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Proton pump inhibition

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...
October 19, 2016: Pflügers Archiv: European Journal of Physiology
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
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
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
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
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
Somnath Mazumder, Rudranil De, Souvik Sarkar, Asim Azhar Siddiqui, Shubhra Jyoti Saha, Chinmoy Banerjee, Mohd Shameel Iqbal, Shiladitya Nag, Subhashis Debsharma, Uday Bandyopadhyay
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat multiple inflammatory diseases and pain but severe gastric mucosal damage is the worst outcome of NSAID-therapy. Here we report that mitoTEMPO, a mitochondrially targeted superoxide (O2(-)) scavenger protected as well as healed gastric injury induced by diclofenac (DCF), the most commonly used NSAID. Common existing therapy against gastric injury involves suppression of gastric acid secretion by proton pump inhibitors and histamine H2 receptor antagonists; however, dyspepsia, vitamin B12 deficiency and gastric microfloral dysbalance are the major drawbacks of acid suppression...
September 28, 2016: Biochemical Pharmacology
Iftikhar Ahmad Asim Syed, Syed Hasan Abbas Naqvi
Proton pump inhibitors are most widely prescribed medicines all over the world. Since their introduction in pharmacy, life of millions of people has changed completely. Their ability to inhibit acid secretion in stomach has changed the natural history of many once-dreaded conditions like peptic ulcer and gastroesophageal reflux disease. Operation like gastrectomy and partial gastrectomy are carried out very rarely. These medicines are considered very cost-effective, have excellent safety profile, and provide prompt symptomatic relief...
October 2016: JPMA. the Journal of the Pakistan Medical Association
Taejong Song, Hye-Kyung Jeon, Ji Eun Hong, Jung-Joo Choi, Tae-Joong Kim, Chel Hun Choi, Duk-Soo Bae, Byoung-Gie Kim, Jeong-Won Lee
Purpose: This study was conducted to investigate whether a proton pump inhibitor (PPI) could enhance chemosensitivity via the inhibition of vacuolar-type H+ ATPase (V-ATPase) in cervical cancer. Materials and Methods: The expression of V-ATPase was evaluated in 351 formalin-fixed, paraffin-embedded human cervical cancer tissues using immunohistochemistry and compared with clinicopathologic risk factors for disease prognosis. The influence of cell proliferation and apoptosis following V-ATPase siRNA transfection or esomeprazole pretreatment was assessed in cervical cancer cell lines using MTT and ELSIA assay, respectively...
September 27, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Venkat Reddy Pannala, Amadou K S Camara, Ranjan K Dash
Cytochrome c oxidase (CcO) catalyzes the exothermic reduction of O2 to H2O by utilizing electrons from cytochrome c, and hence plays a crucial role in ATP production. Although details on the enzyme structure and redox centers involved in O2 reduction have been known, there still remains a considerable ambiguity on its mechanism of action, e.g. the number of sequential electrons donated to O2 in each catalytic step, the sites of protonation and proton pumping, and nitric oxide (NO) inhibition mechanism. In this work, we developed a thermodynamically-constrained mechanistic mathematical model for the catalytic action of CcO based on available kinetic data...
September 15, 2016: Journal of Applied Physiology
Elena G Govorunova, Shane R Cunha, Oleg A Sineshchekov, John L Spudich
Optical control of the heart muscle is a promising strategy for cardiology because it is more specific than traditional electrical stimulation, and allows a higher temporal resolution than pharmacological interventions. Anion channelrhodopsins (ACRs) from cryptophyte algae expressed in cultured neonatal rat ventricular cardiomyocytes produced inhibitory currents at less than one-thousandth of the light intensity required by previously available optogenetic tools, such as the proton pump archaerhodopsin-3 (Arch)...
2016: Scientific Reports
Morten Würtz, Erik L Grove
Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular diseases. Upper gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed.PPIs provide gastroprotection by changing the intragastric milieu, essentially by raising intragastric pH. In recent years, it has been heavily discussed whether PPIs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel...
September 15, 2016: Advances in Experimental Medicine and Biology
Mitchell L Schubert
PURPOSE OF REVIEW: The present review summarizes the past year's literature, both clinical and basic science, regarding neuroendocrine and intracellular regulation of gastric acid secretion and proper use of antisecretory medications. RECENT FINDINGS: Gastric acid kills microorganisms, modulates the gut microbiome, assists in digestion of protein, and facilitates absorption of iron, calcium, and vitamin B12. The main stimulants of acid secretion are gastrin, released from antral G cells; histamine, released from oxyntic enterochromaffin-like cells; and acetylcholine, released from antral and oxyntic intramural neurons...
November 2016: Current Opinion in Gastroenterology
Camillo Benetti, Lisa Flammini, Valentina Vivo, Paolo Colombo, Gaia Colombo, Lisa Elviri, Carmelo Scarpignato, Francesca Buttini, Ruggero Bettini, Elisabetta Barocelli, Alessandra Rossi
The aim of this work was to study the esomeprazole activity on the control of gastric secretion after administration of a novel immediate release tablet. The ex vivo permeation of esomeprazole across porcine gastric mucosa from immediate release tablets, containing sodium carbonate or magnesium oxide as alkalinizing agents, was firstly assessed. Pharmacokinetics and pharmacodynamics studies in conscious rats following the administration of immediate release tablets with sodium carbonate, in comparison with delayed-release tablets having the same formula, were also conducted...
October 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Xingyang Yi, Qiang Zhou, Chun Wang, Jing Lin, Wen Cheng, Lifen Chi
BACKGROUND AND PURPOSE: Conflicting data exist as to whether proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel. We, therefore, assessed the effect of concomitant PPI use in ischemic stroke (IS) patients receiving clopidogrel. METHODS: We consecutively enrolled 535 IS patients receiving clopidogrel, 166 of whom were concomitantly taking PPIs. Platelet aggregation was measured before and after 7-10 days of treatment with clopidogrel. Single nucleotide polymorphisms of CYP3A4, CYP3A5, CYP2C19*2, and CYP2C19*3 were examined...
August 18, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Lucas C Pinheiro, Gustavo H Oliveira-Paula, Rafael L Portella, Danielle A Guimarães, Celio D de Angelis, Jose E Tanus-Santos
Proton pump inhibitors (PPIs) are widely used drugs that may increase the cardiovascular risk by mechanisms not entirely known. While PPIs increase asymmetric dimethylarginine (ADMA) levels and inhibit nitric oxide production, it is unknown whether impaired vascular redox biology resulting of increased xanthine oxidoreductase (XOR) activity mediates PPIs-induced endothelial dysfunction (ED). We examined whether increased XOR activity impairs vascular redox biology and causes ED in rats treated with omeprazole...
August 4, 2016: Redox Biology
Nobuhiro Inatomi, Jun Matsukawa, Yuuichi Sakurai, Kazuyoshi Otake
Acid-related diseases (ARDs), such as peptic ulcers and gastroesophageal reflux disease, represent a major health-care concern. Some major milestones in our understanding of gastric acid secretion and ARD treatment reached during the last 50years include 1) discovery of histamine H2-receptors and development of H2-receptor antagonists, 2) identification of H(+),K(+)-ATPase as the parietal cell proton pump and development of proton pump inhibitors (PPIs), and 3) identification of Helicobacter pylori (H. pylori) as the major cause of peptic ulcers and development of effective eradication regimens...
August 8, 2016: Pharmacology & Therapeutics
Joachim Mössner
BACKGROUND: Proton pump inhibitors (PPI) are the most effective drugs for inhibiting gastric acid secretion. They have been in clinical use for more than 25 years, In 2014, 3.475 billion daily defined doses (DDD) of PPI were prescribed in Germany. This high number alone calls for a critical analysis of the spectrum of indications for PPI and their potential adverse effects. METHODS: This review is based on pertinent publications retrieved by a selective search in the PubMed and Cochrane Library databases, with particular emphasis on randomized, prospective multicenter trials, cohort studies, case-control studies, and meta-analyses...
July 11, 2016: Deutsches Ärzteblatt International
Kenji Ikemura, Yugo Hamada, Chinatsu Kaya, Tomoyuki Enokiya, Yuichi Muraki, Hiroki Nakahara, Hajime Fujimoto, Tetsu Kobayashi, Takuya Iwamoto, Masahiro Okuda
Pemetrexed, a multitargeted antifolate, is eliminated by tubular secretion via human organic anion transporter 3 (hOAT3). Although proton pump inhibitors (PPIs) are frequently used in cancer patients, the drug interaction between PPIs and pemetrexed remains to be clarified. In this study, we examined the drug interaction between pemetrexed and PPIs in hOAT3-expressing cultured cells, and retrospectively analyzed the impact of PPIs on the development of hematologic toxicity in 108 patients who received pemetrexed and carboplatin treatment of nonsquamous non-small cell lung cancer for the first time between January 2011 and June 2015...
October 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Hideaki Tanaka, Kouji Masumoto, Takato Sasaki, Naoya Sakamoto, Chikashi Gotoh, Yasuhisa Urita, Toko Shinkai, Hajime Takayasu, Noriyuki Nakano, Masayuki Noguchi, Toyoichiro Kudo
BACKGROUND: Hypergastrinemia and the resultant peptic ulcer related to an enteric duplication has been quite rarely reported in the literature. CASE PRESENTATION: We herein report the case of a 4-year-old girl who presented with hypergastrinemia and a duodenal ulcer at 2 years of age. She had been followed up with a proton pump inhibitor, which resulted in resolution of the ulcer; however, unexplained hypergastrinemia had continued. A cystic lesion at the antrum was discovered at 4 years of age, which we suspected to be a gastric duplication...
December 2016: Surgical Case Reports
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