W1720 Effects of Proton Pump Inhibitors on Healing of NSAID-Induced Gastric Ulcerations in the Presence of a Continued NSAID Treatment: Characterization of Molecular Mechanisms

Proton-pump inhibitors (PPIs), such as omeprazole, lansoprazole and rabeprazole, are used for the treatment of gastroesophageal reflux disease and peptic ulcer disease. The use of PPIs has increased, especially in older individuals, and a pharmacoepidemiological study indicated the use of PPIs peaks in people aged 80 years or older. In this population, Alzheimer's disease (AD) is a common neurological disorder and type of dementia, occurring with a frequency of approximately 10%. Currently, over 45 million people are estimated to have dementia worldwide, and it is a major cause of death in the elderly. Recent clinical studies have indicated that chronic use of PPIs can be a risk factor for increased incidence of dementia, including AD. Potential molecular mechanisms related to the pathophysiology of AD (e.g., modulation of amyloid protein processing) have also been reported in both in vitro and in vivo studies. Although the clinical implications of these results are inconclusive, a literature review of the current knowledge is important for future basic and clinical research. This review summarizes the possible mechanisms connecting the use of PPIs and the incidence of AD. Additionally, we summarize results from clinical studies to highlight the influence in humans.

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Underuse of proton-pump inhibitors in older patients newly starting NSAID treatment

International Journal of Clinical Practice ◽

10.1111/ijcp.12611 ◽

2015 ◽

Vol 69 (7) ◽

pp. 791-795 ◽

Cited By ~ 7

Author(s):

F. Hoffmann ◽

G. Glaeske ◽

G. Schmiemann

Keyword(s):

Proton Pump Inhibitors ◽

Proton Pump ◽

Older Patients ◽

Nsaid Treatment

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Molecular mechanisms involved in anti-inflammatory effects of proton pump inhibitors

Inflammation Research ◽

10.1007/s00011-006-6056-4 ◽

2006 ◽

Vol 55 (11) ◽

pp. 476-480 ◽

Cited By ~ 68

Author(s):

O. Handa ◽

N. Yoshida ◽

N. Fujita ◽

Y. Tanaka ◽

M. Ueda ◽

...

Keyword(s):

Proton Pump Inhibitors ◽

Proton Pump ◽

Molecular Mechanisms ◽

Anti Inflammatory

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Histopathologic and Immunohistochemical Characterization of Human Gastric Oxyntic Mucosa with Parietal Cell Protrusions and Investigation into the Association Between Such Mucosal Changes of the Stomach and Use of Proton Pump Inhibitors

Journal of St Marianna University ◽

10.17264/stmarieng.6.119 ◽

2015 ◽

Vol 6 (2) ◽

pp. 119-130 ◽

Cited By ~ 7

Author(s):

Saeko Naruki ◽

Takashi Fujino ◽

Shigeko Ohnuma ◽

Akira Endo ◽

Hirotaka Koizumi ◽

...

Keyword(s):

Proton Pump Inhibitors ◽

Parietal Cell ◽

Proton Pump ◽

Oxyntic Mucosa ◽

Mucosal Changes

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444 - Characterization of Conditions Underlying Heartburn Refractory to Proton Pump Inhibitors (PPIS) in a VA Cooperative Study of Medical and Surgical Treatments for PPI-Refractory Heartburn

Gastroenterology ◽

10.1016/s0016-5085(18)30778-9 ◽

2018 ◽

Vol 154 (6) ◽

pp. S-101-S-102

Author(s):

Stuart J. Spechler ◽

Robert H. Lee ◽

Brian R. Smith ◽

Hiroshi Mashimo ◽

Vivian Sanchez ◽

...

Keyword(s):

Proton Pump Inhibitors ◽

Proton Pump ◽

Cooperative Study ◽

Surgical Treatments

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Proton Pump Inhibitors and Radiofrequency Ablation for Treatment of Barrett's Esophagus

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666191015203636 ◽

2020 ◽

Vol 20 (11) ◽

pp. 975-987 ◽

Cited By ~ 1

Author(s):

Predrag Dugalic ◽

Srdjan Djuranovic ◽

Aleksandra Pavlovic-Markovic ◽

Vladimir Dugalic ◽

Ratko Tomasevic ◽

...

Keyword(s):

Proton Pump Inhibitors ◽

Proton Pump ◽

Molecular Mechanisms ◽

Bile Reflux ◽

Gastrin Level ◽

White Light Endoscopy ◽

Total Fundoplication ◽

Wide Range ◽

Mucosal Necrosis ◽

Ablative Techniques

Gastroesophageal Reflux Disease (GERD) is characterized by acid and bile reflux in the distal oesophagus, and this may cause the development of reflux esophagitis and Barrett’s oesophagus (BE). The natural histological course of untreated BE is non-dysplastic or benign BE (ND), then lowgrade (LGD) and High-Grade Dysplastic (HGD) BE, with the expected increase in malignancy transfer to oesophagal adenocarcinoma (EAC). The gold standard for BE diagnostics involves high-resolution white-light endoscopy, followed by uniform endoscopy findings description (Prague classification) with biopsy performance according to Seattle protocol. The medical treatment of GERD and BE includes the use of proton pump inhibitors (PPIs) regarding symptoms control. It is noteworthy that long-term use of PPIs increases gastrin level, which can contribute to transfer from BE to EAC, as a result of its effects on the proliferation of BE epithelium. Endoscopy treatment includes a wide range of resection and ablative techniques, such as radio-frequency ablation (RFA), often concomitantly used in everyday endoscopy practice (multimodal therapy). RFA promotes mucosal necrosis of treated oesophagal region via high-frequency energy. Laparoscopic surgery, partial or total fundoplication, is reserved for PPIs and endoscopy indolent patients or in those with progressive disease. This review aims to explain distinct effects of PPIs and RFA modalities, illuminate certain aspects of molecular mechanisms involved, as well as the effects of their concomitant use regarding the treatment of BE and prevention of its transfer to EAC.

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