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Proton pump inhibition

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https://www.readbyqxmd.com/read/29285882/systemic-rnai-of-v-atpase-subunit-b-causes-molting-defect-and-developmental-abnormalities-in-periplaneta-fuliginosa
#1
Kazuki Sato, Keita Miyata, Sota Ozawa, Koichi Hasegawa
The vacuolar (H+ )-ATPases (V-ATPases) are ATP-driven proton pumps with multiple functions in many organisms. In this study, we performed structural and functional analysis of vha55 gene that encodes V-ATPase subunit B in the smokybrown cockroach Periplaneta fuliginosa (Blattodea). We observed a high homology score of the deduced amino acid sequences between 10 species in seven orders. RNAi of the vha55 gene in P. fuliginosa caused nymphal/nymphal molting defects with incomplete shedding of old cuticles, growth inhibition, as well as bent and wrinkled cuticles of thoraxes and abdominal segments...
December 29, 2017: Insect Science
https://www.readbyqxmd.com/read/29281635/optical-silencing-of-body-wall-muscles-induces-pumping-inhibition-in-caenorhabditis-elegans
#2
Megumi Takahashi, Shin Takagi
Feeding, a vital behavior in animals, is modulated depending on internal and external factors. In the nematode Caenorhabditis elegans, the feeding organ called the pharynx ingests food by pumping driven by the pharyngeal muscles. Here we report that optical silencing of the body wall muscles, which drive the locomotory movement of worms, affects pumping. In worms expressing the Arch proton pump or the ACR2 anion channel in the body wall muscle cells, the pumping rate decreases after activation of Arch or ACR2 with light illumination, and recovers gradually after terminating illumination...
December 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29247277/surface-ph-changes-suggest-a-role-for-h-oh-channels-in-salinity-response-of-chara-australis
#3
Marketa Absolonova, Mary J Beilby, Aniela Sommer, Marion C Hoepflinger, Ilse Foissner
To understand salt stress, the full impact of salinity on plant cell physiology has to be resolved. Electrical measurements suggest that salinity inhibits the proton pump and opens putative H+/OH- channels all over the cell surface of salt sensitive Chara australis (Beilby and Al Khazaaly 2009; Al Khazaaly and Beilby 2012). The channels open transiently at first, causing a characteristic noise in membrane potential difference (PD), and after longer exposure remain open with a typical current-voltage (I/V) profile, both abolished by the addition of 1 mM ZnCl2, the main known blocker of animal H+ channels...
December 15, 2017: Protoplasma
https://www.readbyqxmd.com/read/29237921/impact-of-proton-pump-inhibitors-on-the-pharmacodynamic-effect-and-clinical-outcomes-in-patients-receiving-dual-antiplatelet-therapy-after-percutaneous-coronary-intervention-a-propensity-score-analysis
#4
Pei Zhu, Zhan Gao, Xiao-Fang Tang, Jing-Jing Xu, Yin Zhang, Li-Jian Gao, Jue Chen, Shu-Bin Qiao, Yue-Jin Yang, Run-Lin Gao, Bo Xu, Jin-Qing Yuan
BACKGROUND: Prior studies have reported controversial conclusions regarding the risk of adverse cardiovascular events in patients using proton-pump inhibitors (PPIs) combined with clopidogrel therapy, causing much uncertainty in clinical practice. We sought to evaluate the safety of PPIs use among high-risk cardiovascular patients who underwent percutaneous coronary intervention (PCI) in a long-term follow-up study. METHODS: A total of 7868 consecutive patients who had undergone PCI and received dual antiplatelet therapy (DAPT) at a single center from January 2013 to December 2013 were enrolled...
December 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29219812/helicobacter-pylori-resistance-in-the-netherlands-a-growing-problem
#5
R Ruiter, H F Wunderink, R A Veenendaal, L G Visser, M G J de Boer
Helicobacter pylori infection is clinically associated with dyspepsia, gastric and duodenal ulcers, and gastric cancer. Increasing antimicrobial resistance in H. pylori is a worldwide problem and failure of eradication with standard triple therapy (high-dose proton pump inhibition, amoxicillin and clarithromycin) is directly related to the presence of a resistant strain. Other treatment combinations have been investigated, but with inconsistent results. Based on a review of the recent literature in conjunction with an analysis of the regional resistance data, we address the increasing complexity of H...
November 2017: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/29206128/conformational-study-of-z-5-4-chlorobenzylidene-2-4-2-hydroxyethyl-piperazin-1-yl-3h-imidazol-4-5h-one-in-different-environments-insight-into-the-structural-properties-of-bacterial-efflux-pump-inhibitors
#6
Ewa Żesławska, Wojciech Nitek, Jadwiga Handzlik
The 2-amine derivatives of 5-arylidene-3H-imidazol-4(5H)-one are a new class of bacterial efflux pump inhibitors, the chemical compounds that are able to restore antibiotic efficacy against multidrug resistant bacteria. 5-Arylidene-3H-imidazol-4(5H)-ones with a piperazine ring at position 2 reverse the mechanisms of multidrug resistance (MDR) of the particularly dangerous Gram-negative bacteria E. coli by inhibition of the efflux pump AcrA/AcrB/TolC (a main multidrug resistance mechanism in Gram-negative bacteria, consisting of a membrane fusion protein, AcrA, a Resistant-Nodulation-Division protein, AcrB, and an outer membrane factor, TolC)...
December 1, 2017: Acta Crystallographica. Section C, Structural Chemistry
https://www.readbyqxmd.com/read/29158567/optogenetic-silencing-of-nociceptive-primary-afferents-reduces-evoked-and-ongoing-bladder-pain
#7
Vijay K Samineni, Aaron D Mickle, Jangyeol Yoon, Jose G Grajales-Reyes, Melanie Y Pullen, Kaitlyn E Crawford, Kyung Nim Noh, Graydon B Gereau, Sherri K Vogt, H Henry Lai, John A Rogers, Robert W Gereau
Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) suffer from chronic pain that severely affects quality of life. Although the underlying pathophysiology is not well understood, inhibition of bladder sensory afferents temporarily relieves pain. Here, we explored the possibility that optogenetic inhibition of nociceptive sensory afferents could be used to modulate bladder pain. The light-activated inhibitory proton pump Archaerhodopsin (Arch) was expressed under control of the sensory neuron-specific sodium channel (sns) gene to selectively silence these neurons...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29156525/esomeprazole-ameliorates-ccl4-induced-liver-fibrosis-in-rats-via-modulating-oxidative-stress-inflammatory-fibrogenic-and-apoptotic-markers
#8
Heba M Eltahir, Maiiada H Nazmy
BACKGROUND: Hepatic fibrosis is a major health problem that requires further medical attention. Proton pump inhibitors are proven to possess other therapeutic potentials apart of their acid anti-secretory actions. AIM OF THE WORK: To test possible anti-fibrotic effect of esomeprazole magnesium trihydrate in management of liver fibrosis compared to silymarin, the well-known hepatoprotective agent. MATERIALS & METHODS: 40 male albino rats were divided into 4 groups: normal control group; CCl4-treated group (1 mL/kg 40% CCl4, diluted in olive oil) I...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29139202/lego-inspired-drug-design-unveiling-of-the-novel-class-of-benzo-d-thiazole-containing-a-3-4-dihydroxyphenyl-moiety-as-plasma-membrane-h-atpase-inhibitors
#9
Truong Thanh Tung, Dao Trong Tuan, Marta Grifell Junyent, Michael Palmgren, Thomas Günther-Pomorski, Anja Thoe Fuglsang, Søren Brøgger Christensen, John Nielsen
The fungal plasma membrane H+-ATPase (Pma1p) is a potential target for the discovery of new antifungal agents. Surprisingly, no structure-activity relationship studies for small molecules targeting Pma1p have been reported. Herein, we disclose a LEGO-inspired fragment assembly strategy for design, synthesis and discovery of benzo[d]thiazoles containing a 3,4-dihydroxyphenyl moiety as potential Pma1p inhibitors. A series of 2-(benzo[d]thiazol-2-ylthio)-1-(3,4-dihydroxyphenyl)ethanones was found to inhibit Pma1p with the most potent IC50 of 8 µM in an in vitro plasma membrane H+-ATPase assay...
November 15, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29105152/proton-pump-inhibitor-alters-oral-microbiome-in-gastrointestinal-tract-of-healthy-volunteers
#10
Tsuyoshi Mishiro, Kentaro Oka, Yasutoshi Kuroki, Motomichi Takahashi, Kasumi Tatsumi, Tsukasa Saitoh, Hiroshi Tobita, Norihisa Ishimura, Shuichi Sato, Shunji Ishihara, Joji Sekine, Koichiro Wada, Yoshikazu Kinoshita
BACKGROUND AND AIM: Acid suppressive agents including proton pump inhibitors (PPIs) are used as first-line treatment for various acid-related gastrointestinal disorders. Although known to profoundly reduce gastric acid production, their influence on inhibition of acid secretion as part of the function of the gastrointestinal tract microbiome remains to be elucidated. The aim of the present study was to examine the effects of PPI usage on oral and gut microbiota in healthy volunteers. METHODS: Ten healthy adult volunteers receiving no medications were enrolled...
November 4, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29070456/-characterization-of-chromate-resistance-in-genetically-engineered-escherichia-coli-expressing-chromate-ion-transporter-chra
#11
Si-Min Zhou, Lan-Lan Dong, Yuan He, Hong Xiao
OBJECTIVE: To construct a genetically engineered Escherichia coli expressing chromate (Cr) ion transporter ChrA and test its Cr resistance capacity. METHODS: ChrA gene was cloned by PCR from the DNA template of Serratia sp. S2 and linked with the prokaryotic vector pET-28a (+). The recombinant vector was transformed into E.coli BL21 (DE3) cells for expression of ChrA protein. Cr (VI) risistance and Cr (VI) uptake and efflux of the engineered bacteria were tested, and the effects of Cr loading time, oxyanions (ulfate, molybdate, vanadate, tungstate), and respiratory inhibitors (valinomycin, CN(-), oligomycin, and NADH) on Cr (VI) efflux were examined to analyze the pathway of Cr (VI) transport by ChrA protein...
October 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29060457/a-pharmacokinetic-model-of-drug-drug-interaction-between-clopidogrel-and-omeprazole-at-cyp2c19-in-humans
#12
Wimonchat Tangamornsuksan, Pongpak Thiansupornpong, Thirawut Morasuk, Ornrat Lohitnavy, Manupat Lohitnavy
BACKGROUND: Clopidogrel is a thienopryridine antiplatelet agent commonly used in the management of cardiovascular diseases. Clopidogrel is metabolized by hepatic CYP2C19 and CYP2B6, therefore, co-administration of clopidogrel and CYP2C19 inhibitors can alter pharmacokinetics of clopidogrel. Omeprazole is a proton pump inhibitor used for decreasing gastric acid production. Omeprazole is known to be a potent inhibitor of CYP2C19. Thus when the drugs are simultaneously administered, clopidogrel plasma concentration levels can be increased...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29055186/designed-inhibitors-with-hetero-linkers-for-gastric-proton-pump-h-k-atpase-steered-molecular-dynamics-and-metadynamics-studies
#13
Kalyanashis Jana, Tusar Bandyopadhyay, Bishwajit Ganguly
Acid suppressant SCH28080 and its derivatives reversibly reduce acid secretion activity of the H(+),K(+)-ATPase in a K(+) competitive manner. The results on homologation of the SCH28080 by varying the linker chain length suggested the improvement in efficacy. However, the pharmacokinetic studies reveal that the hydrophobic nature of the CH2 linker units may not help it to function as a better acid suppressant. We have exploited the role of linker unit to enhance the efficacy of such reversible acid suppressant drug molecules using hetero linker, i...
October 12, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29043071/recent-advances-in-the-management-of-peptic-ulcer-bleeding
#14
REVIEW
Ian Beales
Acute upper gastrointestinal haemorrhage due to peptic ulcer bleeding remains an important cause of emergency presentation and hospital admission. Despite advances in many aspects of management, peptic ulcer bleeding is still associated with significant morbidity, mortality, and healthcare costs. Comprehensive international guidelines have been published, but advances as well as controversies continue to evolve. Important recent advances include the evidence supporting a more restrictive transfusion strategy aiming for a target haemoglobin of 70-90 g/l...
2017: F1000Research
https://www.readbyqxmd.com/read/29038303/f-actin-reorganization-by-v-atpase-inhibition-in-prostate-cancer
#15
Yamhilette Licon-Munoz, Vera Michel, Colleen A Fordyce, Karlett J Parra
The vacuolar ATPase (V-ATPase) proton pump sustains cellular pH homeostasis, and its inhibition triggers numerous stress responses. However, the cellular mechanisms involved remain largely elusive in cancer cells. We studied V-ATPase in the prostate cancer (PCa) cell line PC-3, which has characteristics of highly metastatic PCa. V-ATPase inhibitors impaired endo-lysosomal pH, vesicle trafficking, migration, and invasion. V-ATPase accrual in the Golgi and recycling endosomes suggests that traffic of internalized membrane vesicles back to the plasma membrane was particularly impaired...
November 15, 2017: Biology Open
https://www.readbyqxmd.com/read/29018343/impact-of-gastric-h-k-atpase-rs2733743-on-the-intragastric-ph-values-of-dexlansoprazole-injection-in-chinese-subjects
#16
Lu-Ning Sun, Yang Cao, Yue-Qi Li, Yun-Qian Fang, Hong-Wen Zhang, Mei-Feng Wang, Li-Jun Xie, Juan Chen, Zhi-Cheng Yang, Ming-Liang Bian, Hao Li, Pei-Pei Zhang, Ji-Fu Wei, Ling Meng, Xue-Hui Zhang, Ping Zhao, Yong-Qing Wang
Background: Not all patients with acid-related disorders receiving proton pump inhibitor (PP) treatment get adequate gastric pH control. The genetic variation of receptors, metabolic enzymes, and transporters are known to cause failures of therapies. We have conducted a study to evaluate the influence of gastric H(+)/K(+)-ATPase, CYP2C19, and ABCB1 polymorphisms on the pharmacokinetic and pharmacodynamic profiles of dexlansoprazole injection in healthy Chinese subjects. Methods: A total of 51 subjects were enrolled for pharmacokinetic and pharmacodynamic study after a single intravenous administration of 20 or 30 mg dexlansoprazole...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28979813/tumor-microenvironment-interruption-a-novel-anti-cancer-mechanism-of-proton-pump-inhibitor-in-gastric-cancer-by-suppressing-the-release-of-microrna-carrying-exosomes
#17
Xu-Wen Guan, Fang Zhao, Jing-Ya Wang, Hai-Yan Wang, Shao-Hua Ge, Xia Wang, Le Zhang, Rui Liu, Yi Ba, Hong-Li Li, Ting Deng, Li-Kun Zhou, Ming Bai, Tao Ning, Hai-Yang Zhang, Ding-Zhi Huang
Poor prognosis of gastric cancer is related to not only malignancy of gastric cancer cells, but also the tumor microenvironment. Thus drugs, which can inhibit both of them, are urgently needed to be explored. Studies on effect of Proton-pump inhibitors (PPIs) in anti-neoplasms are increasing, but is rare in gastric in gastric cancer. Here we investigated how the gastric cancer microenvironment is regulated by PPIs. The objective response rate of gastric cancer patients in our hospital treated by PPIs is investigated...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28978047/restoring-microenvironmental-redox-and-ph-homeostasis-inhibits-neoplastic-cell-growth-and-migration-therapeutic-efficacy-of-esomeprazole-plus-sulfasalazine-on-3-mca-induced-sarcoma
#18
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...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968600/the-h-k-atpase-inhibitor-sch-28080-inhibits-insulin-secretion-and-induces-cell-death-in-ins-1e-rat-insulinoma-cells
#19
Martin Jakab, Nina Ketterl, Johannes Fürst, Marlena Beyreis, Michael Kittl, Tobias Kiesslich, Cornelia Hauser-Kronberger, Martin Gaisberger, Markus Ritter
BACKGROUND/AIMS: Glucose-stimulated insulin secretion (GSIS) of pancreatic β-cells involves glucose uptake and metabolism, closure of KATP channels and depolarization of the cell membrane potential (Vmem), activation of voltage-activated Ca2+ currents (ICav) and influx of Ca2+, which eventually triggers hormone exocytosis. Beside this classical pathway, KATP-independent mechanisms such as changes in intracellular pH (pHi) or cell volume, which also affect β-cell viability, can elicit or modify insulin release...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28938598/proton-pump-inhibitors-increase-the-chemosensitivity-of-patients-with-advanced-colorectal-cancer
#20
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...
August 29, 2017: Oncotarget
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