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Proton pump inhibition

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https://www.readbyqxmd.com/read/27932981/proton-pump-inhibitors-display-antitumor-effects-in-barrett-s-adenocarcinoma-cells
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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...
October 24, 2016: Nature
https://www.readbyqxmd.com/read/27757581/secretagogue-dependent-and-independent-transport-of-zinc-hydration-forms-in-rat-parietal-cells
#15
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
https://www.readbyqxmd.com/read/27748935/proton-pump-inhibitor-pantoprazole-inhibits-the-proliferation-self%C3%A2-renewal-and-chemoresistance-of-gastric-cancer-stem-cells-via-the-emt-%C3%AE-%C3%A2-catenin-pathways
#16
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
https://www.readbyqxmd.com/read/27748817/release-from-optimal-compressive-force-suppresses-osteoclast-differentiation
#17
Masaaki Ikeda, Yoshitaka Yoshimura, Takashi Kikuiri, Mino Matsuno, Tomokazu Hasegawa, Kumu Fukushima, Takako Hayakawa, Hajime Minamikawa, Kuniaki Suzuki, Junichiro Iida
Bone remodeling is an important factor in orthodontic tooth movement. During orthodontic treatment, osteoclasts are subjected to various mechanical stimuli, and this promotes or inhibits osteoclast differentiation and fusion. It has been previously reported that the release from tensile force induces osteoclast differentiation. However, little is known about how release from compressive force affects osteoclasts. The present study investigated the effects of release from compressive force on osteoclasts. The number of tartrate‑resistant acid phosphatase (TRAP)‑positive multinucleated osteoclasts derived from RAW264...
October 5, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27734291/clinical-pharmacokinetics-and-pharmacodynamics-of-cabozantinib
#18
Steven A Lacy, Dale R Miles, Linh T Nguyen
Cabozantinib inhibits receptor tyrosine kinases involved in tumor angiogenesis and metastasis. The capsule formulation (Cometriq(®)) is approved for the treatment of progressive metastatic medullary thyroid cancer at a 140-mg free base equivalent dose. The tablet formulation (Cabometyx™, 60-mg free base equivalent dose) is approved for the treatment of renal cell carcinoma following anti-angiogenic therapy. Cabozantinib displays a long terminal plasma half-life (~120 h) and accumulates ~fivefold by day 15 following daily dosing based on area under the plasma concentration-time curve (AUC)...
October 12, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27717558/proton-pump-inhibitors-decrease-eotaxin-3-ccl26-expression-in-patients-with-chronic-rhinosinusitis-with-nasal-polyps-possible-role-of-the-nongastric-h-k-atpase
#19
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
https://www.readbyqxmd.com/read/27694141/hypoxia-inducible-factor-2%C3%AE-plays-a-role-in-mediating-oesophagitis-in-gord
#20
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
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