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Proton pump inhibition

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https://www.readbyqxmd.com/read/28442261/identification-of-a-novel-fluoropyrrole-derivative-as-a-potassium-competitive-acid-blocker-with-long-duration-of-action
#1
Haruyuki Nishida, Yasuyoshi Arikawa, Keizo Hirase, Toshihiro Imaeda, Nobuhiro Inatomi, Yasunobu Hori, Jun Matsukawa, Yasushi Fujioka, Teruki Hamada, Motoo Iida, Mitsuyoshi Nishitani, Akio Imanishi, Hideo Fukui, Fumio Itoh, Masahiro Kajino
With the aim to find a novel long-lasting potassium-competitive acid blocker (P-CAB) that would perfectly overcome the limitations of proton pump inhibitors (PPIs), we tried various approaches based on pyrrole derivative 1b as a lead compound. As part of a comprehensive approach to identification of a new drug, we explored excellent compounds that have low lipophilicity by introducing a polar hetero-aromatic group at position 5 of the pyrrole ring. Among the compounds synthesized, fluoropyrrole derivative 37c, which has a 2-F-3-Py group at the fifth position, lower pKa, and much lower ClogP and logD values than 1b dose, showed potent gastric-acid suppressive action resulting from gastric H(+),K(+)-ATPase inhibition in animal models...
April 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28397430/the-effect-of-proton-pump-inhibitors-on-the-gastric-mucosal-microenvironment
#2
Yen-Chun Peng, Lan-Ru Huang, Hui-Ching Ho, Chi-Sen Chang, Shou-Wu Lee, Ching-Chang Cheng, May-Ching Wen, Hong-Zen Yeh, Shu-Peng Ho
BACKGROUND: Proton pump inhibitors (PPIs) are widely applied for acid related disorders, and possess pleiotropic biological functions. The effect of PPIs on the gastric mucosa, neutrophil and Helicobacter pylori (H. pylori) infiltration and glandular atrophy has not been well investigated, particularly the duration of the effects of PPIs. OBJECTIVES: To investigate the effects of PPIs on neutrophil infiltration, H. pylori infiltration and the gastric mucosa. MATERIAL AND METHODS: A total of 76 adult patients with gastrointestinal symptoms who had undergone upper gastrointestinal endoscopy were enrolled in the study...
January 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28395788/diagnosis-and-treatment-of-chronic-mesenteric-ischemia-an-update
#3
REVIEW
Jeroen J Kolkman, Robert H Geelkerken
Although the prevalence of mesenteric artery stenoses (MAS) is high, symptomatic chronic mesenteric ischemia (CMI) is rare. The collateral network in the mesenteric circulation, a remnant of the extensive embryonal vascular network, serves to prevent most cases of ischemia. This explains the high incidence of MAS and relative rarity of cases of CMI. The number of affected vessels is the major determinant in CMI development. Most subjects with single vessel mesenteric stenosis do not develop ischemic complaints...
February 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28388576/proton-pump-inhibitor-ilaprazole-suppresses-cancer-growth-by-targeting-t-cell-originated-protein-kinase
#4
Mengzhu Zheng, Shanshan Luan, Suyu Gao, Li Cheng, Bin Hao, Jiacheng Li, Yao Chen, Xuemei Hou, Lixia Chen, Hua Li
T-cell-originated protein kinase (TOPK) is highly and frequently expressed in various cancer tissues and plays an indispensable role in the mitosis of cancer cells, and therefore, it is an important target for drug treatment of tumor. Ilaprazole was identified to be a potent TOPK inhibitor. The data indicated that ilaprazole inhibited TOPK activities with high affinity and selectivity. In vitro studies showed that ilaprazole inhibited TOPK activities in HCT116, ES-2, A549, SW1990 cancer cells. Moreover, knockdown of TOPK in these cells decreased their sensitivities to ilaprazole...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28382327/proton-pump-inhibitor-is-a-risk-factor-for-recurrence-of-common-bile-duct-stones-after-endoscopic-sphincterotomy-propensity-score-matching-analysis
#5
Nobuhiko Fukuba, Shunji Ishihara, Hiroki Sonoyama, Noritsugu Yamashita, Masahito Aimi, Yoshiyuki Mishima, Tsuyoshi Mishiro, Hiroshi Tobita, Koutarou Shibagaki, Naoki Oshima, Ichiro Moriyama, Kousaku Kawashima, Tatsuya Miyake, Norihisa Ishimura, Shuichi Sato, Yoshikazu Kinoshita
Background and study aims Recurrence of common bile duct stones (CBDS) in patients treated with endoscopic sphincterotomy (ES) can lead to deterioration in their quality of life. Although the pathology and related factors are unclear, we speculated that proton pump inhibiter (PPI) administration increases the risk of CBDS recurrence by altering the bacterial mixture in the bile duct. Patients and methods The primary endpoint of this retrospective study was recurrence-free period. Several independent variables considered to have a relationship with CBDS recurrence including PPI use were analyzed using a COX proportional hazard model, with potential risk factors then evaluated by propensity score matching analysis...
April 2017: Endoscopy International Open
https://www.readbyqxmd.com/read/28378028/up-regulation-of-autophagy-is-a-mechanism-of-resistance-to-chemotherapy-and-can-be-inhibited-by-pantoprazole-to-increase-drug-sensitivity
#6
Qian Tan, A M Joshua, M Wang, R G Bristow, B G Wouters, C J Allen, Ian F Tannock
BACKGROUND: Autophagy is a survival mechanism that allows recycling of cellular breakdown products, particularly in stressed cells. Here we evaluate the hypotheses that up-regulation of autophagy is a common mechanism of resistance to chemotherapy, and that drug resistance can be reversed by inhibiting autophagy with a proton pump inhibitor. METHODS: We exposed human PC3, LNCaP and MCF7 cells to seven clinically-used chemotherapy drugs ± pantoprazole, examined the up-regulation of autophagy and the effect on cellular proliferation by Western Blots, MTS assay and colony-forming assay...
April 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28364288/co-administration-of-proton-pump-inhibitors-ameliorates-nephrotoxicity-in-patients-receiving-chemotherapy-with-cisplatin-and-fluorouracil-a-retrospective-cohort-study
#7
Kenji Ikemura, Kosuke Oshima, Tomoyuki Enokiya, Akiharu Okamoto, Hiroyasu Oda, Toshiro Mizuno, Hajime Ishinaga, Yuichi Muraki, Takuya Iwamoto, Kazuhiko Takeuchi, Naoyuki Katayama, Masahiro Okuda
PURPOSE: The nephrotoxicity of cisplatin (CDDP) is its dose-limiting side effect, and is caused by renal accumulation of CDDP mainly via organic cation transporter 2 (OCT2). Because proton pump inhibitors (PPIs) are known to inhibit OCT2 activity, PPI might ameliorate CDDP-induced nephrotoxicity. In the present study, we retrospectively investigated the effect of co-administration of PPI on CDDP-induced nephrotoxicity. METHODS: We analyzed the impact of PPI on the development of nephrotoxicity in 133 patients who received CDDP and fluorouracil (5-FU) therapy for the treatment of esophageal cancer or head and neck cancer...
March 31, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28361440/acid-suppressive-therapy-and-risk-of-infections-pros-and-cons
#8
REVIEW
Leon Fisher, Alexander Fisher
This narrative review summarises the benefits, risks and appropriate use of acid-suppressing drugs (ASDs), proton pump inhibitors and histamine-2 receptor antagonists, advocating a rationale balanced and individualised approach aimed to minimise any serious adverse consequences. It focuses on current controversies on the potential of ASDs to contribute to infections-bacterial, parasitic, fungal, protozoan and viral, particularly in the elderly, comprehensively and critically discusses the growing body of observational literature linking ASD use to a variety of enteric, respiratory, skin and systemic infectious diseases and complications (Clostridium difficile diarrhoea, pneumonia, spontaneous bacterial peritonitis, septicaemia and other)...
March 30, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28321555/medical-treatment-of-gastroesophageal-reflux-disease
#9
Daniel A Kroch, Ryan D Madanick
Medical treatment is effective in the majority of patients with gastroesophageal reflux disease (GERD). Lifestyle modifications are often recommended for patients with GERD, although the data supporting lifestyle recommendations are limited. Antacids are often used to treat the symptoms of GERD, but their effect is short-lived. H2-receptor antagonists and proton-pump inhibitors provide more effective options for remission of GERD symptoms and healing of esophagitis. Prokinetic medications (e.g., metoclopramide) have not been proven to help in the control of symptoms...
March 20, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28321159/proton-pump-inhibitor-induced-collagen-expression-in-colonocytes-is-associated-with-collagenous-colitis
#10
Shiori Mori, Yui Kadochi, Yi Luo, Rina Fujiwara-Tani, Yukiko Nishiguchi, Shingo Kishi, Kiyomu Fujii, Hitoshi Ohmori, Hiroki Kuniyasu
AIM: To elucidate the role of proton pump inhibitors (PPIs) in collagenous disease, direct effect of PPI on colonocytes was examined. METHODS: Collagenous colitis is a common cause of non-bloody, watery diarrhea. Recently, there has been increasing focus on the use of proton PPIs as a risk factor for developing collagenous colitis. Mouse CT26 colonic cells were treated with PPI and/or PPI-induced alkaline media. Expression of fibrosis-associated genes was examined by RT-PCR...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28302654/palmitate-induced-vacuolar-type-h-atpase-inhibition-feeds-forward-into-insulin-resistance-and-contractile-dysfunction
#11
Yilin Liu, Laura K M Steinbusch, Miranda Nabben, Dimitris Kapsokalyvas, Marc van Zandvoort, Patrick Schönleitner, Gudrun Antoons, Peter J Simons, Will A Coumans, Amber Geomini, Dipanjan Chanda, Jan F C Glatz, Dietbert Neumann, Joost J F P Luiken
Dietary fat overconsumption leads to myocardial lipid accumulation through mechanisms that are incompletely resolved. Previously, we identified increased translocation of the fatty acid transporter CD36 from its endosomal storage compartment to the sarcolemma as primary mechanism of excessive myocellular lipid import. Here, we show that increased CD36 translocation is caused by alkalinization of endosomes due to inhibition of proton pumping activity of vacuolar-type H(+)-ATPase (v-ATPase). Endosomal alkalinization was observed in hearts from rats fed a lard-based high fat-diet and in rodent and human cardiomyocytes upon palmitate overexposure, and appeared as early lipid-induced event preceding the onset of insulin resistance...
March 16, 2017: Diabetes
https://www.readbyqxmd.com/read/28296633/the-vacuolar-atpase-complex-and-assembly-factors-tmem199-and-ccdc115-control-hif1%C3%AE-prolyl-hydroxylation-by-regulating-cellular-iron-levels
#12
Anna L Miles, Stephen P Burr, Guinevere L Grice, James A Nathan
Hypoxia Inducible transcription Factors (HIFs) are principally regulated by the 2-oxoglutarate and Iron(II) prolyl hydroxylase (PHD) enzymes, which hydroxylate the HIFα subunit, facilitating its proteasome-mediated degradation. Observations that HIFα hydroxylation can be impaired even when oxygen is sufficient emphasise the importance of understanding the complex nature of PHD regulation. Here, we use an unbiased genome-wide genetic screen in near-haploid human cells to uncover cellular processes that regulate HIF1α...
March 15, 2017: ELife
https://www.readbyqxmd.com/read/28291036/potential-mechanisms-of-hematological-adverse-drug-reactions-in-patients-receiving-clozapine-in-combination-with-proton-pump-inhibitors
#13
Michał Wiciński, Mateusz M Węclewicz, Mateusz Miętkiewicz, Bartosz Malinowski, Elżbieta Grześk, Joanna Klonowska
Clozapine is a second-generation antipsychotic which has proven efficacy in treating the symptoms of schizophrenia. Although clozapine therapy is associated with a number of adverse drug reactions, it is frequently used. One of the most common adverse drug reactions is gastroesophageal reflux disease which is an indication for treatment with proton pump inhibitors (PPIs). Coadministration of clozapine and PPIs increases the risk of hematological adverse drug reactions, including neutropenia and agranulocytosis...
March 2017: Journal of Psychiatric Practice
https://www.readbyqxmd.com/read/28290590/the-ca-2-atpase-pump-facilitates-bidirectional-proton-transport-across-the-sarco-endoplasmic-reticulum
#14
L Michel Espinoza-Fonseca
Ca(2+) transport across the sarco/endoplasmic reticulum (SR) plays an essential role in intracellular Ca(2+) homeostasis, signalling, cell differentiation and muscle contractility. During SR Ca(2+) uptake and release, proton fluxes are required to balance the charge deficit generated by the exchange of Ca(2+) and other ions across the SR. During Ca(2+) uptake by the SR Ca(2+)-ATPase (SERCA), two protons are countertransported from the SR lumen to the cytosol, thus partially compensating for the charge moved by Ca(2+) transport...
March 28, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28290523/a-phylogenetically-distinctive-and-extremely-heat-stable-light-driven-proton-pump-from-the-eubacterium-rubrobacter-xylanophilus-dsm-9941-t
#15
Kanae Kanehara, Susumu Yoshizawa, Takashi Tsukamoto, Yuki Sudo
Rhodopsins are proteins that contain seven transmembrane domains with a chromophore retinal and that function as photoreceptors for light-energy conversion and light-signal transduction in a wide variety of organisms. Here we characterized a phylogenetically distinctive new rhodopsin from the thermophilic eubacterium Rubrobacter xylanophilus DSM 9941(T) that was isolated from thermally polluted water. Although R. xylanophilus rhodopsin (RxR) is from Actinobacteria, it is located between eukaryotic and archaeal rhodopsins in the phylogenetic tree...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28271587/strategies-for-reduction-in-the-duration-of-intravenous-drug-use-interest-of-drug-tracers-as-quality-indicators-to-improve-intravenous-to-oral-switch
#16
Jennifer Corny, Simon Perreau, Anne-Pauline Thivilliers, Céline Leplay, Delphine Chevalier, Hélène Beaussier, Yvonnick Bézie
RATIONALE, AIMS, AND OBJECTIVES: Intravenous (IV) to oral (PO) drug switch is a challenge for tertiary care institutions for several reasons: catheter-related infections, patient's pain and discomfort or higher costs, and overuse of IV drugs considered as an irrational use of medicines. The objective was to evaluate yearly acetaminophen and proton-pump inhibiters' (PPIs) IV/PO ratios from 2011 to 2015 and to determine their correlation with all drugs IV/PO ratios and their relevance as drug tracers...
March 7, 2017: Journal of Evaluation in Clinical Practice
https://www.readbyqxmd.com/read/28254863/bone-pain-induced-by-multiple-myeloma-is-reduced-by-targeting-v-atpase-and-asic3
#17
Masahiro Hiasa, Tatsuo Okui, Yohance M Allette, Matthew S Ripsch, Ge-Hong Sun-Wada, Hiroki Wakabayashi, G David Roodman, Fletcher A White, Toshiyuki Yoneda
Multiple myeloma patients experience severe bone pain (MMBP) that is undertreated and poorly understood. In this study, we studied MMBP in an intratibial mouse xenograft model that employs JJN3 human multiple myeloma cells. In this model, mice develop MMBP associated in bone with increased sprouting of calcitonin gene-related peptide-positive (CGRP(+)) sensory nerves and in dorsal root ganglia (DRG) with upregulation of phosphorylated ERK1/2 (pERK1/2) and pCREB, two molecular indicators of neuron excitation...
March 15, 2017: Cancer Research
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
#18
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
#19
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
#20
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
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