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Proton pump inhibition

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https://www.readbyqxmd.com/read/28223391/evaluation-of-para-aminosalicylic-acid-pas-as-a-substrate-of-multiple-solute-carrier-slc-uptake-transporters-and-possible-drug-interactions-with-nsaids-in-vitro
#1
Md Masud Parvez, Ho Jung Shin, Jin Ah Jung, Jae-Gook Shin
para-Aminosalicylic acid (PAS) is a second-line anti-tuberculosis drug used to treat multidrug-resistant and extensively drug-resistant tuberculosis for more than 60 years. Renal secretion and glomerular filtration are the major pathways for elimination of PAS. We comprehensively studied PAS transport by using cell lines that overexpressed various transporters, and found that PAS acts as a novel substrate of organic anionic polypeptide (OATP1B1), organic cationic transporters (OCT1 and OCT2), and organic anion transporters (OAT1 and OAT3) but not a substrate of any ATP-binding cassette (ABC) transporters...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28210286/bilastine-in-allergic-rhinoconjunctivitis-and-urticaria-a-practical-approach-to-treatment-decisions-based-on-queries-received-by-the-medical-information-department
#2
REVIEW
Amalia Leceta, Ander Sologuren, Román Valiente, Cristina Campo, Luis Labeaga
BACKGROUND: Bilastine is a safe and effective commonly prescribed non-sedating H1-antihistamine approved for symptomatic treatment in patients with allergic disorders such as rhinoconjunctivitis and urticaria. It was evaluated in many patients throughout the clinical development required for its approval, but clinical trials generally exclude many patients who will benefit in everyday clinical practice (especially those with coexisting diseases and/or being treated with concomitant drugs)...
2017: Drugs in Context
https://www.readbyqxmd.com/read/28184197/therapeutic-efficacy-of-esomeprazole-in-cotton-smoke-induced-lung-injury-model
#3
Christina Nelson, Jameisha Lee, Kang Ko, Andrew G Sikora, Mark D Bonnen, Perenlei Enkhbaatar, Yohannes T Ghebre
Proton pump inhibitors (PPIs) are well-known antacid drugs developed to treat gastric disorders. Emerging studies demonstrate that PPIs possess biological activities that extend beyond inhibition of H(+)/K(+) ATPase (proton pumps) expressed in parietal cells of the stomach. Some of the extra-gastric activities of PPIs include modulation of epithelial, endothelial, and immune cell functions. Recently, we reported that PPIs suppress the expression of several proinflammatory and profibrotic molecules, as well as enhance antioxidant mechanisms in order to favorably regulate lung inflammation and fibrosis in an animal model of bleomycin-induced lung injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28169223/insights-into-the-ion-coupling-mechanism-in-the-mate-transporter-norm-vc
#4
Alexander Krah, Ulrich Zachariae
Bacteria have developed a variety of different mechanisms to defend themselves from compounds that are toxic to them, such as antibiotics. One of these defence mechanisms is the expulsion of drugs or other noxious compounds by multidrug efflux pumps. Multidrug and toxic compound extrusion (MATE) transporters are efflux pumps that extrude metabolic waste and a variety of antibiotics out of the cell, using an ion gradient as energy source. They function via an alternative-access mechanism. When ions bind in the outward facing conformation, a large conformational change to the inward facing conformation is induced, from which the ion is released and the extruded chemical compound is bound...
February 7, 2017: Physical Biology
https://www.readbyqxmd.com/read/28154253/protective-effects-of-genipin-on-gastrointestinal-disorders
#5
Yoon Ah Sohn, In Young Hwang, Sun Yi Lee, Hyo Sun Cho, Choon Sik Jeong
Genipin, an aglycone of geniposide, is a major component of gardeniae fructus, and has been used to treat jaundice, various inflammatory disorders, and liver disease, and has also been used as a natural cross-linking agent. The authors conducted several experiments to evaluate the protective effects of genipin on gastrointestinal disorders, such as, gastritis and gastric ulcers. Genipin showed inhibitory effects against HCl·ethanol-induced acute gastritis and indomethacin-induced gastric ulcers in rats and increased prostaglandin E2 (PGE2) in AGS gastric cancer cell...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28121478/mitoq-regulates-autophagy-by-inducing-a-pseudo-mitochondrial-membrane-potential-pmmp
#6
Chao Sun, Xiongxiong Liu, Cuixia Di, Zhenhua Wang, Xiangquan Mi, Yang Liu, Qiuyue Zhao, Aihong Mao, Weiqiang Chen, Lu Gan, Hong Zhang
During the process of oxidative phosphorylation, protons are pumped into the mitochondrial intermembrane space to establish a mitochondrial membrane potential (MMP). The electrochemical gradient generated allows protons to return to the matrix through the ATP synthase complex and generates ATP in the process. MitoQ is a lipophilic cationic drug that is adsorbed to the inner mitochondrial membrane; however, the cationic moiety of MitoQ remains in the intermembrane space. We found that the positive charges in MitoQ inhibited the activity of respiratory chain complexes I, III, and IV, reduced proton production, and decreased oxygen consumption...
January 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28110633/h-k-atpase-inhibition-causes-left-right-aortic-arch-inversion-in-mouse-development
#7
Yukihisa Miyachi
An organ known as a "node" forms during embryogenesis and plays a vital role in determining laterality in vertebrates. However, according to some reports in vertebrates, left-right patterning may be determined long before the node has developed. In this study, we analyzed left-right asymmetry formation in mammals based on ion-signaling factors, which has never been attempted before. First, a proton pump inhibitor was injected into pregnant mice to investigate whether H(+)/K(+)-ATPase is involved in the differentiation of pharyngeal arch arteries during embryonic development...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28109748/chronic-proton-pump-inhibition-therapy-in-the-diagnostic-accuracy-of-serum-pepsinogen-i-and-gastrin-concentrations-to-identify-pernicious-anaemia
#8
Mariam Martín-Alcolea, Inés Rodríguez-Hernández, Marta Aldea, Irene Rosas, Jordi Juncà, Maria Luisa Granada
BACKGROUND: Chronic use of proton pump inhibitors (PPIs) leads to increases in gastrin and pepsinogen-I serum concentrations. AIM: To asses if chronic treatment with PPIs has an effect on serum gastrin and pepsinogen-I concentrations for the diagnosis of pernicious anaemia (PA). MATERIALS AND METHODS: Serum gastrin and pepsinogen-I were measured in 38 patients with PA and 74 without PA (controls); 17/38 PA patients and 36/74 controls were treated with PPIs...
January 18, 2017: Clinical Biochemistry
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
#9
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
#10
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
#11
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
#12
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...
January 2017: 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
#13
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
#14
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
#15
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
#16
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...
February 2017: Autophagy
https://www.readbyqxmd.com/read/27922734/population-pharmacokinetics-of-ceritinib-in-adult-patients-with-tumors-characterized-by-genetic-abnormalities-in-anaplastic-lymphoma-kinase
#17
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
#18
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
#19
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
#20
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
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