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Gastrin AND PPI

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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
#1
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/27698822/bioinformatics-analysis-of-the-molecular-mechanism-of-diffuse-intrinsic-pontine-glioma
#2
Lei Deng, Pengju Xiong, Yunhui Luo, Xiao Bu, Suokai Qian, Wuzhao Zhong
The present study aimed to elucidate key molecular mechanisms in the progression of diffuse intrinsic pontine glioma (DIPG). The gene expression profile GSE50021, which consisted of 35 pediatric DIPG samples and 10 normal brain samples, was downloaded from the Gene Expression Omnibus database. The differentially-expressed genes (DEGs) in the pediatric DIPG samples were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathways of DEGs were enriched and analyzed. The protein-protein interaction (PPI) network of the DEGs was constructed and functional modules of the PPI network were disclosed using ClusterONE...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27607343/gastric-acid-secretion
#3
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
https://www.readbyqxmd.com/read/27591354/gastrin-and-upper-gi-cancers
#4
Yoku Hayakawa, Wenju Chang, Guangchun Jin, Timothy C Wang
Gastrin was initially identified as the hormone primarily responsible for gastric acid secretion, but was subsequently shown to be a growth factor for the proximal stomach, acting through the gastrin receptor CCK2R. Studies in the past several decades have explored the role of gastrin, along with its incompletely processed precursors, in cancer development. The growth in long-term PPI use has frequently led to elevations in serum gastrin levels in patients with upper GI disease, including GERD, peptic ulcers, and chronic gastritis...
August 31, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27581154/identification-of-key-pathways-and-genes-in-colorectal-cancer-using-bioinformatics-analysis
#5
Bin Liang, Chunning Li, Jianying Zhao
Colorectal cancer (CRC) is the most common malignant tumor of digestive system. The aim of this study was to identify gene signatures during CRC and uncover their potential mechanisms. The gene expression profiles of GSE21815 were downloaded from GEO database. The GSE21815 dataset contained 141 samples, including 132 CRC and 9 normal colon epitheliums. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software...
October 2016: Medical Oncology
https://www.readbyqxmd.com/read/27562401/impact-of-proton-pump-inhibitor-treatment-on-pancreatic-beta-cell-area-and-beta-cell-proliferation-in-humans
#6
Thomas G K Breuer, Laura Borker, Daniel R Quast, Andrea Tannapfel, Wolfgang E Schmidt, Waldemar Uhl, Juris J Meier
INTRODUCTION: Gastrin has been shown to promote beta-cell proliferation in rodents, but its effects in adult humans are largely unclear. Proton pump inhibitors (PPIs) lead to endogenous hypergastrinaemia, and improved glucose control during PPI therapy has been reported in patients with diabetes. Therefore, we addressed whether PPI treatment is associated with improved glucose homoeostasis, islet cell hyperplasia or increased new beta-cell formation in humans. PATIENTS AND METHODS: Pancreatic tissue specimens from 60 patients with and 33 patients without previous PPI therapy were examined...
November 2016: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27448962/gastrin-stimulates-a-cholecystokinin-2-receptor-expressing-cardia-progenitor-cell-and-promotes-progression-of-barrett-s-like-esophagus
#7
Yoomi Lee, Aleksandra M Urbanska, Yoku Hayakawa, Hongshan Wang, Andrew S Au, Aesis M Luna, Wenju Chang, Guangchun Jin, Govind Bhagat, Julian A Abrams, Richard A Friedman, Andrea Varro, Kenneth K Wang, Malcolm Boyce, Anil K Rustgi, Antonia R Sepulveda, Michael Quante, Timothy C Wang
OBJECTIVE: The incidence of esophageal adenocarcinoma (EAC) is increasing, but factors contributing to malignant progression of its precursor lesion, Barrett's esophagus (BE), have not been defined. Hypergastrinemia caused by long-term use of proton pump inhibitors (PPIs), has been suggested as one possible risk factor. The gastrin receptor, CCK2R, is expressed in the cardia and upregulated in BE, suggesting the involvement of the gastrin-CCK2R pathway in progression. In the L2-IL-1β mouse model, Barrett's-like esophagus arises from the gastric cardia...
July 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27159420/study-of-gender-differences-in-proton-pump-inhibitor-dose-requirements-for-gerd-a-double-blind-randomized-trial
#8
Hólmfridur Helgadóttir, David C Metz, Sigrún H Lund, Sveinbjorn Gizurarson, Elin I Jacobsen, Gudrún A Asgeirsdóttir, Yrsa Yngadóttir, Einar S Björnsson
GOALS: To determine the proportion of patients with gastroesophageal reflux disease who are on proton pump inhibitors (PPIs) who could reduce their prior dosage by half, and identify predictors of successful step-down. BACKGROUND: Appropriate hypergastrinemia results from gastric acid inhibition. A gender difference in fasting gastrin with higher levels among women than among men on long-term PPI therapy has been demonstrated. STUDY: Patients with endoscopically verified erosive esophagitis on long-term PPI therapy were randomized double blindly to step down their dose by half or continue with the same dose for 8 weeks...
May 6, 2016: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/27062346/a-prospective-placebo-controlled-pilot-evaluation-of-the-effect-of-omeprazole-on-serum-calcium-magnesium-cobalamin-gastrin-concentrations-and-bone-in-cats
#9
E Gould, C Clements, A Reed, L Giori, J M Steiner, J A Lidbury, J S Suchodolski, M Brand, T Moyers, L Emery, M K Tolbert
BACKGROUND: Chronic proton pump inhibitor administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hypergastrinemia, and rebound acid hypersecretion in humans. It is unknown if this occurs in cats. OBJECTIVES: Prolonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats. ANIMALS: Six healthy adult DSH cats...
May 2016: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/26376477/functional-anatomy-and-physiology-of-gastric-secretion
#10
REVIEW
Mitchell L Schubert
PURPOSE OF REVIEW: This review summarizes the past year's literature regarding the neuroendocrine and intracellular regulation of gastric acid secretion, discussing both basic and clinical aspects. RECENT FINDINGS: Gastric acid facilitates the digestion of protein as well as the absorption of iron, calcium, vitamin B12, and certain medications. High acidity kills ingested microorganisms and limits bacterial overgrowth, enteric infection, and possibly spontaneous bacterial peritonitis...
November 2015: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/26369775/the-first-in-class-potassium-competitive-acid-blocker-vonoprazan-fumarate-pharmacokinetic-and-pharmacodynamic-considerations
#11
Hirotoshi Echizen
Vonoprazan fumarate (Takecab) is a first-in-class potassium-competitive acid blocker that has been available in the market in Japan since February 2015. Vonoprazan is administered orally at 20 mg once daily for the treatment of gastroduodenal ulcer, at 20 and 10 mg once daily for the treatment and secondary prevention of reflux esophagitis, respectively, at 10 mg once daily for the secondary prevention of low-dose aspirin- or non-steroidal anti-inflammatory drug-induced peptic ulcer, and at 20 mg twice daily in combination with clarithromycin and amoxicillin for the eradication of Helicobacter pylori...
April 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/26342486/gastric-hypersecretory-states-investigation-and-management
#12
Jennifer Phan, Jihane N Benhammou, Joseph R Pisegna
Hypersecretory conditions affecting the stomach account for significant morbidity and mortality manifested in some cases with peptic ulcer, gastrointestinal hemorrhage, and/or gastroesophageal reflux disease (GERD). The diagnosis of gastric acid hypersecretory states can be challenging and relies on the use of quantitative assays to measure gastric acid secretion and serum gastrin. The most common etiology for hypergastrinemia is the use of potent gastric acid inhibitors such as the proton pump inhibitors. The differential diagnosis of this condition is of critical importance, and will dictate management decisions...
December 2015: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/26240800/diagnostic-and-treatment-approaches-for-refractory-peptic-ulcers
#13
REVIEW
Heung Up Kim
Refractory peptic ulcers are defined as ulcers that do not heal completely after 8 to 12 weeks of standard anti-secretory drug treatment. The most common causes of refractory ulcers are persistent Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Simultaneous use of two or more H. pylori diagnostic methods are recommended for increased sensitivity. Serologic tests may be useful for patients currently taking proton pump inhibitors (PPIs) or for suspected false negative results, as they are not affected by PPI use...
July 2015: Clinical Endoscopy
https://www.readbyqxmd.com/read/26177572/systematic-review-the-effects-of-long-term-proton-pump-inhibitor-use-on-serum-gastrin-levels-and-gastric-histology
#14
REVIEW
L Lundell, M Vieth, F Gibson, P Nagy, P J Kahrilas
BACKGROUND: Proton pump inhibitors (PPIs) have a well-established safety profile. However, concerns have been raised about a potential relationship between PPI-induced hypergastrinaemia and the development of enterochromaffin-like (ECL) cell hyperplasia, neuroendocrine tumours and gastric cancer during long-term therapy. AIM: To review the effects of long-term PPI use on serum gastrin levels and gastric histopathology. METHODS: A systematic literature search was conducted in PubMed on 21 April 2015 to identify studies reporting the effects of long-term (defined as >3 years) PPI use on gastrin levels and gastric histopathology...
September 2015: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/26111126/safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-single-rising-tak-438-vonoprazan-doses-in-healthy-male-japanese-non-japanese-subjects
#15
Yuuichi Sakurai, Akira Nishimura, Gale Kennedy, Mark Hibberd, Richard Jenkins, Hiroyuki Okamoto, Tomoki Yoneyama, Helen Jenkins, Kiyoshi Ashida, Shin Irie, Jörg Täubel
OBJECTIVES: To evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-438 (vonoprazan, a potassium-competitive acid blocker) in healthy male subjects. METHODS: In two phase I, randomized, double-blind, placebo-controlled, single rising-dose studies, healthy male subjects (Japan N=84; UK N=63) received a single TAK-438 dose (1-120 mg in Japan and 1-40 mg in the UK). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (intragastric pH)...
2015: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/26059834/gastric-neuroendocrine-neoplasms-and-proton-pump-inhibitors-fact-or-coincidence
#16
Federica Cavalcoli, Alessandra Zilli, Dario Conte, Clorinda Ciafardini, Sara Massironi
OBJECTIVE: Reporting on three cases of gastric neuroendocrine tumors (g-NETs) in patients taking long-term proton pump inhibitors (PPIs). These tumors are not classifiable considering current criteria. g-NETs are currently grouped as: types 1 and 2, related to hypergastrinemia due to chronic atrophic gastritis and Zollinger-Ellison syndrome respectively, and type 3, normogastrinemic and more aggressive. Although the g-NETs onset in patients taking PPIs is biologically plausible, only a few cases have been reported so far...
2015: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/26017085/endoscopic-and-histopathologic-gastric-changes-in-chronic-users-of-proton-pump-inhibitors
#17
Sílvia Maria Perrone Camilo, Élia Cláudia de Souza Almeida, Benito André Silveira Miranzi, Juliano Carvalho Silva, Rosemary Simões Nomelini, Renata Margarida Etchebehere
BACKGROUND: Proton-pump inhibitors have been used for at least two decades. They are among the most commonly sold drugs in the world. However, some controversy remains about the indications for their use and the consequences of their prolonged use. OBJECTIVES: To evaluate and compare the endoscopic and histopathologic gastric changes in chronic users of proton-pump inhibitors to changes in non-users. METHODS: A prospective study performed at a tertiary Public Hospital involving 105 patients undergoing upper-gastrointestinal endoscopy...
January 2015: Arquivos de Gastroenterologia
https://www.readbyqxmd.com/read/25977510/gastrin-stimulates-mmp-1-expression-in-gastric-epithelial-cells-putative-role-in-gastric-epithelial-cell-migration
#18
J Dinesh Kumar, Islay Steele, Andrew R Moore, Senthil V Murugesan, Zoltan Rakonczay, Viktoria Venglovecz, D Mark Pritchard, Rodney Dimaline, Laszlo Tiszlavicz, Andrea Varro, Graham J Dockray
The pyloric antral hormone gastrin plays a role in remodeling of the gastric epithelium, but the specific targets of gastrin that mediate these effects are poorly understood. Glandular epithelial cells of the gastric corpus express matrix metalloproteinase (MMP)-1, which is a potential determinant of tissue remodeling; some of these cells express the CCK-2 receptor at which gastrin acts. We have now examined the hypothesis that gastrin stimulates expression of MMP-1 in the stomach. We determined MMP-1 transcript abundance in gastric mucosal biopsies from Helicobacter pylori negative human subjects with normal gastric mucosal histology, who had a range of serum gastrin concentrations due in part to treatment with proton pump inhibitors (PPI)...
July 15, 2015: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/25903947/role-of-proton-pump-inhibitors-in-preventing-hypergastrinemia-associated-carcinogenesis-and-in-antagonizing-the-trophic-effect-of-gastrin
#19
REVIEW
Y-M Han, J-M Park, N Kangwan, M Jeong, S Lee, J Y Cho, W J Ko, K B Hahm
Gastrin is the main hormone stimulating gastric acid secretion, but it exerts proliferative and anti-apoptotic actions on various cancer cell types, in addition to its well-known trophic effect on enterochromaffin-like cells. As treatment with proton pump inhibitors (PPIs) increases the biosynthesis and secretion of gastrin, it has been postulated that treatment with PPIs could increase the risk of cancer, especially in Barrett's esophagus, gastric carcinoids, and colorectal cancer (CRC). Some tumors produce gastrin of their own, which can act in an autocrine manner to promote tumor growth...
April 2015: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/25858519/long-term-safety-of-proton-pump-inhibitor-therapy-assessed-under-controlled-randomised-clinical-trial-conditions-data-from-the-sopran-and-lotus-studies
#20
COMPARATIVE STUDY
S E Attwood, C Ell, J P Galmiche, R Fiocca, J G Hatlebakk, B Hasselgren, G Långström, M Jahreskog, S Eklund, T Lind, L Lundell
BACKGROUND: Control of chronic gastro-oesophageal reflux disease may be achieved either by anti-reflux surgery (ARS) or by long-term medical therapy with proton pump inhibitors (PPIs). The primary efficacy results of the SOPRAN study, comparing long-term omeprazole use with open ARS, and the LOTUS study, comparing long-term esomeprazole use with laparoscopic ARS, have been reported. A secondary objective of these studies was to address the long-term safety of these respective therapeutic strategies and thereby provide a valid scientific platform for assessing long-term PPI safety...
June 2015: Alimentary Pharmacology & Therapeutics
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