from stress ulceration is low and recent observational studies suggest these agents may increase infections. Therefore, a large randomized clinical trial (RCT) is needed to inform modern practice. The aim of this multicenter pilot trial is to determine the feasibility of performing a large RCT to investigate the efficacy and safety of withholding intravenous pantoprazole...
November 2016: Annals of Saudi Medicine
https://www.readbyqxmd.com/read/27892894/overuse-of-proton-pump-inhibitors-and-its-consequences
#11
Marcin Kazberuk, Szymon Brzósko, Tomasz Hryszko, Beata Naumnik
Direct inhibition of H+ ion excretion to the gastric lumen makes proton pump inhibitors (PPI) the most effective drugs against gastric acid-related diseases. Over recent years usage of proton pump inhibitors has increased dramatically. Due to the low costs, high efficacy and rarity of adverse effects, their use is prevalent and often it does not correspond with existing medical guidelines. The literature lists stress ulcer prophylaxis among patients with low risk of bleeding, routine 'gastroprotective' medication during treatment and non-specific abdominal symptoms as the most common patterns of off-label PPI use...
October 14, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/27890768/proton-pump-inhibitor-and-histamine-2-receptor-antagonist-use-and-iron-deficiency
#12
Jameson R Lam, Jennifer L Schneider, Charles P Quesenberry, Douglas A Corley
BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) suppress gastric acid production, which may inhibit iron absorption. However, little data exist regarding whether these medications increase the risk of clinical iron deficiency. METHODS: A community-based case-control study evaluated the association between acid-suppressing medication use and the subsequent risk of iron deficiency. It contrasted 77,046 patients with new iron deficiency diagnoses (January, 1999-December, 2013), with 389,314 controls...
November 24, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27843960/addition-of-cranberry-to-proton-pump-inhibitor-based-triple-therapy-for-helicobacter-pylori-eradication
#13
Mohammadreza Seyyedmajidi, Anahita Ahmadi, Shahin Hajiebrahimi, Seyedali Seyedmajidi, Majid Rajabikashani, Mona Firoozabadi, Jamshid Vafaeimanesh
OBJECTIVE: Proton pump inhibitor-based triple therapy with two antibiotics for Helicobacter pylori eradication is widely accepted, but this combination fails in a considerable number of cases. Some studies have shown that cranberry inhibits the adhesion of a wide range of microbial pathogens, including H. pylori. The aim of this study was to assess the effect of cranberry on H. pylori eradication with a standard therapy including lansoprazole, clarithromycin, and amoxicillin (LCA) in patients with peptic ulcer disease (PUD)...
October 2016: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/27830269/inhibition-of-the-multidrug-efflux-pump-lmrs-from-staphylococcus-aureus-by-cumin-spice-cuminum-cyminum
#14
Prathusha Kakarla, Jared Floyd, MunMun Mukherjee, Amith R Devireddy, Madhuri A Inupakutika, Indrika Ranweera, Ranjana Kc, Ugina 'Shrestha, Upender Rao Cheeti, Thomas Mark Willmon, Jaclyn Adams, Merissa Bruns, Shravan Kumar Gunda, Manuel F Varela
Staphylococcus aureus is a serious causative agent of infectious disease. Multidrug-resistant strains like methicillin-resistant S. aureus compromise treatment efficacy, causing significant morbidity and mortality. Active efflux represents a major antimicrobial resistance mechanism. The proton-driven multidrug efflux pump, LmrS, actively exports structurally distinct antimicrobials. To circumvent resistance and restore clinical efficacy of antibiotics, efflux pump inhibitors are necessary, and natural edible spices like cumin are potential candidates...
November 9, 2016: Archives of Microbiology
https://www.readbyqxmd.com/read/27825384/inhibiting-the-proton-pump-mechanisms-benefits-harms-and-questions
#15
Jeffrey K Aronson
Inhibition of the H(+)/K(+)-adenosine triphosphatase (the proton pump) is the final common mechanistic pathway in reducing gastric acid secretion pharmacologically. Proton pump inhibitors are widely used in upper gastrointestinal diseases, including gastric and duodenal ulcers, eradication of Helicobacter pylori in combination with antibiotics, gastroesophageal reflux disease, Zollinger-Ellison syndrome, eosinophilic esophagitis, and prevention of non-steroidal anti-inflammatory drug-induced peptic ulceration...
November 9, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27821031/does-helicobacter-pylori-eradication-therapy-trigger-or-protect-against-crohn-s-disease
#16
REVIEW
H As Murad
Helicobacter pylori (H. pylori) infection is involved in multiple gastrointestinal and extra-gastrointestinal disorders. This review focuses on possible link between H. pylori eradication and Crohn's disease (CD) which is a chronic inflammatory bowel disease (IBD). Fecal calprotectin and; to lesser extent; fecal lactoferrin are sensitive and specific markers for monitoring CD activity. Data about link between H. pylori eradication and CD are limited and inconclusive. The infection likely shifts equilibrium between T helper 1 (Th1) and Th2 immune responses to the Th2 pattern...
July 2016: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/27803739/vonoprazan-based-therapy-for-helicobacter-pylori-eradication-experience-and-clinical-evidence
#17
REVIEW
Yuko Akazawa, Daisuke Fukuda, Yutaka Fukuda
Stable suppression of gastric acid secretion is a crucial factor in Helicobacter pylori eradication. Vonoprazan is a potassium-competitive acid blocker recently approved for use in Japan. As vonoprazan has a long duration of action and causes rapid and strong inhibition of gastric acid secretion, it has gained clinical attention for treating erosive oesophagitis, peptic ulcers, and H. pylori infection. In this review, we discuss the recent knowledge regarding the safety and efficacy of vonoprazan, focusing on its use in H...
November 2016: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/27796466/randomised-trial-of-the-effect-of-a-gastrin-cck2-receptor-antagonist-on-esomeprazole-induced-hypergastrinaemia-evidence-against-rebound-hyperacidity
#18
Malcolm Boyce, Frans van den Berg, Toni Mitchell, Kate Darwin, Steve Warrington
PURPOSE: Hypergastrinaemia induced by proton pump inhibitor (PPI) therapy may cause ECL-cell and parietal-cell hyperplasia and rebound hyperacidity and dyspepsia after PPI withdrawal. The aim of the study was to assess the effect of different dosage-regimens of netazepide, a gastrin/CCK2 receptor antagonist, on PPI-induced hypergastrinaemia and elevated chromogranin A (CgA). METHODS: Six groups of eight healthy subjects participated in a randomised, double-blind study of esomeprazole 40 mg daily for 28 days, in combination with netazepide 1, 5 or 25 mg or placebo, daily, during the last 14 days of esomeprazole or during 14 days after treatment withdrawal...
October 29, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27776355/atomic-model-for-the-membrane-embedded-vo-motor-of-a-eukaryotic-v-atpase
#19
Mohammad T Mazhab-Jafari, Alexis Rohou, Carla Schmidt, Stephanie A Bueler, Samir Benlekbir, Carol V Robinson, John L Rubinstein
Vacuolar-type ATPases (V-ATPases) are ATP-powered proton pumps involved in processes such as endocytosis, lysosomal degradation, secondary transport, TOR signalling, and osteoclast and kidney function. ATP hydrolysis in the soluble catalytic V1 region drives proton translocation through the membrane-embedded VO region via rotation of a rotor subcomplex. Variability in the structure of the intact enzyme has prevented construction of an atomic model for the membrane-embedded motor of any rotary ATPase. We induced dissociation and auto-inhibition of the V1 and VO regions of the V-ATPase by starving the yeast Saccharomyces cerevisiae, allowing us to obtain a ~3...
November 3, 2016: Nature
https://www.readbyqxmd.com/read/27757581/secretagogue-dependent-and-independent-transport-of-zinc-hydration-forms-in-rat-parietal-cells
#20
Florentina Sophie Ferstl, Alice Miriam Kitay, Rebecca Marion Trattnig, Abrar Alsaihati, John Peter Geibel
Prolonged exposure to gastric acid is a leading cause of gastroesophageal reflux disease (GERD) and esophagitis. With the ever increasing number of patients showing insensitivity to proton-pump-inhibitor (PPI) therapy with recurrence of symptoms over time, alternative treatment options remain an important issue. Previous studies from our laboratory have shown that a zinc sulfate salt can inhibit HCl generation at the cellular level of the parietal cell. In this paper, we examine the difference between two hydration forms of ZnSO4 (monohydrate H2O and heptahydrate 7H2O) in their entry characteristics into the parietal cell under several physiological conditions associated with acid secretion...
November 2016: Pflügers Archiv: European Journal of Physiology
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