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Sample records for proton-pump inhibitor ppi

  1. Association of Proton Pump Inhibitor (PPI Use with Energy Intake, Physical Activity, and Weight Gain

    Directory of Open Access Journals (Sweden)

    Jennifer L. Czwornog

    2015-10-01

    Full Text Available Studies suggest proton pump inhibitor (PPI use impacts body weight regulation, though the effect of PPIs on energy intake, energy extraction, and energy expenditure is unknown. We used data on 3073 eligible adults from the National Health and Nutrition Examination Survey (NHANES. Medication use, energy intake, diet composition, and physical activity were extracted from NHANES. Multivariate regression models included confounding variables. Daily energy intake was similar between PPI users and non-users (p = 0.41. Diet composition was similar between the two groups, except that PPI users consumed a slightly greater proportion of calories from fat (34.5% vs. 33.2%; p = 0.02. PPI users rated themselves as being as physically active as their age/gender-matched peers and reported similar frequencies of walking or biking. However, PPI users were less likely to have participated in muscle-strengthening activities (OR: 0.53; 95% CI: 0.30–0.95. PPI users reported similar sedentary behaviors to non-users. Male PPI users had an increase in weight (of 1.52 ± 0.59 kg; p = 0.021 over the previous year compared to non-users, while female PPI users had a non-significant increase in weight. The potential mechanisms for PPI-associated weight gain are unclear as we did not find evidence for significant differences in energy intake or markers of energy expenditure.

  2. Dietary Inulin Fibers Prevent Proton-Pump Inhibitor (PPI)-Induced Hypocalcemia in Mice.

    Science.gov (United States)

    Hess, Mark W; de Baaij, Jeroen H F; Gommers, Lisanne M M; Hoenderop, Joost G J; Bindels, René J M

    2015-01-01

    Proton-pump inhibitor-induced hypomagnesemia (PPIH) is the most recognized side effect of proton-pump inhibitors (PPIs). Additionally, PPIH is associated with hypocalcemia and hypokalemia. It is hypothesized that PPIs reduce epithelial proton secretion and thereby increase the pH in the colon, which may explain the reduced absorption of and Mg2+ and Ca2+. Fermentation of dietary oligofructose-enriched inulin fibers by the microflora leads to acidification of the intestinal lumen and by this enhances mineral uptake. This study aimed, therefore, to improve mineral absorption by application of dietary inulin to counteract PPIH. Here, C57BL/J6 mice were supplemented with omeprazole and/or inulin. Subsequently, Mg2+ and Ca2+ homeostasis was assessed by means of serum, urine and fecal electrolyte measurements. Moreover, the mRNA levels of magnesiotropic and calciotropic genes were examined in the large intestine and kidney by real-time PCR. Treatment with omeprazole significantly reduced serum Mg2+ and Ca2+ levels. However, concomitant addition of dietary inulin fibers normalized serum Ca2+ but not serum Mg2+ concentrations. Inulin abolished enhanced expression of Trpv6 and S100g in the colon by omeprazole. Additionally, intestinal and renal mRNA levels of the Trpm6 gene were reduced after inulin intake. This study suggests that dietary inulin counteracts reduced intestinal Ca2+ absorption upon PPI treatment. In contrast, inulin did not increase intestinal absorption of Mg2+ sufficiently to recover serum Mg2+. The clinical potential of dietary inulin treatment should be the subject of future studies.

  3. Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy

    OpenAIRE

    Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

    2016-01-01

    Background/Aims The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups recei...

  4. Proton pump inhibitors and osteoporosis

    DEFF Research Database (Denmark)

    Andersen, Bjarne Nesgaard; Johansen, Per Birger; Abrahamsen, Bo

    2016-01-01

    PURPOSE OF REVIEW: The purpose of the review is to provide an update on recent advances in the evidence based on proton pump inhibitors (PPI) as a possible cause of osteoporosis and osteoporotic fractures. This review focuses, in particular, on new studies published in the last 18 months and a di......PURPOSE OF REVIEW: The purpose of the review is to provide an update on recent advances in the evidence based on proton pump inhibitors (PPI) as a possible cause of osteoporosis and osteoporotic fractures. This review focuses, in particular, on new studies published in the last 18 months...... and a discussion of these findings and how this has influenced our understanding of this association, the clinical impact and the underlying pathophysiology. RECENT FINDINGS: New studies have further strengthened existing evidence linking use of PPIs to osteoporosis. Short-term use does not appear to pose a lower...... risk than long-term use. There is a continued lack of conclusive studies identifying the pathogenesis. Direct effects on calcium absorption or on osteoblast or osteoclast action cannot at present plausibly explain the mechanism. SUMMARY: The use of PPIs is a risk factor for development of osteoporosis...

  5. Proton pump inhibitors affect the gut microbiome

    NARCIS (Netherlands)

    Imhann, Floris; Bonder, Marc Jan; Vich Vila, Arnau; Fu, Jingyuan; Mujagic, Zlatan; Vork, Lisa; Feenstra, Ettje T.; Jankipersadsing, Soesma A; Cenit, Maria Carmen; Harmsen, Hermie J M; Dijkstra, Gerard; Franke, Lude; Xavier, Ramnik J; Jonkers, Daisy; Wijmenga, Cisca; Weersma, Rinse K; Zhernakova, Alexandra

    BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or

  6. Negative Effect of Proton-pump Inhibitors (PPIs) on Helicobacter pylori Growth, Morphology, and Urease Test and Recovery after PPI Removal--An In vitro Study.

    Science.gov (United States)

    Saniee, Parastoo; Shahreza, Somayeh; Siavoshi, Farideh

    2016-04-01

    Proton-pump inhibitor (PPI) consumption does lead to false-negative results of Helicobacter pylori diagnostic tests such as biopsy culture and rapid urease test (RUT). Helicobacter pylori isolates from 112 dyspeptic patients with (56.5%) or without (43.5%) PPI consumption were recruited for examining the negative effects of omeprazole (OMP), lansoprazole (LPZ), and pantoprazole (PAN) on H. pylori viability, morphology, and urease, in vitro. The effect of a sublethal concentration of OMP on bacterial features and their recovery after removal of OMP was also assessed. Of 112 culture-positive gastric biopsies, 87.5% were RUT positive and 12.5% RUT negative. There was a significant correlation between negative RUT results and PPI consumption (p urease of 90.3% of isolates between 0 and 40 minutes and 54.4% between 20 and 40 minutes, respectively. PAN did not inhibit H. pylori growth and urease. Three 3-day (9 days) consecutive subcultures of H. pylori on brucella blood agar (BBA) supplemented with OMP resulted in reduced bacterial viability (1+), compared with control (4+), change of spiral morphology to coccoid, and reduction in pink color intensity in urea agar. Bacterial growth (1+), morphology, and urease test did not improve after the first 3-day and second 3-day (6 days) subcultures on BBA. However, relative recovery occurred after the third 3-day (9 days) subculture and complete recovery was observed after the fourth 3-day (12 days) subculture, as confluent growth (4+), 100% spiral cells, and strong urease test. Proton-pump Inhibitors exert transient negative effects on H. pylori viability, morphology, and urease test. Accordingly, cessation of PPI consumption at least 12 days before endoscopy could help avoiding false-negative results of H. pylori diagnostic tests. © 2015 John Wiley & Sons Ltd.

  7. Proton pump inhibitors and gastroenteritis

    International Nuclear Information System (INIS)

    Hassing, Robert-Jan; Verbon, Annelies; Visser, Herman de; Hofman, Albert; Stricker, Bruno H.

    2016-01-01

    An association between proton pump inhibitor (PPI) therapy and bacterial gastroenteritis has been suggested as well as contradicted. The aim of this study was to examine the association between the use of PPIs and occurrence of bacterial gastroenteritis in the prospective Rotterdam Study. The Rotterdam Study is a population-based cohort study among 14,926 subjects aged 45 years and older with up to 24 years of follow-up. Analyses were performed with a generalized estimating equations method in participants who handed-in a diagnostic stool sample. Furthermore, a nested case–control analysis was performed using the total cohort as a reference group. A bacterial microorganism was isolated in 125 samples, whereas 1174 samples were culture negative. In the generalized estimating equations analysis, we found that participants with a bacterial gastroenteritis were more likely than controls to be current users of PPIs (adjusted OR 1.94; 95 % CI 1.15–3.25). Different sensitivity analyses did not change this result. A considerably higher effect was observed (adjusted OR 6.14; 95 % CI 3.81–9.91), using the total cohort as a reference in a nested case–control analysis. Current PPI therapy is associated with an increased risk of bacterial gastroenteritis. However, by reducing the risk of selection and information bias in our study design, we demonstrated that the effect is lower than previously assumed.

  8. Use of proton pump inhibitors after anti-reflux surgery

    DEFF Research Database (Denmark)

    Lodrup, A.; Pottegård, Anton; Hallas, J.

    2014-01-01

    Objective Antireflux surgery (ARS) has been suggested as an alternative to lifelong use of proton pump inhibitors (PPI) in reflux disease. Data from clinical trials on PPI use after ARS have been conflicting. We investigated PPI use after ARS in the general Danish population using nationwide...

  9. Proton-pump inhibitors

    African Journals Online (AJOL)

    chronic pancreatitis, diabetic gastroparesis, and a number of medications. Frequently ... PPI prophylaxis in those who have additional risk factors for gastrointestinal bleeding. ... PPIs are associated with the increased development of gastric.

  10. Proton Pump Inhibitors and Risk of Rhabdomyolysis.

    Science.gov (United States)

    Duncan, Scott J; Howden, Colin W

    2017-01-01

    Proton pump inhibitors (PPIs) have been associated with a variety of adverse events, although the level of evidence for many of these is weak at best. Recently, one national regulatory authority has mandated a change to the labeling of one PPI based on reports of possible associated rhabdomyolysis. Thus, in this review we summarize the available evidence linking PPI use with rhabdomyolysis. The level of evidence is insufficient to establish a causal relationship and is largely based on sporadic case reports. In general, patients with suspected PPI-associated rhabdomyolysis have not been re-challenged with a PPI after recovery. The mechanism whereby PPIs might have been associated with rhabdomyolysis is unclear but possibly related to interaction with concomitantly administered drugs such as HMG-CoA reductase inhibitors (statins). For patients with rhabdomyolysis, a careful search must be made for possible etiological factors. In patients who recover from an episode of possible PPI-related rhabdomyolysis but do not have a genuine requirement for PPI treatment, the PPI should not be re-introduced. For those with a definite indication for ongoing PPI treatment, the PPI can be re-introduced but should preferably not be administered with a statin.

  11. Proton pump inhibitors: potential cost reductions by applying prescribing guidelines.

    LENUS (Irish Health Repository)

    Cahir, Caitriona

    2012-01-01

    There are concerns that proton pump inhibitors (PPI) are being over prescribed in both primary and secondary care. This study aims to establish potential cost savings in a community drug scheme for a one year period according to published clinical and cost-effective guidelines for PPI prescribing.

  12. Three cases of radiation esophagitis controlled with proton pump inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, Ryuji; Saito, Ryuichi; Miyazaki, Toshiyuki [Kumamoto Red Cross Hospital (Japan)

    2002-04-01

    Radiation esophagitis sometimes interrupts the radiation therapy due to swallowing pain and dysplasia. We experienced three cases of radiation-induced esophagitis controlled with proton pump inhibitor (PPI). These cases suggested etiologic relationship radiation esophagitis and gastroesophageal reflux disease (GERD). We should consider PPI as treatment option for radiation esophagitis. (author)

  13. 1-Arylsulfonyl-2-(Pyridylmethylsulfinyl) Benzimidazoles as New Proton Pump Inhibitor Prodrugs

    Science.gov (United States)

    Shin, Jai Moo; Sachs, George; Cho, Young-moon; Garst, Michael

    2010-01-01

    New arylsulfonyl proton pump inhibitor (PPI) prodrug forms were synthesized. These prodrugs provided longer residence time of an effective PPI plasma concentration, resulting in better gastric acid inhibition. PMID:20032890

  14. Proton pump inhibitors inhibit pancreatic secretion

    DEFF Research Database (Denmark)

    Wang, Jing; Barbuskaite, Dagne; Tozzi, Marco

    2015-01-01

    +/K+-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar...... of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO3-, pancreas also secretes K+. In conclusion, this study calls for a revision of the basic model for HCO3- secretion. We propose that proton transport is driving secretion, and that in addition...

  15. Proton Pump Inhibitors in Gastroesophageal Reflux Disease: Friend or Foe.

    Science.gov (United States)

    Gyawali, C Prakash

    2017-09-01

    Proton pump inhibitor (PPI) use in gastroesophageal reflux disease (GERD) has been redefined, in light of recent advances highlighting GERD phenotypes that respond to PPIs, and fresh revelations of potential risks of long-term PPI therapy. Erosive esophagitis predicts excellent response to PPI therapy, but non-erosive reflux disease (NERD) with abnormal reflux parameters on ambulatory reflux monitoring also demonstrates a similar response. In contrast, response is suboptimal in the absence of abnormal reflux parameters. In this setting, if an alternate appropriate indication for PPI therapy does not coexist, risks may outweigh benefits of PPI therapy. Adverse events from long-term PPI therapy continue to be reported, most based on association rather than cause-and-effect. Appropriate indications need to be established before embarking on long-term PPI therapy. Future research will define true risks of long-term PPI therapy, and develop alternate management options for acid peptic diseases.

  16. Strategies for discontinuation of proton pump inhibitors

    DEFF Research Database (Denmark)

    Haastrup, Peter; Paulsen, Maja S; Begtrup, Luise M

    2014-01-01

    PURPOSE: Proton pump inhibitors (PPIs) are considered to be overprescribed. Consensus on how to attempt discontinuation is, however, lacking. We therefore conducted a systematic review of clinical studies on discontinuation of PPIs. METHODS: Systematic review based on clinical studies investigating...

  17. Bacterial infections in cirrhosis: Role of proton pump inhibitors and intestinal permeability

    NARCIS (Netherlands)

    L.G. van Vlerken (Lotte); E.J. Huisman (Ellen); B. van Hoek (Bart); W. Renooij (W.); F.W.M. de Rooij (Felix); P.D. Siersema (Peter); K.J. van Erpecum (Karel)

    2012-01-01

    textabstractBackground Cirrhotic patients are at considerable risk for bacterial infections, possibly through increased intestinal permeability and bacterial overgrowth. Proton pump inhibitors (PPIs) may increase infection risk. We aimed to explore the potential association between PPI use and

  18. Association Between Proton Pump Inhibitor Use and Spontaneous Bacterial Peritonitis in Cirrhotic Patients with Ascites

    Directory of Open Access Journals (Sweden)

    Mélissa Ratelle

    2014-01-01

    Full Text Available BACKGROUND: There are data suggesting a link between proton pump inhibitor (PPI use and the development of spontaneous bacterial peritonitis (SBP in cirrhotic patients with ascites; however, these data are controversial.

  19. The appropriateness of a proton pump inhibitor prescription.

    LENUS (Irish Health Repository)

    Moran, N

    2014-11-01

    Proton pump inhibitors (PPIs) are one of the most commonly prescribed groups of drug in Ireland, at great expense to the Irish healthcare executive. This study aims to evaluate the appropriateness of PPI prescriptions on admission and discharge in a tertiary referral hospital. All non-elective admissions in the Emergency Department in one week were included in the study. 102 patients in total were included, with 36 (35.4%) treated with a PPI on admission. Of these, only 3 (8.3%) had a clear indication noted as per current NICE guidelines. 18 new in-hospital PPI prescriptions were documented. 11 (61%) of which were present on discharge prescriptions. Continuing PPI prescription on discharge into the community may be inappropriate, costly and potentially harmful. Brief interventions aimed at reducing inappropriate PPI prescriptions have been shown to be effective at reducing the cost and potential harm of unnecessary treatment.

  20. Occupational Airborne Contact Dermatitis From Proton Pump Inhibitors.

    Science.gov (United States)

    DeKoven, Joel G; Yu, Ashley M

    2015-01-01

    Few published reports have described occupational contact dermatitis from proton pump inhibitor (PPI) exposure in the literature. We present an additional case of a 58-year-old male pharmaceutical worker with an occupational airborne allergic contact dermatitis to PPIs confirmed by patch testing. This is a novel report of workplace exposure to dexlansoprazole and esomeprazole PPIs with resultant clinical contact allergy and relevant positive patch test results to these 2 agents. A literature review of all previously reported cases of occupational contact dermatitis to PPI is summarized. The case also emphasizes the importance of even minute exposures when considering workplace accommodation.

  1. RENAL SAFETY OF PROTON PUMP INHIBITORS

    Directory of Open Access Journals (Sweden)

    A. I. Dyadyk

    2017-01-01

    Full Text Available Proton pump inhibitors are a widely used in clinical practice, and are taken by millions of patients around the world for a long time. While proton pump inhibitors are well-tolerated class of drugs, the number of publications has been raised about adverse renal effects, specially their association with acute tubulointerstitial nephritis. It is one of the leading causes of acute renal injury and have catastrophic long-term consequences called chronic kidney disease. In this review, we consider epidemiology, pathogenesis, diagnostic criteria (including biopsy and morphological pattern, clinical manifestations and treatment of proton pump inhibitors-induced acute tubulointerstitial nephritis. A subclinical course without classical manifestations of a cell-mediated hypersensitivity reaction (fever, skin rash, eosinophilia, arthralgia is characteristic of acute tubulointerstitial nephritis. Increased serum creatinine, decreased glomerular filtration rate, electrolyte disorders, pathological changes in urine tests are not highly specific indicators, but allow to suspect the development of acute tubulointerstitial nephritis. The “gold” standard of diagnosis is the intravital morphological examination of the kidney tissue. Timely diagnosis and immediate discontinuation of the potentially causative drug is the mainstay of therapy and the first necessary step in the early management of suspected or biopsy-proven drug-induced acute tubulointerstitial nephritis. The usage of proton pump inhibitors should be performed only on strict indications with optimal duration of treatment and careful monitoring of kidney function. Multiple comorbidities (older age, heart failure, diabetes, cirrhosis, chronic kidney disease, hypovolemia increase potential nephrotoxicity. Awareness of this iatrogenic complication will improve diagnosis of proton pump inhibitors-induced acute tubulointerstitial nephritis by multidisciplinary specialists and increase the possibility

  2. Limited ability of the proton-pump inhibitor test to identify patients with gastroesophageal reflux disease

    DEFF Research Database (Denmark)

    Bytzer, Peter; Jones, Roger; Vakil, Nimish

    2012-01-01

    The efficacy of proton-pump inhibitor (PPI) therapy often is assessed to determine whether patients' symptoms are acid-related and if patients have gastroesophageal reflux disease (GERD), although the accuracy of this approach is questionable. We evaluated the diagnostic performance of the PPI test...

  3. The safety of proton pump inhibitors in pregnancy

    DEFF Research Database (Denmark)

    Nielsen, Gunnar Lauge; Sørensen, Henrik Toft; Thulstrup, Ane Marie

    1999-01-01

    AIM: To assess the safety of proton pump inhibitors during pregnancy. METHODS: Fifty-one pregnant women exposed to proton pump inhibitors around the time of conception or during pregnancy were compared with 13 327 controls without exposure to any prescribed drug in a population-based study based...... birth weight or number of preterm deliveries in pregnancies exposed to proton pump inhibitors. However, further monitoring is warranted in order to establish or rule out a potential association between the use of proton pump inhibitors and increased risk of either cardiac malformations or preterm birth....

  4. Pharmacokinetics and pharmacodynamics of the proton pump inhibitors.

    Science.gov (United States)

    Shin, Jai Moo; Kim, Nayoung

    2013-01-01

    Proton pump inhibitor (PPI) is a prodrug which is activated by acid. Activated PPI binds covalently to the gastric H(+), K(+)-ATPase via disulfide bond. Cys813 is the primary site responsible for the inhibition of acid pump enzyme, where PPIs bind. Omeprazole was the first PPI introduced in market, followed by pantoprazole, lansoprazole and rabeprazole. Though these PPIs share the core structures benzimidazole and pyridine, their pharmacokinetics and pharmacodynamics are a little different. Several factors must be considered in understanding the pharmacodynamics of PPIs, including: accumulation of PPI in the parietal cell, the proportion of the pump enzyme located at the canaliculus, de novo synthesis of new pump enzyme, metabolism of PPI, amounts of covalent binding of PPI in the parietal cell, and the stability of PPI binding. PPIs have about 1hour of elimination half-life. Area under the plasmic concentration curve and the intragastric pH profile are very good indicators for evaluating PPI efficacy. Though CYP2C19 and CYP3A4 polymorphism are major components of PPI metabolism, the pharmacokinetics and pharmacodynamics of racemic mixture of PPIs depend on the CYP2C19 genotype status. S-omeprazole is relatively insensitive to CYP2C19, so better control of the intragastric pH is achieved. Similarly, R-lansoprazole was developed in order to increase the drug activity. Delayed-release formulation resulted in a longer duration of effective concentration of R-lansoprazole in blood, in addition to metabolic advantage. Thus, dexlansoprazole showed best control of the intragastric pH among the present PPIs. Overall, PPIs made significant progress in the management of acid-related diseases and improved health-related quality of life.

  5. Partial symptom-response to proton pump inhibitors in patients with non-erosive reflux disease or reflux oesophagitis - a post hoc analysis of 5796 patients

    DEFF Research Database (Denmark)

    Bytzer, P; van Zanten, S Veldhuyzen; Mattsson, H

    2012-01-01

    Although most patients with gastro-oesophageal reflux disease (GERD) benefit from proton pump inhibitor (PPI) therapy, some experience only partial symptom relief.......Although most patients with gastro-oesophageal reflux disease (GERD) benefit from proton pump inhibitor (PPI) therapy, some experience only partial symptom relief....

  6. Role of Acid and Weakly Acidic Reflux in Gastroesophageal Reflux Disease Off Proton Pump Inhibitor Therapy

    OpenAIRE

    Sung, Hea Jung; Cho, Yu Kyung; Moon, Sung Jin; Kim, Jin Su; Lim, Chul Hyun; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gye

    2012-01-01

    Background/Aims Available data about reflux patterns and symptom determinants in the gastroesophageal reflux disease (GERD) subtypes off proton pump inhibitor (PPI) therapy are lacking. We aimed to evaluate reflux patterns and determinants of symptom perception in patients with GERD off PPI therapy by impedance-pH monitoring. Methods We retrospectively reviewed the impedance-pH data in patients diagnosed as GERD based on results of impedance-pH monitoring, endoscopy and/or typical symptoms. T...

  7. Practical considerations in the management of proton-pump inhibitors

    Directory of Open Access Journals (Sweden)

    Lara Aguilera-Castro

    Full Text Available Proton-pump inhibitors (PPIs are one of the most active ingredients prescribed in Spain. In recent decades there has been an overuse of these drugs in both outpatient clinics and hospitals that has lead to a significant increase in healthcare spending and to an increase in the risk of possible side effects. It is important for health professionals to know the accepted indications and the correct doses for the use of these drugs. On the market there are different types of PPI: omeprazole, pantoprazole, lansoprazole, rabeprazole and esomeprazole. Omeprazole is the oldest and most used PPI, being also the cheapest. Although there are no important differences between PPIs in curing diseases, esomeprazole, a new-generation PPI, has proved to be more effective in eradicating H. pylori and in healing severe esophagitis compared to other PPIs. In recent years the use of generic drugs has spread; these drugs have the same bioavailability than the original drugs. In the case of PPIs, the few comparative studies available in the literature between original and generic drugs have shown no significant differences in clinical efficacy.

  8. Obscure bleeding colonic duplication responds to proton pump inhibitor therapy.

    Science.gov (United States)

    Jacques, Jérémie; Projetti, Fabrice; Legros, Romain; Valgueblasse, Virginie; Sarabi, Matthieu; Carrier, Paul; Fredon, Fabien; Bouvier, Stéphane; Loustaud-Ratti, Véronique; Sautereau, Denis

    2013-09-21

    We report the case of a 17-year-old male admitted to our academic hospital with massive rectal bleeding. Since childhood he had reported recurrent gastrointestinal bleeding and had two exploratory laparotomies 5 and 2 years previously. An emergency abdominal computed tomography scan, gastroscopy and colonoscopy, performed after hemodynamic stabilization, were considered normal. High-dose intravenous proton pump inhibitor (PPI) therapy was initiated and bleeding stopped spontaneously. Two other massive rectal bleeds occurred 8 h after each cessation of PPI which led to a hemostatic laparotomy after negative gastroscopy and small bowel capsule endoscopy. This showed long tubular duplication of the right colon, with fresh blood in the duplicated colon. Obscure lower gastrointestinal bleeding is a difficult medical situation and potentially life-threatening. The presence of ulcerated ectopic gastric mucosa in the colonic duplication explains the partial efficacy of PPI therapy. Obscure gastrointestinal bleeding responding to empiric anti-acid therapy should probably evoke the diagnosis of bleeding ectopic gastric mucosa such as Meckel's diverticulum or gastrointestinal duplication, and gastroenterologists should be aware of this potential medical situation.

  9. Proton pump inhibitors alter the composition of the gut microbiota.

    Science.gov (United States)

    Jackson, Matthew A; Goodrich, Julia K; Maxan, Maria-Emanuela; Freedberg, Daniel E; Abrams, Julian A; Poole, Angela C; Sutter, Jessica L; Welter, Daphne; Ley, Ruth E; Bell, Jordana T; Spector, Tim D; Steves, Claire J

    2016-05-01

    Proton pump inhibitors (PPIs) are drugs used to suppress gastric acid production and treat GI disorders such as peptic ulcers and gastro-oesophageal reflux. They have been considered low risk, have been widely adopted, and are often over-prescribed. Recent studies have identified an increased risk of enteric and other infections with their use. Small studies have identified possible associations between PPI use and GI microbiota, but this has yet to be carried out on a large population-based cohort. We investigated the association between PPI usage and the gut microbiome using 16S ribosomal RNA amplification from faecal samples of 1827 healthy twins, replicating results within unpublished data from an interventional study. We identified a significantly lower abundance in gut commensals and lower microbial diversity in PPI users, with an associated significant increase in the abundance of oral and upper GI tract commensals. In particular, significant increases were observed in Streptococcaceae. These associations were replicated in an independent interventional study and in a paired analysis between 70 monozygotic twin pairs who were discordant for PPI use. We propose that the observed changes result from the removal of the low pH barrier between upper GI tract bacteria and the lower gut. Our findings describe a significant impact of PPIs on the gut microbiome and should caution over-use of PPIs, and warrant further investigation into the mechanisms and their clinical consequences. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Obesity does not affect treatment outcomes with proton pump inhibitors.

    Science.gov (United States)

    Sharma, Prateek; Vakil, Nimish; Monyak, John T; Silberg, Debra G

    2013-09-01

    Obesity is associated with increased risk of gastroesophageal reflux disease (GERD). To evaluate the effect of obesity on symptom resolution in patients with nonerosive reflux disease (NERD) and healing rates in patients with erosive esophagitis (EE). Two post hoc analyses were performed. Analyses included pooled data from randomized, double-blind, multicenter studies of proton pump inhibitors (PPIs) in GERD patients. Analysis 1 included 704 patients with NERD receiving esomeprazole 20 mg, esomeprazole 40 mg, or placebo. Analysis 2 included 11,027 patients with EE receiving esomeprazole 40 mg, omeprazole 20 mg, or lansoprazole 30 mg. For NERD patients, no significant association between baseline heartburn severity and body mass index (BMI) was observed. In EE patients, overweight (BMI 25 to <35 kg/m) and obese (BMI ≥35 kg/m) patients had significantly higher rates of Los Angeles (LA) grade C or D EE than patients with BMI <25 kg/m (P<0.0001). Percentages of PPI-treated patients who achieved heartburn resolution or EE healing within a given LA grade were similar across BMI categories. Heartburn resolution was significantly associated with treatment (esomeprazole vs. placebo), increasing age, and for men versus women (all P≤0.0284). EE healing was significantly associated with PPI treatment (esomeprazole and lansoprazole vs. omeprazole), increasing age, race, presence of a hiatal hernia, and lower LA grade at baseline (all P≤0.0183). In patients with GERD, high BMI was associated with more severe EE at baseline. However, during PPI treatment, BMI is not a significant independent predictor of heartburn resolution or EE healing.

  11. Proton pump inhibitor-responsive chronic cough without acid reflux: a case report

    Directory of Open Access Journals (Sweden)

    Nobata Kouichi

    2007-08-01

    Full Text Available Abstract Background Because 24-h esophageal pH monitoring is quite invasive, the diagnosis of gastroesophageal reflux disease (GERD-associated cough has usually been made based merely on the clinical efficacy of treatment with proton pump inhibitor (PPI. Case presentation We recently encountered two patients with PPI-responsive chronic non-productive cough for whom switching from bronchodilators and glucocorticosteroids to PPI resulted in improvement of cough. The cough returned nearly to pre-administration level a few weeks after discontinuation of PPI. Though GERD-associated cough was suspected, 24-h esophageal pH monitoring revealed that the cough rarely involved gastric acid reflux. Following re-initiation of PPI, the cough disappeared again. Conclusion PPI may improve cough unrelated to gastric acid reflux.

  12. [Pharmacogenic osteoporosis beyond cortisone. Proton pump inhibitors, glitazones and diuretics].

    Science.gov (United States)

    Kann, P H; Hadji, P; Bergmann, R S

    2014-05-01

    [corrected] There are many drugs which can cause osteoporosis or at least favor its initiation. The effect of hormones and drugs with antihormonal activity, such as glucocorticoids and aromatase inhibitors, on initiation of osteoporosis is well known. In addition, proton pump inhibitors, glitazones and diuretics also influence the formation of osteoporosis. The results of currently available studies on the correlation between proton pump inhibitors, glitazones and diuretics on formation of osteoporosis were evaluated and summarized. Proton pump inhibitors and glitazones increase the risk for osteoporotic fractures. Loop diuretics may slightly increase fracture risk, whereas thiazides were shown to be osteoprotective by reducing fracture probability on a relevant scale. Proton pump inhibitors should not be prescribed without serious consideration and then only as long as necessary. Alternatively, the administration of the less effective H2 antagonists should be considered when possible due to the reduction of acid secretion. Because the long-term intake of thiazides is associated with a clinically relevant reduction in the risk of fractures and they are economic and well-tolerated, prescription can be thoroughly recommended within the framework of differential diagnostic considerations in an appropriate clinical context. The briefly increased risk of falling immediately after starting diuretic therapy is the only point which needs to be considered.

  13. [Adherence with proton pump inhibitor therapy, by continuously taking nonsteroidal anti-inflammatory drugs].

    Science.gov (United States)

    Pimanov, S I; Makarenko, E V; Dikareva, E A

    2015-01-01

    To estimate the impact of adherence with proton pump inhibitor (PPI) therapy on the incidence of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy (NSAID gastropathy) in patients with rheumatoid arthritis (RA). PPI pharmacotherapy adherence was estimated using the Medication Adherence Questionnaire (MAQ) in 92 patients with RA, including 32 patients did not take a PPI and 60 used a PPI. The groups were matched for age, disease duration, and used NSAIDs. All those asked underwent video esophagogastroduodenoscopy. According to the data of MAQ survey, low, moderate, and high adherence subgroups could be identified among the patients treated with a PPI. NSAID gastropathy was detected in 43.8% of the patients taking no PPI, in 50% of those with low PPI treatment adherence, in 12.5% with moderate adherence, and in 4.5% with high adherence. In the patients with low adherence to PPI therapy, NSAID gastropathy was recorded 11 times more frequently than in those with high adherence (c2 = 7.77; p = 0.005). This condition occurred in 28.6% of the patients taking NSAID without preventively using a PPI in the absence of risk factors for NSAID gastropathy. Only 36.7% patients who had been recommended to use a PPI for the prevention of NSAID gastropathy strictly observed their doctor's directions. Low PPI pharmacotherapy adherence may serve as an additional risk factor for NSAID gastropathy in patients in whom preventive antisecretory therapy used in combination with NSAID is indicated.

  14. Proton pump inhibitor-refractory gastroesophageal reflux disease: challenges and solutions

    Science.gov (United States)

    Mermelstein, Joseph; Chait Mermelstein, Alanna; Chait, Maxwell M

    2018-01-01

    A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist. PMID:29606884

  15. Use of proton pump inhibitors and the risk of listeriosis

    DEFF Research Database (Denmark)

    Jensen, Anne Kvistholm; Simonsen, Jacob; Ethelberg, Steen

    2017-01-01

    BACKGROUND: Recent studies suggest that proton pump inhibitors (PPIs) may increase the risk for listeriosis. We aimed to investigate a potential association in cases of non-pregnancy associated listeriosis, using registry data. METHODS: We conducted a population-based case-control study using...

  16. Shortcomings of the first-generation proton pump inhibitors

    NARCIS (Netherlands)

    Tytgat, G. N.

    2001-01-01

    Proton pump inhibitors (PPIs) are widely prescribed for the treatment of gastro-oesophageal reflux disease (GORD) as well as gastric and duodenal ulcers, and these agents are now considered the drugs of choice for managing such acid-related disorders. Despite their well-documented efficacy and

  17. Effectiveness of ranitidine bismuth citrate and proton pump inhibitor ...

    African Journals Online (AJOL)

    Effectiveness of ranitidine bismuth citrate and proton pump inhibitor based triple therapies of Helicobacter pylori in Turkey. ... Results: When we look at the eradication rates of the treatment groups, only two groups (ranitidine bismuth citrate and rabeprazole groups) had eradication rates greater than 80%, both at intention to ...

  18. Inulin significantly improves serum magnesium levels in proton pump inhibitor-induced hypomagnesaemia.

    Science.gov (United States)

    Hess, M W; de Baaij, J H F; Broekman, M; Bisseling, T M; Haarhuis, B; Tan, A; Te Morsche, R; Hoenderop, J G J; Bindels, R J M; Drenth, J P H

    2016-06-01

    Proton pump inhibitors (PPI) are among the most widely prescribed drugs to treat gastric acid-related disorders. PPI-induced hypomagnesaemia, a defect in intestinal absorption of Mg(2+) , can be a severe side effect of chronic PPI use. To restore serum Mg(2+) concentrations in PPI-induced hypomagnesaemia patients by dietary supplementation with inulin fibres. Eleven patients with PPI-induced hypomagnesaemia and 10 controls were treated with inulin (20 g/day). Each trial consisted of two cycles of 14-day inulin treatment followed by a washout period of 14 days. Patients continued to use their PPI. Serum Mg(2+) levels served as the primary endpoint. Inulin significantly enhanced serum Mg(2+) levels from 0.60 to 0.68 mmol/L in PPI-induced hypomagnesaemia patients, and from 0.84 to 0.93 mmol/L in controls. As a consequence 24 h urinary Mg(2+) excretion was significantly increased in patients with PPI-induced hypomagnesaemia (0.3-2.2 mmol/day). Symptoms related to hypomagnesaemia, including muscle cramps and paraesthesia, were reduced during intervention with inulin. Inulin increases serum Mg(2+) concentrations under PPI maintenance in patients with PPI-induced hypomagnesaemia. © 2016 John Wiley & Sons Ltd.

  19. Clinical Efficacy of Proton Pump Inhibitor versus Prompt Endoscopy for Management of People with Dyspepsia

    DEFF Research Database (Denmark)

    Kjeldsen, Hans Christian; Lauritzen, Torsten; Christensen, Bo

      Title:   Clinical Efficacy of Proton Pump Inhibitor versus Prompt Endoscopy for Management of People with Dyspepsia: A Randomized Clinical Trial in General Practice.     Purpose: To compare the clinical efficacy of two strategies for management of dyspepsia in general practice in a RCT design.......   Setting: June 2000 to August 2002, 41 GPs, Aarhus County, Denmark   Methods: 368 people with dyspepsia (epigastric pain/discomfort, no alarm symptoms) were randomly assigned to treatment with omeprazol 40 mg/day for two weeks (PPI group, n:185) or endoscopy (endoscopy group, n:183). Due to migration......, dyspeptic contacts to GP or patients' satisfaction. Conclusions: Prompt endoscopy was superior to proton pump inhibitor concerning symptom improvement in management of dyspepsia in general practice when pain/discomfort was the primary symptom. There were no differences between the two strategies in respect...

  20. Proton Pump Inhibitor Use Is Associated With a Reduced Risk of Infection with Intestinal Protozoa.

    Science.gov (United States)

    Sheele, Johnathan M

    2017-12-01

    Proton pump inhibitors (PPIs) can kill some human protozoan parasites in cell culture better than the drug metronidazole. Clinical data showing an antiprotozoal effect for PPIs are lacking. The objective of the study is to determine if PPI use is associated with a reduced risk of having intestinal parasites. We obtained electronic medical record data for all persons who received a stool ova and parasite (O & P) examination at our tertiary care academic medical center in Cleveland, Ohio, between January 2000 and September 2014. We obtained the person's age, whether they were taking a PPI at the time of the O & P examination, and whether the pathology report indicated the presence of any parasites. χ 2 with Yates correction was used to determine if PPI use was associated with stool protozoa. Three intestinal protozoa were identified in 1199 patients taking a PPI (0.3%), and 551 intestinal parasites were identified in the 14,287 patients not taking a PPI (3.9%). There was a statistically significant lower likelihood of finding protozoa in the stool of a person taking a PPI compared with those not taking a PPI (P protozoa reported on stool O & P examination compared with those not taking a PPI. Copyright © 2017 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  1. Rikkunshito improves globus sensation in patients with proton-pump inhibitor-refractory laryngopharyngeal reflux.

    Science.gov (United States)

    Tokashiki, Ryoji; Okamoto, Isaku; Funato, Nobutoshi; Suzuki, Mamoru

    2013-08-21

    To investigate the effect of rikkunshito on laryngopharyngeal reflux (LPR) symptoms and gastric emptying in patients with proton-pump inhibitor (PPI)-refractory LPR. In total, 22 patients with LPR were enrolled. Following a 2-wk treatment with PPI monotherapy, PPI-refractory LPR patients were randomly divided into two treatment groups (rikkunshito alone or rikkunshito plus the PPI, lansoprazole). LPR symptoms were assessed using a visual analog scale (VAS) score, gastrointestinal symptoms were assessed using the gastrointestinal symptom rating scale (GSRS), and gastric emptying was assessed using the radio-opaque marker method prior to and 4 wk following treatments. The 4-wk treatment with rikkunshito alone and with rikkunshito plus the PPI significantly decreased the globus sensation VAS scores. The VAS score for sore throat was significantly decreased following treatment with rikkunshito plus PPI but not by rikkunshito alone. Neither treatment significantly changed the GSRS scores. Rikkunshito improved delayed gastric emptying. We found a significant positive correlation between improvements in globus sensation and in gastric emptying (r² = 0.4582, P sensation in patients with PPI-refractory LPR, in part, because of stimulation of gastric emptying. Thus, rikkunshito is an effective treatment for PPI-refractory LPR.

  2. The potential drug-drug interaction between proton pump inhibitors and warfarin

    DEFF Research Database (Denmark)

    Henriksen, Daniel Pilsgaard; Stage, Tore Bjerregaard; Hansen, Morten Rix

    2015-01-01

    BACKGROUND: Proton pump inhibitors (PPIs) have been suggested to increase the effect of warfarin, and clinical guidelines recommend careful monitoring of international normalized ratio (INR) when initiating PPI among warfarin users. However, this drug-drug interaction is sparsely investigated...... in a clinical setting. The aim was to assess whether initiation of PPI treatment among users of warfarin leads to increased INR values. METHODS: The study was an observational self-controlled study from 1998 to 2012 leveraging data on INR measurements on patients treated with warfarin from primary care...... and outpatient clinics and their use of prescription drugs. Data were analyzed in 2015. We assessed INR, warfarin dose, and dose/INR ratio before and after initiating PPI treatment using the paired student's t-test. RESULTS: We identified 305 warfarin users initiating treatment with PPIs. The median age was 71...

  3. Effect of proton-pump inhibitor treatment on symptoms and quality of life in GERD patients depends on the symptom-reflux association

    NARCIS (Netherlands)

    Aanen, Marissa C.; Weusten, Bas L. A. M.; Numans, Mattijs E.; de Wit, Niek J.; Samsom, Melvin; Smout, Andre J. P. M.

    2008-01-01

    Backgound: Gastroesophageal reflux disease patients demonstrate various pathophysiologic backgrounds. Therefore, a heterogeneous response to proton-pump inhibitor (PPI) treatment can be expected. We investigated the effect of short-term PPI treatment on symptoms and quality of life (QOL) in primary

  4. Clopidogrel and proton pump inhibitors--where do we stand in 2012?

    LENUS (Irish Health Repository)

    Drepper, Michael D

    2012-05-14

    Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events. Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines. Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19 (CYP2C19) and proton pump inhibitors (PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well. Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole, but not for pantoprazole. Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events, when under clopidogrel and PPI treatment at the same time. These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI (especially omeprazole) in the same year. In contrast, more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel. Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality, with high and moderate quality studies not reporting any association, rising concern about unmeasured confounders biasing the low quality studies. Thus, no definite evidence exists for an effect on mortality. Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding, combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.

  5. The Role of Proton Pump Inhibitors in the Management of Pediatric Eosinophilic Esophagitis

    Directory of Open Access Journals (Sweden)

    Carolina Gutiérrez-Junquera

    2018-05-01

    Full Text Available Eosinophilic esophagitis (EoE is a chronic, local, immune-mediated disorder characterized by symptoms of esophageal dysfunction and the presence of a dense eosinophilic infiltrate in the esophageal mucosa. Consensus diagnostic recommendations for EoE diagnosis included absence of histological response to a proton-pump inhibitor (PPI trial, to exclude gastro-oesophageal reflux disease (GERD-associated esophagitis. This recommendation exposed an entity known as “proton pump inhibitor-responsive esophageal eosinophilia” (PPI-REE, which refers to patients with EoE phenotype who are PPI-responsive and do not present GERD. In recent years, there is evidence which indicates that PPI-REE is a sub-phenotype of EoE with similar clinical, endoscopic, histological and genetic characteristics, as well as Th2-related inflammatory response. As a result, PPIs should be considered another treatment for EoE and not a diagnostic tool. PPI-REE was originally described in a case series which included two children and in two retrospective pediatric series. Later, a prospective pediatric study showed a high rate of response to PPIs at high doses with long-term maintenance at lower doses. PPI monotherapy in children with esophageal eosinophilia (EE has been observed to reduce eotaxin-3 expression in epithelial cells and to practically reverse the allergy and inflammatory transcriptome. These data reveal that PPIs are also an effective treatment for EoE in pediatric patients, although more studies are necessary in order to define the best induction and maintenance treatment regimen, the long-term safety profile and their influence on the occurrence of fibrosis and esophageal remodeling.

  6. A rationale for the use of proton pump inhibitors as antineoplastic agents.

    Science.gov (United States)

    De Milito, Angelo; Marino, Maria Lucia; Fais, Stefano

    2012-01-01

    It is becoming increasingly acknowledged that tumorigenesis is not simply characterized by the accumulation of rapidly proliferating, genetically mutated cells. Microenvironmental biophysical factors like hypoxia and acidity dramatically condition cancer cells and act as selective forces for malignant cells, adapting through metabolic reprogramming towards aerobic glycolysis. Avoiding intracellular accumulation of lactic acid and protons, otherwise detrimental to cell survival is crucial for malignant cells to maintain cellular pH homeostasis. As a consequence of the upregulated expression and/or function of several pH-regulating systems, cancer cells display an alkaline intracellular pH (pHi) and an acidic extracellular pH (pHe). Among the pH-regulating proteins, proton pumps play an important role in both drug-resistance and metastatic spread, thus representing a suitable therapeutic target. Proton pump inhibitors (PPI) have been reported as cytotoxic drugs active against several human tumor cells and preclinical data have prompted the investigation of PPI as anticancer agents in humans. This review will update the current knowledge on the antitumor activities of PPI and their potential applications.

  7. Proton-pump inhibitor use does not affect semen quality in subfertile men

    Directory of Open Access Journals (Sweden)

    Sorena Keihani

    2018-01-01

    Full Text Available Proton-pump inhibitors (PPIs are among the most widely used drugs worldwide. PPI use has recently been linked to adverse changes in semen quality in healthy men; however, the effects of PPI use on semen parameters remain largely unknown specifically in cases with male factor infertility. We examined whether PPI use was associated with detrimental effects on semen parameters in a large population of subfertile men. We retrospectively reviewed data from 12 257 subfertile men who had visited our fertility clinic from 2003 to 2013. Patients who reported using any PPIs for >3 months before semen sample collection were included; 7698 subfertile men taking no medication served as controls. Data were gathered on patient age, medication use, and conventional semen parameters; patients taking any known spermatotoxic medication were excluded. Linear mixed-effect regression models were used to test the effect of PPI use on semen parameters adjusting for age. A total of 248 patients (258 samples used PPIs for at least 3 months before semen collection. In regression models, PPI use (either as the only medication or when used in combination with other nonspermatotoxic medications was not associated with statistically significant changes in semen parameters. To our knowledge, this is the largest study to compare PPI use with semen parameters in subfertile men. Using PPIs was not associated with detrimental effects on semen quality in this retrospective study.

  8. Proton-pump inhibitor use does not affect semen quality in subfertile men.

    Science.gov (United States)

    Keihani, Sorena; Craig, James R; Zhang, Chong; Presson, Angela P; Myers, Jeremy B; Brant, William O; Aston, Kenneth I; Emery, Benjamin R; Jenkins, Timothy G; Carrell, Douglas T; Hotaling, James M

    2018-01-01

    Proton-pump inhibitors (PPIs) are among the most widely used drugs worldwide. PPI use has recently been linked to adverse changes in semen quality in healthy men; however, the effects of PPI use on semen parameters remain largely unknown specifically in cases with male factor infertility. We examined whether PPI use was associated with detrimental effects on semen parameters in a large population of subfertile men. We retrospectively reviewed data from 12 257 subfertile men who had visited our fertility clinic from 2003 to 2013. Patients who reported using any PPIs for >3 months before semen sample collection were included; 7698 subfertile men taking no medication served as controls. Data were gathered on patient age, medication use, and conventional semen parameters; patients taking any known spermatotoxic medication were excluded. Linear mixed-effect regression models were used to test the effect of PPI use on semen parameters adjusting for age. A total of 248 patients (258 samples) used PPIs for at least 3 months before semen collection. In regression models, PPI use (either as the only medication or when used in combination with other nonspermatotoxic medications) was not associated with statistically significant changes in semen parameters. To our knowledge, this is the largest study to compare PPI use with semen parameters in subfertile men. Using PPIs was not associated with detrimental effects on semen quality in this retrospective study.

  9. Celecoxib versus a non-selective NSAID plus proton-pump inhibitor: what are the considerations?.

    Science.gov (United States)

    Chen, Judy T; Pucino, Frank; Resman-Targoff, Beth H

    2006-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are extensively used worldwide. However, associated adverse gastrointestinal effects (NSAID gastropathy) such as bleeding, perforation and obstruction result in considerable morbidity, mortality, and expense. Although it is essential to employ gastroprotective strategies to minimize these complications in patients at risk, controversy remains on whether celecoxib alone or a non-selective NSAID in conjunction with a proton-pump inhibitor (PPI) is a superior choice. Recent concerns regarding potential cardiovascular toxicities associated with cox-2 selective inhibitors may favor non-selective NSAID/PPI co-therapy as the preferred choice. Concomitant use of low-dose aspirin with any NSAID increases the risk of gastrointestinal complications and diminishes the improved gastrointestinal safety profile of celecoxib; whereas use of ibuprofen plus PPI regimens may negate aspirin's antiplatelet benefits. Evidence shows that concurrent use of a non-selective NSAID (such as naproxen) plus a PPI is as effective in preventing NSAID gastropathy as celecoxib, and may be more cost-effective. Patients failing or intolerant to this therapy would be candidates for celecoxib at the lowest effective dose for the shortest duration of time. Potential benefits from using low-dose celecoxib with a PPI in patients previously experiencing bleeding ulcers while taking NSAIDs remains to be proven. An evidence-based debate is presented to assist clinicians with the difficult decision-making process of preventing NSAID gastropathy while minimizing other complications.

  10. Lack of Association Between Proton Pump Inhibitor Use and Cognitive Decline

    DEFF Research Database (Denmark)

    Wod, Mette; Hallas, Jesper; Andersen, Kjeld

    2018-01-01

    from surveys of middle-aged individuals (46-67 years old; the Middle Aged Danish Twin study) and older individuals (the Longitudinal Study of Aging Danish Twins) who underwent cognitive assessments (a 5-component test battery) over a 10-year period (middle-age study, n=2346) or a 2-year period...... PPI use and a composite score of cognitive function at baseline and decreases in scores during the follow-up periods. RESULTS: Use of PPIs before study enrollment was associated with a slightly lower mean cognitive score at baseline in the middle age study. The adjusted difference in mean score......BACKGROUND & AIMS: Studies of association between use of proton pump inhibitors (PPI) and dementia have yielded conflicting results. We investigated the effects of PPIs on cognitive decline in a study of middle-aged and elderly twins in Denmark. METHODS: In a prospective study, we collected data...

  11. Overutilization of proton pump inhibitors: a review of cost-effectiveness and risk [corrected].

    Science.gov (United States)

    Heidelbaugh, Joel J; Goldberg, Kathleen L; Inadomi, John M

    2009-03-01

    Proton pump inhibitors (PPIs) are superior to histamine-2 receptor antagonists for the treatment of gastroesophageal reflux disease (GERD) and erosive esophagitis. Antisecretory therapy (AST), however, accounts for significant cost expenditure in the United States including over-the-counter and prescription formulations. Moreover, emerging data illustrate the potential risks associated with long-term PPI therapy including variations in bioavailability of common medications, vitamin B12 deficiency, Clostridium difficile-associated diarrhea, community-acquired pneumonia, and hip fracture. For these reasons, it is imperative to use the lowest dose of drug necessary to achieve desired therapeutic goals. This may entail the use of step-down, step-off, or on-demand PPI therapy for the treatment of GERD. In addition, PPIs are the most commonly used medications for stress ulcer prophylaxis (SUP), despite little evidence to support their use. Compounding this problem is evidence that patients erroneously administered SUP are often discharged on long-term PPI therapy. Pharmacy-driven step-down orders, limitation of the use of PPIs for SUP in non-ICU settings, and meticulous chart review to ensure that hospitalized patients are not discharged home on a PPI without an appropriate indication are interventions that can ensure proper PPI utilization with minimal of risk and optimization of cost-effectiveness.

  12. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

    International Nuclear Information System (INIS)

    Becker, Jan C.; Grosser, Nina; Waltke, Christian; Schulz, Stephanie; Erdmann, Kati; Domschke, Wolfram; Schroeder, Henning; Pohle, Thorsten

    2006-01-01

    Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection

  13. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Jan C [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Grosser, Nina [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Waltke, Christian [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Schulz, Stephanie [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Erdmann, Kati [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Domschke, Wolfram [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Schroeder, Henning [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Pohle, Thorsten [Department of Medicine B, University of Muenster, 48149 Muenster (Germany)

    2006-07-07

    Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection.

  14. Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients' bed.

    Science.gov (United States)

    Ferrari, Stefano; Perut, Francesca; Fagioli, Franca; Brach Del Prever, Adalberto; Meazza, Cristina; Parafioriti, Antonina; Picci, Piero; Gambarotti, Marco; Avnet, Sofia; Baldini, Nicola; Fais, Stefano

    2013-10-24

    Major goals in translational oncology are to reduce systemic toxicity of current anticancer strategies and improve effectiveness. An extremely efficient cancer cell mechanism to avoid and/or reduce the effects of highly cytotoxic drugs is the establishment of an acidic microenvironment, an hallmark of all malignant tumors. The H +-rich milieu that anticancer drugs meet once they get inside the tumor leads to their protonation and neutralization, therefore hindering their access into tumor cells. We have previously shown that proton pump inhibitors (PPI) may efficiently counterattack this tumor advantage leading to a consistent chemosensitization of tumors. In this study, we investigated the effects of PPI in chemosensitizing osteosarcoma. MG-63 and Saos-2 cell lines were used as human osteosarcoma models. Cell proliferation after pretreatment with PPI and subsequent treatment with cisplatin was evaluated by using erythrosin B dye vital staining. Tumour growth was evaluated in xenograft treated with cisplatin after PPI pretreatment. Subsequently, a multi-centre historically controlled trial, was performed to evaluate the activity of a pre-treatment administration of PPIs as chemosensitizers during neoadjuvant chemotherapy based on methotrexate, cisplatin, and adriamycin. Preclinical experiments showed that PPI sensitize both human osteosarcoma cell lines and xenografts to cisplatin. A clinical study subsequently showed that pretreatment with PPI drug esomeprazole leads to an increase in the local effect of chemotherapy, as expressed by percentage of tumor necrosis. This was particularly evident in chondroblastic osteosarcoma, an histological subtype that normally shows a poor histological response. Notably, no significant increase in toxicity was recorded in PPI treated patients. This study provides the first evidence that PPI may be beneficially added to standard regimens in combination to conventional chemotherapy.

  15. The proton-pump inhibitor lansoprazole enhances amyloid beta production.

    Science.gov (United States)

    Badiola, Nahuai; Alcalde, Victor; Pujol, Albert; Münter, Lisa-Marie; Multhaup, Gerd; Lleó, Alberto; Coma, Mireia; Soler-López, Montserrat; Aloy, Patrick

    2013-01-01

    A key event in the pathogenesis of Alzheimer's disease (AD) is the accumulation of amyloid-β (Aβ) species in the brain, derived from the sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Based on a systems biology study to repurpose drugs for AD, we explore the effect of lansoprazole, and other proton-pump inhibitors (PPIs), on Aβ production in AD cellular and animal models. We found that lansoprazole enhances Aβ37, Aβ40 and Aβ42 production and lowers Aβ38 levels on amyloid cell models. Interestingly, acute lansoprazole treatment in wild type and AD transgenic mice promoted higher Aβ40 levels in brain, indicating that lansoprazole may also exacerbate Aβ production in vivo. Overall, our data presents for the first time that PPIs can affect amyloid metabolism, both in vitro and in vivo.

  16. Survey of findings in patients having persistent heartburn on proton pump inhibitor therapy.

    Science.gov (United States)

    Mandaliya, R; DiMarino, A J; Cohen, S

    2016-01-01

    In patients with refractory heartburn while on proton pump inhibitor (PPI) therapy, changing drugs or increasing treatment to a twice a day (b.i.d.) dose has become a common practice. This study aims to study patients with persistent heartburn while on PPI therapy and to determine if persistent symptom indicates the need for more aggressive or different therapy. A retrospective review of impedance-pH tracings on PPI therapy (q.d. or b.i.d.) for patients with persistent heartburn was performed. DeMeester score, impedance, and symptom sensitive index (SSI) were used as indices. Statistical analyses were performed using chi-squared test with Yates correction and paired t-test. One hundred consecutive patients, (female 50%, male 50%, mean age 54 [range 16-83] years) were studied on q.d. (n = 45) or b.i.d. PPI (n = 55). Only 20% of the patients had abnormal DeMeester score; 41% had an abnormal impedance score and 56% had abnormal SSI; 29% had all indices normal. There was no difference between patients taking q.d. versus b.i.d. PPI for abnormal DeMeester score (22 vs. 18%), impedance (38 vs. 44%) and SSI (53 vs. 58%); P = 0.80, 0.69, and 0.77, respectively. In 56 patients with positive SSI, symptoms were due to acid reflux in 8 (14%) patients, nonacid reflux in 31 (55%) patients, and combined acid and nonacid reflux in 17 (30%) patients. Patients with persistent heartburn on PPI therapy show a variety of disorders: (i) acid reflux (20%); (ii) nonacid reflux (26%); (iii) positive SSI (56%); (iv) all normal indices (29%). These studies indicate that persistent heartburn on PPI therapy is a complex problem that may not respond to simply increasing acid inhibition. © 2014 International Society for Diseases of the Esophagus.

  17. Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease.

    Science.gov (United States)

    Cicala, Michele; Emerenziani, Sara; Guarino, Michele Pier Luca; Ribolsi, Mentore

    2013-10-21

    Gastro-esophageal reflux disease (GERD) is one of the most prevalent chronic diseases. Although proton pump inhibitors (PPIs) represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief, several studies have shown that up to 40% of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily. Several mechanisms have been proposed as involved in PPIs resistance, including ineffective control of gastric acid secretion, esophageal hypersensitivity, ultrastructural and functional changes in the esophageal epithelium. The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation, upper endoscopy, esophageal manometry and ambulatory pH-impedance monitoring, which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn. Treatment has been primarily based on doubling the PPI dose or switching to another PPI. Patients with proven disease, not responding to PPI twice daily, are eligible for anti-reflux surgery.

  18. Association between baseline impedance values and response proton pump inhibitors in patients with heartburn.

    Science.gov (United States)

    de Bortoli, Nicola; Martinucci, Irene; Savarino, Edoardo; Tutuian, Radu; Frazzoni, Marzio; Piaggi, Paolo; Bertani, Lorenzo; Furnari, Manuele; Franchi, Riccardo; Russo, Salvatore; Bellini, Massimo; Savarino, Vincenzo; Marchi, Santino

    2015-06-01

    Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for

  19. Effect of long-term proton pump inhibitor administration on gastric mucosal atrophy: A meta-analysis

    Science.gov (United States)

    Li, Zhong; Wu, Cong; Li, Ling; Wang, Zhaoming; Xie, Haibin; He, Xiaozhou; Feng, Jin

    2017-01-01

    Background/Aims: Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related gastrointestinal diseases. Recently, some studies have reported that PPIs can alter the gastric mucosal architecture; however, the relationship remains controversial. This meta-analysis study was designed to quantify the association between long-term PPI administration and gastric atrophy. Materials and Methods: A PubMed search was conducted to identify studies using the keywords proton pump inhibitors or PPI and gastric atrophy or atrophic gastritis; the timeframe of publication searched was up to May 2016. Heterogeneity among studies was tested with the Q test; odds ratios (OR) and 95% confidence intervals (CI) were calculated. P values were calculated by I2 tests and regarded as statistically significant when <0.05. Results: We identified 13 studies that included 1465 patients under long-term PPI therapy and 1603 controls, with a total gastric atrophy rate of 14.50%. There was a higher presence of gastric atrophy (15.84%; statistically significant) in PPI group compared to the control group (13.29%) (OR: 1.55, 95% CI: 1.00–2.41). Conclusions: The pooled data suggest that long-term PPI use is associated with increased rates of gastric atrophy. Large-scale multicenter studies should be conducted to further investigate the relationship between acid suppressants and precancerous diseases. PMID:28721975

  20. Proton pump inhibitor responders who are not confirmed as GERD patients with impedance and pH monitoring: who are they?

    NARCIS (Netherlands)

    de Bortoli, N.; Martinucci, I.; Savarino, E.; Bellini, M.; Bredenoord, A. J.; Franchi, R.; Bertani, L.; Furnari, M.; Savarino, V.; Blandizzi, C.; Marchi, S.

    2014-01-01

    A short-course of proton pump inhibitors (PPIs) is often used to confirm gastroesophageal reflux disease (GERD). However, some patients with PPI responsive heartburn do not seem to have evidence of GERD on impedance-pH monitoring (MII-pH). The aim of the study was to evaluate patients with reflux

  1. The influence of hospital drug formulary policies on the prescribing patterns of proton pump inhibitors in primary care

    DEFF Research Database (Denmark)

    Larsen, Michael Due; Schou, Mette; Kristiansen, Anja Sparre

    2014-01-01

    decreased from 33.5 to 9.4 %, corresponding to a risk ratio of 0.28. In primary care after discharge, 13.4 % of esomeprazole use was initiated in the hospital, and this was 8.4 % for PPIs in general. After the change of hospital drug policy, this decreased to 6.5 % for esomeprazole and increased......AIM: This study had two aims: Firstly, to describe how prescriptions for proton pump inhibitor (PPI) in primary care were influenced by a change of the hospital drug policy, and secondly, to describe if a large discount on an expensive PPI (esomeprazole) to a hospital would influence prescribing...... policy on prescribings in primary care was measured by the likelihood of having a high-cost PPI prescribed before and after change of drug policy. RESULTS: In total, 9,341 hospital stays in 2009 and 2010 were included. The probability of a patient to be prescribed an expensive PPI after discharge...

  2. Association of Proton Pump Inhibitors Usage with Risk of Pneumonia in Dementia Patients.

    Science.gov (United States)

    Ho, Sai-Wai; Teng, Ying-Hock; Yang, Shun-Fa; Yeh, Han-Wei; Wang, Yu-Hsun; Chou, Ming-Chih; Yeh, Chao-Bin

    2017-07-01

    To determine the association between usages of proton pump inhibitors (PPIs) and subsequent risk of pneumonia in dementia patients. Retrospective cohort study. Taiwanese National Health Insurance Research Database. The study cohort consisted of 786 dementia patients with new PPI usage and 786 matched dementia patients without PPI usage. The study endpoint was defined as the occurrence of pneumonia. The Cox proportional hazard model was used to estimate the pneumonia risk. Defined daily dose methodology was applied to evaluate the cumulative and dose-response relationships of PPI. Incidence of pneumonia was higher among patients with PPI usage (adjusted hazard ratio (HR) = 1.89; 95% CI = 1.51-2.37). Cox model analysis also demonstrated that age (adjusted HR = 1.05; 95% CI = 1.03-1.06), male gender (adjusted HR = 1.57; 95% CI = 1.25-1.98), underlying cerebrovascular disease (adjusted HR = 1.30; 95% CI = 1.04-1.62), chronic pulmonary disease (adjusted HR = 1.39; 95% CI = 1.09-1.76), congestive heart failure (adjusted HR = 1.54; 95% CI = 1.11-2.13), diabetes mellitus (adjusted HR = 1.54; 95% CI = 1.22-1.95), and usage of antipsychotics (adjusted HR = 1.29; 95% CI = 1.03-1.61) were independent risk factors for pneumonia. However, usage of cholinesterase inhibitors and histamine receptor-2 antagonists were shown to decrease pneumonia risk. PPI usage in dementia patients is associated with an 89% increased risk of pneumonia. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  3. Esophageal mucosal breaks in gastroesophageal reflux disease partially responsive to proton pump inhibitor therapy.

    Science.gov (United States)

    Shaheen, Nicholas J; Denison, Hans; Björck, Karin; Silberg, Debra G

    2013-04-01

    Approximately 20-30% of patients with gastroesophageal reflux disease (GERD) do not experience complete symptom resolution during proton pump inhibitor (PPI) therapy. The aim of this study was to determine the prevalence of esophageal mucosal breaks among patients who have a partial response to PPI therapy. This was an analysis of data from a phase 2b clinical trial carried out to assess the efficacy and safety of a reflux inhibitor, lesogaberan (AZD3355), as an add-on to PPI therapy in this patient population (clinicaltrials.gov reference: NCT01005251). A total of 661 patients with persistent GERD symptoms who had received a minimum of 4 weeks of PPI therapy were included in the study. The prevalence of esophageal mucosal breaks was assessed according to (i) the most recent endoscopy results from within the previous 24 months, if available ("historical" endoscopies), and (ii) the results of endoscopies performed at study baseline ("baseline" endoscopies). Baseline endoscopies were not carried out in patients who had a historical endoscopy showing an absence of esophageal mucosal breaks. Historical endoscopy results were available for 244 patients, of whom 48 (19.7%) had esophageal mucosal breaks. Baseline endoscopies were carried out in 465 patients, of whom 146 (31.4%) had esophageal mucosal breaks. Sensitivity analyses showed a prevalence of esophageal mucosal breaks of 20-30%. In both the historical and baseline endoscopies, most esophageal mucosal breaks were Los Angeles grades A or B. In patients with GERD symptoms partially responsive to PPI therapy, mild-to-moderate severity esophageal mucosal breaks are common (prevalence 20-30%), and may contribute to symptom etiology.

  4. Evaluation of potential interactions between mycophenolic acid derivatives and proton pump inhibitors.

    Science.gov (United States)

    Gabardi, Steven; Olyaei, Ali

    2012-01-01

    To evaluate the incidence of gastrointestinal (GI) complications in solid organ transplant (SOT) recipients, impact of the complications on transplant outcomes, and the potential interactions between mycophenolic acid (MPA) derivatives and proton pump inhibitors (PPIs). An unrestricted literature search (1980-January 2012) was performed with MEDLINE and EMBASE using the following key words: drug-drug interaction, enteric-coated mycophenolic acid, GI complications, mycophenolate mofetil, solid organ transplant, and proton pump inhibitor, including individual agents within the class. Abstracts from scientific meetings were also evaluated. Additionally, reference citations from identified publications were reviewed. Relevant English-language, original research articles and review articles were evaluated if they focused on any of the topics identified in the search or included substantial content addressing GI complications in SOT recipients or drug interactions. GI complications are frequent among SOT recipients, with some studies showing prevalence rates as high as 70%. Transplant outcomes among renal transplant recipients are significantly impacted by GI complications, especially in patients requiring immunosuppressant dosage reductions or premature discontinuation. To this end, PPI use among patients receiving transplants is common. Recent data demonstrate that PPIs significantly reduce the overall exposure to MPA after oral administration of mycophenolate mofetil. Similar studies show this interaction does not exist between PPIs and enteric-coated mycophenolic acid (EC-MPA). Unfortunately, most of the available data evaluating this interaction are pharmacokinetic analyses that do not investigate the clinical impact of this interaction. A significant interaction exists between PPIs and mycophenolate mofetil secondary to reduced dissolution of mycophenolate mofetil in higher pH environments. EC-MPA is not absorbed in the stomach; therefore, low intragastric acidity

  5. Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy.

    Science.gov (United States)

    Kawara, Fumiaki; Fujita, Tsuyoshi; Morita, Yoshinori; Uda, Atsushi; Masuda, Atsuhiro; Saito, Masaya; Ooi, Makoto; Ishida, Tsukasa; Kondo, Yasuyuki; Yoshida, Shiei; Okuno, Tatsuya; Yano, Yoshihiko; Yoshida, Masaru; Kutsumi, Hiromu; Hayakumo, Takanobu; Yamashita, Kazuhiko; Hirano, Takeshi; Hirai, Midori; Azuma, Takeshi

    2017-03-21

    To elucidate the factors associated with residual gastroesophageal reflux disease (GERD) symptoms in patients receiving proton pump inhibitor (PPI) maintenance therapy in clinical practice. The study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed. The FSSG scores ranged from 1 to 28 points (median score: 7.5 points), and 19 patients (48.7%) had a score of 8 points or more. The patients' GSRS scores were significantly correlated with their FSSG scores (correlation coefficient = 0.47, P reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P reflux disease patients were significantly lower than those of the other patients (total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01). Approximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.

  6. Is there an overprescription of proton pump inhibitors in oncohematologic patients undergoing ambulatory oncospecific treatment?

    Directory of Open Access Journals (Sweden)

    Meritxell Pujal Herranz

    2016-09-01

    Full Text Available Objective: The aim of this study is to evaluate the prevalence of proton pump inhibitors (PPIs prescription, and the level of adequacy of the indication of these drugs in oncohematologic patients under ambulatory oncoespecific treatment. Method: An observational descriptive study in oncohematologic patients under ambulatory oncoespecific treatment. A protocol for the rational use of PPI targeted to oncohematologic patients based on the PPI protocol of our hospital was designed. Patients under active treatment with PPIs were quantified and the appropriateness of their indications evaluated. Results: 111 patients (71 oncologic and 40 hematologic were included. 56% of all oncologic patients and 63% of all hematologic patients were under active treatment with PPIs. After reviewing the indications for PPI in all patients, 72% of oncologic and 12% of hematologic patients did not present evidence justifying treatment with these drugs. Conclusion: It is important the pharmacist to detect unappropriated prescriptions of PPIs, especially among oncologic patients, and to promote a deprescription of these drugs

  7. Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine.

    Science.gov (United States)

    El Rouby, Nihal; Lima, John J; Johnson, Julie A

    2018-04-01

    Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism. Areas covered: This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism. Additionally, the role of CYP2C19 genetic variability in the therapeutic effectiveness or outcomes of PPI therapy is highlighted in details, to provide supporting evidence for the potential value of CYP2C19 genotype-guided approaches to PPI drug therapy. Expert opinion: There is a large body of evidence describing the impact of CYP2C19 variability on PPIs and its potential role in individualizing PPI therapy, yet, CYP2C19 pharmacogenetics has not been widely implemented into clinical practice. More data are needed but CYP2C19 genotype-guided dosing of PPIs is likely to become increasingly common and is expected to improve clinical outcomes, and minimize side effects related to PPIs.

  8. Use of proton pump inhibitors is associated with increased mortality due to nosocomial pneumonia in bedridden patients receiving tube feeding.

    Science.gov (United States)

    Hamai, Kosuke; Iwamoto, Hiroshi; Ohshimo, Shinichiro; Wakabayashi, Yu; Ihara, Daisuke; Fujitaka, Kazunori; Hamada, Hironobu; Ono, Koichi; Hattori, Noboru

    2018-05-22

    To investigate the association between the use of proton pump inhibitors (PPI) and nosocomial pneumonia and gastrointestinal bleeding in bedridden patients receiving tube feeding. A total of 116 bedridden hospitalized patients receiving tube feeding, of which 80 were supported by percutaneous endoscopic gastrostomy and 36 by nasogastric tube, were included in the present study. The patients were divided into two groups: 62 patients treated with PPI (PPI group) and 54 patients without PPI (non-PPI group). Mortality due to nosocomial pneumonia was evaluated using the Kaplan-Meier approach and the log-rank test. A total of 36 patients (31%) died of nosocomial pneumonia during the observation period; the mortality rate due to nosocomial pneumonia was significantly higher in the PPI group than in the non-PPI group (P = 0.0395). Cox proportional hazard analysis showed that the use of PPI and lower levels of serum albumin were independent predictors of 2-year mortality due to nosocomial pneumonia. Gastrointestinal bleeding was observed in four patients in the non-PPI group (7.7%) and in one patient in the PPI group (1.6%); there was no significant difference between the two groups. The use of PPI in bedridden tube-fed patients was independently associated with mortality due to nosocomial pneumonia, and the PPI group had a non-significant lower incidence of gastrointestinal bleeding than the non-PPI group. Geriatr Gerontol Int 2018; ••: ••-••. © 2018 The Authors Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.

  9. The effect of endoscopic fundoplication and proton pump inhibitors on baseline impedance and heartburn severity in GERD patients.

    Science.gov (United States)

    Rinsma, N F; Farré, R; Bouvy, N D; Masclee, A A M; Conchillo, J M

    2015-02-01

    Antireflux therapy may lead to recovery of impaired mucosal integrity in gastro-esophageal reflux disease (GERD) patients as reflected by an increase in baseline impedance. The study objective was to evaluate the effect of endoscopic fundoplication and proton pump inhibitor (PPI) PPI therapy on baseline impedance and heartburn severity in GERD patients. Forty-seven GERD patients randomized to endoscopic fundoplication (n = 32) or PPI therapy (n = 15), and 29 healthy controls were included. Before randomization and 6 months after treatment, baseline impedance was obtained during 24-h pH-impedance monitoring. Heartburn severity was evaluated using the GERD-HRQL questionnaire. Before treatment, baseline impedance in GERD patients was lower than in healthy controls (p heartburn severity indicates that other factors may contribute to heartburn perception in GERD. © 2014 John Wiley & Sons Ltd.

  10. A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial

    NARCIS (Netherlands)

    Boeckxstaens, Guy E.; Beaumont, Hanneke; Hatlebakk, Jan G.; Silberg, Debra G.; Björck, Karin; Karlsson, Maria; Denison, Hans

    2011-01-01

    o evaluate the efficacy and tolerability of add-on treatment with lesogaberan (AZD3355), a novel reflux inhibitor, in patients with persistent gastro-oesophageal reflux disease (GORD) symptoms despite proton pump inhibitor (PPI) therapy. double-blind, placebo-controlled, randomised, parallel-group,

  11. Influence of proton pump inhibitors on gastritis diagnosis and pathologic gastric changes.

    Science.gov (United States)

    Nasser, Soumana C; Slim, Mahmoud; Nassif, Jeanette G; Nasser, Selim M

    2015-04-21

    To investigate the influence of proton pump inhibitors (PPIs) exposure on the diagnosis of Helicobacter pylori (H. pylori) gastritis and intestinal metaplasia. Chronic PPI use is associated with masking of H. pylori infection. Patients with H. pylori infection are predisposed to gastric and duodenal ulcers, and long-term infection with this organism has been associated with gastric mucosal atrophy and serious long-term complications, such as gastric lymphoma and adenocarcinoma. Three hundred patients diagnosed with gastritis between January 2008 and April 2010 were included in our study. The computerized medical database of these patients was reviewed retrospectively in order to assess whether the type of gastritis diagnosed (H. pylori vs non-H. pylori gastritis) is influenced by PPI exposure. H. pylori density was graded as low, if corresponding to mild density following the Updated Sydney System, or high, if corresponding to moderate or severe densities in the Updated Sydney System. Patients were equally distributed between males and females with a median age at the time of diagnosis of 50 years old (range: 20-87). The histological types of gastritis were classified as H. pylori gastritis (n = 156, 52%) and non-H. pylori gastritis (n = 144, 48%). All patients with non-H. pylori gastritis had inactive chronic gastritis. Patients with no previous PPI exposure were more likely to be diagnosed with H. pylori gastritis than those with previous PPI exposure (71% vs 34.2%, P gastritis and leads to a significant drop in H. pylori densities and to an increased risk of intestinal metaplasia. The use of PPIs masks H. pylori infection, promotes the diagnosis of non-H. pylori inactive chronic gastritis diagnosis, and increases the incidence of intestinal metaplasia.

  12. Proton-pump inhibitors for prevention of upper gastrointestinal bleeding in patients undergoing dialysis.

    Science.gov (United States)

    Song, Young Rim; Kim, Hyung Jik; Kim, Jwa-Kyung; Kim, Sung Gyun; Kim, Sung Eun

    2015-04-28

    To investigate the preventive effects of low-dose proton-pump inhibitors (PPIs) for upper gastrointestinal bleeding (UGIB) in end-stage renal disease. This was a retrospective cohort study that reviewed 544 patients with end-stage renal disease who started dialysis at our center between 2005 and 2013. We examined the incidence of UGIB in 175 patients treated with low-dose PPIs and 369 patients not treated with PPIs (control group). During the study period, 41 patients developed UGIB, a rate of 14.4/1000 person-years. The mean time between the start of dialysis and UGIB events was 26.3 ± 29.6 mo. Bleeding occurred in only two patients in the PPI group (2.5/1000 person-years) and in 39 patients in the control group (19.2/1000 person-years). Kaplan-Meier analysis of cumulative non-bleeding survival showed that the probability of UGIB was significantly lower in the PPI group than in the control group (log-rank test, P < 0.001). Univariate analysis showed that coronary artery disease, PPI use, anti-coagulation, and anti-platelet therapy were associated with UGIB. After adjustments for the potential factors influencing risk of UGIB, PPI use was shown to be significantly beneficial in reducing UGIB compared to the control group (HR = 13.7, 95%CI: 1.8-101.6; P = 0.011). The use of low-dose PPIs in patients with end-stage renal disease is associated with a low frequency of UGIB.

  13. Use of proton pump inhibitors for the provision of stress ulcer prophylaxis: clinical and economic consequences.

    Science.gov (United States)

    Barletta, Jeffrey F; Sclar, David A

    2014-01-01

    The provision of stress ulcer prophylaxis (SUP) for the prevention of clinically significant bleeding is widely recognized as a crucial component of care in critically ill patients. Nevertheless, SUP is often provided to non-critically ill patients despite a risk for clinically significant bleeding of roughly 0.1 %. The overuse of SUP therefore introduces added risks for adverse drug events and cost, with minimal expected benefit in clinical outcome. Historically, histamine-2-receptor antagonists (H2RAs) have been the preferred agent for SUP; however, recent data have revealed proton pump inhibitors (PPIs) as the most common modality (76 %). There are no high quality randomized controlled trials demonstrating superiority with PPIs compared with H2RAs for the prevention of clinically significant bleeding associated with stress ulcers. In contrast, PPIs have recently been linked to several adverse effects including Clostridium difficile diarrhea and pneumonia. These complications have substantial economic consequences and have a marked impact on the overall cost effectiveness of PPI therapy. Nevertheless, PPI use remains widespread in patients who are at both high and low risk for clinically significant bleeding. This article will describe the utilization of PPIs for SUP and present the clinical and economic consequences linked to their use/overuse.

  14. Evidence-based support for the use of proton pump inhibitors in cancer therapy.

    Science.gov (United States)

    Fais, Stefano

    2015-11-24

    'We can only cure what we can understand first', said Otto H. Warburg, the 1931 Nobel laureate for his discovery on tumor metabolism. Unfortunately, we still don't know too much the mechanisms underlying of cancer development and progression. One of the unsolved mystery 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 development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. One of the most mechanism to survive to the acidic tumor microenvironment are proton exchangers not allowing intracellular acidification through a continuous elimination of H(+) either outside the cells or within the internal vacuoles. This article wants to comment a translational process through which from the preclinical demonstration that a class of proton pump inhibitors (PPI) exploited worldwide for peptic ulcer treatment and gastroprotection are indeed chemosensitizers as well, we have got to the clinical proof of concept that PPI may well be included in new anti-cancer strategies, and with a solid background and rationale.

  15. The influence of proton pump inhibitors and other commonly used medication on the gut microbiota.

    Science.gov (United States)

    Imhann, Floris; Vich Vila, Arnau; Bonder, Marc Jan; Lopez Manosalva, Ailine G; Koonen, Debby P Y; Fu, Jingyuan; Wijmenga, Cisca; Zhernakova, Alexandra; Weersma, Rinse K

    2017-07-04

    Proton pump inhibitors (PPIs), used to treat gastro-esophageal reflux and prevent gastric ulcers, are among the most widely used drugs in the world. The use of PPIs is associated with an increased risk of enteric infections. Since the gut microbiota can, depending on composition, increase or decrease the risk of enteric infections, we investigated the effect of PPI-use on the gut microbiota. We discovered profound differences in the gut microbiota of PPI users: 20% of their bacterial taxa were statistically significantly altered compared with those of non-users. Moreover, we found that it is not only PPIs, but also antibiotics, antidepressants, statins and other commonly used medication were associated with distinct gut microbiota signatures. As a consequence, commonly used medications could affect how the gut microbiota resist enteric infections, promote or ameliorate gut inflammation, or change the host's metabolism. More studies are clearly needed to understand the role of commonly used medication in altering the gut microbiota as well as the subsequent health consequences.

  16. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury.

    Science.gov (United States)

    Xie, Yan; Bowe, Benjamin; Li, Tingting; Xian, Hong; Yan, Yan; Al-Aly, Ziyad

    2017-06-01

    Proton pump inhibitor (PPI) use is associated with an increased risk of acute kidney injury (AKI), incident chronic kidney disease (CKD), and progression to end-stage renal disease (ESRD). PPI-associated CKD is presumed to be mediated by intervening AKI. However, whether PPI use is associated with an increased risk of chronic renal outcomes in the absence of intervening AKI is unknown. To evaluate this we used the Department of Veterans Affairs national databases to build a cohort of 144,032 incident users of acid suppression therapy that included 125,596 PPI and 18,436 Histamine H2 receptor antagonist (H2 blockers) consumers. Over 5 years of follow-up in survival models, cohort participants were censored at the time of AKI occurrence. Compared with incident users of H2 blockers, incident users of PPIs had an increased risk of an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73m 2 (hazard ratio 1.19; 95% confidence interval 1.15-1.24), incident CKD (1.26; 1.20-1.33), eGFR decline over 30% (1.22; 1.16-1.28), and ESRD or eGFR decline over 50% (1.30; 1.15-1.48). Results were consistent in models that excluded participants with AKI either before chronic renal outcomes, during the time in the cohort, or before cohort entry. The proportion of PPI effect mediated by AKI was 44.7%, 45.47%, 46.00%, and 46.72% for incident eGFR under 60 ml/min/1.73m 2 , incident CKD, eGFR decline over 30%, and ESRD or over 50% decline in eGFR, respectively. Thus, PPI use is associated with increased risk of chronic renal outcomes in the absence of intervening AKI. Hence, reliance on antecedent AKI as warning sign to guard against the risk of CKD among PPI users is not sufficient as a sole mitigation strategy. Published by Elsevier Inc.

  17. Proton pump inhibitor co-prescription with dual antiplatelet therapy among patients with acute coronary syndrome in Qatar.

    Science.gov (United States)

    Awaisu, Ahmed; Hamou, Fatima; Mekideche, Lylia; El Muabby, Nisrine; Mahfouz, Ahmed; Mohammed, Shaban; Saad, Ahmad

    2016-04-01

    There are increasing concerns about clinically significant interactions between proton pump inhibitors (PPIs) and clopidogrel, resulting in adverse cardiovascular outcomes in patients with acute coronary syndromes (ACS). However, published evidence on the prevalence and predictors of PPI use with dual antiplatelet therapy (DAPT) is scarce. This study investigated the prevalence of PPI use among patients with ACS receiving DAPT and possible predictors of co-prescribing the PPIs with the DAPT. Heart Hospital, a specialized tertiary care center in Qatar. A retrospective observational study of a prescription database was conducted. Subjects included 626 patients admitted between January and December 2012 with the diagnosis of ACS who received DAPT and discharged with or without a PPI. Univariate analysis and multivariate binary logistic regression analysis were performed to determine the predictors of PPI-DAPT co-prescription. Prevalence of PPI co-prescribing with DAPT in proportions and percentages and odd ratios for the predictors of PPI-DAPT co-prescribing. A total of 626 patients were analyzed for PPI prevalence, with 200 patients (32 %) being prescribed PPI with DAPT upon discharge. After controlling for confounders, PPI use on admission (aOR 14.5; 95 % CI 7.6-27.6, p < 0.001), nationality (aOR 3.2; 95 % CI 1.1-9.9, p = 0.041), and having a history of diabetes (aOR 0.5; 95 % CI 0.24-0.99, p = 0.046) significantly influenced PPI-DAPT co-prescribing. Users of PPI on admission compared to nonusers were about 15 times more likely to be prescribed PPI with DAPT upon discharge; likewise, having Qatari nationality increased the likelihood of co-prescribing PPI with DAPT upon discharge by three folds. Lastly, patients with a history of diabetes were 50 % less likely to be prescribed PPIs upon discharge compared to those with no history of diabetes. The rate of PPI co-prescribing with DAPT in the population studied was relatively high. The strongest predictor of PPI co

  18. Association of Proton Pump Inhibitors with Reduced Risk of Warfarin-related Serious Upper Gastrointestinal Bleeding

    Science.gov (United States)

    Ray, Wayne A.; Chung, Cecilia P.; Murray, Katherine T.; Smalley, Walter E.; Daugherty, James R.; Dupont, William D.; Stein, C. Michael

    2016-01-01

    Background & Aims Proton-pump inhibitors (PPIs) might reduce the risk of serious warfarin-related upper gastrointestinal bleeding, but the evidence of their efficacy for this indication is limited. A gastroprotective effect of PPIs would be particularly important for patients who take warfarin with antiplatelet drugs or nonselective non-steroidal anti-inflammatory drugs (NSAIDs), which further increase the risk of gastrointestinal bleeding. Methods This retrospective cohort study of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample identified 97,430 new episodes of warfarin treatment with 75,720 person-years of follow up. The study endpoints were hospitalizations for upper gastrointestinal bleeding potentially preventable by PPIs and for bleeding at other sites. Results Patients who took warfarin without PPI co-therapy had 119 hospitalizations for upper gastrointestinal bleeding per 10,000 person-years of treatment. The risk decreased by 24% among patients who received PPI co-therapy (adjusted hazard ratio [HR], 0.76; 95% CI, 0.63–0.91). There was no significant reduction in the risk of other gastrointestinal bleeding hospitalizations (HR, 1.07; 95% CI, 0.94–1.22) or non-gastrointestinal bleeding hospitalizations (HR, 0.98; 95% CI, 0.84–1.15) in this group. Among patients concurrently using antiplatelet drugs or NSAIDs, those without PPI co-therapy had 284 upper gastrointestinal bleeding hospitalizations per 10,000 person-years of warfarin treatment. The risk decreased by 45% (HR, 0.55; 95% CI, 0.39–0.77) with PPI co-therapy. PPI co-therapy had no significant protective effect for warfarin patients not using antiplatelet drugs or NSAIDs (HR, 0.86; 95% CI, 0.70-1.06). Findings were similar in both study populations. Conclusions In an analysis of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample, PPI co-therapy was associated with reduced risk of warfarin-related upper

  19. Lifestyle factors among proton pump inhibitor users and nonusers: a cross-sectional study in a population-based setting.

    Science.gov (United States)

    Hvid-Jensen, Frederik; Nielsen, Rikke B; Pedersen, Lars; Funch-Jensen, Peter; Drewes, Asbjørn Mohr; Larsen, Finn B; Thomsen, Reimar W

    2013-01-01

    Lifestyle factors may influence observed associations between proton pump inhibitor (PPI) usage and health outcomes. The aim of the study reported here was to examine characteristics and differences in lifestyle among PPI users and nonusers. This cross-sectional study utilized data from a 2006 population-based health survey of 21,637 persons in the Central Danish Region. All persons using prescribed PPIs were identified through linkage to a population-based prescription database. Biometric measures and prevalence of smoking, excessive alcohol consumption, diet, and physical exercise were analyzed, comparing PPI users with nonusers. Among 10,129 (46.8%) male and 11,508 (53.2%) female survey respondents, 1,356 (13.4%) males and 1,691 (14.7%) females reported ever use of PPIs. PPI users were more obese (16.7%) than nonusers (13.1%), with an age- and sex-standardized prevalence ratio (PR) of 1.3 (95% confidence interval [CI]: 1.2-1.4). The prevalence of smokers was also higher in the PPI group (26.2% vs 22.3% [PR =1.2, 95% CI: 1.1-1.3]), as was the prevalence of ex-smokers (41.0% vs 32.0% [PR =1.2, 95% CI: 1.1-1.2]). Unhealthy diet was slightly more common among PPI users than among nonusers (15.4% vs 13.0%), with a PR of 1.2 (95% CI: 1.1-1.3). Physical exercise level and alcohol consumption were similar in the two groups. Hospital-diagnosed comorbidity was observed in 35% of PPI users (a Charlson Comorbidity Index score of 1 or more) compared with only 15% among nonusers. PPI users are more obese, smoke more, and have significantly more comorbidities than PPI nonusers. These data are important when evaluating unmeasured confounding in observational studies of PPI effects.

  20. Role of Acid and Weakly Acidic Reflux in Gastroesophageal Reflux Disease Off Proton Pump Inhibitor Therapy

    Science.gov (United States)

    Sung, Hea Jung; Moon, Sung Jin; Kim, Jin Su; Lim, Chul Hyun; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gye

    2012-01-01

    Background/Aims Available data about reflux patterns and symptom determinants in the gastroesophageal reflux disease (GERD) subtypes off proton pump inhibitor (PPI) therapy are lacking. We aimed to evaluate reflux patterns and determinants of symptom perception in patients with GERD off PPI therapy by impedance-pH monitoring. Methods We retrospectively reviewed the impedance-pH data in patients diagnosed as GERD based on results of impedance-pH monitoring, endoscopy and/or typical symptoms. The characteristics of acid and weakly acidic reflux were evaluated. Symptomatic and asymptomatic reflux were compared according to GERD subtypes and individual symptoms. Results Forty-two patients (22 males, mean age 46 years) were diagnosed as GERD (17 erosive reflux disease, 9 pH(+) non-erosive reflux disease [NERD], 9 hypersensitive esophagus and 7 symptomatic NERD). A total of 1,725 reflux episodes were detected (855 acid [50%], 857 weakly acidic [50%] and 13 weakly alkaline reflux [reflux was more frequently symptomatic and bolus clearance was longer compared with weakly acidic reflux. In terms of globus, weakly acidic reflux was more symptomatic. Symptomatic reflux was more frequently acid and mixed reflux; these associations were more pronounced in erosive reflux disease and symptomatic NERD. The perception of regurgitation was related to acid reflux, while that of globus was more related to weakly acidic reflux. Conclusions In patients not taking PPI, acid reflux was more frequently symptomatic and had longer bolus clearance. Symptomatic reflux was more frequently acid and mixed type; however, weakly acidic reflux was associated more with globus. These data suggest a role for impedance-pH data in the evaluation of globus. PMID:22837877

  1. Esophageal Baseline Impedance Reflects Mucosal Integrity and Predicts Symptomatic Outcome With Proton Pump Inhibitor Treatment.

    Science.gov (United States)

    Xie, Chenxi; Sifrim, Daniel; Li, Yuwen; Chen, Minhu; Xiao, Yinglian

    2018-01-30

    Esophageal baseline impedance, which is decreased in gastroesophageal reflux disease (GERD) patients, is related to the severity of acid reflux and the integrity of the esophageal mucosa. The study aims to compare the baseline impedance and the dilated intercellular spaces (DIS) within patients with typical reflux symptoms and to evaluate the correlation of baseline impedance with DIS, esophageal acid exposure, as well as the efficacy of proton pump inhibitor (PPI) treatment. Ninety-two patients and 10 healthy controls were included in the study. Erosive esophagitis (EE) was defined by esophageal mucosal erosion under upper endoscopy. Patients without mucosa erosion were divided into groups with pathologic acid reflux (non-erosive reflux disease [NERD]) or with hypersensitive esophagus. The biopsies of esophageal mucosa were taken 2-4 cm above the gastroesophageal junction Z-line during upper endoscopy for DIS measurement. All the patients received esomeprazole 20 mg twice-daily treatment for 8 weeks. The efficacy of esomeprazole was evaluated among all patients. The intercellular spaces were dilated in both EE and NERD patients ( P baseline impedance was decreased in both EE patients and NERD patients, and negatively correlated to the acid exposure time ( r = -0.527, P baseline impedance ( r = -0.230, P Baseline impedance > 1764 Ω" was an independent predictor for PPI failure (OR, 11.9; 95% CI, 2.4-58.9; P baseline impedance was observed in patients with mucosa erosion or pathological acid reflux. The baseline impedance reflected the mucosal integrity, it was more sensitive to esophageal acid exposure. Patients with high impedance might not benefit from the PPI treatment.

  2. Role of Acid and weakly acidic reflux in gastroesophageal reflux disease off proton pump inhibitor therapy.

    Science.gov (United States)

    Sung, Hea Jung; Cho, Yu Kyung; Moon, Sung Jin; Kim, Jin Su; Lim, Chul Hyun; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gye

    2012-07-01

    Available data about reflux patterns and symptom determinants in the gastroesophageal reflux disease (GERD) subtypes off proton pump inhibitor (PPI) therapy are lacking. We aimed to evaluate reflux patterns and determinants of symptom perception in patients with GERD off PPI therapy by impedance-pH monitoring. We retrospectively reviewed the impedance-pH data in patients diagnosed as GERD based on results of impedance-pH monitoring, endoscopy and/or typical symptoms. The characteristics of acid and weakly acidic reflux were evaluated. Symptomatic and asymptomatic reflux were compared according to GERD subtypes and individual symptoms. Forty-two patients (22 males, mean age 46 years) were diagnosed as GERD (17 erosive reflux disease, 9 pH(+) non-erosive reflux disease [NERD], 9 hypersensitive esophagus and 7 symptomatic NERD). A total of 1,725 reflux episodes were detected (855 acid [50%], 857 weakly acidic [50%] and 13 weakly alkaline reflux [Acid reflux was more frequently symptomatic and bolus clearance was longer compared with weakly acidic reflux. In terms of globus, weakly acidic reflux was more symptomatic. Symptomatic reflux was more frequently acid and mixed reflux; these associations were more pronounced in erosive reflux disease and symptomatic NERD. The perception of regurgitation was related to acid reflux, while that of globus was more related to weakly acidic reflux. In patients not taking PPI, acid reflux was more frequently symptomatic and had longer bolus clearance. Symptomatic reflux was more frequently acid and mixed type; however, weakly acidic reflux was associated more with globus. These data suggest a role for impedance-pH data in the evaluation of globus.

  3. Effects of Proton Pump Inhibitor Administration and Intake of a Combination of Yogurt and Galactooligosaccharides on Bone and Mineral Metabolism in Rats

    Directory of Open Access Journals (Sweden)

    Satoshi Takasugi

    2016-10-01

    Full Text Available The aim of this study was to investigate the effects of proton pump inhibitor (PPI, the most potent acid-suppressing drug, administration and intake of a combination of yogurt and galactooligosaccharides (YG on bone and mineral metabolism in adult rats. Twelve-week-old male Wistar rats were divided into three groups: a control group fed the control diet with vehicle administration, a PPI group fed the control diet with PPI administration and a YG + PPI group fed the YG diet with PPI administration. All of the groups received their respective experimental diets and daily subcutaneous injection of the vehicle or PPI for 12 weeks. The PPI group showed significantly lower bone mineral density (BMD of the femur and the lumbar vertebrae and serum fibroblast growth factor 23 (FGF23 and significantly higher phosphorus absorption and serum 1,25-dihydroxyvitamin D (1,25(OH2D than the control group, although PPI did not affect calcium absorption. The PPI + YG group showed significantly higher BMD and serum FGF23 and significantly lower phosphorus absorption and serum 1,25(OH2D than the PPI group. Furthermore, the PPI + YG group showed higher calcium absorption than the control group. These results suggest that although PPI administration did not affect calcium absorption, it adversely affected BMD and influenced phosphorus metabolism in adult rats. Furthermore, the YG diet beneficially affected BMD and attenuated the effects of PPI administration on phosphorus metabolism.

  4. Proton pump inhibitor failure in gastro-oesophageal reflux disease: a perspective aided by the Gartner hype cycle.

    Science.gov (United States)

    Heading, Robert C

    2017-04-01

    Some patients with gastro-oesophageal reflux disease (GORD) experience symptoms despite proton pump inhibitor (PPI) treatment. In the early years of their availability, these drugs were thought to be a highly effective treatment for GORD and realisation that symptom relief was often incomplete came as a disappointment. This review considers the evolution of thinking with the aid of the Gartner hype cycle - a graphical depiction of the process of innovation, evolution and adoption of new technologies. Acknowledging that over-simplistic concepts of GORD have been largely responsible for inflated expectations of PPI therapy is an important step forward in establishing how patients with persistent symptoms, despite PPIs, should be assessed and treated. © Royal College of Physicians 2017. All rights reserved.

  5. Unexplained abdominal pain as a driver for inappropriate therapeutics: an audit on the use of intravenous proton pump inhibitors.

    Science.gov (United States)

    Lai, Pauline Siew Mei; Wong, Yin Yen; Low, Yong Chia; Lau, Hui Ling; Chin, Kin-Fah; Mahadeva, Sanjiv

    2014-01-01

    Background. Proton pump inhibitors (PPIs) are currently the most effective agents for acid-related disorders. However, studies show that 25-75% of patients receiving intravenous PPIs had no appropriate justification, indicating high rates of inappropriate prescribing. Objective. To examine the appropriate use of intravenous PPIs in accordance with guidelines and the efficacy of a prescribing awareness intervention at an Asian teaching institution. Setting. Prospective audit in a tertiary hospital in Malaysia. Method. Every 4th intravenous PPI prescription received in the pharmacy was screened against hospital guidelines. Interventions for incorrect indication/dose/duration were performed. Patients' demographic data, medical history and the use of intravenous PPI were collected. Included were all adult inpatients prescribed intravenous PPI. Main Outcome Measure. Proportion of appropriate IV PPI prescriptions. Results. Data for 106 patients were collected. Most patients were male [65(61.3%)], Chinese [50(47.2%)], with mean age ± SD = 60.3 ± 18.0 years. Most intravenous PPI prescriptions were initiated by junior doctors from the surgical [47(44.3%)] and medical [42(39.6%)] departments. Only 50/106(47.2%) patients had upper gastrointestinal endoscopy/surgery performed to verify the source of bleeding. Unexplained abdominal pain [81(76.4%)] was the main driver for prescribing intravenous PPIs empirically, out of which 73(68.9%) were for suspected upper gastrointestinal bleed. Overall, intravenous PPI was found to be inappropriately prescribed in 56(52.8%) patients for indication, dose or duration. Interventions on the use of intravenous PPI were most effective when performed by senior doctors (100%), followed by clinical pharmacists (50%), and inpatient pharmacists (37.5%, p = 0.027). Conclusion. Inappropriate intravenous PPI usage is still prevalent despite the enforcement of hospital guidelines. The promotion of prescribing awareness and evidence-based prescribing

  6. Unexplained abdominal pain as a driver for inappropriate therapeutics: an audit on the use of intravenous proton pump inhibitors

    Directory of Open Access Journals (Sweden)

    Pauline Siew Mei Lai

    2014-06-01

    Full Text Available Background. Proton pump inhibitors (PPIs are currently the most effective agents for acid-related disorders. However, studies show that 25–75% of patients receiving intravenous PPIs had no appropriate justification, indicating high rates of inappropriate prescribing.Objective. To examine the appropriate use of intravenous PPIs in accordance with guidelines and the efficacy of a prescribing awareness intervention at an Asian teaching institution.Setting. Prospective audit in a tertiary hospital in Malaysia.Method. Every 4th intravenous PPI prescription received in the pharmacy was screened against hospital guidelines. Interventions for incorrect indication/dose/duration were performed. Patients’ demographic data, medical history and the use of intravenous PPI were collected. Included were all adult inpatients prescribed intravenous PPI.Main Outcome Measure. Proportion of appropriate IV PPI prescriptions.Results. Data for 106 patients were collected. Most patients were male [65(61.3%], Chinese [50(47.2%], with mean age ± SD = 60.3 ± 18.0 years. Most intravenous PPI prescriptions were initiated by junior doctors from the surgical [47(44.3%] and medical [42(39.6%] departments. Only 50/106(47.2% patients had upper gastrointestinal endoscopy/surgery performed to verify the source of bleeding. Unexplained abdominal pain [81(76.4%] was the main driver for prescribing intravenous PPIs empirically, out of which 73(68.9% were for suspected upper gastrointestinal bleed. Overall, intravenous PPI was found to be inappropriately prescribed in 56(52.8% patients for indication, dose or duration. Interventions on the use of intravenous PPI were most effective when performed by senior doctors (100%, followed by clinical pharmacists (50%, and inpatient pharmacists (37.5%, p = 0.027.Conclusion. Inappropriate intravenous PPI usage is still prevalent despite the enforcement of hospital guidelines. The promotion of prescribing awareness and evidence

  7. Use of proton pump inhibitors is associated with fractures in young adults: a population-based study.

    Science.gov (United States)

    Freedberg, D E; Haynes, K; Denburg, M R; Zemel, B S; Leonard, M B; Abrams, J A; Yang, Y-X

    2015-10-01

    Proton pump inhibitors (PPIs) are associated with risk for fracture in osteoporotic adults. In this population-based study, we found a significant association between PPIs and fracture in young adults, with evidence of a dose-response effect. Young adults who use PPIs should be cautioned regarding risk for fracture. Proton pump inhibitors (PPIs) are associated with fracture in adults with osteoporosis. Because PPI therapy may interfere with bone accrual and attainment of peak bone mineral density, we studied the association between use of PPIs and fracture in children and young adults. We conducted a population-based, case-control study nested within records from general medical practices from 1994 to 2013. Participants were 4-29 years old with ≥ 1 year of follow-up who lacked chronic conditions associated with use of long-term acid suppression. Cases of fracture were defined as the first incident fracture at any site. Using incidence density sampling, cases were matched with up to five controls by age, sex, medical practice, and start of follow-up. PPI exposure was defined as 180 or more cumulative doses of PPIs. Conditional logistic regression was used to estimate the odds ratio and confidence interval for use of PPIs and fracture. We identified 124,799 cases and 605,643 controls. The adjusted odds ratio for the risk of fracture associated with PPI exposure was 1.13 (95% CI 0.92 to 1.39) among children aged young adults aged 18-29 years old. In young adults but not children, we observed a dose-response effect with increased total exposure to PPIs (p for trend young adults, but overall evidence did not support a PPI-fracture relationship in children. Young adults who use PPIs should be cautioned regarding potentially increased risk for fracture, even if they lack traditional fracture risk factors.

  8. Proton Pump Inhibitors Intake and Iron and Vitamin B12 Status: A Prospective Comparative Study with a Follow up of 12 Months

    OpenAIRE

    Qorraj-Bytyqi, Hasime; Hoxha, Rexhep; Sadiku, Shemsedin; Bajraktari, Ismet H.; Sopjani, Mentor; Thaçi, Kujtim; Thaçi, Shpetim; Bahtiri, Elton

    2018-01-01

    BACKGROUND: Proton pump inhibitors (PPIs) represent the most widely prescribed antisecretory agents, but their prolonged use, may influence iron and vitamin B12 status, which could have important implications for clinical practice. AIM: We undertook this study aiming to investigate the association between PPIs use for 12 months and potential changes in iron and vitamin B12 status, as well as whether this potential association varies among four specific PPI drugs used in the study. MET...

  9. Use of antacids, alginates and proton pump inhibitors

    DEFF Research Database (Denmark)

    Lødrup, Anders; Reimer, Christine; Bytzer, Peter

    2014-01-01

    : A cross-sectional survey was conducted in an internet panel representative of the Danish adult population in 2012. Data queried included antacid/alginate and PPI use, reason for therapy, co-medication, and presence of upper gastrointestinal symptoms. Long-term PPI use was defined as using PPI ≥1/3...... of the last year (∼120 days). Risk of long-term PPI use was estimated by logistic regression. RESULTS: A total of 18,223 people received the questionnaire, of which 52% (9390) responded. Antacid/alginate use was reported by 23%; 16% reported use of only antacid/alginate. PPI use was reported by 13.6%; 6....../e-mail, using co-medication, and having started on PPI for several reasons. Combination of antacid/alginate and PPI was reported by approximately 50% of those on therapy with weekly or daily symptoms. CONCLUSION: 23% of Danish adults were using antacids or alginates and 14% were using PPI, of which one...

  10. Effects of Helicobacter pylori infection and long-term proton pump inhibitor use on enterochromaffin-like cells

    Science.gov (United States)

    Bektaş, Mehmet; Saraç, Nurşen; Çetinkaya, Hülya; Törüner, Murat; Erdemli, Esra; Keskin, Onur; Soykan, İrfan; Oktay, Esen Ismet; Korkut, Esin; Üstün, Yusuf; Bahar, Kadir

    2012-01-01

    Background Excessive release of gastrin leads to hypertrophy and hyperplasia of enterochromaffin-like cells (ECL) and prolonged stimulation of these cells causes functional impairment. The purpose of this study was to investigate the effect of Helicobacter pylori (H. pylori) infection and long-term proton pump inhibitors (PPI) use on ECL cells. Methods Fifteen patients who underwent endoscopy because of dyspeptic symptoms were enrolled in the present study. Biopsies were taken from corpus and antrum and existence of H. pylori was investigated with culture, cytology and CLOtest. The patients were divided into 3 groups. Group-A: H. pylori-negative, never treated previously with PPI; Group-B: H. pylori-positive, never treated previously with PPI; and group-C: H. pylori-negative and continuously treated with PPI for more than 6 months before the subject recruitment period. The features of ECL cell in oxyntic glands were examined with electron microscopy on biopsy specimens. Results ECL cells were completely normal in Group A. In group B, moderate hyperplasia and vacuolization was seen in ECL cells. In group C, ECL cell hyperplasia was observed and vacuoles with greater amounts of granules in enlarged vesicles were found more intensely in cytoplasm. Conclusion The use of PPI for a long period of time and presence of H. pylori infection are risk factors for ECL hyperplasia. PMID:24714139

  11. Cognitive impact after short-term exposure to different proton pump inhibitors: assessment using CANTAB software.

    Science.gov (United States)

    Akter, Sanjida; Hassan, Md Rajib; Shahriar, Mohammad; Akter, Nahia; Abbas, Md Golam; Bhuiyan, Mohiuddin Ahmed

    2015-12-27

    Studies have shown that proton pump inhibitors (PPIs) increase the brain burden of amyloid-beta (Aβ) and also create vitamin B12 deficiency. However, these two phenomena have deleterious effect on cognition and Alzheimer's disease (AD). Since the use of PPIs has increased tremendously for the last few years, it is of great public health importance to investigate the cognitive impact of PPIs. Hence, the purpose of this study was to investigate the degree of neuropsychological association of each PPI with different cognitive functions. Sixty volunteers of either gender were recruited and divided randomly into six groups: five test groups for five classes of PPIs and one control group. All the groups participated in the five computerized neuropsychological tests (nine subtests) of the Cambridge Neuropsychological Test Automated Battery twice: at the beginning of the study and 7 days thereafter. We found statistically and clinically significant impairment in visual memory, attention, executive function, and working and planning function. One-way analysis of variance findings showed that all PPIs had a similar negative impact on cognition. However, paired-samples t tests indicated that omeprazole showed significant (p benefits of prescribing these medications. A study done for a longer period of time with a larger sample size might yield better results.

  12. Gastroesophageal reflux symptoms not responding to proton pump inhibitor: GERD, NERD, NARD, esophageal hypersensitivity or dyspepsia?

    Science.gov (United States)

    Bashashati, Mohammad; Hejazi, Reza A; Andrews, Christopher N; Storr, Martin A

    2014-01-01

    Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy. PMID:24719900

  13. Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use.

    Science.gov (United States)

    Kinoshita, Yoshikazu; Ishimura, Norihisa; Ishihara, Shunji

    2018-04-30

    Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed. PPIs tend to be given for conditions in which the necessity of the drug has not been clarified, thus otherwise rare adverse effects are presented as clinically relevant. Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit and to continue to investigate their adverse effects with high quality prospective studies.

  14. [Proton pump inhibitors in gastro-oesophageal reflux disease: what is the further step?].

    Science.gov (United States)

    Simon, Mireille; Zerbib, Frank

    2013-01-01

    Optimisation of proton pump inhibitors use may improve reflux symptoms in 20-25% of the patients. Pathological gastro-oesophageal reflux should be documented in a patient with refractory reflux symptoms using upper endoscopy and/or pH testing. While on proton pump inhibitors twice daily, persistent symptoms are not related to gastro-oesophageal refluxdisease(GERD) in 50% of the patients. The new anti-reflux compounds have yet a limited efficacy and side effects that currently limit their development. Copyright © 2012. Published by Elsevier Masson SAS.

  15. Incidence of Clostridium difficile infection in patients receiving high-risk antibiotics with or without a proton pump inhibitor.

    Science.gov (United States)

    Gordon, D; Young, L R; Reddy, S; Bergman, C; Young, J D

    2016-02-01

    Considering the incidence and severity of Clostridium difficile infection (CDI), risk reduction strategies are crucial. Prior studies suggest that proton pump inhibitor (PPI) use can increase the risk of CDI over antibiotics alone; however, data and guidelines have been conflicting. The aim was to compare CDI incidence in patients receiving high-risk antibiotics, comparing rates in those prescribed a PPI versus those without overlapping PPI exposure. This retrospective cohort study assessed the incidence of CDI in veterans receiving high-risk antibiotics over an approximately three-year period. High-risk antibiotics were defined as: ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, ceftriaxone, cefotaxime, ceftazidime, or cefixime. We identified subjects who were prescribed any high-risk antibiotic, finding 3513 on a concomitant PPI and 6149 not taking a PPI. Of these subjects, 111 were diagnosed with CDI and met inclusion criteria. Baseline characteristics, CDI severity, length of hospitalization and antibiotic therapy prior to infection were similar in both groups. The incidence of CDI was significantly higher in patients prescribed a PPI (odds ratio: 2.2; 95% confidence interval: 1.52-3.23; P=0.0001). A strong association was found between concurrent PPI use with fluoroquinolones (P=0.005) and clindamycin (P=0.045). The use of PPIs together with high-risk antibiotics was associated with a significantly higher incidence of CDI. Our study provides further support for the CDI prevention strategy of judicious PPI use, especially in patients receiving high-risk antibiotics. Prudent avoidance of PPIs may reduce the incidence of CDI, a major cause of morbidity and mortality worldwide. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  16. Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population.

    Directory of Open Access Journals (Sweden)

    Nigam H Shah

    Full Text Available Proton pump inhibitors (PPIs have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.Using a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population.In multiple data sources, we found gastroesophageal reflux disease (GERD patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09-1.24 with myocardial infarction (MI. Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07-3.78; P = 0.031 increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.Consistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.

  17. Rational use of nonsteroidal anti-inflammatory drugs and proton pump inhibitors in combination for rheumatic diseases

    Directory of Open Access Journals (Sweden)

    Wolfgang W Bolten

    2010-09-01

    Full Text Available Wolfgang W BoltenDivision of Rheumatology, Klaus-Miehlke Klinik, Wiesbaden, GermanyAbstract: Nonsteroidal anti-inflammatory drugs (NSAIDs are successfully used to alleviate pain and inflammation in rheumatic diseases. In an appreciable percentage of cases, the use of systemic NSAIDs is associated with adverse lesions of the gastrointestinal (GI mucosa up to life-threatening perforations, ulcers, and bleeding. Reliable warning signals mostly do not arise. Therefore, it is important to take preventive measures to reduce the GI risk. One established method is to assign cyclooxygenase 2 (COX-2-specific inhibitors (coxibs instead of traditional NSAIDs (tNSAIDs. Coxibs spare in part the endogenous gastroprotective mechanisms. Another reliable choice to improve the GI safety is the comedication of proton pump inhibitors (PPIs to suppress gastric acid. A fixed NSAID/PPI combination ensures expected protective effects by improving patients’ PPI adherence and physicians’ PPI prescription persistence. A fixed combination of enteric-coated naproxen and immediate-release esomeprazole has just been approved by the US Food and Drug Administration. PPI combinations with aspirin, other tNSAIDs, and coxibs are desirable. Patients in all risk groups, even patients at low risk of GI adverse events, benefit from concomitant protective measures. Moreover, the literature suggests that NSAID/PPI combinations are cost effective, including for patients in low-GI-risk groups. Pricing of fixed NSAID/PPI combinations will play a pivotal role for their broad acceptance in the future.Keywords: PPI, NSAID, fixed combination, gastrointestinal, adverse events, prevention

  18. Evaluation of a Proton Pump Inhibitor for Sleep Bruxism: A Randomized Clinical Trial.

    Science.gov (United States)

    Ohmure, H; Kanematsu-Hashimoto, K; Nagayama, K; Taguchi, H; Ido, A; Tominaga, K; Arakawa, T; Miyawaki, S

    2016-12-01

    Bruxism is a repetitive jaw-muscle activity characterized by clenching or grinding of the teeth and/or bracing or thrusting of the mandible. Recent advances have clarified the relationship between gastroesophageal reflux and sleep bruxism (SB). However, the influence of pharmacological elimination of gastric acid secretion on SB has not been confirmed. The authors aimed to assess the efficacy of a proton pump inhibitor (PPI) on SB and to examine the gastrointestinal (GI) symptoms and endoscopic findings of the upper GI tract in SB patients. The authors performed a randomized double-blind placebo-controlled crossover study at Kagoshima University Hospital. Twelve patients with polysomnography (PSG)-diagnosed SB underwent an assessment of GI symptoms using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) and esophagogastroduodenoscopy. At baseline (i.e., before interventions), the mean frequencies of electromyography (EMG) bursts and rhythmic masticatory muscle activity (RMMA) episodes were 65.4 ± 49.0 bursts/h and 7.0 ± 4.8 episodes/h, respectively, and at least 1 RMMA episode with grinding noise was confirmed in all participants. The mean FSSG score was 8.4 ± 5.6, and 41.7% of patients were diagnosed with gastroesophageal reflux disease. Mild reflux esophagitis was confirmed in 6 patients. PSG, including EMG of the left masseter muscle and audio-video recording, was performed on days 4 and 5 of administration of 10 mg of the PPI (rabeprazole) or placebo. PPI administration yielded a significant reduction in the frequency of EMG bursts, RMMA episodes, and grinding noise. No significant differences were observed regarding the swallowing events and sleep variables. Since the clinical application of PPI for SB treatment should remain on hold at present, the results of this trial highlight the potential application of pharmacological gastroesophageal reflux disease treatment for SB patients. Larger scale studies are warranted to

  19. Proton pump inhibitors therapy vs H2 receptor antagonists therapy for upper gastrointestinal bleeding after endoscopy: A meta-analysis.

    Science.gov (United States)

    Zhang, Ying-Shi; Li, Qing; He, Bo-Sai; Liu, Ran; Li, Zuo-Jing

    2015-05-28

    To compare the therapeutic effects of proton pump inhibitors vs H₂ receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy. We searched the Cochrane library, MEDLINE, EMBASE and PubMed for randomized controlled trials until July 2014 for this study. The risk of bias was evaluated by the Cochrane Collaboration's tool and all of the studies had acceptable quality. The main outcomes included mortality, re-bleeding, received surgery rate, blood transfusion units and hospital stay time. These outcomes were estimated using odds ratios (OR) and mean difference with 95% confidence interval (CI). RevMan 5.3.3 software and Stata 12.0 software were used for data analyses. Ten randomized controlled trials involving 1283 patients were included in this review; 678 subjects were in the proton pump inhibitors (PPI) group and the remaining 605 subjects were in the H₂ receptor antagonists (H₂RA) group. The meta-analysis results revealed that after successful endoscopic therapy, compared with H₂RA, PPI therapy had statistically significantly decreased the recurrent bleeding rate (OR = 0.36; 95%CI: 0.25-0.51) and receiving surgery rate (OR = 0.29; 95%CI: 0.09-0.96). There were no statistically significant differences in mortality (OR = 0.46; 95%CI: 0.17-1.23). However, significant heterogeneity was present in both the numbers of patients requiring blood transfusion after treatment [weighted mean difference (WMD), -0.70 unit; 95%CI: -1.64 - 0.25] and the time that patients remained hospitalized [WMD, -0.77 d; 95%CI: -1.87 - 0.34]. The Begg's test (P = 0.283) and Egger's test (P = 0.339) demonstrated that there was no publication bias in our meta-analysis. In patients with upper gastrointestinal bleeding after successful endoscopic therapy, compared with H₂RA, PPI may be a more effective therapy.

  20. Time esophageal pH < 4 overestimates the prevalence of pathologic esophageal reflux in subjects with gastroesophageal reflux disease treated with proton pump inhibitors

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    Sloan Sheldon

    2008-05-01

    Full Text Available Abstract Background A Stanford University study reported that in asymptomatic GERD patients who were being treated with a proton pump inhibitor (PPI, 50% had pathologic esophageal acid exposure. Aim We considered the possibility that the high prevalence of pathologic esophageal reflux might simply have resulted from calculating acidity as time pH Methods We calculated integrated acidity and time pH Results The prevalence of pathologic 24-hour esophageal reflux in both studies was significantly higher when measured as time pH Conclusion In GERD subjects treated with a PPI, measuring time esophageal pH

  1. Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach

    NARCIS (Netherlands)

    Rohof, Wout O.; Bennink, Roelof J.; Boeckxstaens, Guy E.

    2014-01-01

    The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease

  2. Should Helicobacter pylori be eradicated before starting long-term proton pump inhibitors?

    NARCIS (Netherlands)

    Rauws, E. A.

    1997-01-01

    Symptomatic gastro-oesophageal reflux disease is a common disorder characterized by pathological exposure of the distal oesophagus to acid. The management requires the control of symptoms, prevention of relapse and complications. Proton pump inhibitors are without doubt the most effective agents in

  3. Causes of, and Therapeutic Approaches for, Proton Pump Inhibitor-Resistant Gastroesophageal Reflux Disease in Asia

    OpenAIRE

    Kinoshita, Yoshikazu; Ishihara, Shunji

    2008-01-01

    Proton pump inhibitors (PPIs) are the most widely used drugs for treatment of gastroesophageal reflux disease. However, approximately 20% of patients with reflux esophagitis and 40% of those with nonerosive reflux diseases complain of troublesome symptoms, even during treatment with PPIs. In patients with reflux esophagitis, dose escalation and co-administration with a histamine ...

  4. Long-term proton pump inhibitor therapy and falls and fractures in elderly women: a prospective cohort study.

    Science.gov (United States)

    Lewis, Joshua R; Barre, Deka; Zhu, Kun; Ivey, Kerry L; Lim, Ee Mun; Hughes, Jeff; Prince, Richard L

    2014-11-01

    Proton pump inhibitors (PPIs) are widely used in the elderly. Recent studies have suggested that long-term PPI therapy is associated with fractures in the elderly, however the mechanism remains unknown. We investigated the association between long-term PPI therapy ≥1 year and fracture risk factors including bone structure, falls, and balance-related function in a post hoc analysis of a longitudinal population-based prospective cohort of elderly postmenopausal women and replicated the findings in a second prospective study of falling in elderly postmenopausal women. Long-term PPI therapy was associated with increased risk of falls and fracture-related hospitalizations; adjusted odds ratio (AOR) 2.17; 95% CI, 1.25-3.77; p = 0.006 and 1.95; 95% CI, 1.20-3.16; p = 0.007, respectively. In the replication study, long-term PPI use was associated with an increased risk of self-reported falling; AOR, 1.51; 95% CI, 1.00-2.27; p = 0.049. No association of long-term PPI therapy with bone structure was observed; however, questionnaire-assessed falls-associated metrics such as limiting outdoor activity (p = 0.002) and indoor activity (p = 0.001) due to fear of falling, dizziness (p risk in subjects on long-term PPI therapy. This increase in fracture risk in elderly women, already at high risk of fracture, appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long-term PPI therapy. © 2014 American Society for Bone and Mineral Research.

  5. Implementation of Global Strategies to Prevent Hospital-Onset Clostridium difficile Infection: Targeting Proton Pump Inhibitors and Probiotics.

    Science.gov (United States)

    Lewis, Paul O; Lundberg, Timothy S; Tharp, Jennifer L; Runnels, Clay W

    2017-10-01

    Proton pump inhibitors (PPIs) have been identified as a significant risk factor for the development of Clostridium difficile infection (CDI). Probiotics given concurrently with antibiotics have been shown to have a moderate impact on preventing CDI. To evaluate the effectiveness of hospital-wide interventions designed to reduce PPI use and increase probiotics and whether these interventions were associated with a change in the incidence of hospital onset (HO)-CDI. This retrospective cohort study compared 2 fiscal years: July 2013 to June 2014 (FY14) and July 2014 to June 2015 (FY15). In July of FY15, global educational initiatives were launched targeting PPIs. Additionally, a HO-CDI prevention bundle was added to antibiotic-containing order sets targeting probiotics. Overall PPI use, probiotic use, and incidence of HO-CDI were recorded and compared for each cohort. Charts were also reviewed for patients who developed HO-CDI for the presence and appropriateness of a PPI and presence of probiotics. The interventions resulted in a decrease in PPI use by 14% or 96 doses/1000 patient days (TPD; P = 0.0002) and a reduction in IV PPI use by 31% or 71 doses/TPD ( P = 0.0008). Probiotic use increased by 130% or 126 doses/TPD ( P = 0.0006). The incidence of HO-CDI decreased by 20% or 0.1 cases/TPD ( P = 0.04). A collaborative, multifaceted educational initiative directed at highlighting the risks associated with PPI use was effective in reducing PPI prescribing. The implementation of a probiotic bundle added to antibiotic order sets was effective in increasing probiotic use. These interventions were associated with a decrease in incidence of HO-CDI.

  6. Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species.

    Science.gov (United States)

    De Milito, Angelo; Iessi, Elisabetta; Logozzi, Mariantonia; Lozupone, Francesco; Spada, Massimo; Marino, Maria Lucia; Federici, Cristina; Perdicchio, Maurizio; Matarrese, Paola; Lugini, Luana; Nilsson, Anna; Fais, Stefano

    2007-06-01

    Proton pumps like the vacuolar-type H+ ATPase (V-ATPase) are involved in the control of cellular pH in normal and tumor cells. Treatment with proton pump inhibitors (PPI) induces sensitization of cancer cells to chemotherapeutics via modifications of cellular pH gradients. It is also known that low pH is the most suitable condition for a full PPI activation. Here, we tested whether PPI treatment in unbuffered culture conditions could affect survival and proliferation of human B-cell tumors. First, we showed that PPI treatment increased the sensitivity to vinblastine of a pre-B acute lymphoblastic leukemia (ALL) cell line. PPI, per se, induced a dose-dependent inhibition of proliferation of tumor B cells, which was associated with a dose- and time-dependent apoptotic-like cytotoxicity in B-cell lines and leukemic cells from patients with pre-B ALL. The effect of PPI was mediated by a very early production of reactive oxygen species (ROS), that preceded alkalinization of lysosomal pH, lysosomal membrane permeabilization, and cytosol acidification, suggesting an early destabilization of the acidic vesicular compartment. Lysosomal alterations were followed by mitochondrial membrane depolarization, release of cytochrome c, chromatin condensation, and caspase activation. However, inhibition of caspase activity did not affect PPI-induced cell death, whereas specific inhibition of ROS by an antioxidant (N-acetylcysteine) significantly delayed cell death and protected both lysosomal and mitochondrial membranes. The proapoptotic activity of PPI was consistent with a clear inhibition of tumor growth following PPI treatment of B-cell lymphoma in severe combined immunodeficient mice. This study further supports the importance of acidity and pH gradients in tumor cell homeostasis and suggests new therapeutic approaches for human B-cell tumors based on PPI.

  7. Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease.

    Science.gov (United States)

    Gweon, Tae-Geun; Park, Jong-Hyung; Kim, Byung-Wook; Choi, Yang Kyu; Kim, Joon Sung; Park, Sung Min; Kim, Chang Whan; Kim, Hyung-Gil; Chung, Jun-Won

    2018-01-15

    The aim of this study was to investigate the effects of rebamipide on tight junction proteins in the esophageal mucosa in a rat model of gastroesophageal reflux disease (GERD). GERD was created in rats by tying the proximal stomach. The rats were divided into a control group, a proton pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups. An additional dose of rebamipide (100 mg/kg) was administered orally to the PPI+R group. Mucosal erosions, epithelial thickness, and leukocyte infiltration into the esophageal mucosa were measured in isolated esophagi 14 days after the procedure. A Western blot analysis was conducted to measure the expression of claudin-1, -3, and -4. The mean surface area of mucosal erosions, epithelial thickness, and leukocyte infiltration were lower in the PPI group and the PPI+R group than in the control group. Western blot analysis revealed that the expression of claudin-3 and -4 was significantly higher in the PPI+R group than in the control group. Rebamipide may exert an additive effect in combination with PPI to modify the tight junction proteins of the esophageal mucosa in a rat model of GERD. This treatment might be associated with the relief of GERD symptoms.

  8. High risk of drug-induced microscopic colitis with concomitant use of NSAIDs and proton pump inhibitors

    NARCIS (Netherlands)

    Verhaegh, B P M; de Vries, F; Masclee, A A M; Keshavarzian, A; de Boer, A; Souverein, P C; Pierik, M J; Jonkers, D M A E

    2016-01-01

    BACKGROUND: Microscopic colitis (MC) is a chronic bowel disorder characterised by watery diarrhoea. Nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs) and statins have been associated with MC. However, underlying mechanisms

  9. Increased prandial air swallowing and postprandial gas-liquid reflux among patients refractory to proton pump inhibitor therapy.

    Science.gov (United States)

    Bravi, Ivana; Woodland, Philip; Gill, Ravinder S; Al-Zinaty, Mohannad; Bredenoord, Albert J; Sifrim, Daniel

    2013-07-01

    Many patients with gastroesophageal reflux disease (GERD) have persistent reflux despite treatment with proton pump inhibitors (PPIs). Mixed gas-liquid reflux events are more likely to be perceived as symptomatic. We used esophageal impedance monitoring to investigate whether esophageal gas is processed differently among patients with GERD who do and do not respond to PPI therapy. We performed a prospective study of 44 patients with typical reflux symptoms with high levels of esophageal acid exposure during a 24-hour period; 18 patients were fully responsive, and 26 did not respond to PPI therapy. Twenty-four-hour pH impedance recordings were analyzed for fasting and prandial air swallows and reflux characteristics, including the presence of gas in the refluxate. PPI-refractory patients had a higher number (83.1 ± 12.7 vs 47.8 ± 7.3, P gas-liquid reflux. Symptoms of PPI-refractory patients were more often preceded by mixed gas-liquid reflux events than those of PPI responders. Fasting air swallowing and other reflux characteristics did not differ between patients who did and did not respond to PPIs. Some patients with GERD who do not respond to PPI therapy swallow more air at mealtime than those who respond to PPIs and also have more reflux episodes that contain gas. These factors, combined with mucosal sensitization by previous exposure to acid, could affect perception of symptoms. These patients, who can be identified on standard 24-hour pH impedance monitoring, might be given behavioral therapy to reduce mealtime air swallowing. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. EFFECTS OF PROTON PUMP INHIBITORS ON DENTAL EROSIONS CAUSED BY GASTROESOPHAGEAL REFLUX DISEASE

    Directory of Open Access Journals (Sweden)

    Andrei Vasile OLTEANU

    2015-12-01

    Full Text Available Background: Numerous studies worldwide have assessed the association between dental erosions or other related oral manifestations, and the gastroesophageal reflux disease (GERD. Nowadays, one of the main therapeutic resources of GERD is represented by proton pump inhibitors (PPIs. Adequate salivary secretions and flow are considered mandatory for the protection of both teeth and esophageal mucosa. The aim of the present study was to evaluate the possible correlation between GERD treatment options and subsequent control of oral manifestation, taking as premises that either PPIs or dietary and lifestyle changes may control oral patterns of GERD by acting on salivary secretions. Methods: 48 clinically diagnosed GERD adult patients with oral manifestations, mainly erosions, were included in the study, none of which showing alarming symptoms that would require further gastroenterologic examination. Oral examination evaluated the DMF (decayed, missing, filled and OHI-S (Simplified Oral Hygiene indices. Salivary flow was evaluated by the Saxon test. 25 patients were prescribed dietary and lifestyle measures and PPIs (omeprazole – 20 mg, whereas 23 patients were managed only through dietary and lifestyle modifications. General assessment was performed at the time of diagnosis and 4 weeks afterwards. Results: No significant differences as to the DMF index, OHI-S index or Saxon test were found over the 4 weeks management between the groups. Conclusions: Oral manifestation of GERD may be caused by impaired salivary secretions and flow, otherwise no - positive or negative - effect could be secondary to PPI therapy. Accordingly, complex oral rehabilitation of GERD patients and collaboration between gastroenterologists and dentists should be promoted.

  11. Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors.

    Science.gov (United States)

    Yu, Man; Lee, Carol; Wang, Marina; Tannock, Ian F

    2015-10-01

    Cellular causes of resistance and limited drug distribution within solid tumors limit therapeutic efficacy of anticancer drugs. Acidic endosomes in cancer cells mediate autophagy, which facilitates survival of stressed cells, and may contribute to drug resistance. Basic drugs (e.g. doxorubicin) are sequestered in acidic endosomes, thereby diverting drugs from their target DNA and decreasing penetration to distal cells. Proton pump inhibitors (PPIs) may raise endosomal pH, with potential to improve drug efficacy and distribution in solid tumors. We determined the effects of the PPI lansoprazole to modify the activity of doxorubicin. To gain insight into its mechanisms, we studied the effects of lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and of biomarkers reflecting its activity, using in vitro and murine models. Lansoprazole showed concentration-dependent effects to raise endosomal pH and to inhibit endosomal sequestration of doxorubicin in cultured tumor cells. Lansoprazole was not toxic to cancer cells but potentiated the cytotoxicity of doxorubicin and enhanced its penetration through multilayered cell cultures. In solid tumors, lansoprazole improved the distribution of doxorubicin but also increased expression of biomarkers of drug activity throughout the tumor. Combined treatment with lansoprazole and doxorubicin was more effective in delaying tumor growth as compared to either agent alone. Together, lansoprazole enhances the therapeutic effects of doxorubicin both by improving its distribution and increasing its activity in solid tumors. Use of PPIs to improve drug distribution and to inhibit autophagy represents a promising strategy to enhance the effectiveness of anticancer drugs in solid tumors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  12. Clinical usefulness of limited sampling strategies for estimating AUC of proton pump inhibitors.

    Science.gov (United States)

    Niioka, Takenori

    2011-03-01

    Cytochrome P450 (CYP) 2C19 (CYP2C19) genotype is regarded as a useful tool to predict area under the blood concentration-time curve (AUC) of proton pump inhibitors (PPIs). In our results, however, CYP2C19 genotypes had no influence on AUC of all PPIs during fluvoxamine treatment. These findings suggest that CYP2C19 genotyping is not always a good indicator for estimating AUC of PPIs. Limited sampling strategies (LSS) were developed to estimate AUC simply and accurately. It is important to minimize the number of blood samples because of patient's acceptance. This article reviewed the usefulness of LSS for estimating AUC of three PPIs (omeprazole: OPZ, lansoprazole: LPZ and rabeprazole: RPZ). The best prediction formulas in each PPI were AUC(OPZ)=9.24 x C(6h)+2638.03, AUC(LPZ)=12.32 x C(6h)+3276.09 and AUC(RPZ)=1.39 x C(3h)+7.17 x C(6h)+344.14, respectively. In order to optimize the sampling strategy of LPZ, we tried to establish LSS for LPZ using a time point within 3 hours through the property of pharmacokinetics of its enantiomers. The best prediction formula using the fewest sampling points (one point) was AUC(racemic LPZ)=6.5 x C(3h) of (R)-LPZ+13.7 x C(3h) of (S)-LPZ-9917.3 x G1-14387.2×G2+7103.6 (G1: homozygous extensive metabolizer is 1 and the other genotypes are 0; G2: heterozygous extensive metabolizer is 1 and the other genotypes are 0). Those strategies, plasma concentration monitoring at one or two time-points, might be more suitable for AUC estimation than reference to CYP2C19 genotypes, particularly in the case of coadministration of CYP mediators.

  13. Review of proton pump inhibitors for the initial treatment of heartburn: is there a dose ceiling effect?

    Science.gov (United States)

    Kushner, Pamela R; Peura, David A

    2011-05-01

    Proton pump inhibitors (PPIs) are widely used in clinical practice. However, concerns have been expressed about their long-term use, particularly with regard to bone health, Clostridium difficile infections, and drug interactions with platelet aggregation inhibitors. There has been limited guidance for clinicians concerning appropriate dose selection of PPIs for the initial treatment of heartburn. This review explored whether published clinical trials provide evidence of a ceiling above which higher PPI doses do not provide additional clinical benefit over the lowest approved dose. All articles of randomized, controlled clinical trials in nonerosive gastroesophageal reflux disease (GERD) in which the effects of two or more doses of the same PPI on symptomatic relief of heartburn were quantified as a study endpoint were identified and analyzed through PubMed searches up to the end of September 2010. The majority of trials evaluated provided no evidence that higher PPI doses were superior to the lowest approved dose for the initial treatment of heartburn. There were no clinically relevant findings with respect to dose dependence and safety outcomes in these studies. Efficacy outcomes from the trials suggest there may be a dose ceiling effect and highlight the need for further research on the use of the lowest effective PPI doses as an appropriate strategy in the initial treatment of uncomplicated heartburn. Observational studies and some meta-analyses have suggested that long-term PPI pharmacotherapy might be associated with safety concerns, which necessitate the periodic evaluation of therapeutic benefit in terms of symptom resolution and regimen tolerability. However, evidence to date suggests that use of the lowest effective dose for the indication is not associated with significant adverse events, particularly in the short term. Clinical practice suggests that patients requiring long-term treatment should be maintained on the lowest dose necessary to control

  14. What is the place of empirical proton pump inhibitor testing in the diagnosis of gastroesophageal reflux disease? (Description, duration, and dosage).

    Science.gov (United States)

    Vardar, Rukiye; Keskin, Muharrem

    2017-12-01

    Empirical acid suppression tests that are performed with proton pump inhibitors (PPI) are used to detect both the presence of acid-related gastrointestinal symptoms and gastroesophageal reflux disease (GERD). In comparison to other diagnostic methods, it is non-invasive, easily applicable, and cost-effective in the diagnosis of GERD. In addition to typical reflux symptoms, it can also be used for diagnostic purposes in patients with non-cardiac chest pain (NCCP). If the symptom response is 50% and above when obtained using the PPI test in patients with NCCP, it can be considered as positive and the treatment should be continued sensitivity of the PPI test in patients with typical symptoms of GERD is 27%-89%, while its specificity is 35%-83%. Although there are differences related to the duration and dosage of the PPI test, a significant difference has not been found according to the type of PPI. When PPI test sensitivity and specificity were calculated by cumulatively evaluating the data regarding the PPI test in the literature, a sensitivity of 82.3% and specificity of 51.5% was obtained. It has been found that high doses of PPI were mostly used in studies, and the duration of the median test was 14 days. As a result, the sensitivity of PPI trial test is good, but the specificity is low in the diagnosis of GERD in patients with typical reflux symptoms.

  15. Proton pump inhibitor-induced tumour cell death by inhibition of a detoxification mechanism.

    Science.gov (United States)

    Fais, S

    2010-05-01

    This review presents a possible new approach against cancer, as represented by inhibition of proton pumps, a mechanism used by tumour cells to avoid intracellular accumulation of toxic substances. Proton pump inhibitors (PPIs) belong to a family of pro-drugs that are currently used in the treatment of peptic diseases needing acidity to be activated. PPIs target the acidic tumour mass, where they are metabolized, thus blocking proton traffic. Proton pump inhibition triggers a rapid cell death as a result of intracellular acidification, caspase activation and early accumulation of reactive oxygen species into tumour cells. As a whole, the devastating effect of PPIs on tumour cells suggest the triggering of a fatal cell toxification. Many human tumours, including melanoma, osteosarcoma, lymphomas and various adenocarcinomas are responsive to PPIs. This appears highly conceivable, in as much as almost all human tumours are acidic and express high levels of proton pumps. Paradoxically, metastatic tumours appear to be more responsive to PPIs being more acidic than the majority of primary tumours. However, two clinical trials test the effectiveness of PPIs in chemosensitizing melanoma and osteosarcoma patients. Indeed, tumour acidity represents a very potent mechanism of chemoresistance. A majority of cytotoxic agents, being weak bases, are quickly protonated outside and do not enter the cells, thus preventing drugs to reach specific cellular targets. Clinical data will provide the proof of concept on the use of PPIs as a new class of antitumour agent with a very low level of systemic toxicity as compared with standard chemotherapeutic agents.

  16. Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Imad M Tleyjeh

    Full Text Available INTRODUCTION: Emerging epidemiological evidence suggests that proton pump inhibitor (PPI acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI. METHODS: Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. RESULTS: We identified 47 eligible citations (37 case-control and 14 cohort studies with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85, I(2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26-1.83. In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. CONCLUSIONS: In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class for an association between PPI use and CDI that does not support a cause-effect relationship.

  17. Impact of gastro-oesophageal reflux disease on work productivity despite therapy with proton pump inhibitors in Germany

    Directory of Open Access Journals (Sweden)

    Gross M

    2010-03-01

    Full Text Available Abstract Background Gastro-oesophageal reflux disease (GERD is a common disorder with consequences for the patient's health-related quality of life (HRQoL. In Germany, few data are available on the impact of GERD on work-related productivity. Aim To study the impact of GERD on work productivity despite proton pump inhibitor (PPI therapy and the association between productivity and symptom duration, severity, and HRQoL. Methods Retrospective data from randomly selected patients with chronic GERD symptoms, treated by office-based general practitioners or general internists with routine clinical care, were analyzed together with information from self-administered instruments assessing work productivity (WPAI-GERD, symptoms (RDQ, and HRQoL (QOLRAD. Results Reduced productivity was reported by 152 of 249 patients (61.0%, although 89.5% of them were treated with PPI. The reduction in work productivity was 18.5% in all patients and 30.3% in those with reduced productivity. Patients with impaired productivity showed a significantly lower HRQoL and more-severe symptoms of reflux disease. In all patients, the mean sick leave attributable to reflux symptoms was 0.6 hours in the previous seven days and 1.4 work days in the previous three months. Conclusion GERD has a substantial impact on work productivity in Germany, even in patients receiving routine clinical care and PPI therapy.

  18. Comparison and Analysis of Delirium Induced by Histamine H2 Receptor Antagonists and Proton Pump Inhibitors in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Shiro Fujii

    2012-07-01

    Full Text Available Objective: H2 blockers have been reported to be responsible for drug-induced delirium. We compared the incidence of delirium between two groups of patients who were treated with H2 blockers (H2 group or proton pump inhibitors (PPI group for anastomotic ulcer prevention following surgical treatment of esophageal cancer. Method: The incidence and severity of delirium were retrospectively compared in patients of the H2 group (30 cases; age, 65.2 ± 8.1 years and the PPI group (30 cases; 65.2 ± 6.5 years. The diagnosis of delirium was based on the Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision. Delirium severity was rated on the Delirium Rating Scale (DRS. Results: The incidence of delirium was significantly lower in the PPI group than in the H2 group (p = 0.047. In the 11 patients from the H2 group who developed delirium, discontinuation of H2 blockers resulted in a significant reduction in the DRS score (p = 0.009. In three patients for whom H2 blockers were discontinued, DRS scores decreased by 50% or more three days after discontinuation compared to the prediscontinuation score. Conclusions: These results suggested that switching antiulcer drugs from H2 blockers to PPIs reduced delirium and thus provided an appropriate coping method for drug-induced delirium from antiulcer drugs.

  19. Multi-indication Pharmacotherapeutic Multicriteria Decision Analytic Model for the Comparative Formulary Inclusion of Proton Pump Inhibitors in Qatar.

    Science.gov (United States)

    Al-Badriyeh, Daoud; Alabbadi, Ibrahim; Fahey, Michael; Al-Khal, Abdullatif; Zaidan, Manal

    2016-05-01

    The formulary inclusion of proton pump inhibitors (PPIs) in the government hospital health services in Qatar is not comparative or restricted. Requests to include a PPI in the formulary are typically accepted if evidence of efficacy and tolerability is presented. There are no literature reports of a PPI scoring model that is based on comparatively weighted multiple indications and no reports of PPI selection in Qatar or the Middle East. This study aims to compare first-line use of the PPIs that exist in Qatar. The economic effect of the study recommendations was also quantified. A comparative, evidence-based multicriteria decision analysis (MCDA) model was constructed to follow the multiple indications and pharmacotherapeutic criteria of PPIs. Literature and an expert panel informed the selection criteria of PPIs. Input from the relevant local clinician population steered the relative weighting of selection criteria. Comparatively scored PPIs, exceeding a defined score threshold, were recommended for selection. Weighted model scores were successfully developed, with 95% CI and 5% margin of error. The model comprised 7 main criteria and 38 subcriteria. Main criteria are indication, dosage frequency, treatment duration, best published evidence, available formulations, drug interactions, and pharmacokinetic and pharmacodynamic properties. Most weight was achieved for the indications selection criteria. Esomeprazole and rabeprazole were suggested as formulary options, followed by lansoprazole for nonformulary use. The estimated effect of the study recommendations was up to a 15.3% reduction in the annual PPI expenditure. Robustness of study conclusions against variabilities in study inputs was confirmed via sensitivity analyses. The implementation of a locally developed PPI-specific comparative MCDA scoring model, which is multiweighted indication and criteria based, into the Qatari formulary selection practices is a successful evidence-based cost-cutting exercise

  20. The effects of proton pump inhibitors on autonomic tone in patients with erosive and non-erosive esophagitis.

    Science.gov (United States)

    Jones, E L; Perring, S; Khattab, A; Allenby-Smith, O

    2016-05-01

    Reduction in autonomic tone as measured by heart rate variability (HRV) has been associated with various inflammatory conditions including reflux disease. The nature of and permanence of this damage have not been fully assessed. Fourteen individuals with non-erosive reflux disease (NERD) and 10 individuals with erosive reflux disease (ERD) as identified on endoscopy were assessed for HRV prior to starting a course of proton pump inhibitor (PPI) therapy and 8 weeks from the start of PPI therapy. Reflux symptoms were significantly improved by PPI therapy (p = 0.001), with no significant difference in reflux symptoms between the NERD and ERD groups either before (p = 0.45) or following therapy (p = 0.17). The ERD group displayed reduced HRV prior to PPI therapy as compared with a non-symptomatic group. There was significant improvement of HRV resulting from PPI therapy in the ERD group as measured by inspiration/expiration ratio on forced breathing (p = 0.02), Valsalva ratio (p = 0.03), and extended metronome-guided breathing at 6 breaths per minute (p = 0.03). While a similar pattern was seen in the NERD group, the effects were not as strong and did not reach statistical significance. The results are consistent with a growing body of evidence that cardiac autonomic neuropathy as measured by HRV is associated with gastro-esophageal reflux disease and also suggest that successful treatment of the inflammation can lead to reversal of the deterioration of autonomic tone associated with that inflammation. © 2016 John Wiley & Sons Ltd.

  1. Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics

    DEFF Research Database (Denmark)

    Schjerning Olsen, Anne-Marie; Lindhardsen, Jesper; Gislason, Gunnar H

    2015-01-01

    STUDY QUESTION: What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)? METHODS: This was a nationwide cohort study based on linked.......95) regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. The main limitation of the study is its observational non-randomised design. The results suggest that PPI treatment probably has a beneficial effect regardless of underlying gastrointestinal risk and that when NSAIDs cannot...... of NSAID, and type of PPI used. FUNDING, COMPETING INTERESTS, DATA SHARING: AMSO has received a grant from the Danish Council of Independent Research (grant 12-132760). GHG is supported by an unrestricted research scholarship from the Novo Nordisk Foundation....

  2. Porphyromonas gingivalis is highly sensitive to inhibitors of a proton-pumping ATPase.

    Science.gov (United States)

    Sekiya, Mizuki; Shimoyama, Yu; Ishikawa, Taichi; Sasaki, Minoru; Futai, Masamitsu; Nakanishi-Matsui, Mayumi

    2018-04-15

    Porphyromonas gingivalis is a well-known Gram-negative bacterium that causes periodontal disease. The bacterium metabolizes amino acids and peptides to obtain energy. An ion gradient across its plasma membrane is thought to be essential for nutrient import. However, it is unclear whether an ion-pumping ATPase responsible for the gradient is required for bacterial growth. Here, we report the inhibitory effect of protonophores and inhibitors of a proton-pumping ATPase on the growth of P. gingivalis. Among the compounds examined, curcumin and citreoviridin appreciably reduced the bacterial growth. Furthermore, these compounds inhibited the ATPase activity in the bacterial membrane, where the A-type proton-pumping ATPase (A-ATPase) is located. This study suggests that curcumin and citreoviridin inhibit the bacterial growth by inhibiting the A-ATPase in the P. gingivalis membrane. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Decreasing incidence of peptic ulcer complications after the introduction of the proton pump inhibitors, a study of the Swedish population from 1974–2002

    Directory of Open Access Journals (Sweden)

    Ranstam Jonas

    2009-04-01

    Full Text Available Abstract Background Despite a decreasing incidence of peptic ulcer disease, most previous studies report a stabile incidence of ulcer complications. We wanted to investigate the incidence of peptic ulcer complications in Sweden before and after the introduction of the proton pump inhibitors (PPI in 1988 and compare these data to the sales of non-steroid anti-inflammatory drugs (NSAID and acetylsalicylic acid (ASA. Methods All cases of gastric and duodenal ulcer complications diagnosed in Sweden from 1974 to 2002 were identified using the National hospital discharge register. Information on sales of ASA/NSAID was obtained from the National prescription survey. Results When comparing the time-periods before and after 1988 we found a significantly lower incidence of peptic ulcer complications during the later period for both sexes (p Conclusion When comparing the periods before and after the introduction of the proton pump inhibitors we found a significant decrease in the incidence of peptic ulcer complications in the Swedish population after 1988 when PPI were introduced on the market. The cause of this decrease is most likely multifactorial, including smoking habits, NSAID consumption, prevalence of Helicobacter pylori and the introduction of PPI. Sales of prescribed NSAID/ASA increased, especially in middle-aged and elderly women. This fact seems to have had little effect on the incidence of peptic ulcer complications.

  4. Use of Proton-Pump Inhibitors Predicts Heart Failure and Death in Patients with Coronary Artery Disease.

    Directory of Open Access Journals (Sweden)

    Ana María Pello Lázaro

    Full Text Available Proton-pump inhibitors (PPIs seem to increase the incidence of cardiovascular events in patients with coronary artery disease (CAD, mainly in those using clopidogrel. We analysed the impact of PPIs on the prognosis of patients with stable CAD.We followed 706 patients with CAD. Primary outcome was the combination of secondary outcomes. Secondary outcomes were 1 acute ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack and 2 heart failure (HF or death.Patients on PPIs were older [62.0 (53.0-73.0 vs. 58.0 (50.0-70.0 years; p = 0.003] and had a more frequent history of stroke (4.9% vs. 1.1%; p = 0.004 than those from the non-PPI group, and presented no differences in any other clinical variable, including cardiovascular risk factors, ejection fraction, and therapy with aspirin and clopidogrel. Follow-up was 2.2±0.99 years. Seventy-eight patients met the primary outcome, 53 developed acute ischaemic events, and 33 HF or death. PPI use was an independent predictor of the primary outcome [hazard ratio (HR = 2.281 (1.244-4.183; p = 0.008], along with hypertension, body-mass index, glomerular filtration rate, atrial fibrillation, and nitrate use. PPI use was also an independent predictor of HF/death [HR = 5.713 (1.628-20.043; p = 0.007], but not of acute ischaemic events. A propensity score showed similar results.In patients with CAD, PPI use is independently associated with an increased incidence of HF and death but not with a high rate of acute ischaemic events. Further studies are needed to confirm these findings.

  5. Pneumonia prevention in intubated patients given sucralfate versus proton-pump inhibitors and/or histamine II receptor blockers.

    Science.gov (United States)

    Grindlinger, Gene A; Cairo, Sarah B; Duperre, Carole B

    2016-12-01

    Ventilator-associated pneumonia (VAP) is a common cause of infectious morbidity and mortality in the intensive care unit (ICU). The type of stress-ulcer prophylaxis (SUP) given to ventilated patients may, in part, be responsible. We observed an increase in VAP as ventilator bundle compliance increased and a decrease in VAP when bundle compliance decreased. We reasoned that SUP which raises gastric pH such as proton-pump inhibitors (PPIs) and histamine II (H2) receptor antagonists as opposed to SUP which does not raise pH such as sucralfate (S) may be responsible and also may alter the causative bacteria. This is a single-center retrospective cohort analysis of all intubated, adult surgical patients admitted to the surgical ICU between January and June during the 3-y period 2012-2014. Demographics, APACHE II, Injury Severity Score, VAP occurrence, culprit bacteria, ventilator days, and ICU days were recorded based on the type of SUP given. There were 45 instances of VAP in the 504 study patients, 33 in the PPI/H2 group, and 12 in the S group (P < 0.01). VAP per 1000 ventilator days were 10.2 for PPI/H2 and 3.7 for S (P < 0.01). Culprit bacteria were mostly Pseudomonas, gram-negative bacilli, and methicillin-resistant Staphylococcus aureus in PPI/H2 patients (n = 29) compared with oropharyngeal flora in S patients (n = 6; P < 0.001). There was a substantial difference in VAP occurrence and in the culprit bacteria between S and PPI/H2 treated patients due perhaps to gastric alkalization. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. In vitro dissolution of proton-pump inhibitor products intended for paediatric and geriatric use in physiological bicarbonate buffer.

    Science.gov (United States)

    Liu, Fang; Shokrollahi, Honaz

    2015-05-15

    Proton-pump inhibitor (PPI) products based on enteric coated multiparticulates are design to meet the needs of patients who cannot swallow tablets such as children and older adults. Enteric coated PPI preparations exhibit delays in in vivo absorption and onset of antisecretory effects, which is not reflected by the rapid in vitro dissolution in compendial pH 6.8 phosphate buffer commonly used for assessment of these products. A more representative and physiological medium, pH 6.8 mHanks bicarbonate buffer, was used in this study to evaluate the in vitro dissolution of enteric coated multiparticulate-based PPI products. Commercially available omeprazole, lansoprazole and esomeprazole products were subject to dissolution tests using USP-II apparatus in pH 4.5 phosphate buffer saline for 45 min (acid stage) followed by pH 6.8 phosphate buffer or pH 6.8 mHanks bicarbonate buffer. In pH 6.8 phosphate buffer, all nine tested products displayed rapid and comparable dissolution profiles meeting the pharmacopeia requirements for delayed release preparations. In pH 6.8 mHanks buffer, drug release was delayed and failed the pharmacopeia requirements from most enteric coated preparations. Despite that the same enteric polymer, methacrylic acid-ethyl acrylate copolymer (1:1), was applied to all commercial multiparticulate-based products, marked differences were observed between dissolution profiles of these preparations. The use of pH 6.8 physiological bicarbonate (mHanks) buffer can serve as a useful tool to provide realistic and discriminative in vitro release assessment of enteric coated PPI preparations and to assist rational formulation development of these products. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Proton Pump Inhibitors and the Risk for Fracture at Specific Sites: Data Mining of the FDA Adverse Event Reporting System.

    Science.gov (United States)

    Wang, Liwei; Li, Mei; Cao, Yuying; Han, Zhengqi; Wang, Xueju; Atkinson, Elizabeth J; Liu, Hongfang; Amin, Shreyasee

    2017-07-17

    Proton pump inhibitors (PPIs) are widely used to treat gastric acid-related disorders. Concerns have been raised about potential fracture risk, especially at the hip, spine and wrist. However, fracture risk at other bone sites has not been as well studied. We investigated the association between PPIs and specific fracture sites using an aggregated knowledge-enhanced database, the Food and Drug Administration Adverse Event Reporting System Data Mining Set (AERS-DM). Proportional reporting ratio (PRR) was used to detect statistically significant associations (signals) between PPIs and fractures. We analyzed both high level terms (HLT) and preferred terms (PT) for fracture sites, defined by MedDRA (Medical Dictionary for Regulatory Activities). Of PPI users reporting fractures, the mean age was 65.3 years and the female to male ratio was 3.4:1. Results revealed signals at multiple HLT and PT fracture sites, consistent for both sexes. These included fracture sites with predominant trabecular bone, not previously reported as being associated with PPIs, such as 'rib fractures', where signals were detected for overall PPIs as well as for each of 5 generic ingredients (insufficient data for dexlansoprazole). Based on data mining from AERS-DM, PPI use appears to be associated with an increased risk for fractures at multiple sites.

  8. Comparison of health care resource utilization and costs among patients with GERD on once-daily or twice-daily proton pump inhibitor therapy

    Directory of Open Access Journals (Sweden)

    Mody R

    2013-04-01

    Full Text Available Reema Mody,1 Debra Eisenberg,2 Likun Hou,2 Siddhesh Kamat,2 Joseph Singer,2 Lauren B Gerson3 1Takeda Pharmaceuticals International Inc, Deerfield, IL, 2HealthCore Inc, Wilmington, DE, 3Stanford University School of Medicine, Stanford, CA, USA Background: The purpose of this study was to assess differences in health care resource utilization and costs associated with once-daily and twice-daily proton pump inhibitor (PPI therapy. Most patients with gastroesophageal reflux disease (GERD achieve symptom control on once-daily PPI therapy, but approximately 20%–30% require twice-daily dosing. Methods: Patients were ≥18 years of age with at least one medical claim for GERD and at least two PPI claims from HealthCore's Integrated Research Database (HIRDSM during 2004–2009. Patients were continuously eligible for 12 months before and after the index date (date of first PPI claim. Based on PPI dosing throughout the post-index period (quantity of medication dispensed/number of days supply, patients were classified as once-daily (dose ≤ 1.5 pills per day or twice-daily (≥1.5 PPI users. Results: The study cohort included 248,386 patients with GERD (mean age 52.8 ± 13.93 years, 56% females of whom 90% were once-daily and 10% were twice-daily PPI users. The Deyo-Charlson Comorbidity Index for once-daily and twice-daily PPI users was 0.70 ± 1.37 and 0.89 ± 1.54, respectively (P < 0.05. More once-daily patients had claims for Barrett's esophagus (5% versus 2%, P < 0.0001 than twice-daily patients. Post-index, higher proportions of twice-daily patients had at least one GERD-related inpatient visit (7% versus 5%, outpatient visit (60% versus 49%, and office visit (48% versus 38% versus once-daily patients (P < 0.0001. Mean total GERD-related health care costs were $2065 ± $6636 versus $3749 ± $11,081 for once-daily and twice-daily PPI users, respectively (P < 0.0001. Conclusion: Patients receiving twice-daily PPI therapy were likely to have more

  9. Increased proximal reflux in a hypersensitive esophagus might explain symptoms resistant to proton pump inhibitors in patients with gastroesophageal reflux disease.

    Science.gov (United States)

    Rohof, Wout O; Bennink, Roelof J; de Jonge, Hugo; Boeckxstaens, Guy E

    2014-10-01

    Approximately 30% of patients with gastroesophageal reflux disease have symptoms resistant to treatment with proton pump inhibitors (PPIs). Several mechanisms such as esophageal hypersensitivity, increased mucosal permeability, and possibly the position of the gastric acid pocket might underlie a partial response to PPIs. To what extent these mechanisms interact and contribute to PPI-resistant symptoms, however, has not been investigated previously. In 18 gastroesophageal reflux disease patients (9 PPI responders and 9 PPI partial responders), esophageal sensitivity, mucosal permeability, and postprandial reflux parameters were determined during PPI use. Esophageal sensitivity for distension was measured by gradual balloon inflation at 5 and 15 cm above the lower esophageal sphincter. The mucosal permeability of 4 esophageal biopsy specimens per patient was determined in Ussing chambers by measuring the transepithelial electrical resistance and transmucosal flux of fluorescein. Postprandial reflux parameters were determined using concurrent high-resolution manometry/pH impedance after a standardized meal. In addition, the acid pocket was visualized using scintigraphy. No difference in the rate of postprandial acid reflux, in the pH of the acid pocket (PPI responders 3.7 ± 0.7 vs PPI partial responders 4.2 ± 0.4; P = .54), or in the position of the acid pocket was observed in PPI partial responders compared with PPI responders. In addition, the permeability of the esophageal mucosa was similar in both groups, as shown by a similar transepithelial electrical resistance and flux of fluorescein. PPI partial responders had more reflux episodes with a higher mean proximal extent, compared with PPI responders, and were more sensitive to balloon distension, both in the upper and lower esophagus. PPI-resistant symptoms most likely are explained by increased proximal reflux in a hypersensitive esophagus and less likely by increased mucosal permeability or the position of

  10. pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity.

    Science.gov (United States)

    De Milito, Angelo; Canese, Rossella; Marino, Maria Lucia; Borghi, Martina; Iero, Manuela; Villa, Antonello; Venturi, Giulietta; Lozupone, Francesco; Iessi, Elisabetta; Logozzi, Mariantonia; Della Mina, Pamela; Santinami, Mario; Rodolfo, Monica; Podo, Franca; Rivoltini, Licia; Fais, Stefano

    2010-07-01

    Metastatic melanoma is associated with poor prognosis and still limited therapeutic options. An innovative treatment approach for this disease is represented by targeting acidosis, a feature characterizing tumor microenvironment and playing an important role in cancer malignancy. Proton pump inhibitors (PPI), such as esomeprazole (ESOM) are prodrugs functionally activated by acidic environment, fostering pH neutralization by inhibiting proton extrusion. We used human melanoma cell lines and xeno-transplated SCID mice to provide preclinical evidence of ESOM antineoplastic activity. Human melanoma cell lines, characterized by different mutation and signaling profiles, were treated with ESOM in different pH conditions and evaluated for proliferation, viability and cell death. SCID mice engrafted with human melanoma were used to study ESOM administration effects on tumor growth and tumor pH by magnetic resonance spectroscopy (MRS). ESOM inhibited proliferation of melanoma cells in vitro and induced a cytotoxicity strongly boosted by low pH culture conditions. ESOM-induced tumor cell death occurred via rapid intracellular acidification and activation of several caspases. Inhibition of caspases activity by pan-caspase inhibitor z-vad-fmk completely abrogated the ESOM-induced cell death. ESOM administration (2.5 mg kg(-1)) to SCID mice engrafted with human melanoma reduced tumor growth, consistent with decrease of proliferating cells and clear reduction of pH gradients in tumor tissue. Moreover, systemic ESOM administration dramatically increased survival of human melanoma-bearing animals, in absence of any relevant toxicity. These data show preclinical evidence supporting the use of PPI as novel therapeutic strategy for melanoma, providing the proof of concept that PPI target human melanoma modifying tumor pH gradients.

  11. Functional and morphological changes of the mucous membrane of the stomach after long application of proton pump inhibitors

    Directory of Open Access Journals (Sweden)

    M. V. Markina

    2010-04-01

    Full Text Available Changes of mucous membrane of rats’ stomach after long term application of proton pump inhibition – Omeprazole. Increase of pepsin concentration, volume and рН in both fasting and basal gastric juice in comparison with the control was observed. It is established that the content of nitrates and nitrites in gastric juice and in the rats’ mixed saliva after the 12th day of introduction of proton pump inhibitors is 3:1.

  12. Evaluation of costs accrued through inadvertent continuation of hospital-initiated proton pump inhibitor therapy for stress ulcer prophylaxis beyond hospital discharge: a retrospective chart review

    Directory of Open Access Journals (Sweden)

    Shin S

    2015-04-01

    Full Text Available Sooyoung Shin Ajou University College of Pharmacy, Yeongtong-gu, Suwon-si, Gyeonggi-do, South Korea Background: Stress ulcers and related upper gastrointestinal bleeding are well-known complications in intensive care unit (ICU patients. Proton pump inhibitor (PPI-based stress ulcer prophylaxis (SUP has been widely prescribed in noncritically ill patients who are at low risk for clinically significant bleeding, which is then injudiciously continued after hospital discharge. This study aimed to evaluate the incidence of inappropriate prescribing of PPI-based preventative therapy in ICU versus non-ICU patients that subsequently continued postdischarge, and to estimate the costs incurred by the unwarranted outpatient continuation of PPI therapy.Methods: A retrospective review of patient data at a major teaching hospital in Korea was performed. During the 4-year study period, adult patients who were newly initiated on PPI-based SUP during hospital admission and subsequently discharged on a PPI without a medical indication for such therapy were captured for data analysis. The incidence rates of inappropriate prescribing of PPIs were compared between ICU and non-ICU patients, and the costs associated with such therapy were also examined.Results: A total of 4,410 patients, more than half of the inpatient-initiated PPI users, were deemed to have been inadvertently prescribed a PPI at discharge in the absence of a medical need for acid suppression. The incidence of inappropriate outpatient continuation of the prophylaxis was higher among ICU patients compared with non-ICU patients (57.7% versus 52.2%, respectively; P=0.001. The total expenditure accrued through the continuation of nonindicated PPI therapy was approximately US$40,175.Conclusion: This study confirmed that excess usage of PPIs for SUP has spread to low-risk, non-ICU patients. The overuse of unwarranted PPI therapy can incur large health care expenditure, as well as clinical complications

  13. Brand name and generic proton pump inhibitor prescriptions in the United States: insights from the national ambulatory medical care survey (2006-2010).

    Science.gov (United States)

    Gawron, Andrew J; Feinglass, Joseph; Pandolfino, John E; Tan, Bruce K; Bove, Michiel J; Shintani-Smith, Stephanie

    2015-01-01

    Introduction. Proton pump inhibitors (PPI) are one of the most commonly prescribed medication classes with similar efficacy between brand name and generic PPI formulations. Aims. We determined demographic, clinical, and practice characteristics associated with brand name PPI prescriptions at ambulatory care visits in the United States. Methods. Observational cross sectional analysis using the National Ambulatory Medical Care Survey (NAMCS) of all adult (≥18 yrs of age) ambulatory care visits from 2006 to 2010. PPI prescriptions were identified by using the drug entry code as brand name only or generic available formulations. Descriptive statistics were reported in terms of unweighted patient visits and proportions of encounters with brand name PPI prescriptions. Global chi-square tests were used to compare visits with brand name PPI prescriptions versus generic PPI prescriptions for each measure. Poisson regression was used to determine the incidence rate ratio (IRR) for generic versus brand PPI prescribing. Results. A PPI was prescribed at 269.7 million adult ambulatory visits, based on 9,677 unweighted visits, of which 53% were brand name only prescriptions. In 2006, 76.0% of all PPI prescriptions had a brand name only formulation compared to 31.6% of PPI prescriptions in 2010. Visits by patients aged 25-44 years had the greatest proportion of brand name PPI formulations (57.9%). Academic medical centers and physician-owned practices had the greatest proportion of visits with brand name PPI prescriptions (58.9% and 55.6% of visits with a PPI prescription, resp.). There were no significant differences in terms of median income, patient insurance type, or metropolitan status when comparing the proportion of visits with brand name versus generic PPI prescriptions. Poisson regression results showed that practice ownership type was most strongly associated with the likelihood of receiving a brand name PPI over the entire study period. Compared to HMO visits

  14. Association of Proton Pump Inhibitors With Reduced Risk of Warfarin-Related Serious Upper Gastrointestinal Bleeding.

    Science.gov (United States)

    Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Smalley, Walter E; Daugherty, James R; Dupont, William D; Stein, C Michael

    2016-12-01

    Proton pump inhibitors (PPIs) might reduce the risk of serious warfarin-related upper gastrointestinal bleeding, but the evidence of their efficacy for this indication is limited. A gastroprotective effect of PPIs would be particularly important for patients who take warfarin with antiplatelet drugs or nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), which further increase the risk of gastrointestinal bleeding. This retrospective cohort study of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample identified 97,430 new episodes of warfarin treatment with 75,720 person-years of follow-up. The study end points were hospitalizations for upper gastrointestinal bleeding potentially preventable by PPIs and for bleeding at other sites. Patients who took warfarin without PPI co-therapy had 119 hospitalizations for upper gastrointestinal bleeding per 10,000 person-years of treatment. The risk decreased by 24% among patients who received PPI co-therapy (adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63-0.91). There was no significant reduction in the risk of other gastrointestinal bleeding hospitalizations (HR, 1.07; 95% CI, 0.94-1.22) or non-gastrointestinal bleeding hospitalizations (HR, 0.98; 95% CI, 0.84-1.15) in this group. Among patients concurrently using antiplatelet drugs or NSAIDs, those without PPI co-therapy had 284 upper gastrointestinal bleeding hospitalizations per 10,000 person-years of warfarin treatment. The risk decreased by 45% (HR, 0.55; 95% CI, 0.39-0.77) with PPI co-therapy. PPI co-therapy had no significant protective effect for warfarin patients not using antiplatelet drugs or NSAIDs (HR, 0.86; 95% CI, 0.70-1.06). Findings were similar in both study populations. In an analysis of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample, PPI co-therapy was associated with reduced risk of warfarin-related upper gastrointestinal bleeding; the

  15. Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits.

    Science.gov (United States)

    Gwee, Kok Ann; Goh, Vernadine; Lima, Graca; Setia, Sajita

    2018-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are often coadministered with proton-pump inhibitors (PPIs) to reduce NSAID-induced gastrointestinal (GI) adverse events. This coadministration is generally regarded as safe, and is included in many of the guidelines on NSAID prescription. However, recent evidence indicates that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs. This review discusses the GI effects and complications of NSAIDs and how PPIs may potentiate these effects, options for prevention of GI side effects, and appropriate use of PPIs in combination with NSAIDs.

  16. Are proton-pump inhibitors harmful for the semen quality of men in couples who are planning pregnancy?

    Science.gov (United States)

    Huijgen, Nicole A; de Ridder, Maria A J; Verhamme, Katia M; Dohle, Gert R; Vanrolleghem, Ann M; Sturkenboom, Miriam C J M; Laven, Joop S E; Steegers-Theunissen, Régine P M

    2016-12-01

    To determine associations between proton-pump inhibitor (PPI) use and semen parameters in young men of couples who are planning pregnancy. Case-control study of a population-based registry. Not applicable. General practitioner patients comprising 2,473 men from couples planning pregnancy with a recorded semen analysis: 241 with a low total motile sperm count (TMSC ≤1) and 714 with TMSC >1 as matched controls. None. Exposure to PPI; PPI dosage. The study of data from between 1996 and 2013 from the Integrated Primary Care Information database in the Netherlands, which incorporates the medical records of 1.5 million patients from 720 general practitioners, found that the use of PPIs in the period between 12 and 6 months before semen analysis was associated with a threefold higher risk of low TMSC (odds ratio 2.96; 95% confidence interval 1.26-6.97) adjusted for age and other medication. Use of PPIs during the 6 months immediately before the semen analysis was not statistically significantly associated with low TMSC. The use of PPIs in the period 12 to 6 months preceding semen analysis is associated with a threefold higher risk of low TMSC, which suggests that a long-term increase in gastric pH results in a decline of sperm quality. This finding emphasizes the need for more preconceptional research and counseling on the potential effects of medication use on semen quality. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  17. Antitumor effect of combination of the inhibitors of two new oncotargets: proton pumps and reverse transcriptase.

    Science.gov (United States)

    Lugini, Luana; Sciamanna, Ilaria; Federici, Cristina; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Fais, Stefano

    2017-01-17

    Tumor therapy needs new approaches in order to improve efficacy and reduce toxicity of the current treatments. The acidic microenvironment and the expression of high levels of endogenous non-telomerase reverse transcriptase (RT) are common features of malignant tumor cells. The anti-acidic proton pump inhibitor Lansoprazole (LAN) and the non-nucleoside RT inhibitor Efavirenz (EFV) have shown independent antitumor efficacy. LAN has shown to counteract drug tumor resistance. We tested the hypothesis that combination of LAN and EFV may improve the overall antitumor effects. We thus pretreated human metastatic melanoma cells with LAN and then with EFV, both in 2D and 3D spheroid models. We evaluated the treatment effect by proliferation and cell death/apoptosis assays in classical and in pulse administration experiments. The action of EFV was negatively affected by the tumor microenvironmental acidity, and LAN pretreatment overcame the problem. LAN potentiated the cytotoxicity of EFV to melanoma cells and, when administered during the drug interruption period, prevented the replacement of tumor cell growth.This study supports the implementation of the current therapies with combination of Proton Pumps and Reverse Transcriptase inhibitors.

  18. The prophylactic use of a proton pump inhibitor before food and alcohol.

    LENUS (Irish Health Repository)

    O'Leary, C

    2012-02-03

    BACKGROUND: Patients report that the prophylactic consumption of a proton pump inhibitor minimizes gastrointestinal symptoms expected to be provoked by late-night food and alcohol consumption. The efficacy of this practice has not been studied formally. AIM: To perform a randomized, double-blind, placebo-controlled trial of a single dose of lansoprazole (30 mg) taken prior to a large meal and alcohol consumption. METHODS: Study subjects were recruited randomly from local primary care and hospital physicians. Each participant (n = 56; 37 male, 19 female; mean age, 38 years) completed questionnaires before and after the meal. Approximately 90 min prior to the provocative meal, participants were witnessed taking either placebo or 30 mg lansoprazole. Bar tokens were dispensed to permit the accurate quantification of alcohol consumption (mean, 15 units). RESULTS: Forty per cent of subjects reported significant reflux symptoms. For the entire group, there was no significant difference between lansoprazole and placebo. Post-prandial reflux was more frequent in those consuming > 15 units of alcohol (13\\/26, 50%) compared with those consuming < 15 units (7\\/30, 24%; P < 0.05). In the group who consumed > 15 units of alcohol, lansoprazole was associated with a lower rate of heartburn (5\\/15, 33%) compared with placebo (8\\/11, 73%; P < 0.05). CONCLUSION: A single dose of a proton pump inhibitor prior to indulgence was only associated with reduced heartburn in those consuming > 15 units of alcohol.

  19. BENEFITS VERSUS RISKS OF PROTON PUMP INHIBITORS: ARE WE OPENING THE CAN OF WORMS

    Directory of Open Access Journals (Sweden)

    Naser Ashraf Tadvi

    2016-01-01

    Full Text Available Proton pump inhibitors (PPIs are one of the most commonly used drugs worldwide They are indicated for treatment of Gastro-esophageal Reflux Disease (GERD, acid peptic disorders, stress ulcers and prophylaxis of NSAID induced ulcers.[1] PPIs are more efficacious than other drugs like histamine -2 receptor blockers for the treatment of these disorders.[1] Though PPIs are highly potent and effective acid suppressors they are often misused and prescribed irrationally. The incidence of irrational use of PPIs varies from 40-70 % in different studies. [2] In one of our previous studies 58 % of PPIs prescriptions were irrational. [2] These findings become much more significant in the light of recent findings which suggest correlation of long term use of PPIs to myocardial infarction and kidney injury. [3,4] The PPIs may be deemed safe for short term use but chronic use carries risk of hip fractures, infection with clostridium difficle, community acquired pneumonia.[2] PPIs exposure in elderly population was also found to be associated with hyperparathyroidism in one recently conducted study.[5] The ongoing long term studies for assessing the safety and association of PPIs with various serious outcomes may open up a new can of worms. Keeping in mind the benefits as well as risks of proton pump inhibitors, clinicians should judiciously use these drugs in practice. The patients should also be educated regarding the adverse outcomes of PPIs on long term therapy as these drugs are easily available without prescription.

  20. Esomeprazole use is independently associated with significant reduction of BMD: 1-year prospective comparative safety study of four proton pump inhibitors.

    Science.gov (United States)

    Bahtiri, Elton; Islami, Hilmi; Hoxha, Rexhep; Qorraj-Bytyqi, Hasime; Rexhepi, Sylejman; Hoti, Kreshnik; Thaçi, Kujtim; Thaçi, Shpetim; Karakulak, Çağla

    2016-09-01

    Because of the efficacy of proton pump inhibitors (PPIs), their the use is increasing dramatically. The risk of adverse effects of short-term PPI therapy is low, but there are important safety concerns for potential adverse effects of prolonged PPI therapy. Findings from studies assessing the association between PPI use and bone mineral density (BMD) and/or fracture risk are contradictory. The aim of this study was to prospectively assess potential association of PPI treatment with the 12-month change in BMD of the lumbar spine, femur neck, and total hip. The study was performed in 200 PPI users and 50 PPI nonusers. Lumbar spine (L1-L4), femur neck, and total hip BMD were measured by dual-energy X-ray absorptiometry at the baseline and at 12 months. A total of 209 subjects completed the entire 12 months of the study and were included in the final analysis. A Wilcoxon signed-rank test showed that at 12 months PPI use was associated with statistically significant reductions in femur neck and total hip T scores (Z = -2.764, p = 0.005 and Z = -3.281, p = 0.001, respectively). A multiple linear regression analysis showed that only esomeprazole added significantly to the prediction of total lumbar spine and femur neck T scores (p = 0.048 and p = 0.037, respectively). Compared with the baseline, 12 months of PPI treatment resulted in lower femur neck and total hip BMD T scores. Among the four PPIs studied, esomeprazole was independently associated with significant reduction of BMD, whereas omeprazole had no effects on BMD. Considering the widespread use of PPIs, BMD screening should be considered in the case of prolonged PPI use.

  1. Esophageal Motility and Rikkunshito Treatment for Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease: A Prospective, Uncontrolled, Open-Label Pilot Study Trial.

    Science.gov (United States)

    Odaka, Takeo; Yamato, Shigeru; Yokosuka, Osamu

    2017-01-01

    Only a few reports focused on esophageal motility in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) and there has been no established strategy for treatment. To clarify the characteristics of esophageal motility in patients with PPI-refractory NERD, we evaluated esophageal function using combined multichannel intraluminal impedance and esophageal manometry (MII-EM). In addition, we evaluated the efficacy of rikkunshito (RKT), which is a gastrointestinal prokinetic agent. Thirty patients with NERD were enrolled and underwent MII-EM. After 8 weeks of RKT (7.5 g/d) treatment, MII-EM was repeated on patients with PPI-refractory NERD. Symptoms were assessed by the Gastrointestinal Symptom Rating Scale. In patients with PPI-refractory NERD, measures of complete bolus transit, peristaltic contractions, and residual pressure of the lower esophageal sphincter during swallowing deviated from the standard values and esophageal clearance was found to be deteriorated. RKT significantly improved the peristaltic contractions ( P esophageal sphincter ( P disorders of esophageal and lower esophageal sphincter motility that were improved by RKT. Further studies examining esophageal motor activity of RKT in PPI-refractory NERD are required. University hospital Medical Information Network (UMIN) Clinical Trial Registry identifier: UMIN000003092.

  2. Glad you brought it up: a patient-centred programme to reduce proton-pump inhibitor prescribing in general medical practice.

    Science.gov (United States)

    Murie, Jill; Allen, Jane; Simmonds, Ray; de Wet, Carl

    2012-01-01

    Many patients unnecessarily receive proton-pump inhibitor (PPI) drugs long term with significant financial and safety implications. Educating, empowering and supporting patients to self-manage their symptoms can lead to significant and sustained reductions in PPI prescribing. We aimed to implement a programme to reduce inappropriate PPI prescribing. Eligible patients in one general medical practice in rural Scotland were invited for participation between November 2008 and February 2010. Patients attended special nurse advisor clinics, completed dyspepsia questionnaires, received information, formulated self-management plans and were offered flexible support. Of the study population, 437/2883 (15%) were prescribed PPIs. Of these, 166 (38%) were judged eligible for participation. After 12 months, 138/157 (83%) had reduced or stopped their PPIs, while 19/157 (11%) had reverted. The estimated annual net saving in the prescribing budget was ?3180.67. Self-reported understanding of symptom self-management increased from 6/20 (30%) to 18/20 (90%) patients after participation in the programme. A patient-centred programme delivered by a specialist nurse significantly reduced PPI prescribing with financial and potential therapeutic benefits. The vast majority of eligible patients were able to 'step down and off' or 'step off' PPI use after 12 months without any complications or deteriorating symptom control. Further research with larger cohorts of practices and patients is needed to develop a feasible, acceptable and effective programme if similar benefits are to be achieved for primary care in general.

  3. Proton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy.

    Science.gov (United States)

    Spugnini, Enrico P; Citro, Gennaro; Fais, Stefano

    2010-05-08

    The vacuolar ATPases are ATP-dependent proton pumps whose functions include the acidification of intracellular compartments and the extrusion of protons through the cell cytoplasmic membrane. These pumps play a pivotal role in the regulation of cell pH in normal cells and, to a much greater extent, in tumor cells. In fact, the glucose metabolism in hypoxic conditions by the neoplasms leads to an intercellular pH drift towards acidity. The acid microenvironment is modulated through the over-expression of H+ transporters that are also involved in tumor progression, invasiveness, distant spread and chemoresistance. Several strategies to block/downmodulate the efficiency of these transporters are currently being investigated. Among them, proton pump inhibitors have shown to successfully block the H+ transporters in vitro and in vivo, leading to apoptotic death. Furthermore, their action seems to synergize with conventional chemotherapy protocols, leading to chemosensitization and reversal of chemoresistance. Aim of this article is to critically revise the current knowledge of this cellular machinery and to summarize the therapeutic strategies developed to counter this mechanism.

  4. Proton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy

    Directory of Open Access Journals (Sweden)

    Fais Stefano

    2010-05-01

    Full Text Available Abstract The vacuolar ATPases are ATP-dependent proton pumps whose functions include the acidification of intracellular compartments and the extrusion of protons through the cell cytoplasmic membrane. These pumps play a pivotal role in the regulation of cell pH in normal cells and, to a much greater extent, in tumor cells. In fact, the glucose metabolism in hypoxic conditions by the neoplasms leads to an intercellular pH drift towards acidity. The acid microenvironment is modulated through the over-expression of H+ transporters that are also involved in tumor progression, invasiveness, distant spread and chemoresistance. Several strategies to block/downmodulate the efficiency of these transporters are currently being investigated. Among them, proton pump inhibitors have shown to successfully block the H+ transporters in vitro and in vivo, leading to apoptotic death. Furthermore, their action seems to synergize with conventional chemotherapy protocols, leading to chemosensitization and reversal of chemoresistance. Aim of this article is to critically revise the current knowledge of this cellular machinery and to summarize the therapeutic strategies developed to counter this mechanism.

  5. Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits

    Directory of Open Access Journals (Sweden)

    Gwee KA

    2018-02-01

    Full Text Available Kok Ann Gwee,1 Vernadine Goh,2 Graca Lima,3 Sajita Setia4 1Stomach, Liver, and Bowel Centre, Gleneagles Hospital, 2Department of Pharmacy, National University of Singapore, Singapore; 3Global Medical Affairs, Asia-Pacific Region, Pfizer, Hong Kong; 4Medical Affairs, Pfizer, Singapore Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs are often coadministered with proton-pump inhibitors (PPIs to reduce NSAID-induced gastrointestinal (GI adverse events. This coadministration is generally regarded as safe, and is included in many of the guidelines on NSAID prescription. However, recent evidence indicates that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs. This review discusses the GI effects and complications of NSAIDs and how PPIs may potentiate these effects, options for prevention of GI side effects, and appropriate use of PPIs in combination with NSAIDs. Keywords: PPIs, COX2 inhibitors, NSAIDs, enteropathy, gastrointestinal

  6. Connections between nutritional status and proton pump inhibitor therapy in patients scheduled for cardiovascular rehabilitation after treatment for ischaemic and valvular heart disease.

    Science.gov (United States)

    Boban, Marko; Persic, Viktor; Petricevic, Mate; Biocina, Bojan; Sipic, Tomislav; Pehar-Pejcnovic, Vesna; Balen, Sanja; Zulj, Marinko; Vcev, Aleksandar

    Multiple and yet uncertain connections exist between cardiovascular diseases and the nutritional status of patients, particularly in relation to cardiovascular treatments. Proton pump inhibitors (PPI) are among the most commonly used group of drugs. To analyse utilisation of PPI in association with nutritional risk of patients scheduled for rehabilitation after treatment for ischaemic and valvular heart disease. Retrospective analyses on a consecutive sample of patients, which included drug utilisation of PPI and nutritional risk screening, using a standardised NRS-2002 tool. The patients (n = 536) were divided into groups based on previous cardiovascular treatments and use of PPI. Nearly half of the patients (244, 46.1%) had PPI in their chronic therapy despite the clinically negligible prevalence of conditions that are their fundamental indications. The odds for using PPI in patients with increased nutritional risk, estimated by logistic regression, were 3.34 (95% confidence intervals [CI] 2.26-4.94), p 3: positive likelihood-ratio (LR) 2.35 (95% CI 2.10-2.60); negative LR 0.46 (95% CI 0.4-0.6); area under the curve (AUC) 0.720; p 6.36% (positive LR 2.22 [95% CI 2.00-2.50]; negative LR 0.41 [95% CI 0.30-0.50]; AUC 0.707; p < 0.001). Utilisation of PPI was found to be of relatively high prevalence and significantly associated with parameters of nutritional risk screening. Furthermore, it was in correlation with the age of patients and the existence of chronic kidney disease, which are well-established predispositions for poor nutritional status. Nutritional risk seems to be additionally negatively challenged by utilisation of PPI due to gastric malabsorption and anaemia.

  7. [Impact of an evaluation of the professional practices on the relevance of proton pump inhibitors prescriptions pertinence at the hospital].

    Science.gov (United States)

    Daumas, A; Garros, E; Mendizabal, H; Gayet, S; Bernard, F; Bagnères, D; Demoux, A-L; Rossi, P; Villani, P; Granel, B

    2018-04-05

    Proton pump inhibitors (PPI) are widely prescribed for unrecognized indications, at high a dose and for a long duration, in spite of side effects and numerous drug interactions. In 2009, the HAS (French Health Authority) published recommendations of good prescription but the latter are poorly respected. In this context of over prescription and additional cost for the society, we performed a professional practice evaluation of on the model of the Deming wheel. The objective of this work was to optimize the relevance of the prescriptions of the IPP in two services of internal medicine and geriatrics through an evaluation of the professional practices. All PPI prescriptions introduced in outpatient visits or during hospitalization were analyzed. Data collection was prospective, over two periods of 2 months and included 163 (first phase), then 139 patients (second phase). An assessment grid of PPI prescriptions was completed by physicians regarding the active substance, the dose, the duration and the indication of the prescription. The relevance of the prescription corresponded to PPI with a conformed indication and duration and to the prescriptions no recommended stopped. Following the first period of data collection, information was given to medical students and physicians on the relevance of their prescriptions with regard to the current recommendations and informative flyers were offered with the aim of improving the practices before the second period of evaluation (second phase). During the first phase, only 25% of the pre-hospital prescriptions and 33% of the hospital prescriptions respected the HAS recommendations. The main indication of the PPI was the prevention of peptic ulcers in a context of associated drug estimated at risk. An improvement of the global relevance of prescription was observed after awareness of the physicians: 26% relevance during the first phase and 60% in the second one (Pprescriptions introduced at hospital decreased from 33 to 17% and

  8. Clinical value of wireless pH-monitoring of gastro-esophageal reflux in children before and after proton pump inhibitors.

    Science.gov (United States)

    Boström, Michaela; Thorsson, Ola; Toth, Ervin; Agardh, Daniel

    2014-12-24

    Wireless pH-monitoring is an accurate method for diagnosing adults with gastroesophageal reflux disease (GERD). The aim of this study was to evaluate the use of the Bravo capsule on children investigated for GERD in terms of safety, tolerability and feasibility before and after administration of proton pump inhibitors. A Bravo capsule was inserted during upper endoscopy under general anaesthesia or deep sedation with propofol. 48-hour pH-metry was performed in 106 children (50 males, 56 females) at the median age of 11 years (range 17 months-18 years). On the second day of investigation, proton pump inhibitor (PPI) was given at a mean dose of 1.6 mg/kg (SD ±0.6 mg). The definition of GERD was set to a reflux index (RI) of ≥5% and DeMeester score (DMS) ≥14.7. Application of the capsule was successful in 103 of the 106 children (97.2%) and interpretable in 99 of these 103 (96.1%). 49 of the children with interpretable results (49.5%) had GERD according to RI, while 51 (56.7%) had GERD according to DMS. After PPI was given on day 2, RI decreased from a median of 4.9% (range 0.3-63.4%) to 2.2% (0-58.0%), while DMS decreased from a median of 17.6 (range 2.2-207.6) to 8.2 (0.3-178.6), respectively (p < 0.0001). No severe adverse events were reported. Wireless pH-metry is a safe and tolerable method when investigating children for GERD. PPI given on the second day of assessment provides additional information on response to treatment suggesting that pH-metry preferably should be extended to 48 hours.

  9. Persistent gastro-oesophageal reflux symptoms despite proton pump inhibitor therapy.

    Science.gov (United States)

    Ang, Daphne; How, Choon How; Ang, Tiing Leong

    2016-10-01

    About one-third of patients with suspected gastro-oesophageal reflux disease (GERD) do not respond symptomatically to proton pump inhibitors (PPIs). Many of these patients do not suffer from GERD, but may have underlying functional heartburn or atypical chest pain. Other causes of failure to respond to PPIs include inadequate acid suppression, non-acid reflux, oesophageal hypersensitivity, oesophageal dysmotility and psychological comorbidities. Functional oesophageal tests can exclude cardiac and structural causes, as well as help to confi rm or exclude GERD. The use of PPIs should only be continued in the presence of acid reflux or oesophageal hypersensitivity for acid reflux-related events that is proven on functional oesophageal tests. Copyright: © Singapore Medical Association.

  10. Cost-Effectiveness of Intravenous Proton Pump Inhibitors in High-Risk Bleeders

    Directory of Open Access Journals (Sweden)

    Sander Veldhuyzen van Zanten

    2004-01-01

    Full Text Available There is unequivocal evidence that proton pump inhibitors (PPIs are currently the most effective acid suppressive agents available. Intravenous (IV formulations have been developed, although only IV pantoprazole is available in Canada. In patients presenting with serious upper gastrointestinal (GI bleeding due to duodenal or gastric ulcers, it has always been believed that IV administration of acid-lowering agents would improve clinical outcomes. The reason behind this thinking is twofold. First, there is in vitro evidence that formed clots are more stable at or near neutral pH (1. Second, by administering the agent intravenously, suppression of acid production is achieved much more quickly, thereby promoting more rapid healing of the ulcer and reducing the risk of persistent or recurrent bleeding. Interestingly and surprisingly, however, the data for intravenous H2-blockers have been disappointing (2. This failure to demonstrate clinical benefit has never been fully explained.

  11. Delirium in the geriatric unit: proton-pump inhibitors and other risk factors.

    Science.gov (United States)

    Otremba, Iwona; Wilczyński, Krzysztof; Szewieczek, Jan

    2016-01-01

    Delirium remains a major nosocomial complication of hospitalized elderly. Predictive models for delirium may be useful for identification of high-risk patients for implementation of preventive strategies. Evaluate specific factors for development of delirium in a geriatric ward setting. Prospective cross-sectional study comprised 675 consecutive patients aged 79.2±7.7 years (66% women and 34% men), admitted to the subacute geriatric ward of a multiprofile university hospital after exclusion of 113 patients treated with antipsychotic medication because of behavioral disorders before admission. Comprehensive geriatric assessments including a structured interview, physical examination, geriatric functional assessment, blood sampling, ECG, abdominal ultrasound, chest X-ray, Confusion Assessment Method for diagnosis of delirium, Delirium-O-Meter to assess delirium severity, Richmond Agitation-Sedation Scale to assess sedation or agitation, visual analog scale and Doloplus-2 scale to assess pain level were performed. Multivariate logistic regression analysis revealed five independent factors associated with development of delirium in geriatric inpatients: transfer between hospital wards (odds ratio [OR] =2.78; confidence interval [CI] =1.54-5.01; P=0.001), preexisting dementia (OR =2.29; CI =1.44-3.65; Pfall incidents (OR =1.76; CI =1.17-2.64; P=0.006), and use of proton-pump inhibitors (OR =1.67; CI =1.11-2.53; P=0.014). Transfer between hospital wards, preexisting dementia, previous delirium incidents, previous fall incidents, and use of proton-pump inhibitors are predictive of development of delirium in the geriatric inpatient setting.

  12. Proton pump inhibitor use and association with spontaneous bacterial peritonitis in patients with cirrhosis and ascites.

    Science.gov (United States)

    Siple, Jolene F; Morey, Jessica M; Gutman, Tracy E; Weinberg, Kathy L; Collins, Peggie D

    2012-10-01

    To evaluate the literature regarding the efficacy and safety of proton pump inhibitors (PPIs) when they are used in patients with cirrhosis and ascites. A literature search was conducted using MEDLINE (1966-May 2012) and Web of Science (1990-May 2012) with the terms proton pump inhibitor, antisecretory therapy, cirrhosis, ascites, spontaneous bacterial peritonitis, and Clostridium difficile. The search was restricted to articles published in English on the use of PPIs in humans. Reference citations from identified published articles were reviewed for relevant information. All articles in English identified from the data sources were evaluated for inclusion. One case series, 8 retrospective case-control trials, and 1 meta-analysis were identified. Cirrhosis may cause complications such as portal hypertension, esophageal varices, and ascites. Patients may be prescribed PPIs without clear indications or because of their propensity to develop upper gastrointestinal symptoms and bleeding. However, gastric acidity is a major nonspecific defense mechanism and there is insufficient evidence on the need for chronic acid suppression in patients with cirrhosis. It is postulated that the portal hypertensive environment in cirrhosis and the acid suppression from PPIs can increase the risk of spontaneous bacterial peritonitis and C. difficile infection in patients with cirrhosis with ascites. Several retrospective studies and 1 meta-analysis have confirmed this association. Patients with cirrhosis and ascites should be monitored carefully while on PPIs for a possible increased risk of infection from spontaneous bacterial peritonitis and C. difficile. Prospective randomized trials are needed to confirm this association. Clinicians should be aware of this lesser known adverse effect of PPIs.

  13. Association between Proton Pump Inhibitors and Respiratory Infections: A Systematic Review and Meta-Analysis of Clinical Trials

    Directory of Open Access Journals (Sweden)

    Nabil Sultan

    2008-01-01

    Full Text Available BACKGROUND: Proton pump inhibitors (PPIs have become the mainstay of treatment for and prevention of many serious gastrointestinal diseases. Laboratory and clinical evidence suggests that the increase in gastric pH caused by PPIs may be linked to increased bacterial colonization of the stomach and may predispose patients to an increased risk for respiratory infections.

  14. Diagnostic value of the proton pump inhibitor test for gastro-oesophageal reflux disease in primary care

    NARCIS (Netherlands)

    Aanen, M. C.; Weusten, B. L. A. M.; Numans, M. E.; de Wit, N. J.; Baron, A.; Smout, A. J. P. M.

    2006-01-01

    AIM: To assess the diagnostic accuracy of the proton pump inhibitor test in a primary care population as well as its additional value over reflux history, using the symptom association probability outcome during 24-h oesophageal pH recording as reference test for gastro-oesophageal reflux disease.

  15. Increased prandial air swallowing and postprandial gas-liquid reflux among patients refractory to proton pump inhibitor therapy

    NARCIS (Netherlands)

    Bravi, Ivana; Woodland, Philip; Gill, Ravinder S.; Al-Zinaty, Mohannad; Bredenoord, Albert J.; Sifrim, Daniel

    2013-01-01

    Many patients with gastroesophageal reflux disease (GERD) have persistent reflux despite treatment with proton pump inhibitors (PPIs). Mixed gas-liquid reflux events are more likely to be perceived as symptomatic. We used esophageal impedance monitoring to investigate whether esophageal gas is

  16. Prolonged Treatment Duration is Required for Successful Helicobacter pylori Eradication with Proton Pump Inhibitor Triple Therapy in Canada

    Directory of Open Access Journals (Sweden)

    Carlo A Fallone

    2013-01-01

    Full Text Available BACKGROUND: Traditional seven-day proton pump inhibitor triple therapy for Helicobacter pylori eradication has recently shown disappointing results outside of Canada. Prolonging therapy may be associated with poorer compliance and, hence, may not have a better outcome in a real-world setting.

  17. Outcomes of peptic ulcer bleeding following treatment with proton pump inhibitors in routine clinical practice: 935 patients with high- or low-risk stigmata.

    Science.gov (United States)

    Lanas, Angel; Carrera-Lasfuentes, Patricia; García-Rodríguez, Luis A; García, Santiago; Arroyo-Villarino, María Teresa; Ponce, Julio; Bujanda, Luis; Calleja, José L; Polo-Tomas, Mónica; Calvet, Xavier; Feu, Faust; Perez-Aisa, Angeles

    2014-10-01

    To assess rates of further bleeding, surgery and mortality in patients hospitalized owing to peptic ulcer bleeding. Consecutive patients hospitalized for peptic ulcer bleeding and treated with a proton pump inhibitor (PPI) (esomeprazole or pantoprazole) were identified retrospectively in 12 centers in Spain. Patients were included if they had high-risk stigmata (Forrest class Ia-IIb, underwent therapeutic endoscopy and received intravenous PPI ≥120 mg/day for ≥24 h) or low-risk stigmata (Forrest class IIc-III, underwent no therapeutic endoscopy and received intravenous or oral PPI [any dose]). Of 935 identified patients, 58.3% had high-risk stigmata and 41.7% had low-risk stigmata. After endoscopy, 88.3% of high-risk patients and 22.1% of low-risk patients received intravenous PPI therapy at doses of at least 160 mg/day. Further bleeding within 72 h occurred in 9.4% and 2.1% of high- and low-risk patients, respectively (p peptic ulcer bleeding and treated with PPIs, patients with high-risk stigmata have a higher risk of further bleeding and surgery, but not of death, than those with low-risk stigmata.

  18. Cost-Effectiveness of Histamine2 Receptor Antagonists Versus Proton Pump Inhibitors for Stress Ulcer Prophylaxis in Critically Ill Patients.

    Science.gov (United States)

    Hammond, Drayton A; Kathe, Niranjan; Shah, Anuj; Martin, Bradley C

    2017-01-01

    To determine the cost-effectiveness of stress ulcer prophylaxis with histamine 2 receptor antagonists (H2RAs) versus proton pump inhibitors (PPIs) in critically ill and mechanically ventilated adults. A decision analytic model estimating the costs and effectiveness of stress ulcer prophylaxis (with H2RAs and PPIs) from a health care institutional perspective. Adult mixed intensive care unit (ICU) population who received an H2RA or PPI for up to 9 days. Effectiveness measures were mortality during the ICU stay and complication rate. Costs (2015 U.S. dollars) were combined to include medication regimens and untoward events associated with stress ulcer prophylaxis (pneumonia, Clostridium difficile infection, and stress-related mucosal bleeding). Costs and probabilities for complications and mortality from complications came from randomized controlled trials and observational studies. A base case scenario was developed with pooled data from an observational study and meta-analysis of randomized controlled trials. Scenarios based on observational and meta-analysis data alone were evaluated. Outcomes were expected and incremental costs, mortalities, and complication rates. Univariate sensitivity analyses were conducted to determine the influence of inputs on cost, mortality, and complication rates. Monte Carlo simulations evaluated second-order uncertainty. In the base case scenario, the costs, complication rates, and mortality rates were $9039, 17.6%, and 2.50%, respectively, for H2RAs and $11,249, 22.0%, and 3.34%, respectively, for PPIs, indicating that H2RAs dominated PPIs. The observational study-based model provided similar results; however, in the meta-analysis-based model, H2RAs had a cost of $8364 and mortality rate of 3.2% compared with $7676 and 2.0%, respectively, for PPIs. At a willingness-to-pay threshold of $100,000/death averted, H2RA therapy was superior or preferred 70.3% in the base case and 97.0% in the observational study-based scenario. PPI therapy

  19. Impact of a Restriction in Reimbursement on Proton Pump Inhibitors in Patients with an Increased Risk of Gastric Complications

    Directory of Open Access Journals (Sweden)

    Linda E. Flinterman

    2018-02-01

    Full Text Available Governments have several options to reduce the increasing costs of health care, including restrictions for the reimbursement of medicines. Next to the intended effect of reduced costs for medicines, reimbursement restriction can have unintended effects such as patients refraining from their treatment which may lead to health problems and increased use of health care. An example of a reimbursement restriction is the one for proton pump inhibitors (PPIs that became effective in the Netherlands in January 2012. A major unintended effect of this measure could be that high-risk patients who start with non-steroidal anti-inflammatory drugs (NSAIDs or low-dose aspirin (aspirin and who have an increased risk of gastric complications for which they are prescribed PPIs refrain from this PPI treatment. The aim of this study was to evaluate the effect of the reimbursement restriction among high-risk users of NSAIDs or aspirin. Do these patients refrain from their PPI treatment and if so do they have an increased risk of gastric complications? Part of the patients starting with NSAIDs or aspirin have an increased risk of gastric complications due to their age, comorbidities, or co-medication. The incidence of PPI use during the 2 years before the reimbursement restriction (2010 and 2011 and 2 years after the introduction of the reimbursement restriction was compared for patients on NSAIDs or aspirin with an increased risk of developing gastric complications. Impact of age, sex, and social economic status (SES was taken into account. Hospital admissions due to gastric complications were studied over the same period (2010–2013. Data were obtained from a large population-based primary care database and a hospital database. The use of PPIs in patients with an increased risk of gastric complications who started NSAID/aspirin increased from 40% in 2010 to 55% in 2013. No impact was found of age, sex, or SES. There was no increase in hospital admissions due

  20. Algorithmic approach to patients presenting with heartburn and epigastric pain refractory to empiric proton pump inhibitor therapy.

    Science.gov (United States)

    Roorda, Andrew K; Marcus, Samuel N; Triadafilopoulos, George

    2011-10-01

    Reflux-like dyspepsia (RLD), where predominant epigastric pain is associated with heartburn and/or regurgitation, is a common clinical syndrome in both primary and specialty care. Because symptom frequency and severity vary, overlap among gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), and RLD, is quite common. The chronic and recurrent nature of RLD and its variable response to proton pump inhibitor (PPI) therapy remain problematic. To examine the prevalence of GERD, NERD, and RLD in a community setting using an algorithmic approach and to assess the potential, reproducibility, and validity of a multi-factorial scoring system in discriminating patients with RLD from those with GERD or NERD. Using a novel algorithmic approach, we evaluated an outpatient, community-based cohort referred to a gastroenterologist because of epigastric pain and heartburn that were only partially relieved by PPI. After an initial symptom evaluation (for epigastric pain, heartburn, regurgitation, dysphagia), an endoscopy and distal esophageal biopsies were performed, followed by esophageal motility and 24-h ambulatory pH monitoring to assess esophageal function and pathological acid exposure. A scoring system based on presence of symptoms and severity of findings was devised. Data was collected in two stages: subjects in the first stage were designated as the derivation cohort; subjects in the second stage were labeled the validation cohort. The total cohort comprised 159 patients (59 males, 100 females; mean age 52). On endoscopy, 30 patients (19%) had complicated esophagitis (CE) and 11 (7%) had Barrett's esophagus (BE) and were classified collectively as patients with GERD. One-hundred and eighteen (74%) patients had normal esophagus. Of these, 94 (59%) had one or more of the following: hiatal hernia, positive biopsy, abnormal pH, and/or abnormal motility studies and were classified as patients with NERD. The remaining 24 patients (15%) had normal functional

  1. Non-steroidal anti-inflammatory drugs and gastroprotection with proton pump inhibitors: a focus on ketoprofen/omeprazole.

    Science.gov (United States)

    Gigante, Antonio; Tagarro, Ignacio

    2012-04-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed agents for rheumatic disorders such as osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Despite the known association between NSAID use and gastropathy, however, only around one-third of patients at risk of NSAID-induced gastrointestinal toxicity receive adequate gastroprotection, and as many as 44% of these patients are non-adherent. We review the co-prescription of proton pump inhibitors (PPIs) for the prevention of NSAID-induced gastropathy, with a particular focus on the first fixed-dose NSAID/PPI formulation: ketoprofen/omeprazole modified-release capsules. The ketoprofen/omeprazole fixed-dose combination is available in doses of 100 mg/20 mg, 150 mg/20 mg or 200 mg/20 mg as a single capsule for once-daily administration. Ketoprofen monotherapy has been shown to be generally equivalent to other NSAIDs when used in the treatment of OA. In RA, ketoprofen has demonstrated equivalent efficacy to diclofenac, indometacin, piroxicam, aceclofenac, phenylbutazone, naproxen and flurbiprofen. Studies comparing ketoprofen with ibuprofen and sulindac in patients with RA have, in general, favoured ketoprofen. Studies in AS have generally reported similar efficacy between ketoprofen and phenylbutazone and pirprofen. Prophylaxis with omeprazole is effective for the prevention of gastroduodenal ulcers, maintenance of remission and alleviation of dyspeptic symptoms in NSAID recipients. Omeprazole is well tolerated, and adverse events are generally gastrointestinal in nature. The fixed-dose combination of ketoprofen and omeprazole has demonstrated bioequivalence to the respective monotherapies. The incidence of digestive symptoms and the need for dose reduction was reported to be lower with the combination than with its components. Ketoprofen/omeprazole modified-release capsules are the first fixed-dose NSAID/PPI formulation to be approved. This formulation

  2. Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics

    DEFF Research Database (Denmark)

    Schjerning Olsen, Anne-Marie; Lindhardsen, Jesper; Gislason, Gunnar H

    2015-01-01

    STUDY QUESTION: What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)? METHODS: This was a nationwide cohort study based on linked...... plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models. STUDY ANSWER AND LIMITATIONS: The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated...... gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0...

  3. Multifaceted intervention to curb in-hospital over-prescription of proton pump inhibitors: A longitudinal multicenter quasi-experimental before-and-after study.

    Science.gov (United States)

    Del Giorno, Rosaria; Ceschi, Alessandro; Pironi, Michela; Zasa, Anna; Greco, Angela; Gabutti, Luca

    2018-04-01

    Proton pump inhibitors (PPIs) are indicated for a restricted number of clinical conditions, and their misuse can lead to several adverse effects. Despite that, the proportion of overuse is alarmingly high. To test the efficacy of a multifaceted strategy in order to achieve a significant reduction of new PPI prescriptions at discharge in hospitalized patients. Multicenter longitudinal quasi-experimental before-and-after study conducted from July 1st, 2014 to June 30th, 2017. 44,973 admissions in a network of 5 public teaching hospitals of the Italian-speaking region of Switzerland. Multifaceted strategy consisting in a continuous transparent monitoring-benchmarking and in capillary educational interventions applied in the internal medicine departments. To confirm the causality of the results we monitored the trend of new PPI prescriptions in the, not exposed to the intervention, surgery departments of the same hospital network. New PPI prescriptions at hospital discharge. Over the 36month study period 44,973 patient files were analyzed. At admission, comparing internal medicine vs. surgery departments, 44.9% vs. 23.3% of patients were already being treated with a PPI. The annual rate of new PPI prescriptions, for internal medicine showed a decreasing trend: 19, 19, 18, 16% in years 2014, 2015, 2016, 2017, respectively (pintroduction of a multifaceted intervention significantly reduced the time trend of PPI prescriptions at hospital discharge in internal medicine departments. Further studies are needed to confirm whether the strategy proposed could contribute to optimize the in-hospital drug prescription behavior in other healthcare settings as well. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  4. Construction, internal validation and implementation in a mobile application of a scoring system to predict nonadherence to proton pump inhibitors

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    Emma Mares-García

    2017-06-01

    Full Text Available Background Other studies have assessed nonadherence to proton pump inhibitors (PPIs, but none has developed a screening test for its detection. Objectives To construct and internally validate a predictive model for nonadherence to PPIs. Methods This prospective observational study with a one-month follow-up was carried out in 2013 in Spain, and included 302 patients with a prescription for PPIs. The primary variable was nonadherence to PPIs (pill count. Secondary variables were gender, age, antidepressants, type of PPI, non-guideline-recommended prescription (NGRP of PPIs, and total number of drugs. With the secondary variables, a binary logistic regression model to predict nonadherence was constructed and adapted to a points system. The ROC curve, with its area (AUC, was calculated and the optimal cut-off point was established. The points system was internally validated through 1,000 bootstrap samples and implemented in a mobile application (Android. Results The points system had three prognostic variables: total number of drugs, NGRP of PPIs, and antidepressants. The AUC was 0.87 (95% CI [0.83–0.91], p < 0.001. The test yielded a sensitivity of 0.80 (95% CI [0.70–0.87] and a specificity of 0.82 (95% CI [0.76–0.87]. The three parameters were very similar in the bootstrap validation. Conclusions A points system to predict nonadherence to PPIs has been constructed, internally validated and implemented in a mobile application. Provided similar results are obtained in external validation studies, we will have a screening tool to detect nonadherence to PPIs.

  5. Non-prescription proton-pump inhibitors for self-treating frequent heartburn:the role of the Canadian pharmacist

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    Armstrong, David; Nakhla, Nardine

    2016-01-01

    Heartburn and acid regurgitation are the cardinal symptoms of gastroesophageal reflux and occur commonly in the Canadian population. Multiple non-prescription treatment options are available for managing these symptoms, including antacids, alginates, histamine-H2 receptor antagonists (H2RAs), and proton-pump inhibitors (PPIs). As a result, pharmacists are ideally positioned to recommend appropriate treatment options based upon an individual’s needs and presenting symptoms, prior treatment response, comorbid medical conditions, and other relevant factors. Individuals who experience mild heartburn and/or have symptoms that occur predictably in response to known precipitating factors can manage their symptoms by avoiding known triggers and using on-demand antacids and/or alginates or lower-dose non-prescription H2RAs (e.g. ranitidine 150 mg). For those with moderate symptoms, lifestyle changes, in conjunction with higher-dose non-prescription H2RAs, may be effective. However, for individuals with moderate-to-severe symptoms that occur frequently (i.e. ≥2 days/week), the non-prescription (Schedule II) PPI omeprazole 20 mg should be considered. The pharmacist can provide important support by inquiring about the frequency and severity of symptoms, identifying an appropriate treatment option, and recognizing other potential causes of symptoms, as well as alarm features and atypical symptoms that would necessitate referral to a physician. After recommending an appropriate treatment, the pharmacist can provide instructions for its correct use. Additionally, the pharmacist should inquire about recurrences, respond to questions about adverse events, provide monitoring parameters, and counsel on when referral to a physician is warranted. Pharmacists are an essential resource for individuals experiencing heartburn; they play a crucial role in helping individuals make informed self-care decisions and educating them to ensure that therapy is used in an optimal, safe, and

  6. Cost-effectiveness of histamine receptor-2 antagonist versus proton pump inhibitor for stress ulcer prophylaxis in critically ill patients*.

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    MacLaren, Robert; Campbell, Jon

    2014-04-01

    To examine the cost-effectiveness of using histamine receptor-2 antagonist or proton pump inhibitor for stress ulcer prophylaxis. Decision analysis model examining costs and effectiveness of using histamine receptor-2 antagonist or proton pump inhibitor for stress ulcer prophylaxis. Costs were expressed in 2012 U.S. dollars from the perspective of the institution and included drug regimens and the following outcomes: clinically significant stress-related mucosal bleed, ventilator-associated pneumonia, and Clostridium difficile infection. Effectiveness was the mortality risk associated with these outcomes and represented by survival. Costs, occurrence rates, and mortality probabilities were extracted from published data. A simulation model. A mixed adult ICU population. Histamine receptor-2 antagonist or proton pump inhibitor for 9 days of stress ulcer prophylaxis therapy. Output variables were expected costs, expected survival rates, incremental cost, and incremental survival rate. Univariate sensitivity analyses were conducted to determine the drivers of incremental cost and incremental survival. Probabilistic sensitivity analysis was conducted using second-order Monte Carlo simulation. For the base case analysis, the expected cost of providing stress ulcer prophylaxis was $6,707 with histamine receptor-2 antagonist and $7,802 with proton pump inhibitor, resulting in a cost saving of $1,095 with histamine receptor-2 antagonist. The associated mortality probabilities were 3.819% and 3.825%, respectively, resulting in an absolute survival benefit of 0.006% with histamine receptor-2 antagonist. The primary drivers of incremental cost and survival were the assumptions surrounding ventilator-associated pneumonia and bleed. The probabilities that histamine receptor-2 antagonist was less costly and provided favorable survival were 89.4% and 55.7%, respectively. A secondary analysis assuming equal rates of C. difficile infection showed a cost saving of $908 with histamine

  7. Delirium in the geriatric unit: proton-pump inhibitors and other risk factors

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    Otremba I

    2016-04-01

    Full Text Available Iwona Otremba, Krzysztof Wilczyński, Jan SzewieczekDepartment of Geriatrics, School of Health Sciences in Katowice, Medical University of Silesia, Katowice, PolandBackground: Delirium remains a major nosocomial complication of hospitalized elderly. Predictive models for delirium may be useful for identification of high-risk patients for implementation of preventive strategies.Objective: Evaluate specific factors for development of delirium in a geriatric ward setting.Methods: Prospective cross-sectional study comprised 675 consecutive patients aged 79.2±7.7 years (66% women and 34% men, admitted to the subacute geriatric ward of a multiprofile university hospital after exclusion of 113 patients treated with antipsychotic medication because of behavioral disorders before admission. Comprehensive geriatric assessments including a structured interview, physical examination, geriatric functional assessment, blood sampling, ECG, abdominal ultrasound, chest X-ray, Confusion Assessment Method for diagnosis of delirium, Delirium-O-Meter to assess delirium severity, Richmond Agitation-Sedation Scale to assess sedation or agitation, visual analog scale and Doloplus-2 scale to assess pain level were performed.Results: Multivariate logistic regression analysis revealed five independent factors associated with development of delirium in geriatric inpatients: transfer between hospital wards (odds ratio [OR] =2.78; confidence interval [CI] =1.54–5.01; P=0.001, preexisting dementia (OR =2.29; CI =1.44–3.65; P<0.001, previous delirium incidents (OR =2.23; CI =1.47–3.38; P<0.001, previous fall incidents (OR =1.76; CI =1.17–2.64; P=0.006, and use of proton-pump inhibitors (OR =1.67; CI =1.11–2.53; P=0.014.Conclusion: Transfer between hospital wards, preexisting dementia, previous delirium incidents, previous fall incidents, and use of proton-pump inhibitors are predictive of development of delirium in the geriatric inpatient setting.Keywords: delirium

  8. The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based study [corrected] from the Canadian Multicentre Osteoporosis Study (CaMos).

    Science.gov (United States)

    Targownik, Laura E; Leslie, William D; Davison, K Shawn; Goltzman, David; Jamal, Sophie A; Kreiger, Nancy; Josse, Robert G; Kaiser, Stephanie M; Kovacs, Christopher S; Prior, Jerilynn C; Zhou, Wei

    2012-09-01

    Proton pump inhibitor (PPI) use has been identified as a risk factor for hip and vertebral fractures. Evidence supporting a relationship between PPI use and osteoporosis remains scant. Demonstrating that PPIs are associated with accelerated bone mineral density (BMD) loss would provide supportive evidence for a mechanism through which PPIs could increase fracture risk. We used the Canadian Multicentre Osteoporosis Study data set, which enrolled a population-based sample of Canadians who underwent BMD testing of the femoral neck, total hip, and lumbar spine (L1-L4) at baseline, and then again at 5 and 10 years. Participants also reported drug use and exposure to risk factors for osteoporosis and fracture. Multivariate linear regression was used to determine the independent association of PPI exposure and baseline BMD, and on change in BMD at 5 and 10 years. In all, 8,340 subjects were included in the baseline analysis, with 4,512 (55%) undergoing year 10 BMD testing. After adjusting for potential confounders, PPI use was associated with significantly lower baseline BMD at the femoral neck and total hip. PPI use was not associated with a significant acceleration in covariate-adjusted BMD loss at any measurement site after 5 and 10 years of follow-up. PPI users had lower BMD at baseline than PPI non-users, but PPI use over 10 years did not appear to be associated with accelerated BMD loss. The reasons for discordant findings between PPI use at baseline and during follow-up require further study.

  9. Proton Pump Inhibitors and Serum Magnesium Levels in Patients With Torsades de Pointes

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    Pietro E. Lazzerini

    2018-04-01

    Full Text Available Background: Torsades de pointes (TdP is a life-threatening ventricular tachycardia occurring in long QT-syndrome patients. It usually develops when multiple QT-prolonging factors are concomitantly present, more frequently drugs and electrolyte imbalances. Since proton–pump inhibitors (PPIs-associated hypomagnesemia is an increasingly recognized adverse event, PPIs were recently included in the list of drugs with conditional risk of TdP, despite only few cases of TdP in PPI users have been reported so far.Objectives: Aim of the present study is to evaluate whether PPI-induced hypomagnesemia actually has a significant clinical impact on the risk of TdP in the general population.Methods: Forty-eight unselected patients who experienced TdP were consecutively enrolled (2008-2017. Shortly after the first TdP episode, in those patients who did not receive magnesium sulfate and/or potassium or calcium replacement therapy, serum electrolytes were measured and their relationship with PPI usage analyzed.Results: Many patients (28/48, 58% were under current PPI treatment when TdP occurred. Among TdP patients in whom serum electrolyte determinations were obtained before replacement therapy (27/48, those taking PPIs had significantly lower serum magnesium levels than those who did not. Hypomagnesemia occurred in ~40% of patients receiving PPIs (6/14, in all cases after an extended treatment (>2 weeks. In patients taking PPIs the mean QT-prolonging risk factor number was significantly higher than in those who did not, a difference which was mainly driven by lower magnesium levels.Conclusions: In unselected TdP patients, PPI-induced hypomagnesemia was common and significantly contributed to their cumulative arrhythmic risk. By providing clinical support to current recommendations, our data confirm that more awareness is needed when a PPI is prescribed, specifically as regards the risk of life-threatening arrhythmias.

  10. Potential association between the recent increase in campylobacteriosis incidence in the Netherlands and proton-pump inhibitor use - an ecological study.

    Science.gov (United States)

    Bouwknegt, M; van Pelt, W; Kubbinga, M E; Weda, M; Havelaar, A H

    2014-08-14

    The Netherlands saw an unexplained increase in campylobacteriosis incidence between 2003 and 2011, following a period of continuous decrease. We conducted an ecological study and found a statistical association between campylobacteriosis incidence and the annual number of prescriptions for proton pump inhibitors (PPIs), controlling for the patient's age, fresh and frozen chicken purchases (with or without correction for campylobacter prevalence in fresh poultry meat). The effect of PPIs was larger in the young than in the elderly. However, the counterfactual population-attributable fraction for PPIs was largest for the elderly (ca 45% in 2011) and increased at population level from 8% in 2004 to 27% in 2011. Using the regression model and updated covariate values, we predicted a trend break for 2012, largely due to a decreased number of PPI prescriptions, that was subsequently confirmed by surveillance data. Although causality was not shown, the biological mechanism, age effect and trend-break prediction suggest a substantial impact of PPI use on campylobacteriosis incidence in the Netherlands. We chose the ecological study design to pilot whether it is worthwhile to further pursue the effect of PPI on campylobacteriosis and other gastrointestinal pathogens in prospective cohort studies. We now provide strong arguments to do so.

  11. Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma.

    Science.gov (United States)

    Canitano, Andrea; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Federici, Cristina; Fais, Stefano

    2016-07-01

    Multiple Myeloma (MM) is the second most common hematological malignancy and is responsive to a limited number of drugs. Unfortunately, to date, despite the introduction of novel drugs, no relevant increase in survival rates has been obtained. Proton pump inhibitors (PPIs) have been shown to have significant antitumor action as single agents as well as in combination with chemotherapy. This study investigates the potential anti-tumor effectiveness of two PPIs, Lansoprazole and Omeprazole, against human MM cells. We found that Lansoprazole exerts straightforward efficacy against myeloma cells, even at suboptimal concentrations (50 µM), while Omeprazole has limited cytotoxic action. The Lansoprazole anti-MM effect was mostly mediated by a caspase-independent apoptotic-like cytotoxicity, with only a secondary anti-proliferative action. This study provides clear evidence supporting the use of Lansoprazole in the strive against MM with an efficacy proven much higher than current therapeutical approaches and without reported side effects. It is however conceivable that, consistent with the results obtained in other human tumors, Lansoprazole may well be combined with existing anti-myeloma therapies with the aim to improve the low level of efficacy of the current strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Proton pump inhibitor Lansoprazole is a nuclear Liver X Receptor agonist

    Science.gov (United States)

    Cronican, Andrea A.; Fitz, Nicholas F.; Pham, Tam; Fogg, Allison; Kifer, Brionna; Koldamova, Radosveta; Lefterov, Iliya

    2010-01-01

    The liver X receptors (LXRα and LXRβ) are transcription factors that control the expression of genes primarily involved in cholesterol metabolism. In brain, in addition to normal neuronal function, cholesterol metabolism is important for APP proteolytic cleavage, secretase activities, Aβ aggregation and clearance. Particularly significant in this respect is the LXR mediated transcriptional control of APOE, which is the only proven risk factor for late onset Alzheimer’s disease. Using a transactivation reporter assay for screening pharmacologically active compounds and off patent drugs we identified the Proton Pump Inhibitor Lansoprazole as an LXR agonist. In secondary screens and counter-screening assays, it was confirmed that Lansoprazole directly activates LXR, increases the expression of LXR target genes in brain-derived human cell lines, and increases Abca1 and Apo-E protein levels in primary astrocytes derived from wild type but not LXRα/β double knockout mice. Other PPIs activate LXR as well, but the efficiency of activation depends on their structural similarities to Lansoprazole. The identification of widely used, drug with LXR agonist-like activity opens the possibility for systematic preclinical testing in at least two diseases – Alzheimer’s disease and atherosclerosis. PMID:20060385

  13. Proton pump inhibitor medication is associated with colonisation of gut flora in the oropharynx.

    Science.gov (United States)

    Tranberg, A; Thorarinsdottir, H R; Holmberg, A; Schött, U; Klarin, B

    2018-03-08

    The normal body exists in mutualistic balance with a large range of microbiota. The primary goal of this study was to establish whether there is an imbalance in the oropharyngeal flora early after hospital or ICU admittance, and whether flora differs between control, ward and critically ill patients. The secondary goal was to explore whether there are patient characteristics that can be associated with a disturbed oropharyngeal flora. Oropharyngeal cultures were obtained from three different study groups: (1) controls from the community, (2) ward patients and (3) critically ill patients, the two latter within 24 h after admittance. Cultures were obtained from 487 individuals: 77 controls, 193 ward patients and 217 critically ill patients. Abnormal pharyngeal flora was more frequent in critically ill and ward patients compared with controls (62.2% and 10.4% vs. 1.3%, P flora in the oropharynx was more frequent in critically ill patients compared with ward patients or controls (26.3% vs. 4.7% and 1.3%, P flora in the oropharynx in both ward and critically ill patients (P = 0.030 and P = 0.044, respectively). This study indicates that abnormal oropharyngeal flora is an early and frequent event in hospitalised patients and more so in the critically ill, compared to controls. Proton pump inhibitor medication is associated with colonisation of gut flora in the oropharynx. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  14. A Benzimidazole Proton Pump Inhibitor Increases Growth and Tolerance to Salt Stress in Tomato

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    Michael J. Van Oosten

    2017-07-01

    Full Text Available Pre-treatment of tomato plants with micromolar concentrations of omeprazole (OP, a benzimidazole proton pump inhibitor in mammalian systems, improves plant growth in terms of fresh weight of shoot and roots by 49 and 55% and dry weight by 54 and 105% under salt stress conditions (200 mM NaCl, respectively. Assessment of gas exchange, ion distribution, and gene expression profile in different organs strongly indicates that OP interferes with key components of the stress adaptation machinery, including hormonal control of root development (improving length and branching, protection of the photosynthetic system (improving quantum yield of photosystem II and regulation of ion homeostasis (improving the K+:Na+ ratio in leaves and roots. To our knowledge OP is one of the few known molecules that at micromolar concentrations manifests a dual function as growth enhancer and salt stress protectant. Therefore, OP can be used as new inducer of stress tolerance to better understand molecular and physiological stress adaptation paths in plants and to design new products to improve crop performance under suboptimal growth conditions.Highlight: Omeprazole enhances growth of tomato and increases tolerance to salinity stress through alterations of gene expression and ion uptake and transport.

  15. Comparison of vonoprazan and proton pump inhibitors for eradication of Helicobacter pylori

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    Satoshi Shinozaki

    2016-05-01

    Full Text Available Alternative eradication therapies for Helicobacter pylori infection are needed because of an increasing failure rate over the past decade. The aim of this study was to determine if vonoprazan, a new potassium-competitive acid blocker, showed superiority to existing proton pump inhibitors for primary eradication of H. pylori in routine clinical practice. Data for 573 patients who underwent primary H. pylori eradication therapy were retrospectively reviewed. Regimens included clarithromycin 200 mg, amoxicillin 750 mg, and an acid-suppressing drug [lansoprazole 30 mg (LAC, rabeprazole 10 mg (RAC, esomeprazole 20 mg (EAC, or vonoprazan 20 mg (VAC] twice daily for 1 week. Eradication was successful in 73% (419/573 of patients using intention-to-treat (ITT analysis and 76% (419/549 of patients in per-protocol (PP analysis. The VAC group had a significantly superior eradication rate compared with the LAC and RAC groups in ITT (VAC 83%, LAC 66% and RAC 67%, p  80% eradication rate regardless of the degree of atrophy.

  16. Hypoalbuminemia is a predictor of mortality and rebleeding in peptic ulcer bleeding under proton pump inhibitor use.

    Science.gov (United States)

    Cheng, Hsiu-Chi; Yang, Er-Hsiang; Wu, Chung-Tai; Wang, Wen-Lun; Chen, Po-Jun; Lin, Meng-Ying; Sheu, Bor-Shyang

    2018-04-01

    Peptic ulcer bleeding remains a deadly disease, and a simple indicator of long-term outcomes is crucial. This study validated whether hypoalbuminemia and its related factors in patients with peptic ulcer bleeding can indicate long-term mortality and rebleeding under proton pump inhibitor use. The prospective cohort study enrolled 426 patients with peptic ulcer bleeding who had high risk stigmata at endoscopy and had received endoscopic hemostasis. They were divided into 79 patients in the hypoalbuminemia group (Hypo-AG, serum albumin ulcer size ≥1.0 cm independently (p peptic ulcer bleeding can be an alarm indicator of all-cause mortality and recurrent bleeding in a long-term follow-up situation under proton pump inhibitor use (NCT01591083). Copyright © 2017. Published by Elsevier B.V.

  17. Characteristics of refractory gastroesophageal reflux disease (GERD) symptoms -is switching proton pump inhibitors based on the patient's CYP2C19 genotype an effective management strategy?

    Science.gov (United States)

    Takeuchi, Toshihisa; Oota, Kazuhiro; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Sanomura, Makoto; Sakaguchi, Masahiro; Hayashi, Katsuyoshi; Hongoh, Yasushi; Itabashi, Tsukasa; Kitae, Hidehiro; Hoshimoto, Masahiro; Takeuchi, Nozomi; Higuchi, Kazuhide

    2015-01-01

    We investigated factors related to proton pump inhibitor (PPI) -refractory gastroesophageal reflux disease (GERD) symptoms, particularly with respect to acid, the CYP2C19 genotype and psychological aspects. Patients with an Frequency Scale for the Symptoms of GERD (FSSG) score of ≥8 after the initial treatment were switched to therapy with rabeprazole at a dose of 20 mg once daily for eight weeks. We investigated the rate of improvement in PPI-refractory GERD symptoms, background factors, the Hospital Anxiety and Depression Scale (HADS) score and the CYP2C19 genotype. Patients Sixty patients endoscopically diagnosed with reflux esophagitis within the past six months who had received omeprazole at a dose of 20 mg once daily for eight weeks or longer were enrolled. In 71.6% of the patients, the FSSG score decreased to GERD symptoms. Significant factors related to omeprazole-refractory GERD symptoms included a longer disease duration (p=0.0004) and higher HADS score (p=0.01). Among the omeprazole-refractory cases, only 23.5% of the patients showed symptom improvement after switching to rabeprazole. There were no significant differences in the average scores for FSSG (p=0.089) or HADS (p=0.182), before or after the drug change. A total of 92% of the rabeprazole poor responders were homo/hetero extensive metabolizers for the CYP2C19 genotype. Our findings suggest that switching the PPI from omeprazole (20 mg once daily) to rabeprazole (20 mg once daily) is not a significant effective therapeutic strategy for improving PPI-refractory GERD symptoms, taking into consideration possible psychometric factors and patients who require stronger acid suppression than that achieved with a double dose of PPIs for PPI-refractory GERD symptoms.

  18. Proton-pump inhibitors adverse effects: a review of the evidence and position statement by the Sociedad Española de Patología Digestiva.

    Science.gov (United States)

    de la Coba Ortiz, Cristóbal; Argüelles Arias, Federico; Martín de Argila de Prados, Carlos; Júdez Gutiérrez, Javier; Linares Rodríguez, Antonio; Ortega Alonso, Aida; Rodríguez de Santiago, Enrique; Rodríguez-Téllez, Manuel; Vera Mendoza, María Isabel; Aguilera Castro, Lara; Álvarez Sánchez, Ángel; Andrade Bellido, Raúl Jesús; Bao Pérez, Fidencio; Castro Fernández, Manuel; Giganto Tomé, Froilán

    2016-04-01

    In the last few years a significant number of papers have related the use of proton-pump inhibitors (PPIs) to potential serious adverse effects that have resulted in social unrest. The goal of this paper was to provide a literature review for the development of an institutional position statement by Sociedad Española de Patología Digestiva (SEPD) regarding the safety of long-term PPI use. A comprehensive review of the literature was performed to draw conclusions based on a critical assessment of the following: a) current PPI indications; b) vitamin B12 deficiency and neurological disorders; c) magnesium deficiency; d) bone fractures; e) enteric infection and pneumonia; f) interactions with thienopyridine derivatives; e) complications in cirrhotic patients. Current PPI indications have remained unchanged for years now, and are well established. A general screening of vitamin B12 levels is not recommended for all patients on a PPI; however, it does seem necessary that magnesium levels be measured at therapy onset, and then monitored in subjects on other drugs that may induce hypomagnesemia. A higher risk for bone fractures is present, even though causality cannot be concluded for this association. The association between PPIs and infection with Clostridium difficile is mild to moderate, and the risk for pneumonia is low. In patients with cardiovascular risk receiving thienopyridines derivatives it is prudent to adequately consider gastrointestinal and cardiovascular risks, given the absence of definitive evidence regardin potential drug-drug interactions; if gastrointestinal risk is found to be moderate or high, effective prevention should be in place with a PPI. PPIs should be cautiously indicated in patients with decompensated cirrhosis. PPIs are safe drugs whose benefits outweigh their potential side effects both short-term and long-term, provided their indication, dosage, and duration are appropriate.

  19. The acidity of the tumor microenvironment is a mechanism of immune escape that can be overcome by proton pump inhibitors

    Science.gov (United States)

    Bellone, Matteo; Calcinotto, Arianna; Filipazzi, Paola; De Milito, Angelo; Fais, Stefano; Rivoltini, Licia

    2013-01-01

    We have recently reported that lowering the pH to values that are frequently detected in tumors causes reversible anergy in both human and mouse CD8+ T lymphocytes in vitro. The same occurs in vivo, in the tumor microenvironment and the administration of proton pump inhibitors, which buffer tumor acidity, can revert T-cell anergy and increase the efficacy of immunotherapy. PMID:23483769

  20. Unexplained abdominal pain as a driver for inappropriate therapeutics: an audit on the use of intravenous proton pump inhibitors

    OpenAIRE

    Pauline Siew Mei Lai; Yin Yen Wong; Yong Chia Low; Hui Ling Lau; Kin-Fah Chin; Sanjiv Mahadeva

    2014-01-01

    Background. Proton pump inhibitors (PPIs) are currently the most effective agents for acid-related disorders. However, studies show that 25–75% of patients receiving intravenous PPIs had no appropriate justification, indicating high rates of inappropriate prescribing. Objective. To examine the appropriate use of intravenous PPIs in accordance with guidelines and the efficacy of a prescribing awareness intervention at an Asian teaching institution. Setting. Prospective audit in a tertiary hosp...

  1. Hyperparathyroidism Associated with Long-Term Proton Pump Inhibitors Independent of Concurrent Bisphosphonate Therapy in Elderly Adults.

    Science.gov (United States)

    Hinson, Andrew M; Wilkerson, Bekka M; Rothman-Fitts, Ivy; Riggs, Ann T; Stack, Brendan C; Bodenner, Donald L

    2015-10-01

    To measure the effect of proton pump inhibitors (PPIs), with and without concurrent bisphosphonates, on parathyroid hormone (PTH), vitamin D, and calcium. Retrospective chart review of individuals 60 years and older. Subjects with reduced renal function (creatinine >1.3 mg/dL) and low vitamin D (hyperparathyroidism regardless of concurrent oral BP administration. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  2. The analysis of Drug - Related Problems in patients with gastroesophageal reflux disease treated with proton-pump inhibitors

    Directory of Open Access Journals (Sweden)

    Milutinović Jelena D.

    2015-01-01

    Full Text Available Introduction: Drug-related problems are frequent in almost all therapeutic areas. Aims: The aim of this paper was to detect drug - related problems in patients with gastroesophageal reflux and to analyze their possible association with the patient characteristics. Material and methods: The study was designed as descriptive, retrospective, crosssectional study aiming to determine the most common drug - related problems in patients with gastro-esophageal reflux disease treated with proton-pump inhibitors. The survey was conducted at the Department of Gastroenterology, Clinical Centre in Kragujevac. The study enrolled all patients treated from gastroesophageal reflux disease with proton pump inhibitors during the time period from 1.1.2014 until 1.1.2015. The study used descriptive statistics (percentage distribution, mean and standard deviation. The correlation between the number of adverse events and patient characteristics was also calculated. Results: The average age of the patients was 55.97±15.811 years, and 43 of the patients (60.6 % were male. The average hospitalization duration was 12.30±8.89 days. Based on the Pharmaceutical Care Network Europe classification, there were 182 Drug-Related Problems which was, on average, 2.56 problems per patient. Only 5 patients (7% did not report any problem while 11 patients (15.49% had over 10 possible drug-drug interactions. The most common problems which occurred were erroneous drug choice, inappropriate administration and possible interactions between medications. Conclusions: Based on the results of this study, one must pay attention to possible drug interactions and other problems which may occur with proton-pump inhibitors. Recognition of different sub-types of drug-related problems and of factors associated with drug related problems may reduce risk from adverse outcomes of gastro-esophageal reflux disease treatment with proton pump inhibitors.

  3. Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan.

    Science.gov (United States)

    Mizuno, Hideki; Matsuhashi, Nobuyuki; Sakaguchi, Masahiro; Inoue, Syuji; Nakada, Koji; Higuchi, Kazuhide; Haruma, Ken; Joh, Takashi

    2015-11-01

    Proton pump inhibitors are the first-line treatment for reflux esophagitis. Because severe reflux esophagitis has very low prevalence in Japan, little is known about the effectiveness of proton pump inhibitors in these patients. This prospective multicenter study assessed the effectiveness of proton pump inhibitors for severe reflux esophagitis in Japan. Patients with modified Los Angeles grade C or D reflux esophagitis were treated with daily omeprazole (10 or 20 mg), lansoprazole (15 or 30 mg), or rabeprazole (10, 20, or 40 mg) for 8 weeks. Healing was assessed endoscopically, with questionnaires administered before and after treatment to measure the extent of reflux and dyspepsia symptoms. Factors affecting healing rates, including patient characteristics and endoscopic findings, were analyzed. Of the 115 patients enrolled, 64 with grade C and 19 with grade D reflux esophagitis completed the study. The healing rate was 67.5% (56/83), with 15 of the other 27 patients (55.6%) improving to grade A or B. No patient characteristic or endoscopic comorbidity was significantly associated with healing rate. Reflux and dyspepsia symptoms improved significantly with treatment. The low healing rate suggests the need of endoscopic examination to assess healing of reflux esophagitis at the end of therapy. (UMIN000005271).

  4. Prolonged utilization of proton pump inhibitors in patients with ischemic and valvular heart disease is associated with surgical treatments, weight loss and aggravates anemia.

    Science.gov (United States)

    Boban, Marko; Zulj, Marinko; Persic, Viktor; Medved, Igor; Zekanovic, Drazen; Vcev, Aleksandar

    2016-09-15

    Proton pump inhibitors (PPIs) are among the commonest drugs used nowadays. The aim of our study was to analyze prolonged utilization of proton pump inhibitors in medical therapy of patients with ischemic and valvular heart disease. Secondly, profile of utilization was scrutinized to patient characteristics and type of cardiovascular treatments. The study included consecutive patients scheduled for cardiovascular rehabilitation 2-6months after index cardiovascular treatment. Two hundred ninety-four patients (n=294/604; 48.7%) have been using proton pump inhibitor in their therapy after index cardiovascular treatment. Cardiovascular treatments were powerfully connected with utilization of PPIs; surgery 5.77 (95%-confidence intervals [CI]: 4.05-8.22; pvalvular heart disease utilized proton pump inhibitor in prolonged courses. Prolonged courses of PPIs were connected with existence and worsening of red blood count indexes, older age, lesser weight of patients and underutilization of cardioprotective drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Increase of weakly acidic gas esophagopharyngeal reflux (EPR) and swallowing-induced acidic/weakly acidic EPR in patients with chronic cough responding to proton pump inhibitors.

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    Kawamura, O; Shimoyama, Y; Hosaka, H; Kuribayashi, S; Maeda, M; Nagoshi, A; Zai, H; Kusano, M

    2011-05-01

    Gastro-esophageal reflux disease (GERD)-related chronic cough (CC) may have multifactorial causes. To clarify the characteristics of esophagopharyngeal reflux (EPR) events in CC patients whose cough was apparently influenced by gastro-esophageal reflux (GER), we studied patients with CC clearly responding to full-dose proton pump inhibitor (PPI) therapy (CC patients). Ten CC patients, 10 GERD patients, and 10 healthy controls underwent 24-h ambulatory pharyngo-esophageal impedance and pH monitoring. Weakly acidic reflux was defined as a decrease of pH by >1 unit with a nadir pH >4. In six CC patients, monitoring was repeated after 8 weeks of PPI therapy. The number of each EPR event and the symptom association probability (SAP) were calculated. Symptoms were evaluated by a validated GERD symptom questionnaire. Weakly acidic gas EPR and swallowing-induced acidic/weakly acidic EPR only occurred in CC patients, and the numbers of such events was significantly higher in the CC group than in the other two groups (P pump inhibitor therapy abolished swallowing-induced acidic/weakly acidic EPR, reduced weakly acidic gas EPR, and improved symptoms (all P gas EPR and swallowing-induced acidic/weakly acidic EPR. A direct effect of acidic mist or liquid refluxing into the pharynx may contribute to chronic cough, while cough may also arise indirectly from reflux via a vago-vagal reflex in some patients. © 2011 Blackwell Publishing Ltd.

  6. Drug Repositioning of Proton Pump Inhibitors for Enhanced Efficacy and Safety of Cancer Chemotherapy

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    Kenji Ikemura

    2017-12-01

    Full Text Available Proton pump inhibitors (PPIs, H+/K+-ATPase inhibitors, are the most commonly prescribed drugs for the treatment of gastroesophageal reflux and peptic ulcer diseases; they are highly safe and tolerable. Since PPIs are frequently used in cancer patients, studies investigating interactions between PPIs and anticancer agents are of particular importance to achieving effective and safe cancer chemotherapy. Several studies have revealed that PPIs inhibit not only the H+/K+-ATPase in gastric parietal cells, but also the vacuolar H+-ATPase (V-ATPase overexpressed in tumor cells, as well as the renal basolateral organic cation transporter 2 (OCT2 associated with pharmacokinetics and/or renal accumulation of various drugs, including anticancer agents. In this mini-review, we summarize the current knowledge regarding the impact of PPIs on the efficacy and safety of cancer chemotherapeutics via inhibition of targets other than the H+/K+-ATPase. Co-administration of clinical doses of PPIs protected kidney function in patients receiving cisplatin and fluorouracil, presumably by decreasing accumulation of cisplatin in the kidney via OCT2 inhibition. In addition, co-administration or pretreatment with PPIs could inhibit H+ transport via the V-ATPase in tumor cells, resulting in lower extracellular acidification and intracellular acidic vesicles to enhance the sensitivity of the tumor cells to the anticancer agents. In the present mini-review, we suggest that PPIs enhance the efficacy and safety of anticancer agents via off-target inhibition (e.g., of OCT2 and V-ATPase, rather than on-target inhibition of the H+/K+-ATPase. The present findings should provide important information to establish novel supportive therapy with PPIs during cancer chemotherapy.

  7. The Effects of Switching to Vonoprazan, a Novel Potassium-Competitive Acid Blocker, on Gastric Acidity and Reflux Patterns in Patients with Erosive Esophagitis Refractory to Proton Pump Inhibitors.

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    Yamashita, Hiroshi; Kanamori, Atsushi; Kano, Chise; Hashimura, Hiroki; Matsumoto, Kei; Tsujimae, Masahiro; Yoshizaki, Tetsuya; Momose, Kenji; Obata, Daisuke; Eguchi, Takaaki; Fujita, Mikio; Okada, Akihiko

    2017-01-01

    The effects of vonoprazan and proton pump inhibitors (PPIs) in patients with reflux esophagitis (RE) have not yet been compared using multichannel intraluminal impedance-pH (MII-pH). A total of 8 patients with persistent gastric mucosal injury, despite completing an 8-week standard PPI therapy, were enrolled in the study. While they were on standard PPI therapy, the baseline values of reflux parameters, holding time ratio (HTR) of gastric pH >4, and esophageal pH 4 HTR was observed, from 26.5 to 78.0% (p = 0.029). A reduction in esophageal pH acid clearance time and the total number of reflux events, including acid and proximal reflux events, were significantly reduced. Vonoprazan may be a better therapy for the treatment of patients with PPI-refractory RE. © 2017 S. Karger AG, Basel.

  8. Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach.

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    Rohof, Wout O; Bennink, Roelof J; Boeckxstaens, Guy E

    2014-07-01

    The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Thirty-six patients with GERD (18 not taking PPIs, 18 taking PPIs; 19 men; age, 55 ± 2.1 y) were analyzed by concurrent high-resolution manometry and pH-impedance monitoring after a standardized meal. The acid pocket was visualized using scintigraphy after intravenous administration of (99m)technetium-pertechnetate. The size of the acid pocket was measured and its position was determined, relative to the diaphragm, using radionuclide markers on a high-resolution manometry catheter. At the end of the study, the acid pocket was aspirated, and its pH level was measured. The number of reflux episodes was comparable between patients on and off PPIs, but the number of acid reflux episodes was reduced significantly in patients on PPIs. In patients on PPIs, the acid pocket was smaller and more frequently located below the diaphragm. The mean pH of the acid pocket was significantly lower in patients not taking PPIs (n = 6) than in those who were (n = 16) (0.9; range, 0.7-1.2 vs 4.0; range, 1.6-5.9; P pH of acid pockets correlated significantly with the lowest pH values measured for refluxate (r = 0.72; P < .01). Based on analyses of acid pockets in patients with GERD, the acid pocket appears to be a reservoir from which reflux occurs when patients are receiving PPIs. PPIs might affect the size, acidity, or position of the acid pocket, which contributes to the efficacy in patients with GERD. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Proton pump inhibitor step-down therapy for GERD: A multi-center study in Japan

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    Tsuzuki, Takao; Okada, Hiroyuki; Kawahara, Yoshiro; Takenaka, Ryuta; Nasu, Junichiro; Ishioka, Hidehiko; Fujiwara, Akiko; Yoshinaga, Fumiya; Yamamoto, Kazuhide

    2011-01-01

    AIM: To investigate the predictors of success in step-down of proton pump inhibitor and to assess the quality of life (QOL). METHODS: Patients who had heartburn twice a week or more were treated with 20 mg omeprazole (OPZ) once daily for 8 wk as an initial therapy (study 1). Patients whose heartburn decreased to once a week or less at the end of the initial therapy were enrolled in study 2 and treated with 10 mg OPZ as maintenance therapy for an additional 6 mo (study 2). QOL was investigated using the gastrointestinal symptom rating scale (GSRS) before initial therapy, after both 4 and 8 wk of initial therapy, and at 1, 2, 3, and 6 mo after starting maintenance therapy. RESULTS: In study 1, 108 patients were analyzed. Their characteristics were as follows; median age: 63 (range: 20-88) years, sex: 46 women and 62 men. The success rate of the initial therapy was 76%. In the patients with successful initial therapy, abdominal pain, indigestion and reflux GSRS scores were improved. In study 2, 83 patients were analyzed. Seventy of 83 patients completed the study 2 protocol. In the per-protocol analysis, 80% of 70 patients were successful for step-down. On multivariate analysis of baseline demographic data and clinical information, no previous treatment for gastroesophageal reflux disease (GERD) [odds ratio (OR) 0.255, 95% CI: 0.06-0.98] and a lower indigestion score in GSRS at the beginning of step-down therapy (OR 0.214, 95% CI: 0.06-0.73) were found to be the predictors of successful step-down therapy. The improved GSRS scores by initial therapy were maintained through the step-down therapy. CONCLUSION: OPZ was effective for most GERD patients. However, those who have had previous treatment for GERD and experience dyspepsia before step-down require particular monitoring for relapse. PMID:21472108

  10. The proton pump inhibitor lansoprazole improves the skeletal phenotype in dystrophin deficient mdx mice.

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    Arpana Sali

    Full Text Available In Duchenne muscular dystrophy (DMD, loss of the membrane stabilizing protein dystrophin results in myofiber damage. Microinjury to dystrophic myofibers also causes secondary imbalances in sarcolemmic ion permeability and resting membrane potential, which modifies excitation-contraction coupling and increases proinflammatory/apoptotic signaling cascades. Although glucocorticoids remain the standard of care for the treatment of DMD, there is a need to investigate the efficacy of other pharmacological agents targeting the involvement of imbalances in ion flux on dystrophic pathology.We designed a preclinical trial to investigate the effects of lansoprazole (LANZO administration, a proton pump inhibitor, on the dystrophic muscle phenotype in dystrophin deficient (mdx mice. Eight to ten week-old female mice were assigned to one of four treatment groups (n = 12 per group: (1 vehicle control; (2 5 mg/kg/day LANZO; (3 5 mg/kg/day prednisolone; and (4 combined treatment of 5 mg/kg/day prednisolone (PRED and 5 mg/kg/day LANZO. Treatment was administered orally 5 d/wk for 3 months. At the end of the study, behavioral (Digiscan and functional outcomes (grip strength and Rotarod were assessed prior to sacrifice. After sacrifice, body, tissue and organ masses, muscle histology, in vitro muscle force, and creatine kinase levels were measured. Mice in the combined treatment groups displayed significant reductions in the number of degenerating muscle fibers and number of inflammatory foci per muscle field relative to vehicle control. Additionally, mice in the combined treatment group displayed less of a decline in normalized forelimb and hindlimb grip strength and declines in in vitro EDL force after repeated eccentric contractions.Together our findings suggest that combined treatment of LANZO and prednisolone attenuates some components of dystrophic pathology in mdx mice. Our findings warrant future investigation of the clinical efficacy of LANZO and

  11. Maintenance of heartburn relief after step-down from twice-daily proton pump inhibitor to once-daily dexlansoprazole modified release.

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    Fass, Ronnie; Inadomi, John; Han, Cong; Mody, Reema; O'Neil, Janet; Perez, M Claudia

    2012-03-01

    Many patients with gastroesophageal reflux disease (GERD) take a proton pump inhibitor (PPI) twice daily to control symptoms. Once-daily dexlansoprazole modified release (MR) has a dual-delayed release formulation, making it attractive for step-down management of patients whose symptoms are well controlled on twice-daily PPIs. We investigated whether step-down to once-daily dexlansoprazole controls heartburn in patients with GERD who were receiving twice-daily PPI therapy. Patients 18 years and older taking a twice-daily PPI for symptom control were enrolled (n = 178) in a single-blind, multicenter study; 163 patients completed the study and 142 patients met criteria for the efficacy analysis. During the 6-week screening and treatment periods, patients recorded the presence of heartburn symptoms twice daily in electronic diaries. Patients' heartburn was considered well controlled if they had an average of 1 symptom or fewer per week during the last 4 weeks of screening and treatment. After screening, qualified patients were switched to masked dexlansoprazole MR 30 mg and placebo for 6 weeks. The primary efficacy end point was the proportion of patients whose heartburn remained well controlled after step-down. GERD-related symptoms and quality of life (QOL) also were evaluated using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) and the PAGI-QOL questionnaires, respectively. After step-down to once-daily dexlansoprazole MR 30 mg, heartburn remained well controlled in 88% of patients (125 of 142). These patients were able to maintain their GERD-related symptom severity and QOL, indicated by marginal changes in the PAGI-SYM and PAGI-QOL total and subscale scores, respectively. Most patients with GERD who take twice-daily PPI to control heartburn are able to successfully step down to once-daily dexlansoprazole 30 mg. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  12. The role of gastroesophageal reflux in relation to symptom onset in patients with proton pump inhibitor-refractory nonerosive reflux disease accompanied by an underlying esophageal motor disorder.

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    Izawa, Shinya; Funaki, Yasushi; Iida, Akihito; Tokudome, Kentaro; Tamura, Yasuhiro; Ogasawara, Naotaka; Sasaki, Makoto; Kasugai, Kunio

    2014-01-01

    The symptom improvement rate is low with proton pump inhibitors (PPIs) in nonerosive reflux disease (NERD). The underlying pathogenic mechanism is complex. Esophageal motility disorders (EMDs) are thought to be a factor, but their prevalence, type, symptoms and the role played by gastroesophageal reflux (GER) in symptom onset have not been fully investigated. To investigate the role of GER in symptom onset in PPI-refractory NERD patients with EMDs. This study comprised 76 patients with PPI-refractory NERD. Manometry was performed during PPI treatment and patients were divided into an EMD group and normal motility (non-EMD) group. Then, multichannel intraluminal impedance-pH monitoring was performed and medical interviews were conducted. Nineteen patients (25%) had an EMD. Data were compared between 17 patients, excluding 2 with achalasia and 57 non-EMD patients. No significant differences were observed between groups in 24-hour intraesophageal pH <4 holding time (HT), mean number of GER episodes or mean number of proximal reflux episodes. The reflux-related symptom index (≥50%) showed a relationship between reflux and symptoms in 70.5% of EMD patients and 75% of non-EMD patients. In the EMD group, the score for FSSG (Frequency Scale for the Symptoms of GERD) question (Q)10 was significantly correlated with the number of GER episodes (r = 0.58, p = 0.02) and the number of proximal reflux episodes (r = 0.63, p = 0.02). In addition, the score for Q9 tended to be correlated with the number of GER episodes (r = 0.44, p = 0.06). Our results suggest that some PPI-refractory NERD patients have EMDs, and that GER plays a role in symptom onset.

  13. Factors influencing the shift of patients from one proton pump inhibitor to another: the effect of direct-to-consumer advertising.

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    Hansen, Richard A; Shaheen, Nicholas J; Schommer, Jon C

    2005-09-01

    Switching from one proton pump inhibitor (PPI) to another is common, and may be related to factors other than efficacy and tolerability. The purposes of this study were to describe the incidence of therapeutic switching among PPI users, quantify direct ambulatory medical costs of switching, and characterize the relationship between product switching and variables hypothesized to influence a switch (eg, direct-to-consumer [DTC] advertising, structure of insurance coverage, disease diagnosis). This was a retrospective cohort study of health plans using 1998 data. The subjects were employees and dependents with employer-sponsored health insurance contributing to the Medstat Market-Scan administrative dataset. Using a commercially available database to quantify DTC advertising by marketing area, market-specific expenditures were matched to eligible subjects. Among PPI users, we identified those who switched from one product to another (switchers) and compared their utilization and spending with nonswitchers. We then evaluated the relationship between drug use and variables hypothesized to affect switching: DTC advertising, insurance characteristics, patient diagnosis, diagnostic procedures, comorbidities, age, and sex. The analysis used data for 396,500 individuals from 47 unique markets that were geographically well distributed, with population density similar to that of the United States overall. The sample was also comparable with US census estimates for age and sex among working adults and their dependents. Only 620 (6.3%) of PPI users switched products during the 1998 calendar year. Annual diagnostic and drug costs were >US $400 higher for switchers than nonswitchers. Subjects in areas with high levels of DTC advertising were 43% more likely to switch from lansoprazole to omeprazole than those in the low-expenditure areas. Additionally, patients paying prescription drug copayments >US $5 were 12% less likely to switch from lansoprazole to omeprazole than patients

  14. A combination of a dairy product fermented by lactobacilli and galactooligosaccharides shows additive effects on mineral balances in growing rats with hypochlorhydria induced by a proton pump inhibitor.

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    Takasugi, Satoshi; Ashida, Kinya; Maruyama, Suyaka; Matsukiyo, Yukari; Kaneko, Tetsuo; Yamaji, Taketo

    2013-06-01

    This study aimed to investigate the effects of a combination of a dairy product fermented by lactobacilli (DFL) and galactooligosaccharides (GOS) on mineral balances in growing rats with hypochlorhydria induced by a proton pump inhibitor (PPI). Three-week-old male rats were assigned to receive one of six diets: a control diet, control diets containing 1.6 or 5.0 % GOS, a DFL diet and DFL diets containing 1.6 or 5.0 % GOS for 9 days. From day 5 of the feeding period, half of the rats fed with control diets were subcutaneously administered with saline, whereas the remaining rats were administered with PPI for 5 days. Calcium (Ca), phosphorus (P), magnesium (Mg), iron (Fe) and zinc (Zn) balances were determined from days 6 to 9. PPI administration significantly decreased the apparent absorption of Ca and Fe and increased urinary P excretion, resulting in decreased Ca, Fe and P retention. GOS dose-dependently increased the apparent absorption of Ca, Mg and Fe and urinary Mg excretion and decreased urinary P excretion. DFL significantly increased the apparent absorption of Ca and Mg and urinary Mg excretion. The combination of DFL and GOS additively affected these parameters, resulting in increased Ca, P and Fe retention, and it further increased the apparent absorption and retention of Zn at 5.0 % GOS. In conclusion, the combination of DFL and GOS improves Ca, P and Fe retention in an additive manner and increases the Zn retention in growing rats with hypochlorhydria induced by PPI.

  15. Pharmacological and Safety Profile of Dexlansoprazole: A New Proton Pump Inhibitor – Implications for Treatment of Gastroesophageal Reflux Disease in the Asia Pacific Region

    Science.gov (United States)

    Goh, Khean Lee; Choi, Myung Gyu; Hsu, Ping I; Chun, Hoon Jai; Mahachai, Varocha; Kachintorn, Udom; Leelakusolvong, Somchai; Kim, Nayoung; Rani, Abdul Aziz; Wong, Benjamin C Y; Wu, Justin; Chiu, Cheng Tang; Shetty, Vikram; Bocobo, Joseph C; Chan, Melchor M; Lin, Jaw-Town

    2016-01-01

    Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade. Gastroesophageal reflux disease is associated with considerable reductions in subjective well-being and work productivity, as well as increased healthcare use. Proton pump inhibitors (PPIs) are currently the most effective treatment for gastroesophageal reflux disease. However, there are limitations associated with these drugs in terms of partial and non-response. Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication to extend the duration of effective plasma drug concentration. Dexlansoprazole has been shown to be effective for healing of erosive esophagitis, and to improve subjective well-being by controlling 24-hour symptoms. Dexlansoprazole has also been shown to achieve good plasma concentration regardless of administration with food, providing flexible dosing. Studies in healthy volunteers showed no clinically important effects on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition, with no dose adjustment of clopidogrel necessary when coprescribed. This review discusses the role of the new generation PPI, dexlansoprazole, in the treatment of gastroesophageal reflux disease in Asia. PMID:26932927

  16. Use of non-steroidal anti-inflammatory drugs and proton pump inhibitors in correlation with incidence, recurrence and death of peptic ulcer bleeding: an ecological study

    Science.gov (United States)

    Lu, Yunxia; Sverdén, Emma; Ljung, Rickard; Söderlund, Claes; Lagergren, Jesper

    2013-01-01

    Background Non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) are regarded as two types of drugs that respectively increase and decrease the risk of peptic ulcer bleeding. However, their relation to occurrence, recurrence and death of bleeding in the population level is not clear. Study objective To clarify recent calendar-time correlations between sales of NSAIDs and PPIs and the occurrence of peptic ulcer bleeding, re-bleeding and death. Design Ecological study. Results The time trend of peptic ulcer bleeding did not correlate with PPI sales but did correlate with NSAIDs in mem (Rmale=0.6571, Pmale=0.05). Sales of PPIs (inverse) and NSAIDs correlated with re-bleeding in women (Rmale=−0.8754, Pmale=0.002 and Rfemale=0.7161, Pfemale=0.03, respectively), but not in men. An inverse correlation between PPI sales and 30-day death after bleeding was found (Rmale=−0.9392, Pmale=0.0002 and Rfemale=−0.8561, Pfemale=0.003), and NSAID sales were found to correlate with increased death after bleeding ((Rmale=0.7278, Pmale=0.03, Rfemale=0.7858, Pfemale=0.01). Conclusions The sales of NSAIDs and PPIs correlate with recurrence of peptic ulcer bleeding in women and death after peptic ulcer bleeding in both genders in the population level. PMID:23293249

  17. Development of urinary incontinence in a 7-year old boy after therapy with proton pump inhibitors and complete resolution of his clinicopathologic features of eosinophilic esophagitis after H2-receptor antagonist treatment: A case report

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    Rok Orel

    2017-06-01

    Full Text Available Background: Several diseases result in profound infltration of esophageal mucosa by eosinophilic granulocites, with gastroesophageal reflux disease (GERD, eosinophilic esophagitis (EoE and proton-pump-inhibitor-responsive esophageal eosinophilia (PPI-REE being the most prevalent. Proton-pump-inhibitor-responsive esophageal eosinophilia (PPI-REE is a newly recognized entity that must be differentiated from eosinophilic esophagitis (EoE.Case presentation: A 7-year old Slovenian male presented with a few-month history of chest pain, regurgitation and heartburn. First endoscopy was performed and revealed pronounced longitudinal furrows, and on hystology examination > 70 eosinophils per high power feld were found through the entire thickness of epithelium and in the submucosis with eosinophilic microabscess formation. Results of 24-hour pH-monitoring (without impedance monitoring excluded pathologic acid reflux. All allergy tests were negative. Te patient started treatment with proton pump inhibitors (PPIs for three times, twice with pantoprazole before the endoscopy and once with esomeprazole after it to exclude the diagnosis of GERD and PPI-REE. Urinary incontinence reappeared each time just few days after starting treatment and disappeared few days after stopping it. Therefore, urinary incontinence was considered as a plausible adverse effect of therapy with PPIs. As treatment with PPIs was not tolerated, a therapy with H2-receptor antagonists ranitidine was applied for more than 2 months followed by a second endoscopy. Both symptoms and esophageal eosinophilia completely resolved with ranitidine. The resolution of esophageal eosinophilia in PPI-REE has been attributed to proton pump independent antiinflammatory effects of PPIs. No such effects have been described in H2-receptor antagonists.Conclusions: Two unique phenomena were observed in the pediatric patient with profound esophageal eosinophilia: urinary incontinence as an adverse e

  18. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.

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    Bryony N Parsons

    2017-11-01

    Full Text Available Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq. Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects.

  19. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use

    Science.gov (United States)

    Eccles, Richard; Duckworth, Carrie A.; Varro, Andrea

    2017-01-01

    Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects. PMID:29095917

  20. A randomized controlled trial of laparoscopic Nissen fundoplication versus proton pump inhibitors for the treatment of patients with chronic gastroesophageal reflux disease (GERD): 3-year outcomes.

    Science.gov (United States)

    Anvari, Mehran; Allen, Christopher; Marshall, John; Armstrong, David; Goeree, Ron; Ungar, Wendy; Goldsmith, Charles

    2011-08-01

    A randomized controlled trial (RCT) investigated patients with gastroesophageal reflux disease (GERD) who were stable and symptomatically controlled with long-term medical therapy to compare ongoing optimized medical therapy with laparoscopic Nissen fundoplication (LNF). Of the 180 patients eligible for randomization, 104 gave informed consent, and 3 withdrew from the study immediately after randomization. The patients randomized to medical therapy received optimized treatment with proton pump inhibitors (PPIs) using a standardized management protocol based on best evidence and published guidelines. The surgical patients underwent LNF by one of four surgeons using a previously published technique. The patients underwent symptom evaluation using the GERD symptom scale (GERSS) and the global visual analog scale (VAS) for overall symptom control. They had 24-h esophageal pH monitoring at baseline and after 3 years. The medical patients were evaluated receiving PPI, and the surgical patients were evaluated not receiving PPI. For the 3-year follow-up assessment, 93 patients were available. At 3 years, surgery was associated with more heartburn-free days, showing a mean difference of -1.35 days per week (p = 0.0077) and a lower VAS score (p = 0.0093) than medical management. Surgical patients reported improved quality of life on the general health subscore of the Medical Outcomes Survey Short Form 36 (SF-36) at 3 years, with a mean difference of -12.19 (p = 0.0124). The groups did not differ significantly in terms of GERSS or acid exposure on 24-h esophageal pH monitoring at 3 years. There were six treatment failures (11.8%) in the surgical group and eight treatment failures (16%) in the medical group by 3 years. For patients whose GERD symptoms are stable and controlled with PPI, continuing medical therapy and laparoscopic antireflux surgery are equally effective, although surgery may result in better symptom control and quality of life.

  1. Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: a meta-analysis.

    Science.gov (United States)

    Sun, S; Cui, Z; Zhou, M; Li, R; Li, H; Zhang, S; Ba, Y; Cheng, G

    2017-02-01

    Proton pump inhibitors (PPIs) are commonly used as potent gastric acid secretion antagonists for gastro-esophageal disorders and their overall safety in patients with gastro-esophageal reflux disease (GERD) is considered to be good and they are well-tolerated. However, recent studies have suggested that PPIs may be a potential independent risk factor for cardiovascular adverse events. The aim of our meta-analysis was to examine the association between PPI monotherapy and cardiovascular events in patients with GERD. A literature search involved examination of relevant databases up to July 2015 including PubMed, Cochrane Library, EMBASE, and ClinicalTrial.gov, as well as selected randomized controlled trials (RCTs) reporting cardiovascular events with PPI exposure in GERD patients. In addition, the pooled risk ratio (RR) and heterogeneity were assessed based on a fixed effects model of the meta-analysis and the I 2 statistic, respectively. Seventeen RCTs covering 7540 patients were selected. The pooled data suggested that the use of PPIs was associated with a 70% increased cardiovascular risk (RR=1.70, 95% CI: [1.13-2.56], P=.01, I 2 =0%). Furthermore, higher risks of adverse cardiovascular events in the omeprazole subgroup (RR=3.17, 95% CI: [1.43-7.03], P=.004, I 2 =25%) and long-term treatment subgroup (RR=2.33, 95% CI: [1.33-4.08], P=.003, I 2 =0%) were found. PPI monotherapy can be a risk factor for cardiovascular adverse events. Omeprazole could significantly increase the risk of cardiovascular events and, so, should be used carefully. © 2016 John Wiley & Sons Ltd.

  2. [Survey of the prescriptions of proton pump inhibitors in patients admitted in an internal medicine ward: how is the compliance to the French guidelines?].

    Science.gov (United States)

    Sauvaget, L; Rolland, L; Dabadie, S; Desblaches, J; Bernard, N; Vandenhende, M-A; Bonnet, F; Pédeboscq, S; Morlat, P

    2015-10-01

    In June 2009, the national French authority for Health reported many off-label uses of proton pump inhibitors (PPI). Our objective was to analyse the justification and modalities of PPI prescriptions in patients before their admission in a department of internal medicine. Data were prospectively collected during 5months. At admission, all prescriptions of PPI by general practitioners (GP) were recorded. The accordance of the prescriptions with the marketing authorization indications and the French guidelines in terms of duration of treatment or dosage was analyzed. These informations were obtained from computerized medical records and, if necessary, by contacting GPs. We collected 173 prescriptions. Fifty-six (32%) were in accordance with marketing authorization indications and, among them, 15 prescriptions (9% of all) respected the French guidelines about dosage and duration of treatment. One hundred and six prescriptions (61%) were not adequate and among them an off-label use was notified in 91 (53% of all); among them 33% for simple dyspeptic disorders, 23% for the prevention of NSAID-induced lesions in patients without risk factors, and finally 17% for the prevention of stress ulcer. Fifty-two prescriptions (30%) were unclassified due to incomplete data. Our study showed that a vast majority of the prescriptions for PPIs are not in accordance with French guidelines. Preventive actions against abusive prescriptions, withdrawal strategies or replacement of already prescribed PPIs should be implemented to reduce the risk of side effects and the economic impact of long term use of PPIs. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  3. Effect of proton pump inhibitors on the serum concentrations of the selective serotonin reuptake inhibitors citalopram, escitalopram, and sertraline.

    Science.gov (United States)

    Gjestad, Caroline; Westin, Andreas A; Skogvoll, Eirik; Spigset, Olav

    2015-02-01

    The selective serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram, and sertraline are all metabolized by the cytochrome P-450 isoenzyme CYP2C19, which is inhibited by the proton pump inhibitors (PPIs) omeprazole, esomeprazole, lansoprazole, and pantoprazole. The aim of the present study was to evaluate the effect of these PPIs on the serum concentrations of citalopram, escitalopram, and sertraline. Serum concentrations from patients treated with citalopram, escitalopram, or sertraline were obtained from a routine therapeutic drug monitoring database, and samples from subjects concomitantly using PPIs were identified. Dose-adjusted SSRI serum concentrations were calculated to compare data from those treated and those not treated with PPIs. Citalopram concentrations were significantly higher in patients treated with omeprazole (+35.3%; P Escitalopram concentrations were significantly higher in patients treated with omeprazole (+93.9%; P escitalopram is affected to a greater extent than are citalopram and sertraline. When omeprazole or esomeprazole are used in combination with escitalopram, a 50% dose reduction of the latter should be considered.

  4. A randomized controlled trial of laparoscopic nissen fundoplication versus proton pump inhibitors for treatment of patients with chronic gastroesophageal reflux disease: One-year follow-up.

    Science.gov (United States)

    Anvari, Mehran; Allen, Christopher; Marshall, John; Armstrong, David; Goeree, Ron; Ungar, Wendy; Goldsmith, Charles

    2006-12-01

    A randomized controlled trial conducted in patients with gastroesophageal reflux disease compared optimized medical therapy using proton pump inhibitor (n = 52) with laparoscopic Nissen fundoplication (n = 52). Patients were monitored for 1 year. The primary end point was frequency of gastroesophageal reflux dis-ease symptoms. Surgical patients had improved symptoms, pH control, and overall quality of life health index after surgery at 1 year compared with the medical group. The overall gastroesophageal reflux disease symptom score at 1 year was unchanged in the medical patients, but improved in the surgical patients. Fourteen patients in the medical arm experienced symptom relapse requiring titration of the proton pump inhibitor dose, but 6 had satisfactory symptom remission. No surgical patients required additional treatment for symptom control. Patients controlled on long-term proton pump inhibitor therapy for chronic gastroesophageal reflux disease are excellent surgical candidates and should experience improved symptom control after surgery at 1 year.

  5. Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study

    DEFF Research Database (Denmark)

    Charlot, Mette; Grove, Erik; Hansen, Peter Riis

    2011-01-01

    OBJECTIVE: To examine the effect of proton pump inhibitors on adverse cardiovascular events in aspirin treated patients with first time myocardial infarction. DESIGN: Retrospective nationwide propensity score matched study based on administrative data. Setting All hospitals in Denmark. PARTICIPANTS...... analysis showed no increase in risk related to use of H(2) receptor blockers (1.04, 0.79 to 1.38; P=0.78). Conclusion In aspirin treated patients with first time myocardial infarction, treatment with proton pump inhibitors was associated with an increased risk of adverse cardiovascular events....

  6. Cost-utility of laparoscopic Nissen fundoplication versus proton pump inhibitors for chronic and controlled gastroesophageal reflux disease: a 3-year prospective randomized controlled trial and economic evaluation.

    Science.gov (United States)

    Goeree, Ron; Hopkins, Rob; Marshall, John K; Armstrong, David; Ungar, Wendy J; Goldsmith, Charles; Allen, Christopher; Anvari, Mehran

    2011-01-01

    Very few randomized controlled trials (RCTs) have compared laparoscopic Nissen fundoplication (LNF) to proton pump inhibitors (PPI) medical management for patients with chronic gastroesophageal reflux disease (GERD). Larger RCTs have been relatively short in duration, and have reported mixed results regarding symptom control and effect on quality of life (QOL). Economic evaluations have reported conflicting results. To determine the incremental cost-utility of LNF versus PPI for treating patients with chronic and controlled GERD over 3 years from the societal perspective. Economic evaluation was conducted alongside a RCT that enrolled 104 patients from October 2000 to September 2004. Primary study outcome was GERD symptoms (secondary outcomes included QOL and cost-utility). Resource utilization and QOL data collected at regular follow-up intervals determined incremental cost/QALY gained. Stochastic uncertainty was assessed using bootstrapping and methodologic assumptions were assessed using sensitivity analysis. No statistically significant differences in GERD symptom scores, but LNF did result in fewer heartburn days and improved QOL. Costs were higher for LNF patients by $3205/patient over 3 years but QOL was also higher as measured by either QOL instrument. Based on total costs, incremental cost-utility of LNF was $29,404/QALY gained using the Health Utility Index 3. Cost-utility results were sensitive to the utility instrument used ($29,404/QALY for Health Utility Index 3, $31,117/QALY for the Short Form 6D, and $76,310/QALY for EuroQol 5D) and if current lower prices for PPIs were used in the analysis. Results varied depending on resource use/costs included in the analysis, the QOL instrument used, and the cost of PPIs; however, LNF was generally found to be a cost-effective treatment for patients with symptomatic controlled GERD requiring long-term management. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR

  7. Randomised clinical trial: alginate (Gaviscon Advance) vs. placebo as add-on therapy in reflux patients with inadequate response to a once daily proton pump inhibitor.

    Science.gov (United States)

    Reimer, C; Lødrup, A B; Smith, G; Wilkinson, J; Bytzer, P

    2016-04-01

    Many reflux patients remain symptomatic on a standard dose of proton pump inhibitor (PPI). Alginates decrease the number of reflux events by forming a raft on top of the stomach content and thus offer a supplemental mechanism of action to acid suppression. To assess the efficacy of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. This was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using the Heartburn Reflux Dyspepsia Questionnaire (HRDQ). Based on symptom score during run-in, eligible patients were randomised to Gaviscon Advance 10 mL four times a day or placebo in addition to a once daily PPI. The primary endpoint was change in HRDQ score post-treatment compared to baseline. One hundred and thirty-six patients were randomised. Change in HRDQ reflux score was significantly greater for Gaviscon Advance (mean: -5.0, s.d.: 4.7) than for placebo (mean: -3.5, s.d.: 5.5) with an LS mean difference of 1.6 [95% CI -3.1 to -0.1], P = 0.03. A decrease in the mean (s.d.) number of nights with symptoms was observed from 3.6 (2.8) to 3.0 (3.0) in the placebo group and from 3.9 (2.8) to 2.2 (2.7) for the Gaviscon Advance group. This reduction was significantly greater in the Gaviscon Advance group than in the placebo group [LS mean difference = -0.9, 95% CI (-1.6 to -0.2), P < 0.01]. In patients with residual reflux symptoms despite PPI treatment, adding an alginate offers additional decrease in the burden of reflux symptoms (EudraCT/IND Number: 2011-005486-21). © 2016 John Wiley & Sons Ltd.

  8. Proton pump inhibitors while belonging to the same family of generic drugs show different anti-tumor effect.

    Science.gov (United States)

    Lugini, Luana; Federici, Cristina; Borghi, Martina; Azzarito, Tommaso; Marino, Maria Lucia; Cesolini, Albino; Spugnini, Enrico Pierluigi; Fais, Stefano

    2016-08-01

    Tumor acidity represents a major cause of chemoresistance. Proton pump inhibitors (PPIs) can neutralize tumor acidity, sensitizing cancer cells to chemotherapy. To compare the anti-tumor efficacy of different PPIs in vitro and in vivo. In vitro experiments PPIs anti-tumor efficacy in terms of cell proliferation and cell death/apoptosis/necrosis evaluation were performed. In vivo PPIs efficacy experiments were carried out using melanoma xenograft model in SCID mice. Lansoprazole showed higher anti-tumor effect when compared to the other PPIs. The lansoprazole effect lasted even upon drug removal from the cell culture medium and it was independent from the lipophilicity of the PPIs formulation. These PPIs have shown different anti-tumoral efficacy, and the most effective at low dose was lansoprazole. The possibility to contrast tumor acidity by off-label using PPIs opens a new field of oncology investigation.

  9. Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial)

    DEFF Research Database (Denmark)

    Krag, Mette; Perner, Anders; Wetterslev, Jørn

    2016-01-01

    BACKGROUND: Critically ill patients in the intensive care unit (ICU) are at risk of clinically important gastrointestinal bleeding, and acid suppressants are frequently used prophylactically. However, stress ulcer prophylaxis may increase the risk of serious adverse events and, additionally......, the quantity and quality of evidence supporting the use of stress ulcer prophylaxis is low. The aim of the SUP-ICU trial is to assess the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the ICU. We hypothesise that stress ulcer prophylaxis reduces the rate...... of gastrointestinal bleeding, but increases rates of nosocomial infections and myocardial ischaemia. The overall effect on mortality is unpredictable. METHODS/DESIGN: The SUP-ICU trial is an investigator-initiated, pragmatic, international, multicentre, randomised, blinded, parallel-group trial of stress ulcer...

  10. Incremental cost-effectiveness of proton pump inhibitors for the prevention of NSAID ulcers: a pharmacoeconomic analysis linked to a case-control study.

    NARCIS (Netherlands)

    Vonkeman, Harald Erwin; Braakman-Jansen, Louise Marie Antoinette; Klok, Rogier M.; Postma, Maarten J.; Brouwers, Jacobus R.B.J.; van de Laar, Mart A F J

    2008-01-01

    Introduction We estimated the cost effectiveness of concomitant proton pump inhibitors (PPIs) in relation to the occurrence of non-steroidal anti-inflammatory drug (NSAID) ulcer complications. Methods This study was linked to a nested case-control study. Patients with NSAID ulcer complications were

  11. Treatment of gastro-oesophageal reflux disease with rabeprazole in primary and secondary care : does Helicobacter pylori infection affect proton pump inhibitor effectiveness?

    NARCIS (Netherlands)

    de Wit, NJ; de Boer, WA; Geldof, H; Hazelhoff, B; Bergmans, P; Tytgat, GNJ; Smout, AJPM

    2004-01-01

    Background: The presence of the gastric pathogen, Helicobacter pylori influences acid suppression by proton pump inhibitors and treatment outcome in patients with gastro-oesophageal reflux disease. Aim: To determine the influence of H. pylori infection on effectiveness of rabeprazole in primary and

  12. Treatment of gastro-oesophageal reflux disease with rabeprazole in primary and secondary care: does Helicobacter pylori infection affect proton pump inhibitor effectiveness?

    NARCIS (Netherlands)

    Wit, N. J.; Boer, W. A.; Geldof, H.; Hazelhoff, B.; Bergmans, P.; Tytgat, G. N. J.; Smout, A. J. P. M.

    2004-01-01

    BACKGROUND: The presence of the gastric pathogen, Helicobacter pylori influences acid suppression by proton pump inhibitors and treatment outcome in patients with gastro-oesophageal reflux disease. AIM: To determine the influence of H. pylori infection on effectiveness of rabeprazole in primary and

  13. Should patients prescribed long-term low-dose aspirin receive proton pump inhibitors? A systematic review and meta-analysis

    NARCIS (Netherlands)

    Tran-Duy, A.; Vanmolkot, F. H.; Joore, M. A.; Hoes, A. W.; Stehouwer, C. D. A.

    2015-01-01

    Background: Several clinical guidelines recommend the use of proton pump inhibitors (PPIs) in patients taking low-dose aspirin but report no or limited supporting data. We conducted a systematic review and meta-analysis to examine the effects of co-administration of PPIs in patients taking low-dose

  14. Effects of 12 weeks' treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hove, K D; Brøns, Charlotte; Færch, Kai Erik Vinther

    2013-01-01

    Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised double-blind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA(1c...

  15. Effectiveness of add-on therapy with domperidone vs alginic acid in proton pump inhibitor partial response gastro-oesophageal reflux disease in systemic sclerosis: randomized placebo-controlled trial.

    Science.gov (United States)

    Foocharoen, Chingching; Chunlertrith, Kitti; Mairiang, Pisaln; Mahakkanukrauh, Ajanee; Suwannaroj, Siraphop; Namvijit, Suwassa; Wantha, Orathai; Nanagara, Ratanavadee

    2017-02-01

    Twice-daily dosing of proton pump inhibitor (PPI), the standard therapy for gastro-oesophageal reflux disease (GERD), is an effective therapy for GERD in SSc. The aim of this study was to compare the efficacy of omeprazole in combination with domperidone vs in combination with algycon in reducing the severity and frequency of reflux symptoms of PPI partial response (PPI-PR) GERD in SSc. Adult SSc patients having PPI-PR GERD were randomly assigned to receive domperidone plus algycon placebo or algycon plus domperidone placebo in a 1:1 ratio plus omeprazole for 4 weeks. The assessment included severity of symptom grading by visual analogue scale, frequency of symptoms by frequency scale for symptoms of GERD and quality of life (QoL) by EuroQol five-dimensions questionnaire scoring. One hundred and forty-eight SSc-GERD patients were enrolled, of whom 88 had PPI-PR. Eighty cases were randomized for either domperidone (n = 38) or algycon (n = 37) therapy. The majority in both groups had the diffuse SSc subset. At the end of the study, no significant difference in symptom grading was found between groups. After treatment and compared with baseline, the severity of symptoms, frequency scale for symptoms of GERD and QoL significantly improved in both groups. Five (13.2%) and 8 (21.6%) respective cases in the domperidone and algycon groups did not respond. The prevalence of PPI-PR GERD is common. Domperidone and algycon are equally effective treatments in combination with omeprazole. However, ∼17% of patients were non-responsive, so the effectiveness of domperidone, algycon and PPI combination therapy should be further investigated. https://clinicaltrials.gov (NCT01878526). © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Efficacy of Vonoprazan for Gastroesophageal Reflux Symptoms in Patients with Proton Pump Inhibitor-resistant Non-erosive Reflux Disease.

    Science.gov (United States)

    Niikura, Ryota; Yamada, Atsuo; Hirata, Yoshihiro; Hayakawa, Yoku; Takahashi, Akihiro; Shinozaki, Tomohiro; Takeuchi, Yoshinori; Fujishiro, Mitsuhiro; Koike, Kazuhiko

    2018-03-30

    Objective Clinically, patients with proton pomp inhibitor (PPI)-resistant gastro-esophageal reflux disease (GERD) are very challenging to treat. The aim of this study was to determine the rates of symptom relief and adverse events among PPI-resistant GERD patients that changed their therapy from a PPI to vonoprazan. Methods Patients with severe gastroesophageal reflux symptoms (total GERD-Q score ≥8) without endoscopic findings of mucosal breaks who changed their medication from a PPI to vonoprazan during a 12-week period from 2015 to 2016 at 2 hospitals were selected. The primary outcome was the self-reported relief of gastroesophageal reflux symptoms. The odds ratio (OR) for the improvement of symptoms was calculated based on an exact binomial distribution using a matched-pair analysis. The secondary outcome was the GERD-Q score and adverse events. Results Twenty-six patients (6 men) with a mean age of 67.5 years were analyzed. After the therapy was changed from a PPI to vonoprazan, 18 patients (69.2%) reported an improvement, 6 (23.1%) reported no change, and 2 (7.7%) reported an exacerbation of symptoms. A change in therapy was significantly associated with improved self-reported symptoms (OR 9.0, pgastroesophageal reflux symptoms. Vonoprazan is one of the most promising treatment options for patients with PPI-resistant GERD.

  17. Value of the Gastroesophageal Reflux Disease Questionnaire (GerdQ) in predicting the proton pump inhibitor response in coronary artery disease patients with gastroesophageal reflux-related chest pain.

    Science.gov (United States)

    He, S; Liu, Y; Chen, Y; Tang, Y; Xu, J; Tang, C

    2016-05-01

    Chest pain experienced by patients with coronary artery disease can be partly due to gastroesophageal reflux-induced chest pain (GERP). Empirical proton pump inhibitor (PPI) therapy has been recommended as an initial clinical approach for treating GERP. However, PPI use may lead to some health problems. The Gastroesophageal Reflux Disease Questionnaire (GerdQ) may represent a noninvasive and cost-effective approach for avoiding PPI misuse and for identifying the appropriate patients for the PPI trial test. The aim of this pilot study was to prospectively evaluate the association between GerdQ scores and PPI response in patients with coronary artery disease (CAD) and GERP to determine whether the GerdQ predicts the PPI response in patients with CAD and GERP and to further validate the clinical application value of the GerdQ. A total of 154 consecutive patients with potential GERP were recruited to complete a GerdQ with subsequent PPI therapy. Based on the PPI trial result, patients were divided into a PPI-positive response group and a PPI-negative response group. The difference in the GerdQ scores between the two groups was assessed. The receiver operating characteristic (ROC) curve of GerdQ score was drawn according to the PPI response as the gold standard. The ability of GerdQ to predict the PPI response was assessed. A total of 96 patients completed the entire study; 62 patients (64.6%) were assigned to the PPI-positive response group, and 34 patients (35.4%) to the PPI-negative response group. The GerdQ score of the PPI-positive response group (8.11 ± 3.315) was significantly higher than that of the PPI-negative response group (4.41 ± 2.743), and the difference was statistically significant (t = 5.863, P = 0.000). The ROC curve was drawn according to a PPI response assessment result with a score above 2 as the gold standard. The area under curve was 0.806. When the critical value of GerdQ score was 7.5, Youden index was up to 0.514, the diagnostic sensitivity

  18. Effect of a therapeutic maximum allowable cost (MAC) program on the cost and utilization of proton pump inhibitors in an employer-sponsored drug plan in Canada.

    Science.gov (United States)

    Mabasa, Vincent H; Ma, Johnny

    2006-06-01

    Therapeutic maximum allowable cost (MAC) is a managed care intervention that uses reference pricing in a therapeutic class or category of drugs or an indication (e.g., heartburn). Therapeutic MAC has not been studied in Canada or the United States. The proton pump inhibitor (PPI) rabeprazole was used as the reference drug in this therapeutic MAC program based on prices for PPIs in the province of Ontario. No PPI is available over the counter in Canada. To evaluate the utilization and anticipated drug cost savings for PPIs in an employer-sponsored drug plan in Canada that implemented a therapeutic MAC program for PPIs. An employer group with an average of 6,300 covered members, which adopted the MAC program for PPIs in June 2003, was compared with a comparison group comprising the book of business throughout Canada (approximately 5 million lives) without a PPI MAC program (non-MAC group). Pharmacy claims for PPIs were identified using the first 6 characters of the generic product identifier (GPI 492700) for a 36-month period from June 1, 2002, through May 31, 2005. The primary comparison was the year prior to the intervention (from June 1, 2002, through May 31, 2003) and the first full year following the intervention (June 1, 2004, through May 31, 2005). Drug utilization was evaluated by comparing the market share of each of the PPIs for the 2 time periods and by the days of PPI therapy per patient per year (PPPY) and days of therapy per prescription (Rx). Drug cost was defined as the cost of the drug (ingredient cost), including allowable provincial pharmacy markup but excluding pharmacy dispense fee. Cost savings were calculated from the allowed drug cost per claim, allowed cost per day, and allowed cost PPPY. (All amounts are in Canadian dollars.) The MAC intervention group experienced an 11.7% reduction in the average cost per day of PPI drug therapy, from 2.14 US dollars in the preperiod to 1.89 US dollars in the postperiod, compared with a 3.7% reduction in

  19. Conflicting results between randomized trials and observational studies on the impact of proton pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy: systematic review.

    Science.gov (United States)

    Melloni, Chiara; Washam, Jeffrey B; Jones, W Schuyler; Halim, Sharif A; Hasselblad, Victor; Mayer, Stephanie B; Heidenfelder, Brooke L; Dolor, Rowena J

    2015-01-01

    Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non-ST-segment-elevation myocardial infarction patients. We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 randomized controlled trials and 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class when compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic end points, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from randomized controlled trials evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole. Large, well-conducted observational studies of PPIs and randomized controlled trials of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in patients with unstable angina/non-ST-segment-elevation myocardial infarction treated with DAPT are warranted. © 2015 American Heart Association, Inc.

  20. The Prevalence and Clinical Features of Non-responsive Gastroesophageal Reflux Disease to Practical Proton Pump Inhibitor Dose in Korea: A Multicenter Study.

    Science.gov (United States)

    Park, Hong Jun; Park, Soo Heon; Shim, Ki Nam; Kim, Yong Sung; Kim, Hyun Jin; Han, Jae Pil; Kim, Yong Sik; Bang, Byoung Wook; Kim, Gwang Ha; Baik, Gwang Ho; Kim, Hyung Hun; Park, Seon Young; Kim, Sung Soo

    2016-07-25

    In Korea, there are no available multicenter data concerning the prevalence of or diagnostic approaches for non-responsive gastroesophageal reflux disease (GERD) which does not respond to practical dose of proton pump inhibitor (PPI) in Korea. The purpose of this study is to evaluate the prevalence and the symptom pattern of non-responsive GERD. A total of 12 hospitals who were members of a Korean GERD research group joined this study. We used the composite score (CS) as a reflux symptom scale which is a standardized questionnaire based on the frequency and severity of typical symptoms of GERD. We defined "non-responsive GERD" as follows: a subject with the erosive reflux disease (ERD) whose CS was not decreased by at least 50% after standard-dose PPIs for 8 weeks or a subject with non-erosive reflux disease (NERD) whose CS was not decreased by at least 50% after half-dose PPIs for 4 weeks. A total of 234 subjects were analyzed. Among them, 87 and 147 were confirmed to have ERD and NERD, respectively. The prevalence of non-responsive GERD was 26.9% (63/234). The rates of non-responsive GERD were not different between the ERD and NERD groups (25.3% vs. 27.9%, respectively, p=0.664). There were no differences between the non-responsive GERD and responsive GERD groups for sex (p=0.659), age (p=0.134), or BMI (p=0.209). However, the initial CS for epigastric pain and fullness were higher in the non-responsive GERD group (p=0.044, p=0.014, respectively). In conclusion, this multicenter Korean study showed that the rate of non-responsive GERD was substantially high up to 26%. In addition, the patients with the non-responsive GERD frequently showed dyspeptic symptoms such as epigastric pain and fullness.

  1. Concomitant use of proton pump inhibitors and clopidogrel in patients with coronary, cerebrovascular, or peripheral artery disease in the factores de Riesgo y ENfermedad Arterial (FRENA) registry.

    Science.gov (United States)

    Muñoz-Torrero, Juan Francisco Sánchez; Escudero, Domingo; Suárez, Carmen; Sanclemente, Carmen; Pascual, Ma Teresa; Zamorano, José; Trujillo-Santos, Javier; Monreal, Manuel

    2011-01-01

    Among patients receiving clopidogrel for coronary artery disease, concomitant therapy with proton pump inhibitors (PPIs) has been associated with an increased risk for recurrent coronary events. Factores de Riesgo y ENfermedad Arterial (FRENA) is an ongoing, multicenter, observational registry of consecutive outpatients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. We retrospectively examined the influence of concomitant use of PPIs on outcome in patients receiving clopidogrel. As of March 2009, 1222 patients were using clopidogrel: 595 had coronary artery disease, 329 cerebrovascular disease, and 298 had peripheral artery disease. Of these, 519 (42%) were concomitantly using PPIs. Over a mean follow-up of 15 months, 131 patients (11%) had 139 subsequent ischemic events: myocardial infarction 44, ischemic stroke 40, and critical limb ischemia 55. Seventeen of them (13%) died within 15 days of the subsequent event. PPI users had a higher incidence of myocardial infarction (rate ratio, 2.5; 95% confidence interval [CI], 1.3-4.8), ischemic stroke (rate ratio, 1.9; 95% CI, 1.03-3.7), and a nonsignificantly higher rate of critical limb ischemia (rate ratio, 1.6; 95% CI, 0.95-2.8) than nonusers. On multivariate analysis, concomitant use of clopidogrel and PPIs was independently associated with an increased risk for subsequent ischemic events both in the whole series of patients (hazard ratio, 1.8; 95% CI, 1.1-2.7) and in those with cerebrovascular disease or peripheral artery disease (hazard ratio, 1.5; 95% CI, 1.01-2.4). In patients with established arterial disease, concomitant use of PPIs and clopidogrel was associated with a nearly doubling of the incidence of subsequent myocardial infarction or ischemic stroke. This higher incidence persisted after multivariate adjustment.

  2. Safety of long-term PPI therapy

    DEFF Research Database (Denmark)

    Reimer, Christina

    2013-01-01

    Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been publishe...... to a careful evaluation of the indication for PPI treatment....

  3. Five-year examination of utilization and drug cost outcomes associated with benefit design changes including reference pricing for proton pump inhibitors in a state employee health plan.

    Science.gov (United States)

    Johnson, Jill T; Neill, Kathryn K; Davis, Dwight A

    2011-04-01

    The Arkansas State Employee Benefits Division (EBD) is a self-insured program comprising public school and other state employees, their spouses, and dependents. Previous research published in JMCP (2006) showed drug cost savings of $2.20 per member per month (PMPM; 37.6%) or annualized savings of $3.4 million associated with a benefit design change and coverage of the proton pump inhibitor (PPI) omeprazole over-the-counter (OTC) beginning in March 2004. On May 1, 2005, brand esomeprazole was excluded from coverage, with current users grandfathered for 4 months until September 2005. Reference pricing for PPIs, including esomeprazole but excluding generic omeprazole, was implemented on September 1, 2005, and the beneficiary cost share for all PPIs except generic omeprazole was determined from comparison of the PPI actual price to the $0.90 omeprazole OTC reference price per unit. To examine PPI utilization and drug costs before and after (a) excluding esomeprazole from coverage (with grandfathering current users) and (b) implementing a therapeutic maximum allowable cost (TMAC), or reference-pricing benefit design, for the PPI class in a large state employee health plan with fairly stable enrollment of approximately 127,500 members in 2005 through 2008 and approximately 128,000 members in 2009 Q1. The pharmacy claims database for the EBD was used to examine utilization and cost data for PPIs in a longitudinal analysis for the 61-month period from March 1, 2004, through March 31, 2009. Pharmacy claims data were compared for the period 14 months prior to esomeprazole exclusion (preperiod), 4 months during the esomeprazole exclusion (postperiod 1), and the ensuing 43 months of PPI reference pricing (postperiod 2). PPI cost and utilization data for the intervention group of approximately 127,500 beneficiaries were compared with a group of 122 self-insured employers with a total of nearly 1 million beneficiaries whose pharmacy benefits did not include reference pricing for

  4. Gender differences in symptoms in partial responders to proton pump inhibitors for gastro-oesophageal reflux disease.

    Science.gov (United States)

    Vakil, N; Niklasson, A; Denison, H; Rydén, A

    2015-10-01

    Gender differences may exist in the symptom experience of patients with gastro-oesophageal reflux disease (GERD) who have a partial response to proton pump inhibitors (PPIs). The purpose of this study was to analyse gender differences in partial responders to PPIs. Patients with GERD who responded partially to PPIs (n = 580; NCT00703534) completed the Reflux Symptom Questionnaire 7-day recall (RESQ-7) and the Gastrointestinal Symptom Rating Scale (GSRS). Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale. Women had significantly higher RESQ-7 domain scores than men for Heartburn (frequency: 4.3 vs 3.9; intensity: 3.1 vs 2.8), Burping (frequency: 4.9 vs 4.4; intensity: 3.1 vs 2.8) and Hoarseness, cough and difficulty swallowing (frequency: 2.6 vs 2.2; intensity: 1.8 vs 1.5), and had higher GSRS domain discomfort scores than men for Abdominal pain (3.51 vs 3.23), Indigestion (3.80 vs 3.45) and Constipation (2.69 vs 2.17) (all p < 0.05). Anxiety and depression were significantly more prevalent in women than in men. In this population of partial responders, women had more frequent/intense heartburn and extra-oesophageal symptoms and more discomfort from abdominal pain, indigestion and constipation than men. Comorbid anxiety and depression may contribute to the increased symptom burden in women.

  5. Analysis, occurrence, fate and risks of proton pump inhibitors, their metabolites and transformation products in aquatic environment: A review.

    Science.gov (United States)

    Kosma, Christina I; Lambropoulou, Dimitra A; Albanis, Triantafyllos A

    2016-11-01

    Proton pump inhibitors (PPIs) which include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole, are extensively used for the relief of gastro-intestinal disorders. Despite their high worldwide consumption, PPIs are extensively metabolized in human bodies and therefore are not regularly detected in monitoring studies. Very recently, however, it has been shown that some omeprazole metabolites may enter and are likely to persist in aquatic environment. Hence, to fully assess the environmental exposures and risks associated with PPIs, it is important to better understand and evaluate the fate and behavior not only of the parent compound but also of their metabolites and their transformation products arising from biotic and abiotic processes (hydrolysis, photodegradation, biodegradation etc.) in the environment. In this light, the purpose of this review is to summarize the present state of knowledge on the introduction and behavior of these chemicals in natural and engineering systems and highlight research needs and gaps. It draws attention to their transformation, the increase contamination by their metabolites/TPs in different environmental matrices and their potential adverse effects in the environment. Furthermore, existing research on analytical developments with respect to sample treatment, separation and detection of PPIs and their metabolites/TPs is provided. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients

    Science.gov (United States)

    Nakagawa, Kenichiro; Koike, Tomoyuki; Iijima, Katsunori; Saito, Masahiro; Kikuchi, Hiroki; Hatta, Waku; Ara, Nobuyuki; Uno, Kaname; Asano, Naoki; Shimosegawa, Tooru

    2015-01-01

    AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease (NERD) patients. METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance - pH on rabeprazole. The symptom index (SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter. RESULTS: In 14 (40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes (46.7%) than in distal ones (5.7%) (P acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (38.5%) and distal ones (20.5%) (NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent (31.0%) than in distal reflux ones (3.3%) (P acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (29.4%) and distal ones (14.3%) (NS). CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy. PMID:26715820

  7. Pathogenesis of Double-Dose Proton Pump Inhibitor-Resistant Non-Erosive Reflux Disease, and Mechanism of Reflux Symptoms and Gastric Acid Secretion-Suppressive Effect in the Presence or Absence of Helicobacter pylori Infection.

    Science.gov (United States)

    Kawami, Noriyuki; Takenouchi, Nana; Umezawa, Mariko; Hoshino, Shintaro; Hanada, Yuriko; Hoshikawa, Yoshimasa; Sano, Hirohito; Hoshihara, Yoshio; Nomura, Tsutomu; Uchida, Eiji; Iwakiri, Katsuhiko

    2017-01-01

    Various mechanisms have been suggested to be responsible for contributing to the occurrence of proton pump inhibitor (PPI)-resistant non-erosive reflux disease (NERD). The aims of this study were to clarify the pathogenesis of PPI-resistant NERD. Fifty-three patients with NERD, who had persistent reflux symptoms despite taking double-dose PPI, were included in this study. After excluding eosinophilic esophagitis (EoE) and primary esophageal motility disorder, esophageal impedance-pH monitoring was carried out. In symptom index (SI)-positive patients, the mechanism of SI positivity and the percent time with intragastric pH >4 were investigated according to the presence or absence of Helicobacter pylori infection. One of the 53 patients had EoE, and 4 had primary esophageal motility disorder. Twenty-three and 2 patients were SI-positive for liquid and gas-only reflux respectively. Of 17 SI-positive, H. pylori-negative patients, 5 were SI-positive for acid reflux, whereas all of the H. pylori-positive patients were SI-positive for non-acid reflux. The percent time with intragastric pH >4 was significantly lower in the H. pylori-negative patients than in the H. pylori-positive patients. The pathogenesis of double-dose PPI-resistant NERD was identified in 57%. In some of H. pylori-negative patients, acid-related symptoms were observed. However, in H. pylori-positive patients, these symptoms were excluded by taking double-dose PPI. © 2017 S. Karger AG, Basel.

  8. Proton pump inhibitors for the treatment of patients with erosive esophagitis and gastroesophageal reflux disease: current evidence and safety of dexlansoprazole

    Directory of Open Access Journals (Sweden)

    Mermelstein J

    2016-07-01

    Full Text Available Joseph Mermelstein,1 Alanna Chait Mermelstein,2 Maxwell M Chait,3 1Department of Medicine, Mount Sinai Beth Israel/Icahn School of Medicine, 2Department of Psychiatry, New York Presbyterian Hospital/Weill Cornell Medicine, 3Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA Abstract: Gastroesophageal reflux disease is the most common upper gastroenterology disorder in the US. It is associated with a variety of complications and significantly impacts quality of life. Proton pump inhibitors are the most effective treatment. Dexlansoprazole modified release (MR is a proton pump inhibitor that employs a novel release formulation that prolongs its absorption and allows for more flexibility in dosing. Dexlansoprazole MR can be dosed without regard to food intake or time of day, and once-daily dosing may replace twice-daily dosing of other agents. Dexlansoprazole MR is effective for healing and maintenance of erosive esophagitis, and for the treatment of nonerosive disease, including nocturnal gastroesophageal reflux disease. Dexlansoprazole MR is safe and well tolerated, and can improve quality of life. Keywords: dexlansoprazole, proton pump inhibitors, gastroesophageal reflux disease, erosive esophagitis

  9. Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis.

    Science.gov (United States)

    Serbin, Michael A; Guzauskas, Gregory F; Veenstra, David L

    2016-08-01

    Uncertainty regarding clopidogrel effectiveness attenuation because of a drug-drug interaction with proton pump inhibitors (PPI) has led to conflicting guidelines on concomitant therapy. In particular, the effect of this interaction in patients who undergo a percutaneous coronary intervention (PCI), a population known to have increased risk of adverse cardiovascular events, has not been systematically evaluated. To synthesize the evidence of the effect of clopidogrel-PPI drug interaction on adverse cardiovascular outcomes in a PCI patient population. We conducted a systematic literature review for studies reporting clinical outcomes in patients who underwent a PCI and were initiated on clopidogrel with or without a PPI. Studies were included in the analysis if they reported at least 1 of the clinical outcomes of interest (major adverse cardiovascular event [MACE], cardiovascular death, all-cause death, myocardial infarction, stroke, stent thrombosis, and bleed events). We excluded studies that were not exclusive to PCI patients or had no PCI subgroup analysis and/or did not report at least a 6-month follow-up. Statistical and clinical heterogeneity were evaluated and HRs and 95% CIs for adverse clinical events were pooled using the DerSimonian and Laird random-effects meta-analysis method. We identified 12 studies comprising 50,277 PCI patients that met our inclusion and exclusion criteria. Our analysis included retrospective analyses of randomized controlled trials (2), health registries (3), claims databases (2), and institutional records (5); no prospective studies of PCI patients were identified. On average, patients were in their mid-60s, male, and had an array of comorbidities, including hyperlipidemia, diabetes, hypertension, and smoking history. Concomitant therapy following PCI resulted in statistically significant increases in composite MACE (HR = 1.28; 95% CI = 1.24-1.32), myocardial infarction (HR = 1.51; 95% CI = 1.40-1.62), and stroke (HR = 1.46; 95

  10. Effects of pancreatic digestive enzymes, sodium bicarbonate, and a proton pump inhibitor on steatorrhoea caused by pancreatic diseases.

    Science.gov (United States)

    Nakamura, T; Takebe, K; Kudoh, K; Ishii, M; Imamura, K; Kikuchi, H; Kasai, F; Tandoh, Y; Yamada, N; Arai, Y

    1995-01-01

    Forty-five patients with pancreatic steatorrhoea (27 with calcified pancreatitis, 13 with non-calcified pancreatitis, two with pancreaticoduodenectomy, one with total pancreatectomy, and two with pancreatic cancer) were divided into four groups and given the following medication for 2 to 4 weeks: 4 to 6 g/day of sodium bicarbonate (group I); 9 g/day of high-lipase pancreatin (lipase, 56,600 U/g, Fédération Internationale Pharmaceutique (FIP); group II); 12 to 24 tablets or 9.0 g of commercial pancreatic enzyme preparations (group III); or 50 mg of omeprazole (group IV). Faecal fat excretion was evaluated before and after drug administration. Faecal fat excretion was reduced by 2.9 g (range, 1.7 to 5.0 g) in group I; 8.8 g (range, 2.9 to 39.9 g) in group II; 10.8 g (range, 2.3 to 21.8 g) in group III; and 4.3 g (range, 3.6 to 5.6 g) in group IV. The pancreatic digestive enzyme preparation was more effective than sodium bicarbonate and agents that raise the pH of the upper small intestine (such as proton-pump inhibitors) in reducing faecal fat excretion. The results indicate that all of the preparations used are effective against mild pancreatic steatorrhoea. If the condition is more advanced, however, a massive dosage of pancreatic digestive enzyme and possibly the combined use of an agent to raise the pH of the upper small intestine are likely to be effective.

  11. Cardiovascular outcomes associated with concomitant use of clopidogrel and proton pump inhibitors in patients with acute coronary syndrome in Taiwan

    Science.gov (United States)

    Lin, Chen-Fang; Shen, Li-Jiuan; Wu, Fe-Lin Lin; Bai, Chyi-Huey; Gau, Churn-Shiouh

    2012-01-01

    AIMS Our study aimed to examine the impact of concomitant use of proton pump inhibitors (PPIs) with clopidogrel on the cardiovascular outcomes of patients with acute coronary syndrome (ACS). Furthermore, we sought to quantify the effects of five individual PPIs when used concomitantly with clopidogrel. METHODS We conducted a retrospective cohort study of patients who were newly hospitalized for ACS between 1 January 2006 and 31 December 2007 retrieved from the Taiwan National Health Insurance Research Database (NHIRD) and who were prescribed clopidogrel (n= 37 099) during the follow-up period. A propensity score technique was used to establish a matched cohort in 1:1 ratio (n= 5173 for each group). The primary clinical outcome was rehospitalization for ACS, while secondary outcomes were rehospitalization for percutaneous transluminal coronary angioplasty (PTCA) with stent, PTCA without stent and revascularization (PTCA or coronary artery bypass graft surgery) after the discharge date for the index ACS event. RESULTS The adjusted hazard ratio of rehospitalization for ACS was 1.052 (95% confidence interval, 0.971–1.139; P= 0.214) in the propensity score matched cohort. Among all PPIs, only omeprazole was found to be statistically significantly associated with an increased risk of rehospitalization for ACS (adjusted hazard ratio, 1.226; 95% confidence interval, 1.066–1.410; P= 0.004). Concomitant use of esomeprazole, pantoprazole, rabeprazole and lansoprazole did not increase the risk. CONCLUSIONS Our study indicated no statistically significant increase in the risk of rehospitalization for ACS due to concurrent use of clopidogrel and PPIs overall. Among individual PPIs, only omeprazole was found to be statistically significantly associated with increased risk of rehospitalization for ACS. PMID:22364155

  12. Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach.

    Science.gov (United States)

    Taylor, Sophie; Spugnini, Enrico Pierluigi; Assaraf, Yehuda G; Azzarito, Tommaso; Rauch, Cyril; Fais, Stefano

    2015-11-01

    Despite the major progresses in biomedical research and the development of novel therapeutics and treatment strategies, cancer is still among the dominant causes of death worldwide. One of the crucial challenges in the clinical management of cancer is primary (intrinsic) and secondary (acquired) resistance to both conventional and targeted chemotherapeutics. Multiple mechanisms have been identifiedthat underlie intrinsic and acquired chemoresistance: these include impaired drug uptake, increased drug efflux, deletion of receptors, altered drug metabolism, quantitative and qualitative alterations in drug targets, increased DNA damage repair and various mechanisms of anti-apoptosis. The fast efflux of anticancer drugs mediated by multidrug efflux pumps and the partial or complete reversibility of chemoresistance combined with the absence of genetic mutations suggests a multifactorial process. However, a growing body of recent evidence suggests that chemoresistance is often triggered by the highly acidic microenvironment of tumors. The vast majority of drugs, including conventional chemotherapeutics and more recent biological agents, are weak bases that are quickly protonated and neutralized in acidic environments, such as the extracellular microenvironment and the acidic organelles of tumor cells. It is therefore essential to develop new strategies to overcome the entrapment and neutralization of weak base drugs. One such strategy is the use of proton pump inhibitors which can enhance tumor chemosensitivity by increasing the pH of the tumor microenvironment. Recent clinical trials in animals with spontaneous tumors have indicated that patient alkalization is capable of reversing acquired chemoresistance in a large percentage of tumors that are refractory to chemotherapy. Of particular interest was the benefit of alkalization for patients undergoing metronomic regimens which are becoming more widely used in veterinary medicine. Overall, these results provide

  13. Asthma symptoms improvement in moderate persistent asthma patients with gastroesophageal reflux disease (GERD: the role of proton-pump inhibitor

    Directory of Open Access Journals (Sweden)

    Agus D. Susanto

    2008-09-01

    Full Text Available This study aimed to evaluate effect of proton pump inhibitor (esomeprazole on asthma symptoms, use of inhaled bronchodilator and peak expiratory flow rate (PEFR in moderate persistent asthma with gastroesofageal refluks disease (GERD. This randomized single blind, controlled clinical trial study was conducted at Persahabatan Hospital, Jakarta from July 2004 until October 2005. Samples were moderate persistent asthma patients with GERD. GERD is diagnosed GERD symptoms and proof of oesophagitis from endoscopy and or histapatologic examination from oesophagus biopsy. Phase 1:2 week run-in period patient received inhaled budesonide 2x200 ug/day. Phase 2: patient randomised to receive inhaled budesonide 2 x 400 ug/day with esomeprazole 40 mg/day or without esomeprazole (control group for 8 weeks. Phase 3: 4 week wash out period, patient receive inhaled budesonide 2 x 200 ug/day. Diary cards were assessed at run-in periode, after treatment 4 weeks, 8 weeks and wash out. There were 32 patients (23 female and 9 male completed the study. Mean total asthma symptoms score daily were significantly decreased on esomeprazole vs without esomeprazole after 8 weeks (-2.29 vs -0.90; p < 0.05. Mean use of inhaled bronchodilator was significantly decreased on esomeprazole vs without esomeprazole after 8 weeks (-1.09 vs -0.42; p < 0.05. Morning and evening PEFR improved higher on esomeprazole than without esomeprazol but were not significantly difference. In conclusion, administration esomeprazole 40 mg daily improved asthma symptoms and lower the use of inhaled bronchodilator in moderate persistent asthma patients with GERD. (Med J Indones 2008; 17: 169-74Keywords: Asthma symptoms, inhaled bronchodilator, moderate persistent asthma, GERD, esomeprazole

  14. Analysis, occurrence, fate and risks of proton pump inhibitors, their metabolites and transformation products in aquatic environment: A review

    International Nuclear Information System (INIS)

    Kosma, Christina I.; Lambropoulou, Dimitra A.; Albanis, Triantafyllos A.

    2016-01-01

    Proton pump inhibitors (PPIs) which include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole, are extensively used for the relief of gastro-intestinal disorders. Despite their high worldwide consumption, PPIs are extensively metabolized in human bodies and therefore are not regularly detected in monitoring studies. Very recently, however, it has been shown that some omeprazole metabolites may enter and are likely to persist in aquatic environment. Hence, to fully assess the environmental exposures and risks associated with PPIs, it is important to better understand and evaluate the fate and behavior not only of the parent compound but also of their metabolites and their transformation products arising from biotic and abiotic processes (hydrolysis, photodegradation, biodegradation etc.) in the environment. In this light, the purpose of this review is to summarize the present state of knowledge on the introduction and behavior of these chemicals in natural and engineering systems and highlight research needs and gaps. It draws attention to their transformation, the increase contamination by their metabolites/TPs in different environmental matrices and their potential adverse effects in the environment. Furthermore, existing research on analytical developments with respect to sample treatment, separation and detection of PPIs and their metabolites/TPs is provided. - Highlights: • Occurrence and fate of PPIs and their metabolites/TPs in the aquatic environment • Overview of the analytical methods applied, using LC-MS techniques • Omeprazole attended the most frequent analysis • Determination and behavior of omeprazole's metabolites/TPs in the environment • More ecotoxicological research is needed to assess the risks of PPIs.

  15. Analysis, occurrence, fate and risks of proton pump inhibitors, their metabolites and transformation products in aquatic environment: A review

    Energy Technology Data Exchange (ETDEWEB)

    Kosma, Christina I. [Department of Chemistry, University of Ioannina, Ioannina, 45110 (Greece); Lambropoulou, Dimitra A., E-mail: dlambro@chem.auth.gr [Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124 (Greece); Albanis, Triantafyllos A. [Department of Chemistry, University of Ioannina, Ioannina, 45110 (Greece)

    2016-11-01

    Proton pump inhibitors (PPIs) which include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole, are extensively used for the relief of gastro-intestinal disorders. Despite their high worldwide consumption, PPIs are extensively metabolized in human bodies and therefore are not regularly detected in monitoring studies. Very recently, however, it has been shown that some omeprazole metabolites may enter and are likely to persist in aquatic environment. Hence, to fully assess the environmental exposures and risks associated with PPIs, it is important to better understand and evaluate the fate and behavior not only of the parent compound but also of their metabolites and their transformation products arising from biotic and abiotic processes (hydrolysis, photodegradation, biodegradation etc.) in the environment. In this light, the purpose of this review is to summarize the present state of knowledge on the introduction and behavior of these chemicals in natural and engineering systems and highlight research needs and gaps. It draws attention to their transformation, the increase contamination by their metabolites/TPs in different environmental matrices and their potential adverse effects in the environment. Furthermore, existing research on analytical developments with respect to sample treatment, separation and detection of PPIs and their metabolites/TPs is provided. - Highlights: • Occurrence and fate of PPIs and their metabolites/TPs in the aquatic environment • Overview of the analytical methods applied, using LC-MS techniques • Omeprazole attended the most frequent analysis • Determination and behavior of omeprazole's metabolites/TPs in the environment • More ecotoxicological research is needed to assess the risks of PPIs.

  16. Analysis of the Interaction between Clopidogrel, Aspirin, and Proton Pump Inhibitors Using the FDA Adverse Event Reporting System Database.

    Science.gov (United States)

    Suzuki, Yukiya; Suzuki, Honami; Umetsu, Ryogo; Uranishi, Hiroaki; Abe, Junko; Nishibata, Yuri; Sekiya, Yasuaki; Miyamura, Nobuteru; Hara, Hideaki; Tsuchiya, Teruo; Kinosada, Yasutomi; Nakamura, Mitsuhiro

    2015-01-01

    Clopidogrel is an antiplatelet agent widely used in combination with aspirin to limit the occurrence of cardiovascular (embolic/thrombotic) events. Consensus guidelines recommend proton pump inhibitors (PPIs) as a gastrointestinal (GI) prophylactic measure for all patients receiving dual antiplatelet therapy with clopidogrel and aspirin. The objective of this study was to analyze the effect of the simultaneous use of clopidogrel, aspirin, and PPIs on hemorrhagic and embolic/thrombotic events using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Reports of hemorrhagic and embolic/thrombotic events between 2004 and 2013 were analyzed with a reporting odds ratio (ROR) algorithm and logistic regression methods. The Medical Dictionary for Regulatory Activities Preferred Terms was used to identify such events. Regarding hemorrhagic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 4.40 (95% confidence interval [CI], 4.02-4.81) and 3.40 (95% CI, 2.84-4.06), respectively. For embolic/thrombotic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 2.37 (95% CI, 2.16-2.59) and 2.38 (95% CI, 2.00-2.84), respectively. Among patients included in the FAERS database, the concurrent use of aspirin and clopidogrel with PPIs reduced the adjusted ROR of GI hemorrhagic events. PPIs had little influence on the adjusted ROR of embolic/thrombotic events. These results support the use of PPIs as a preventive measure against GI hemorrhagic events for patients receiving clopidogrel and aspirin.

  17. Randomized controlled trial of transoral incisionless fundoplication vs. proton pump inhibitors for treatment of gastroesophageal reflux disease

    NARCIS (Netherlands)

    Witteman, B.P.; Conchillo, J.M.; Rinsma, N.F.; Betzel, B; Peeters, A.; Koek, G.H.; Stassen, L.P.; Bouvy, N.D.

    2015-01-01

    OBJECTIVES: Transoral incisionless fundoplication (TIF) was developed in an attempt to create a minimally invasive endoscopic procedure that mimics antireflux surgery. The objective of this trial was to evaluate effectiveness of TIF compared with proton pump inhibition in a population consisting of

  18. Risk factors associated with gastroesophageal reflux disease relapse in primary care patients successfully treated with a proton pump inhibitor.

    Science.gov (United States)

    López-Colombo, A; Pacio-Quiterio, M S; Jesús-Mejenes, L Y; Rodríguez-Aguilar, J E G; López-Guevara, M; Montiel-Jarquín, A J; López-Alvarenga, J C; Morales-Hernández, E R; Ortiz-Juárez, V R; Ávila-Jiménez, L

    There are no studies on the factors associated with gastroesophageal reflux disease (GERD) relapse in primary care patients. To identify the risk factors associated with GERD relapse in primary care patients that responded adequately to short-term treatment with a proton pump inhibitor. A cohort study was conducted that included GERD incident cases. The patients received treatment with omeprazole for 4 weeks. The ReQuest questionnaire and a risk factor questionnaire were applied. The therapeutic success rate and relapse rate were determined at 4 and 12 weeks after treatment suspension. A logistic regression analysis of the possible risk factors for GERD relapse was carried out. Of the 83 patient total, 74 (89.16%) responded to treatment. Symptoms recurred in 36 patients (48.64%) at 4 weeks and in 13 patients (17.57%) at 12 weeks, with an overall relapse rate of 66.21%. The OR multivariate analysis (95% CI) showed the increases in the possibility of GERD relapse for the following factors at 12 weeks after treatment suspension: basic educational level or lower, 24.95 (1.92-323.79); overweight, 1.76 (0.22-13.64); obesity, 0.25 (0.01-3.46); smoking, 0.51 (0.06-3.88); and the consumption of 4-12 cups of coffee per month, 1.00 (0.12-7.84); citrus fruits, 14.76 (1.90-114.57); NSAIDs, 27.77 (1.12-686.11); chocolate, 0.86 (0.18-4.06); ASA 1.63 (0.12-21.63); carbonated beverages, 4.24 (0.32-55.05); spicy food 7-16 times/month, 1.39 (0.17-11.17); and spicy food ≥ 20 times/month, 4.06 (0.47-34.59). The relapse rate after short-term treatment with omeprazole was high. The consumption of citrus fruits and NSAIDs increased the possibility of GERD relapse. Copyright © 2016 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  19. The proton pump inhibitor, omeprazole, but not lansoprazole or pantoprazole, is a metabolism-dependent inhibitor of CYP2C19: implications for coadministration with clopidogrel.

    Science.gov (United States)

    Ogilvie, Brian W; Yerino, Phyllis; Kazmi, Faraz; Buckley, David B; Rostami-Hodjegan, Amin; Paris, Brandy L; Toren, Paul; Parkinson, Andrew

    2011-11-01

    As a direct-acting inhibitor of CYP2C19 in vitro, lansoprazole is more potent than omeprazole and other proton pump inhibitors (PPIs), but lansoprazole does not cause clinically significant inhibition of CYP2C19 whereas omeprazole does. To investigate this apparent paradox, we evaluated omeprazole, esomeprazole, R-omeprazole, lansoprazole, and pantoprazole for their ability to function as direct-acting and metabolism-dependent inhibitors (MDIs) of CYP2C19 in pooled human liver microsomes (HLM) as well as in cryopreserved hepatocytes and recombinant CYP2C19. In HLM, all PPIs were found to be direct-acting inhibitors of CYP2C19 with IC(50) values varying from 1.2 μM [lansoprazole; maximum plasma concentration (C(max)) = 2.2 μM] to 93 μM (pantoprazole; C(max) = 6.5 μM). In addition, we identified omeprazole, esomeprazole, R-omeprazole, and omeprazole sulfone as MDIs of CYP2C19 (they caused IC(50) shifts after a 30-min preincubation with NADPH-fortified HLM of 4.2-, 10-, 2.5-, and 3.2-fold, respectively), whereas lansoprazole and pantoprazole were not MDIs (IC(50) shifts lansoprazole, or pantoprazole, as irreversible (or quasi-irreversible) MDIs of CYP2C19. These results have important implications for the mechanism of the clinical interaction reported between omeprazole and clopidogrel, as well as other CYP2C19 substrates.

  20. Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study

    DEFF Research Database (Denmark)

    Charlot, Mette; Grove, Erik; Hansen, Peter Riis

    2011-01-01

    : All aspirin treated patients surviving 30 days after a first myocardial infarction from 1997 to 2006, with follow-up for one year. Patients treated with clopidogrel were excluded. MAIN OUTCOME MEASURES: The risk of the combined end point of cardiovascular death, myocardial infarction, or stroke...... associated with use of proton pump inhibitors was analysed using Kaplan-Meier analysis, Cox proportional hazard models, and propensity score matched Cox proportional hazard models. Results 3366 of 19 925 (16.9%) aspirin treated patients experienced recurrent myocardial infarction, stroke, or cardiovascular...

  1. Malignant Range Elevation of Serum Chromogranin A due to Inadvertent Use of Proton Pump Inhibitor in a Subject with Pancreatic Incidentaloma

    Directory of Open Access Journals (Sweden)

    Usman Hammawa Malabu

    2011-01-01

    Full Text Available We present a case of highly elevated tenfold rise of serum chromogranin A in a young, morbidly obese, hypertensive female being investigated for pancreatic mass, weight loss, and elevated ESR. Following extensive noninvasive investigations, an ultrasound-guided pancreatic biopsy confirmed benign haemorrhagic cyst. A clue to the etiology of the hyperchromogranin A was the elevated serum gastrin level leading to suspicion of proton pump inhibitor administration confirmed by admittance to its use. Withdrawal of the medication led to dramatic resolution of the neuroendocrine tumor marker.

  2. Gastroesophageal reflux disease-related symptom recurrence in patients discontinuing proton pump inhibitors for Bravo wireless esophageal pH monitoring study

    Directory of Open Access Journals (Sweden)

    R. Schey

    2017-10-01

    Full Text Available Background: Patients with gastroesophageal reflux disease (GERD are treated with proton pump inhibitors (PPIs. Those that do not achieve symptom relief, or non-responders, usually undergo esophageal pH monitoring off PPIs in order to confirm the presence of GERD. Aims: To assess the efficacy of the reverse-PPI trial in evaluating the presence of GERD or its recurrence rates, as well as to identify a correlation between the symptom recurrence rates and GERD severity determined by 48-hour Bravo esophageal pH-monitor testing. Methods: A final total of 205 patients that underwent the 48-hour Bravo esophageal pH-monitoring study were retrospectively included. Patients discontinued PPI usage for at least 7 days prior to testing, and completed symptom questionnaires during the 2-day test. The Bravo test was considered positive if the percentage of time with esophageal pH 4.4%. Results: A total of 363 patients underwent 48-hour Bravo testing and of those patients, 205 were eligible for the study. Ninety-two patients reported symptoms as being «same/better» and 113 as being «worse» after stopping PPIs. Of the 92 patients with improved symptoms, 44 (48% had documented acid reflux during the Bravo study, compared with 65 of 113 (58% patients with worsening symptoms that also complained of acid reflux. Of the 109 patients found to have confirmed GERD upon pH monitoring, 65 (59.6% reported a worsening of symptoms, compared with 48 of 96 (50.0% patients without GERD (p = 0.043. Main symptoms stated to be worse included heartburn, chest pain, regurgitation, nausea, and belching (p  7 days (p = 0.042 Conclusion: Symptom exacerbation following PPI cessation for at least 7 days correlated with acid reflux severity assessed by Bravo testing. Patients off PPIs for 7 days had a higher likelihood of experiencing worsening symptoms, compared with those off PPIs for more than 7 days. These findings suggest that when PPIs are held for 7 days or less prior to

  3. Volume, distribution and acidity of gastric secretion on and off proton pump inhibitor treatment: a randomized double-blind controlled study in patients with gastro-esophageal reflux disease (GERD) and healthy subjects.

    Science.gov (United States)

    Steingoetter, Andreas; Sauter, Matthias; Curcic, Jelena; Liu, Dian; Menne, Dieter; Fried, Michael; Fox, Mark; Schwizer, Werner

    2015-09-02

    Postprandial accumulation of gastric secretions in the proximal stomach above the meal adjacent to the esophagogastric junction (EGJ), referred to as the 'acid pocket', has been proposed as a pathophysiological factor in gastro-esophageal reflux disease (GERD) and as a target for GERD treatment. This study assessed the effect of proton pump inhibitor (PPI) therapy on the volume, distribution and acidity of gastric secretions in GERD and healthy subjects (HS). A randomized, double blind, cross-over study in 12 HS and 12 GERD patients pre-treated with 40 mg pantoprazole (PPI) or placebo b.i.d. was performed. Postprandial secretion volume (SV), formation of a secretion layer and contact between the layer and the EGJ were quantified by Magnetic Resonance Imaging (MRI). Multi-channel pH-monitoring assessed intragastric pH. A distinct layer of undiluted acid secretion was present on top of gastric contents in almost all participants on and off high-dose acid suppression. PPI reduced SV (193 ml to 100 ml, in HS, 227 ml to 94 ml in GERD; p < 0.01) and thickness of the acid layer (26 mm to 7 mm, 36 mm to 9 mm respectively, p < 0.01). No differences in secretion volume or layer thickness were observed between groups; however, off treatment, contact time between the secretion layer and EGJ was 2.6 times longer in GERD compared to HS (p = 0.012). This was not the case on PPI. MRI can visualize and quantify the volume and distribution dynamics of gastric secretions that form a layer in the proximal stomach after ingestion of a liquid meal. The secretion volume and the secretion layer on top of gastric contents is similar in GERD patients and HS; however contact between the layer of undiluted secretion and the EGJ is prolonged in patients. High dose PPI reduced secretion volume by about 50% and reduced contact time between secretion and EGJ towards normal levels. NCT01212614.

  4. Association Between Proton Pump Inhibitors and Metronomic Capecitabine as Salvage Treatment for Patients With Advanced Gastrointestinal Tumors: A Randomized Phase II Trial.

    Science.gov (United States)

    Marchetti, Paolo; Milano, Annalisa; D'Antonio, Chiara; Romiti, Adriana; Falcone, Rosa; Roberto, Michela; Fais, Stefano

    2016-12-01

    The acidification of extracellular compartment represents a conceivable mechanism of drug resistance in malignant cells. In addition, it has been reported to drive proliferation and promote invasion and metastasis. Experimental evidence has shown that proton pump inhibitors can counteract tumor acidification and restore sensitivity to anticancer drugs. Moreover, early clinical data have supported the role of proton pump inhibitors in anticancer treatments. Metronomic capecitabine has demonstrated beneficial effects as salvage chemotherapy for heavily pretreated or frail patients with gastrointestinal cancer. The present study (EudraCT Number: 2013-001096-20) was aimed at investigating the activity and safety of high-dose rabeprazole in combination with metronomic capecitabine in patients with advanced gastrointestinal cancer refractory to standard treatment. A total of 66 patients will be randomized 1:1 to receive capecitabine 1500 mg/daily, continuously with or without rabeprazole 1.5 mg/kg twice a day, 3 days a week until disease progression, undue toxicity, or withdrawal of informed consent. The primary endpoint is progression-free survival. The secondary endpoints are clinical benefit, which reflects the proportion of patients with complete response, partial response, and stable disease, and overall survival. Progression-free and overall survival will be evaluated using a log-rank test to determine the effect of rabeprazole independently at the 2-sided α-level of 0.05. Other assessments will include the frequency and severity of adverse events and changes in laboratory parameters to measure the safety, and the pharmacokinetics of capecitabine. The results are expected in 2016. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steriodal anti-inflammatory drugs: a nested case-control study

    NARCIS (Netherlands)

    Vonkeman, Harald Erwin; Fernandes, Robert W.; van der Palen, Jacobus Adrianus Maria; van Roon, Eric N.; van de Laar, Mart A F J

    2007-01-01

    Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven.

  6. Incremental cost effectiveness of proton pump inhibitors for the prevention of non-steroidal anti-inflammatory drug ulcers : a pharmacoeconomic analysis linked to a case-control study

    NARCIS (Netherlands)

    Vonkeman, H.E.; Braakman-Jansen, L.M.A.; Klok, R.M.; Postma, M.J.; Brouwers, J.R.B.J.; van de Laar, M.A.F.J.

    2008-01-01

    Introduction We estimated the cost effectiveness of concomitant proton pump inhibitors (PPIs) in relation to the occurrence of non-steroidal anti-inflammatory drug (NSAID) ulcer complications. Methods This study was linked to a nested case-control study. Patients with NSAID ulcer complications were

  7. Similar Efficacy of Proton-Pump Inhibitors vs H2-Receptor Antagonists in Reducing Risk of Upper Gastrointestinal Bleeding or Ulcers in High-Risk Users of Low-Dose Aspirin.

    Science.gov (United States)

    Chan, Francis K L; Kyaw, Moe; Tanigawa, Tetsuya; Higuchi, Kazuhide; Fujimoto, Kazuma; Cheong, Pui Kuan; Lee, Vivian; Kinoshita, Yoshikazu; Naito, Yuji; Watanabe, Toshio; Ching, Jessica Y L; Lam, Kelvin; Lo, Angeline; Chan, Heyson; Lui, Rashid; Tang, Raymond S Y; Sakata, Yasuhisa; Tse, Yee Kit; Takeuchi, Toshihisa; Handa, Osamu; Nebiki, Hiroko; Wu, Justin C Y; Abe, Takashi; Mishiro, Tsuyoshi; Ng, Siew C; Arakawa, Tetsuo

    2017-01-01

    It is not clear whether H 2 -receptor antagonists (H2RAs) reduce the risk of gastrointestinal (GI) bleeding in aspirin users at high risk. We performed a double-blind randomized trial to compare the effects of a proton pump inhibitor (PPI) vs a H2RA antagonist in preventing recurrent upper GI bleeding and ulcers in high-risk aspirin users. We studied 270 users of low-dose aspirin (≤325 mg/day) with a history of endoscopically confirmed ulcer bleeding at 8 sites in Hong Kong and Japan. After healing of ulcers, subjects with negative results from tests for Helicobacter pylori resumed aspirin (80 mg) daily and were assigned randomly to groups given a once-daily PPI (rabeprazole, 20 mg; n = 138) or H2RA (famotidine, 40 mg; n = 132) for up to 12 months. Subjects were evaluated every 2 months; endoscopy was repeated if they developed symptoms of upper GI bleeding or had a reduction in hemoglobin level greater than 2 g/dL and after 12 months of follow-up evaluation. The adequacy of upper GI protection was assessed by end points of recurrent upper GI bleeding and a composite of recurrent upper GI bleeding or recurrent endoscopic ulcers at month 12. During the 12-month study period, upper GI bleeding recurred in 1 patient receiving rabeprazole (0.7%; 95% confidence interval [CI], 0.1%-5.1%) and in 4 patients receiving famotidine (3.1%; 95% CI, 1.2%-8.1%) (P = .16). The composite end point of recurrent bleeding or endoscopic ulcers at month 12 was reached by 9 patients receiving rabeprazole (7.9%; 95% CI, 4.2%-14.7%) and 13 patients receiving famotidine (12.4%; 95% CI, 7.4%-20.4%) (P = .26). In a randomized controlled trial of users of low-dose aspirin at risk for recurrent GI bleeding, a slightly lower proportion of patients receiving a PPI along with aspirin developed recurrent bleeding or ulcer than of patients receiving an H2RA with the aspirin, although this difference was not statistically significant. ClincialTrials.gov no: NCT01408186. Copyright © 2017 AGA

  8. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy

    DEFF Research Database (Denmark)

    Reimer, Christina; Søndergaard, Bo; Hilsted, Linda

    2009-01-01

    -controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid...... dyspepsia, heartburn, or acid regurgitation in the PPI group was 13 of 59 (22%) at week 10, 13 of 59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). CONCLUSIONS: PPI therapy...

  9. Proton pump inhibitors suppress iNOS-dependent DNA damage in Barrett's esophagus by increasing Mn-SOD expression

    Energy Technology Data Exchange (ETDEWEB)

    Thanan, Raynoo [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 (Japan); Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 (Japan); Ma, Ning [Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie 513-0293 (Japan); Iijima, Katsunori; Abe, Yasuhiko; Koike, Tomoyuki; Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Hospital, Sendai, Miyaki 980-8574 (Japan); Pinlaor, Somchai [Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 (Thailand); Hiraku, Yusuke; Oikawa, Shinji; Murata, Mariko [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 (Japan); Kawanishi, Shosuke, E-mail: kawanisi@suzuka-u.ac.jp [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 (Japan)

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Inflammation by Barrett's esophagus (BE) is a risk factor of its adenocarcinoma (BEA). Black-Right-Pointing-Pointer 8-Nitroguanine and 8-oxodG are inflammation-related DNA lesions. Black-Right-Pointing-Pointer DNA lesions and iNOS expression were higher in the order, BEA > BE > normal tissues. Black-Right-Pointing-Pointer Proton pump inhibitors suppress DNA damage by increasing Mn-SOD via Nrf2 activation. Black-Right-Pointing-Pointer DNA lesions can be useful biomarkers to predict risk of BEA in BE patients. -- Abstract: Barrett's esophagus (BE), an inflammatory disease, is a risk factor for Barrett's esophageal adenocarcinoma (BEA). Treatment of BE patients with proton pump inhibitors (PPIs) is expected to reduce the risk of BEA. We performed an immunohistochemical study to examine the formation of nitrative and oxidative DNA lesions, 8-nitroguanine and 8-oxo-7,8-dihydro-2 Prime -deoxygaunosine (8-oxodG), in normal esophageal, BE with pre- and post-treatment by PPIs and BEA tissues. We also observed the expression of an oxidant-generating enzyme (iNOS) and its transcription factor NF-{kappa}B, an antioxidant enzyme (Mn-SOD), its transcription factor (Nrf2) and an Nrf2 inhibitor (Keap1). The immunoreactivity of DNA lesions was significantly higher in the order of BEA > BE > normal tissues. iNOS expression was significantly higher in the order of BEA > BE > normal tissues, while Mn-SOD expression was significantly lower in the order of BEA < BE < normal tissues. Interestingly, Mn-SOD expression and the nuclear localization of Nrf2 were significantly increased, and the formation of DNA lesions was significantly decreased in BE tissues after PPIs treatment for 3-6 months. Keap1 and iNOS expression was not significantly changed by the PPIs treatment in BE tissues. These results indicate that 8-nitroguanine and 8-oxodG play a role in BE-derived BEA. Additionally, PPIs treatment may trigger the activation and

  10. A Patient on Long-Term Proton Pump Inhibitors Develops Sudden Seizures and Encephalopathy: An Unusual Presentation of Hypomagnesaemia

    Directory of Open Access Journals (Sweden)

    Nirav Y. Gandhi

    2012-01-01

    Full Text Available Objective. To present an unusual but known cause of hypomagnesaemia induced-hypocalcaemia in a chronic GORD patient with severe symptoms with a review of the current literature. Methods. Analysis of the clinical and laboratory findings of the patient and discussion of the multi-factorial nature of his disease and the underlying mechanisms. Results. Our patient described features of magnesium deficiency such as weakness, muscle twitches, and fits with clinical signs of hypocalcaemia: a carpal pedal spasm and paraesthesia. Preadmission blood results revealed low calcium and magnesium levels. He was admitted to ITU, when he presented with seizures and developed encephalopathy. The total vitamin D level was 52.4 nmol/L (>49.9. His U&Es and LFTs were within the normal range with the exception of potassium. He was on Omeprazole for his GORD. With omission of the PPI 1 day after admission and replacement therapy, his ion levels normalised. Conclusion. Hypomagnesaemia is often undiagnosed and is associated with multiple biochemical abnormalities. Treatment focus should be aimed at stopping the PPI and replacing the magnesium. Over use of PPIs is a problem in practice, with the FDA issuing a warning over long-term use. Continued monitoring and decision making on dose reduction/withdrawal is essential to avoid complications.

  11. Outcomes in patients with nonerosive reflux disease treated with a proton pump inhibitor and alginic acid ± glycyrrhetinic acid and anthocyanosides

    Directory of Open Access Journals (Sweden)

    Di Pierro F

    2013-03-01

    Full Text Available Francesco Di Pierro,1 Mario Gatti,2 Giuliana Rapacioli,3 Leandro Ivaldi4 1Velleja Research, Milan, 2Gastroenterology Department, Giussano Hospital, Monza-Brianza, 3AIOR, Piacenza, 4Digestive Endoscopic Department, Ceva Hospital, Ceva, Cuneo, Italy Background: The purpose of this study was to compare the efficacy of alginic acid alone versus alginic acid combined with low doses of pure glycyrrhetinic acid and bilberry anthocyanosides as an addon to conventional proton pump inhibitor therapy in relieving symptoms associated with nonerosive reflux disease. Methods: This prospective, randomized, 8-week, open-label trial was conducted at two centers. Sixty-three patients with persistent symptoms of gastroesophageal reflux disease and normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A (n = 31 were treated with pantoprazole and a formula (Mirgeal® containing alginic acid and low doses of pure glycyrrhetinic acid + standardized Vaccinium myrtillus extract for 4 weeks, then crossed over to the multi-ingredient formula for a further 4 weeks. Patients in group B (n = 32 were treated pantoprazole and alginic acid alone twice daily, then crossed over to alginic acid twice daily for a further 4 weeks. Efficacy was assessed by medical evaluation of a symptom relief score, estimated using a visual analog scale (0–10. Side effects, tolerability, and compliance were also assessed. Results: Of the 63 patients enrolled in the study, 58 (29 in group A and 29 in group B completed the 8-week trial. The baseline characteristics were comparable between the two groups. During the study, significant differences were recorded in symptom scores for both groups. In group A, symptoms of chest pain, heartburn, and abdominal swelling were less serious than in group B. Treatment A was better tolerated, did not induce hypertension, and had fewer side effects than treatment B. No significant differences in compliance were found between the

  12. High-doses of proton pump inhibitors in refractory gastro-intestinal cancer: A case series and the state of art.

    Science.gov (United States)

    Falcone, Rosa; Roberto, Michela; D'Antonio, Chiara; Romiti, Adriana; Milano, Annalisa; Onesti, Concetta Elisa; Marchetti, Paolo; Fais, Stefano

    2016-12-01

    In recent years, proton pump inhibitors (PPIs) have been investigated at high-dose to modulate tumour microenvironment acidification thus restoring chemotherapeutic sensitivity. Moreover, several clinical data supports the role of cytotoxic drugs at low-dose continuously delivered as anticancer therapy. Clinical records of three patients affected with gastrointestinal cancer refractory to standard treatments, who had received a combination of high-dose rabeprazole and metronomic chemotherapy were reviewed. The first case, a 78-year-old man was treated for lung metastasis from colon adenocarcinoma. The second case, a 73-year-old man was treated for metastatic rectal cancer to the liver. The third one, a 68-year-old man, underwent the combination regimen for colon cancer with lung, liver and peritoneal metastases. Despite the failure of previous standard chemotherapy for metastatic disease, good clinical outcome was shown in these patients treated with an unconventional association of high-dose PPIs and metronomic chemotherapy. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. Comparing omeprazole with fluoxetine for treatment of patients with heartburn and normal endoscopy who failed once daily proton pump inhibitors: double-blind placebo-controlled trial.

    Science.gov (United States)

    Ostovaneh, M R; Saeidi, B; Hajifathalian, K; Farrokhi-Khajeh-Pasha, Y; Fotouhi, A; Mirbagheri, S S; Emami, H; Barzin, G; Mirbagheri, S A

    2014-05-01

    Patients with heartburn but without esophageal erosion respond less well to proton pump inhibitors (PPIs). There is a growing body of evidence implicating the role of psychological comorbidities in producing reflux symptoms. Pain modulators improve symptoms in patients with other functional gastrointestinal disorders. We aimed to compare the efficacy of fluoxetine with omeprazole and placebo to achieve symptomatic relief in patients with heartburn and normal endoscopy who failed once daily PPIs. Endoscopy-negative patients with heartburn who failed once daily PPIs were randomly allocated to receive 6 weeks treatment of fluoxetine, omeprazole, or placebo. Random allocation was stratified according to ambulatory pH monitoring study. Percentage of heartburn-free days and symptom severity was assessed. Sixty patients with abnormal and 84 patients with normal pH test were randomized. Subjects receiving fluoxetine experienced more improvement in percentage of heartburn-free days (median 35.7, IQR 21.4-57.1) than those on omeprazole (median 7.14, IQR 0-50, p heartburn-free days (median improvement, 57.1, IQR 35.7-57.1 vs 13.9, IQR, 0-45.6 and 7.14, 0-23.8, respectively, p heartburn and normal endoscopy who failed once daily PPIs. The superiority of fluoxetine was mostly attributed to those with normal esophageal pH rather than those with abnormal pH (ClinicalTrials.gov, number NCT01269788). © 2014 John Wiley & Sons Ltd.

  14. Prevalence of gastro-esophageal reflux disease in patients with difficult to control asthma and effect of proton pump inhibitor therapy on asthma symptoms, reflux symptoms, pulmonary function and requirement for asthma medications.

    Science.gov (United States)

    Sandur, V; Murugesh, M; Banait, V; Rathi, P M; Bhatia, S J; Joshi, J M; Kate, A

    2014-01-01

    The hypothesis that GER can trigger or exacerbate asthma is supported by several clinical trials that have shown amelioration in asthma symptoms and/or an improvement in pulmonary function after antireflux therapy. To investigate the prevalence of GER in patients with difficult to control asthma and to determine the effect of omeprazole on asthma symptoms, reflux symptoms, pulmonary function and on the requirement of asthma medications. Patients with difficult to control asthma were recruited into the study. All patients underwent esophageal manometry and 24 hour esophageal pH monitoring. Pulmonary function tests were done before and after treatment. The severity of asthma and reflux was assessed by a 1 week pulmonary symptom score(PSS) and reflux symptom score(RSS) respectively before and after treatment. Those who had an abnormal pH study (pH 5% of the time) underwent anti-GER treatment with lifestyle changes, and a proton pump inhibitor (omeprazole 40 mg, bid) for 3 months. Asthma medications were added or deleted based on severity of asthma. Out of 250 asthmatic patients screened, forty patients fulfilled the inclusion criteria. Twenty eight of 40 patients(70%) were diagnosed to have GERD. Of the patients 28 with GER, 8 patients(28.5%) had no reflux symptoms. On 24 hr pH metry, the percentage time pH reflux symptom score(RSS) improved from 22.39 ± 14.99 to 1.04 ± 1.07, pulmonary symptom score(PSS) improved from 27.14 ± 7.49 to 13.82 ± 4.21 and night time asthma symptom score(NASS) improved from 6.71 ± 1.80 to 3.04 ± 1.23 (p-value <0.0001). After treatment, FEV1 and PEFR increased from 1.38 ± 0.57 and 4.14 ± 1.97 to 1.47 ± 0.54 and 5.56 ± 1.72, respectively (p-value 0.00114). PPI therapy improves nocturnal asthma symptoms, daytime asthma symptoms, pulmonary function and decreases requirement of asthma medications in these patients.

  15. Comparative effectiveness and acceptability of the FDA-licensed proton pump inhibitors for erosive esophagitis: A PRISMA-compliant network meta-analysis.

    Science.gov (United States)

    Li, Mei-Juan; Li, Qing; Sun, Min; Liu, Li-Qin

    2017-09-01

    This study compared the effectiveness and acceptability of all Food and Drug Administration (FDA)-recommended dose proton pump inhibitors (PPIs) in erosive esophagitis (EE): Dexlansoprazole 60 mg, Esomeprazole 40 mg, Esomeprazole 20 mg, Pantoprazole 40 mg, Lansoprazole 30 mg, Rabeprazole 20 mg, Omeprazole 20 mg. A systematic literature search was performed using PubMed, Embase, and Cochrane Library. Totally, 25 randomized controlled trials (RCTs) met study selection criteria and were incorporated in this network meta-analysis (NMA) study. For the NMA, eligible RCTs of adults with EE verified by endoscopic examination were randomly assigned to the licensed PPIs at least 4 weeks of continuous therapy. The primary efficacy outcome was the endoscopic healing rates at 4 and 8 weeks. Heartburn relief rates were a secondary efficacy outcome. The rates of withdrawal were analyzed as a safety outcome. In comparison to the common comparator omeprazole 20 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [odds ratio (OR), 1.46 (95% confidence interval, 95% CI, 1.24-1.71)] and 8 weeks [1.58 (1.29-1.92)], and improved the heartburn relief rates [1.29 (1.07-1.56)]. In comparison to lansoprazole 30 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [1.30 (1.10-1.53)] and 8 weeks [1.37 (1.13-1.67)], and improved the heartburn relief rates [1.29 (1.03-1.62)]. In terms of acceptability, only dexlansoprazole 60 mg had significantly more all-cause discontinuation than omeprazole 20 mg [1.54 (1.03-2.29)], pantoprazole 40 mg [1.68 (1.08-2.63)], and lansoprazole 30 mg [1.38 (1.02-1.88)]. The standard-dose esomeprazole 40 mg had more superiority in mucosal erosion healing and heartburn relief. Esomeprazole 40 mg, pantoprazole 40 mg, esomeprazole 20 mg, and lansoprazole 30 mg showed more benefits in effectiveness and acceptability than other interventions.

  16. Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors

    Directory of Open Access Journals (Sweden)

    Rushikesh Sable

    2015-06-01

    Full Text Available Blocking protein-protein interactions (PPI using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers.

  17. Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors.

    Science.gov (United States)

    Sable, Rushikesh; Jois, Seetharama

    2015-06-23

    Blocking protein-protein interactions (PPI) using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers.

  18. PPI therapy is equally effective in well-defined non-erosive reflux disease and in reflux esophagitis: a meta-analysis

    NARCIS (Netherlands)

    Weijenborg, P. W.; Cremonini, F.; Smout, A. J. P. M.; Bredenoord, A. J.

    2012-01-01

    Background Symptomatic response to proton pump inhibitor (PPI) therapy in patients with non-erosive reflux disease (NERD) is often reported as lower than in patients with erosive reflux disease (ERD). However, the definition of NERD differs across clinical trials. This meta-analysis aims to estimate

  19. Esophageal Motility and Rikkunshito Treatment for Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease: A Prospective, Uncontrolled, Open-Label Pilot Study Trial

    Directory of Open Access Journals (Sweden)

    Takeo Odaka, MD, PhD

    2017-01-01

    Conclusions: In the pilot study, patients with PPI-refractory NERD had disorders of esophageal and lower esophageal sphincter motility that were improved by RKT. Further studies examining esophageal motor activity of RKT in PPI-refractory NERD are required. University hospital Medical Information Network (UMIN Clinical Trial Registry identifier: UMIN000003092.

  20. Evaluación del uso de los inhibidores de la bomba de protones en un servicio de medicina interna Assessing the use of proton pump inhibitors in an internal medicine department

    Directory of Open Access Journals (Sweden)

    E. Martín-Echevarría

    2008-02-01

    Full Text Available Introducción: los inhibidores de la bomba de protones (IBP bloquean la enzima H+/K+ ATPasa en las células parietales gástricas, logrando la inhibición de la secreción de ácido clorhídrico de forma basal como tras estimulación. Las indicaciones apropiadas para su uso son: enfermedad por reflujo gastroesofágico, hemorragia digestiva aguda, úlceras activas, gastritis o esofagitis erosiva, dispepsia, gastropatía por AINE, profilaxis de úlcera de estrés en pacientes de riesgo. El objetivo del estudio fue la revisión de las indicaciones de los IBP en nuestro medio y la evaluación de su utilización en el Hospital Universitario de Guadalajara. Material y métodos: se realizó un estudio de corte transversal analítico con selección aleatoria de los pacientes atendidos en el Servicio de Medicina Interna durante todo el año 2003. Se revisaron un total de 208 historias de 832 pacientes (un 25% a los que se administraron IBP. La edad media fue de 67 años (rango 16-92, el 46,2% fueron mujeres y las enfermedades subyacentes más frecuentes fueron: HTA, EPOC y DM. Resultados: un 34,6% de los pacientes tomaban IBP antes del ingreso. De estos, el 68,1% no tenía indicación. Durante el ingreso se prescribió de forma inadecuada el IBP al 73,07% y al alta, se mantenía el IBP sin indicación correcta. Conclusiones: los resultados están en concordancia con los anteriormente publicados, manteniéndose una alta frecuencia de uso incorrecto de los IBP y siendo recomendable una utilización más racional para evitar los efectos secundarios, las interacciones con otros fármacos y aportar una atención médica más eficiente.Introduction: proton pump inhibitors (PPIs block the H+/K+ ATPase enzyme in gastric wall cells, leading to an inhibition of both baseline and stimulated acid secretion. Appropriate indications include: Gastroesophageal reflux, acute upper gastrointestinal bleeding, erosive gastritis or esophagitis, dyspepsia, NSAID

  1. Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease

    Science.gov (United States)

    Penagini, Roberto; Sweis, Rami; Mauro, Aurelio; Domingues, Gerson; Vales, Andres; Sifrim, Daniel

    2015-01-01

    Background/Aims The diagnosis of functional heartburn is important for management, however it stands on fragile pH monitoring variables, ie, acid exposure time varies from day to day and symptoms are often few or absent. Aim of this study was to investigate consistency of the diagnosis of functional heartburn in subsequent days using prolonged wireless pH monitoring and its impact on patients’ outcome. Methods Fifty proton pump inhibitotor refractory patients (11 male, 48 years [range, 38–57 years]) with a diagnosis of functional heart-burn according to Rome III in the first 24 hours of wireless pH monitoring were reviewed. pH variables were analysed in the following 24-hour periods to determine if tracings were indicative of diagnosis of non-erosive reflux disease (either acid exposure time > 5% or normal acid exposure time and symptom index ≥ 50%). Outcome was assessed by review of hospital files and/or telephone interview. Results Fifteen out of 50 patients had a pathological acid exposure time after the first day of monitoring (10 in the second day and 5 in subsequent days), which changed their diagnosis from functional heartburn to non-erosive reflux disease. Fifty-four percent of non-erosive reflux disease vs 11% of functional heartburn patients (P heartburn patients (P heartburn at 24-hour pH-monitoring can be re-classified as non-erosive reflux disease after a more prolonged pH recording period. This observation has a positive impact on patients’ management. PMID:25843078

  2. Solid-phase extraction combined with dispersive liquid-liquid microextraction and chiral liquid chromatography-tandem mass spectrometry for the simultaneous enantioselective determination of representative proton-pump inhibitors in water samples.

    Science.gov (United States)

    Zhao, Pengfei; Deng, Miaoduo; Huang, Peiting; Yu, Jia; Guo, Xingjie; Zhao, Longshan

    2016-09-01

    This report describes, for the first time, the simultaneous enantioselective determination of proton-pump inhibitors (PPIs-omeprazole, lansoprazole, pantoprazole, and rabeprazole) in environmental water matrices based on solid-phase extraction combined with dispersive liquid-liquid microextraction (SPE-DLLME) and chiral liquid chromatography-tandem mass spectrometry. The optimized results of SPE-DLLME were obtained with PEP-2 column using methanol-acetonitrile (1/1, v/v) as elution solvent, dichloroethane, and acetonitrile as extractant and disperser solvent, respectively. The separation and determination were performed using reversed-phase chromatography on a cellulose chiral stationary phase, a Chiralpak IC (250 mm × 4.6 mm, 5 μm) column, under isocratic conditions at 0.6 mL min(-1) flow rate. The analytes were detected in multiple reaction monitoring (MRM) mode by triple quadrupole mass spectrometry. Isotopically labeled internal standards were used to compensate matrix interferences. The method provided enrichment factors of around 500. Under optimal conditions, the mean recoveries for all eight enantiomers from the water samples were 89.3-107.3 % with 0.9-10.3 % intra-day RSD and 2.3-8.1 % inter-day RSD at 20 and 100 ng L(-1) levels. Correlation coefficients (r (2)) ≥ 0.999 were achieved for all enantiomers within the range of 2-500 μg L(-1). The method detection and quantification limits were at very low levels, within the range of 0.67-2.29 ng L(-1) and 2.54-8.68 ng L(-1), respectively. This method was successfully applied to the determination of the concentrations and enantiomeric fractions of the targeted analytes in wastewater and river water, making it applicable to the assessment of the enantiomeric fate of PPIs in the environment. Graphical Abstract Simultaneous enantioselective determination of representative proton-pump inhibitors in water samples.

  3. Proton Pumps: Mechanism of Action and Applications

    Science.gov (United States)

    Lanyi, Janos K.; Pohorille, Andrew; DeVincenzi, Donald L. (Technical Monitor)

    2001-01-01

    Recent progress in understanding molecular structures and mechanisms of action of proton pumps has paved the way to their novel applications in biotechnology. Proton pumps, in particular bacteriorhodopsin and ATP synthases, are capable of continuous, renewable conversion of light to chemical, mechanical or electrical energy, which can be used in macro- or nano-scale devices. The capability of protein systems incorporated into liposomes to generate ATP, which can be further used to drive chemical reactions, and to act as molecular motors has been already demonstrated. Other possible applications of such biochemical devices include targeted drug delivery and biocatalytic re actors. All these devices might prove superior to their inorganic alternatives.

  4. Proton pump inhibition and cancer therapeutics: A specific tumor targeting or it is a phenomenon secondary to a systemic buffering?

    Science.gov (United States)

    Spugnini, Enrico; Fais, Stefano

    2017-04-01

    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. Proton exchangers do not allow intracellular acidification through a continuous elimination of H+ either outside the cells or within the internal vacuoles. This article wants to comment a translational process through that led to the preclinical demonstration that a class of proton pump inhibitors (PPI) exploited worldwide for peptic ulcer treatment and gastroprotection are indeed powerful chemosensitizers as well. In this process we achieved the clinical proof of concept that PPI may well be included in new anti-cancer strategies with a solid background and rationale. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The purified ATPase from chromaffin granule membranes is an anion-dependent proton pump.

    Science.gov (United States)

    Moriyama, Y; Nelson, N

    1987-07-05

    The proton-ATPase of chromaffin granules was purified so as to maintain its proton-pumping activity when reconstituted into phospholipid vesicles. The purification procedure involved solubilization with polyoxyethylene 9 lauryl ether, hydroxylapatite column, precipitation by ammonium sulfate, and glycerol gradient centrifugation. The protease inhibitor mixture used in previous studies inhibited the proton-pumping activity of the enzyme; therefore, the protein was stabilized by pepstatin A and leupeptin. The enzyme was purified at least 50-fold with respect to both ATPase and proton-pumping activity. The ATP-dependent proton uptake activity of the reconstituted enzyme was absolutely dependent on the presence of Cl- or Br- outside the vesicles, whereas sulfate, acetate, formate, nitrate, and thiocyanate were inhibitory. Sulfate inhibition seems to be due to competition with Cl- on the anion-binding site outside the vesicles, whereas nitrate and thiocyanate inhibited only from the internal side. As with the inhibition by N-ethylmaleimide, the proton-pumping activity was much more sensitive to nitrate than the ATPase activity. About 20 mM nitrate were sufficient for 90% inhibition of the proton-pumping activity while 100 mM inhibited only 50% of the ATPase activity both in situ and in the reconstituted enzyme. The possible regulatory effect of anions on the ATP-dependent proton uptake in secretory granules is discussed.

  6. Intrinsic uncoupling of mitochondrial proton pumps. 2. Modeling studies.

    Science.gov (United States)

    Pietrobon, D; Zoratti, M; Azzone, G F; Caplan, S R

    1986-02-25

    The thermodynamic and kinetic properties associated with intrinsic uncoupling in a six-state model of a redox proton pump have been studied by computing the flow-force relations for different degrees of coupling. Analysis of these relations shows the regulatory influence of the thermodynamic forces on the extent and relative contributions of redox slip and proton slip. Inhibition has been introduced into the model in two different ways, corresponding to possible modes of action of experimental inhibitors. Experiments relating the rate of electron transfer to delta microH at static head upon progressive inhibition of the pumps have been simulated considering (1) the limiting case that the nonzero rate of electron transfer at static head is only due to intrinsic uncoupling (no leaks) and (2) the experimentally observed case that about 30% of the nonzero rate of electron transfer at static head is due to a constant proton leakage conductance in parallel with the pumps, the rest being due to intrinsic uncoupling. The same simulations have been performed for experiments in which the rate of electron transfer is varied by varying the substrate concentration rather than by using an inhibitor. The corresponding experimental results obtained by measuring delta microH and the rate of electron transfer at different succinate concentrations in rat liver mitochondria are presented. Comparison between simulated behavior and experimental results leads to the general conclusion that the typical relationship between rate of electron transfer and delta microH found in mitochondria at static head could certainly be a manifestation of some degree of intrinsic uncoupling in the redox proton pumps.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Inhibitor candidates's identification of HCV's RNA polymerase NS5B using virtual screening against iPPI-library

    Science.gov (United States)

    Sulistyawati, Indah; Sulistyo Dwi K., P.; Ichsan, Mochammad

    2016-03-01

    Hepatitis C is one of the major causes of chronic liver failure that caused by Hepatitis C Virus (HCV). Preventing the progression of HCV's replication through the inhibition of The RNA polymerase NS5B of Hepatitis C virus (NS5B) can be achieved via 4 binding regions: Site I (Thumb I), Site II (Thumb II), Site III (Palm I), and Site IV (Palm II). The aim of this research is to identify a candidate of NS5B inhibitor as an alternative for Hepatitis C treatment. An NS5B's 3D structure (PDB ID = 3D5M) used in this study has met some criteria of a good model to be used in virtual screening againts iPPI-lib using MTiOpenScreen webserver. The top two natural compounds resulted here then docked using Pyrix 0.8 and discovered trans-6-Benzamido-2-methyldecahydroisoquinoline (-9,1kcal/mol) and 2,4-dichloro-5-[4-(2 methoxyphenyl) piperazine-1-carbonyl]-N-[3-(trifluoromethyl)phenyl] benzenesulfonamide (9,4 kcal/mol) can bind to Tyr448 similar with all three established inhibitors, such as setrobuvir (-11,4 kcal/mol; site 3 inhibitor), CHEMBL379677 (-9,1 kcal/mol; site 1 inhibitor), and nesbuvir (-7,7 kcal/mol; site 4 inhibitor). The results of this study are relatively still needs to be tested, both in vitro and in vivo, in order to obtain more comprehensive knowledges as a follow-up of this predictive study.

  8. Reflux parameters as modified by laparoscopic fundoplication in 40 patients with heartburn/regurgitation persisting despite PPI therapy: a study using impedance-pH monitoring.

    Science.gov (United States)

    Frazzoni, Marzio; Conigliaro, Rita; Melotti, Gianluigi

    2011-04-01

    Patients with typical reflux symptoms (heartburn/regurgitation) persisting despite proton pump inhibitor (PPI) therapy are not uncommon. Impedance-pH monitoring detects gastroesophageal reflux at all pH levels and may establish if ongoing symptoms on PPI therapy are associated with acid/nonacid reflux. Laparoscopic fundoplication is a therapeutic option in such patients but reflux parameters on PPI therapy and after intervention and their relationship with symptom persistence/remission have been scarcely studied. The aim of this study was to assess reflux parameters and their relationship with symptoms before and after laparoscopic fundoplication, on and off PPI therapy, respectively, in patients with PPI-unresponsive heartburn/regurgitation and with a positive symptom-reflux association and/or abnormal reflux parameters detected on PPI therapy. Impedance-pH monitoring was performed on high-dose PPI therapy and 3 months after laparoscopic fundoplication, off PPI therapy, in 40 patients with PPI-unresponsive heartburn/regurgitation. Symptoms were scored by a validated questionnaire. Esophageal acid exposure time as well as the number of total and proximal reflux events and of acid and weakly acidic refluxes decreased significantly after surgery: normal values were found in 100, 77, 95, 92 and 65% of cases, respectively. Weakly alkaline refluxes increased significantly postoperatively but neither before nor after intervention were associated with symptoms. All patients reported total/subtotal remission of heartburn/regurgitation 3 months after surgery. Laparoscopic fundoplication improves acid and weakly acidic reflux parameters when compared with PPI therapy. This improvement justifies the very high post-surgical symptom remission rate that we observed. Prolonged follow-up is warranted but our findings strongly support the surgical option in PPI failures.

  9. Crystal structure of the plasma membrane proton pump

    DEFF Research Database (Denmark)

    Pedersen, Bjørn P.; Buch-Pedersen, Morten Jeppe; Morth, J. Preben

    2007-01-01

    A prerequisite for life is the ability to maintain electrochemical imbalances across biomembranes. In all eukaryotes the plasma membrane potential and secondary transport systems are energized by the activity of P-type ATPase membrane proteins: H1-ATPase (the proton pump) in plants and fungi1......-3, and Na1,K1-ATPase (the sodium-potassium pump) in animals4. The name P-type derives from the fact that these proteins exploit a phosphorylated reaction cycle intermediate of ATP hydrolysis5.The plasma membrane proton pumps belong to the type III P-type ATPase subfamily, whereas Na1,K1-ATPase and Ca21......- ATPase are type II6. Electron microscopy has revealed the overall shape of proton pumps7, however, an atomic structure has been lacking. Here we present the first structure of a P-type proton pump determined by X-ray crystallography. Ten transmembrane helices and three cytoplasmic domains define...

  10. Proton Pump Inhibition Increases Rapid Eye Movement Sleep in the Rat

    Directory of Open Access Journals (Sweden)

    Munazah Fazal Qureshi

    2014-01-01

    Full Text Available Increased bodily CO2 concentration alters cellular pH as well as sleep. The proton pump, which plays an important role in the homeostatic regulation of cellular pH, therefore, may modulate sleep. We investigated the effects of the proton pump inhibitor “lansoprazole” on sleep-wakefulness. Male Wistar rats were surgically prepared for chronic polysomnographic recordings. Two different doses of lansoprazole (low: 1 mg/kg; high: 10 mg/kg were injected intraperitoneally in the same animal (n=7 and sleep-wakefulness was recorded for 6 hrs. The changes in sleep-wakefulness were compared statistically. Percent REM sleep amount in the vehicle and lansoprazole low dose groups was 9.26±1.03 and 9.09±0.54, respectively, which increased significantly in the lansoprazole high dose group by 31.75% (from vehicle and 34.21% (from low dose. Also, REM sleep episode numbers significantly increased in lansoprazole high dose group. Further, the sodium-hydrogen exchanger blocker “amiloride” (10 mg/kg; i.p. (n=5 did not alter sleep-wake architecture. Our results suggest that the proton pump plays an important role in REM sleep modulation and supports our view that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep.

  11. Proton pump inhibitors in gastroesophageal reflux disease: a custom-tailored therapeutic regimen Diseñando un traje a la medida: los inhibidores de la bomba de protones en la enfermedad por reflujo gastroesofágico

    Directory of Open Access Journals (Sweden)

    Sergio Sobrino-Cossío

    2012-07-01

    Full Text Available The Montreal Definition and Classification divides Gastroesophageal Reflux Disease (GERD into esophageal symptomatic syndromes (and with mucosal damage and extraesophageal syndromes (with acid established association and proposed association. In typical GERD symptoms, an 8-week treatment with PPIs is satisfactory in most cases (> 90%. Response rates to PPIs in GERD are highly variable, as they also rely on an appropriate clinical diagnosis of the disease; endoscopy differentiates the macroscopic GERD phenotype. The non-erosive variety (50-70% prevalence has a different symptomatic response rate, as gastric acid is not the sole etiology of symptoms. The possible explanations of treatment failure include treatment adherence, PPI metabolism alterations and characteristics, and inadequate diagnosis. Refractory symptoms are related to gastric content neutralization by the chronic use of PPIs. Extraesophageal manifestations are associated with other pathophysiological mechanisms where an autonomic nervous system disturbance gives rise to symptoms. In these clinical entities, the relationship between symptoms and acid needs to be established in order to determine the use of PPIs, or consider other drugs. In other words, so as to "custom-tailor the best-fitting therapy" we need to answer the questions for whom, for what, how and for how long. Finally, PPI safety and tolerability are factors to be considered in elderly patients requiring chronic PPI use, who usually have chronic concomitant illnesses.La Clasificación de Montreal divide la enfermedad por reflujo gastro-esofágico (ERGE en síndromes esofágicos sintomáticos y con daño a la mucosa y en síndromes extraesofágicos con asociación establecida al ácido y asociación propuesta. En síntomas ERGE típicos el tratamiento con inhibidores de la bomba de protones (IBP es satisfactorio (> 90% a 8 semanas en la mayoría de los casos. Las tasas de respuesta a los IBP en la ERGE son muy variables

  12. Lansoprazole and carbonic anhydrase IX inhibitors sinergize against human melanoma cells.

    Science.gov (United States)

    Federici, Cristina; Lugini, Luana; Marino, Maria Lucia; Carta, Fabrizio; Iessi, Elisabetta; Azzarito, Tommaso; Supuran, Claudiu T; Fais, Stefano

    2016-01-01

    Proton Pump Inhibitors (PPIs) reduce tumor acidity and therefore resistance of tumors to drugs. Carbonic Anhydrase IX (CA IX) inhibitors have proven to be effective against tumors, while tumor acidity might impair their full effectiveness. To analyze the effect of PPI/CA IX inhibitors combined treatment against human melanoma cells. The combination of Lansoprazole (LAN) and CA IX inhibitors (FC9-399A and S4) has been investigated in terms of cell proliferation inhibition and cell death in human melanoma cells. The combination of these inhibitors was more effective than the single treatments in both inhibiting cell proliferation and in inducing cell death in human melanoma cells. These results represent the first successful attempt in combining two different proton exchanger inhibitors. This is the first evidence on the effectiveness of a new approach against tumors based on the combination of PPI and CA IX inhibitors, thus providing an alternative strategy against tumors.

  13. Protons and how they are transported by proton pumps

    DEFF Research Database (Denmark)

    Buch-Pedersen, Morten Jeppe; Pedersen, Bjørn Panyella; Nissen, Poul

    2008-01-01

    molecular components that allow the plasma membrane proton H(+)-ATPase to carry out proton transport against large membrane potentials. When divergent proton pumps such as the plasma membrane H(+)-ATPase, bacteriorhodopsin, and F(O)F(1) ATP synthase are compared, unifying mechanistic premises for biological...... proton pumps emerge. Most notably, the minimal pumping apparatus of all pumps consists of a central proton acceptor/donor, a positively charged residue to control pK (a) changes of the proton acceptor/donor, and bound water molecules to facilitate rapid proton transport along proton wires....

  14. Quantifying esophagogastric junction contractility with a novel HRM topographic metric, the EGJ-Contractile Integral: normative values and preliminary evaluation in PPI non-responders.

    Science.gov (United States)

    Nicodème, F; Pipa-Muniz, M; Khanna, K; Kahrilas, P J; Pandolfino, J E

    2014-03-01

    Despite its obvious pathophysiological relevance, the clinical utility of measures of esophagogastric junction (EGJ) contractility is unsubstantiated. High-resolution manometry (HRM) may improve upon this with its inherent ability to integrate the magnitude of contractility over time and length of the EGJ. This study aimed to develop a novel HRM metric summarizing EGJ contractility and test its ability distinguish among subgroups of proton pump inhibitor non-responders (PPI-NRs). 75 normal controls and 88 PPI-NRs were studied. All underwent HRM. PPI-NRs underwent pH-impedance monitoring on PPI therapy scored in terms of acid exposure, number of reflux events, and reflux-symptom correlation and grouped as meeting all criteria, some criteria, or no criteria of abnormality. Control HRM studies were used to establish normal values for candidate EGJ contractility metrics, which were then compared in their ability to differentiate among PPI-NR subgroups. The EGJ contractile integral (EGJ-CI), a metric integrating contractility across the EGJ for three respiratory cycles, best distinguished the All Criteria PPI-NR subgroup from controls and other PPI-NR subgroups. Normal values (median, [IQR]) for this measure were 39 mmHg-cm [25-55 mmHg-cm]. The correlation between the EGJ-CI and a previously proposed metric, the lower esophageal sphincter-pressure integral, that used a fixed 10 s time frame and an atmospheric as opposed to gastric pressure reference was weak. Among HRM metrics tested, the EGJ-CI was best in distinguishing PPI-NRs meeting all criteria of abnormality on pH-impedance testing. Future prospective studies are required to explore its utility in management of broader groups of gastroesophageal reflux disease patients. © 2013 John Wiley & Sons Ltd.

  15. Pancreatic bicarbonate secretion involves two proton pumps.

    Science.gov (United States)

    Novak, Ivana; Wang, Jing; Henriksen, Katrine L; Haanes, Kristian A; Krabbe, Simon; Nitschke, Roland; Hede, Susanne E

    2011-01-07

    Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium express H(+)/HCO(3)(-) transporters, which depend on gradients created by the Na(+)/K(+)-ATPase. However, the model cannot fully account for high-bicarbonate concentrations, and other active transporters, i.e. pumps, have not been explored. Here we show that pancreatic ducts express functional gastric and non-gastric H(+)-K(+)-ATPases. We measured intracellular pH and secretion in small ducts isolated from rat pancreas and showed their sensitivity to H(+)-K(+) pump inhibitors and ion substitutions. Gastric and non-gastric H(+)-K(+) pumps were demonstrated on RNA and protein levels, and pumps were localized to the plasma membranes of pancreatic ducts. Quantitative analysis of H(+)/HCO(3)(-) and fluid transport shows that the H(+)-K(+) pumps can contribute to pancreatic secretion in several species. Our results call for revision of the bicarbonate transport physiology in pancreas, and most likely other epithelia. Furthermore, because pancreatic ducts play a central role in several pancreatic diseases, it is of high relevance to understand the role of H(+)-K(+) pumps in pathophysiology.

  16. Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD.

    Science.gov (United States)

    Mukaisho, Ken-ichi; Hagiwara, Tadashi; Nakayama, Takahisa; Hattori, Takanori; Sugihara, Hiroyuki

    2014-09-14

    The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). Diluted human plasma and bile acids have been found to be significant chemoattractants and chemorepellents, respectively, for the bacillus H. pylori. Although only taurine conjugates, with a pKa of 1.8-1.9, are soluble in an acidic environment, glycine conjugates, with a pKa of 4.3-5.2, as well as taurine-conjugated bile acids are soluble in the presence of PPI therapy. Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface. H. pylori may then colonize in the stomach body rather than in the pyloric antrum, which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD.

  17. Inappropriate prescribing of proton pump inhibitors among patients ...

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved. ... marketing surveillance indicate that PPIs are safe and well ... consumer-oriented advertising [17]. Based on this, the ..... evaluate the prescription behavior of these ... afford a basis to establish strategies for.

  18. Inappropriate prescribing of proton pump inhibitors among patients ...

    African Journals Online (AJOL)

    By comparing the patients according to their site of care, 52.4 % (43/82) of ICU patients compared to 87.4 % (97/111) of medically hospitalized patient (non-ICU) were inappropriately receiving PPIs (p = 0.000). Conclusion: Adherence to the current practice guidelines for safe prescription of PPIs is poor. Thus, updating ...

  19. Proton-pump inhibitors | Naidoo | South African Family Practice

    African Journals Online (AJOL)

    South African Family Practice. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 57, No 3 (2015) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Download this PDF file. The PDF file you selected should ...

  20. Proton pump inhibitor-induced subacute cutaneous lupus erythematosus

    DEFF Research Database (Denmark)

    Sandholdt, L H; Laurinaviciene, R; Bygum, Anette

    2014-01-01

    Drug-induced subacute cutaneous lupus erythematosus (SCLE) has been known in the literature since 1985 and is increasingly recognized.......Drug-induced subacute cutaneous lupus erythematosus (SCLE) has been known in the literature since 1985 and is increasingly recognized....

  1. Factors affecting Helicobacter pylori eradication using a seven-day triple therapy with a proton pump inhibitor, tinidazole and clarithromycin, in brazilian patients with peptic ulcer Fatores que afetam a erradicação do Helicobacter pylori usando um tratamento triplo de sete dias com um inibidor de bomba de prótons associado ao tinidazol e a claritromicina, em pacientes brasileiros com úlcera péptica

    Directory of Open Access Journals (Sweden)

    Fernando Marcuz Silva

    2001-01-01

    Full Text Available Triple therapy is accepted as the treatment of choice for H. pylori eradication. In industrialized countries, a proton pump inhibitor plus clarithromycin and amoxicillin or nitroimidazole have shown the best results. Our aims were: 1. To study the eradication rate of the association of a proton pump inhibitor plus tinidazole and clarithromycin on H. pylori infection in our population. 2. To determine if previous treatments, gender, age, tobacco, alcohol use, and non-steroidal anti-inflammatory drugs (NSAIDs change the response to therapy. METHODS: Two hundred patients with peptic ulcer (upper endoscopy and H. pylori infection (histology and rapid urease test - RUT were included. A proton pump inhibitor (lansoprazole 30 mg or omeprazole 20 mg, tinidazole 500 mg, and clarithromycin 250 mg were dispensed twice a day for a seven-day period. Eradication was assessed after 10 to 12 weeks of treatment through histology and RUT. RESULTS: The eradication rate of H. pylori per protocol was 65% (128/196 patients. This rate was 53% for previously treated patients, rising to 76% for not previously treated patients, with a statistical difference pO esquema tríplice tem sido demonstrado como sendo o melhor tratamento para a erradicação do Helicobacter pylori. Nos países industrializados o uso de um inibidor de bomba de prótons associado a claritromicina e a amoxicilina ou a um nitroimidazólico, tem proporcionado os melhores resultados. Objetivamos estudar na nossa população a taxa de erradicação do H. pylori para a associação de um inibidor de bomba de prótons com o tinidazol e a claritromicina e determinar se a resposta ao tratamento é influenciada pelo tratamento prévio, sexo, tabagismo, alcoolismo, idade e uso de anti-inflamatórios não esteroidais (AINEs. PACIENTES E PROCEDIMENTOS: Duzentos pacientes com diagnóstico endoscópico de úlcera péptica e com infecção pelo H. pylori, confirmada pelo exame histológico e pelo teste rápido da

  2. Collateral sensitivity between aminoglycosides and beta-lactam antibiotics depends on active proton pumps.

    Science.gov (United States)

    Azimi, Leila; Rastegar Lari, Abdolaziz

    2017-11-01

    Selection inversion is the hypothesis for antibiotic resistant inhabitation in bacteria and collateral sensitivity is one of the proposed phenomena for achievement of this hypothesis. The presence of collateral sensitivity associated with the proton motivation pump between the aminoglycosides and beta-lactam group of antibiotics is one of the examples of collateral sensitivity in some studies. The aim of this study was to demonstrate that collateral sensitivity between aminoglycosides and beta-lactam antibiotics associated with proton motivation pump may not be true in all cases. In this study, 100 Pseudomonas aeruginosa were surveyed. Gentamicin and imipenem-resistant strains were confirmed by disc diffusion method and MIC. Active proton motivation pumps were screened by pumps inhibitor. Semi-quantitative Real-Time PCR assay was used to confirm gene overexpression. Seventy-six and 79 out of 100 strains were resistant to gentamicin and imipenem, respectively. Seventy-five strains were resistant to both gentamicin and imipenem. The results of proton pump inhibitor test showed the involvement of active proton motivation pump in 22 of 75 imipenem- and gentamicin-resistant strains. According to Real - Time PCR assay, mexX efflux gene was overexpressed in the majority of isolates tested. The collateral sensitivity effect cannot explain the involvement of active proton motivation pumps in both imipenem and gentamicin-resistant strains simultaneously. Active and/or inactive proton pump in gentamicin-sensitive and/or resistant strains cannot be a suitable example for explanation of collateral sensitivity between aminoglycosides and beta-lactam antibiotics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Ionic Polymer Microactuator Activated by Photoresponsive Organic Proton Pumps

    Directory of Open Access Journals (Sweden)

    Khaled M. Al-Aribe

    2015-10-01

    Full Text Available An ionic polymer microactuator driven by an organic photoelectric proton pump transducer is described in this paper. The light responsive transducer is fabricated by using molecular self-assembly to immobilize oriented bacteriorhodopsin purple membrane (PM patches on a bio-functionalized porous anodic alumina (PAA substrate. When exposed to visible light, the PM proton pumps produce a unidirectional flow of ions through the structure’s nano-pores and alter the pH of the working solution in a microfluidic device. The change in pH is sufficient to generate an osmotic pressure difference across a hydroxyethyl methacrylate-acrylic acid (HEMA-AA actuator shell and induce volume expansion or contraction. Experiments show that the transducer can generate an ionic gradient of 2.5 μM and ionic potential of 25 mV, producing a pH increase of 0.42 in the working solution. The ΔpH is sufficient to increase the volume of the HEMA-AA microactuator by 80%. The volumetric transformation of the hydrogel can be used as a valve to close a fluid transport micro-channel or apply minute force to a mechanically flexible microcantilever beam.

  4. Histomorphological differentiation of non-erosive reflux disease and functional heartburn in patients with PPI-refractory heartburn.

    Science.gov (United States)

    Kandulski, A; Jechorek, D; Caro, C; Weigt, J; Wex, T; Mönkemüller, K; Malfertheiner, P

    2013-09-01

    Proton pump inhibitor (PPI)-refractory heartburn may be due to persistent gastro-oesophageal reflux, oesophageal hypersensitivity or functional heartburn (FH). The differentiation between non-erosive reflux disease (NERD) and FH may be very difficult. However, this differentiation is important for appropriate therapeutic management. Dilated intercellular spaces (DIS), papillary elongation (PE) and basal cell hyperplasia (BCH) can be all assessed by light microscopy. Whether these mucosal abnormalities allow the differentiation of NERD from FH in PPI-refractory patients is uncertain. To assess histopathological findings by light microscopy in patients with refractory heartburn to differentiate NERD from FH. Sixty-two patients with PPI-refractory symptoms underwent EGD and MII-pH after pausing PPI medication for 2 weeks before investigation. Twenty-five subjects without upper gastrointestinal symptoms were included as controls. Symptom assessment was based on the reflux disease questionnaire (RDQ). Biopsies were taken 3-5 cm above the gastro-oesophageal junction. DIS, PE, BCH and infiltration of immune cells were evaluated and a sum score was calculated. Based on endoscopy and MII-pH, GERD was diagnosed in 43 patients (NERD: 20; ERD: 23) and FH in 19 patients. There was no difference in symptoms between the groups. Each individual histopathological item was different between the groups (P < 0.0001). Between NERD and FH, the most significant difference was found for DIS and the histopathological sum score (P < 0.001). These findings suggest that oesophageal biopsies are useful to differentiate NERD from FH. Increased DIS and a histological sum score are the most significant histopathological abnormalities in NERD as compared with FH. © 2013 John Wiley & Sons Ltd.

  5. Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report.

    Science.gov (United States)

    Choi, Seong Ji; Kim, Hyo Jung; Kim, Jae Seon; Bak, Young-Tae; Kim, Jun Suk

    2016-08-02

    Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient's symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted.

  6. Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report

    International Nuclear Information System (INIS)

    Choi, Seong Ji; Kim, Hyo Jung; Kim, Jae Seon; Bak, Young-Tae; Kim, Jun Suk

    2016-01-01

    Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient’s symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted

  7. Protons and how they are transported by proton pumps

    DEFF Research Database (Denmark)

    Buch-Pedersen, Morten Jeppe; Pedersen, Bjørn Panyella; Veierskov, Bjarke

    2008-01-01

    The very high mobility of protons in aqueous solutions demands special features of membrane proton transporters to sustain efficient yet regulated proton transport across biological membranes. By the use of the chemical energy of ATP, plasma-membrane-embedded ATPases extrude protons from cells...... of plants and fungi to generate electrochemical proton gradients. The recently published crystal structure of a plasma membrane H(+)-ATPase contributes to our knowledge about the mechanism of these essential enzymes. Taking the biochemical and structural data together, we are now able to describe the basic...... molecular components that allow the plasma membrane proton H(+)-ATPase to carry out proton transport against large membrane potentials. When divergent proton pumps such as the plasma membrane H(+)-ATPase, bacteriorhodopsin, and F(O)F(1) ATP synthase are compared, unifying mechanistic premises for biological...

  8. Early marginal ulcer following Roux-en-Y gastric bypass under proton pump inhibitor treatment: prospective multicentric study Úlcera perianastomótica após derivação gástrica em Y-de-Roux mesmo em uso de inibidor de bomba de prótons: estudo prospectivo multicêntrico

    Directory of Open Access Journals (Sweden)

    Arthur Belarmino Garrido Jr.

    2010-06-01

    Full Text Available CONTEXT: Causal factors of gastrojejunal ulcers after Roux-en-Y gastric bypass include peptic acid secretion from the gastric pouch. Esomeprazole is a potent inhibitor of acid secretion. OBJECTIVE: To assess the occurrence of dyspepsia and gastrojejunal ulcers within the first 2 months after Roux-en-Y gastric bypass during the use of esomeprazole. METHODS: One hundred eighteen morbid obese subjects were submitted to Roux-en-Y gastric bypass. Preoperative upper gastrointestinal tract endoscopy was negative for H. pylori. All subjects received esomeprazole for 60 days after surgery. RESULTS: Two weeks after surgery only 13 mild symptoms were reported. After 2 months, 17 also moderate complaints were registered. Endoscopy around the 60th day showed esophagitis in 10 (8.5%, hiatal hernia in 2 (1.7%, foreign body in the anastomotic line in 12 (10.2% and gastrojejunal ulcers was observed in 9 (7.6% subjects, 2 of which had a suture material or metallic staple granuloma in the gastrojejunostomy. Ten subjects took nonsteroidal anti-inflammatory drugs at least once during study, but none of them developed ulcer. None of the subjects with ulcer had dyspeptic symptoms. CONCLUSION: The incidence of ulcer in the gastrojejunal anastomosis within the first 2 months following Rouxen-Y gastric bypass under proton pump inhibitors is considerable. It was not related to the use of non-steroidal anti-inflammatory drugs, highlighting the possibility of ischemia and foreign body as causal factors. The ulcers were asymptomatic, and all post-surgical dyspeptic symptoms were moderate in severity.CONTEXTO: Sintomas dispépticos são comuns após derivação gástrica em Y-de-Roux. Podem decorrer de úlceras de boca anastomótica, cujos possíveis fatores causais incluem a secreção cloridropéptica da bolsa gástrica, isquemia, efeito de corpo estranho dos materiais de sutura e uso de antiinflamatórios não-esteróides. O esomeprazol é um redutor potente da secre

  9. Prediction of response to PPI therapy and factors influencing treatment outcome in patients with GORD: a prospective pragmatic trial using pantoprazole

    Directory of Open Access Journals (Sweden)

    Tholen Anne

    2011-05-01

    Full Text Available Abstract Background Management of patients with gastro-oesophageal reflux disease (GORD can be assisted by information predicting the likely response to proton pump inhibitor (PPI treatment. The aim was to undertake a study of GORD patients designed to approximate ordinary clinical practice that would identify patient characteristics predicting symptomatic response to pantoprazole treatment. Methods 1888 patients with symptoms of GORD were enrolled in a multicentre, multinational, prospective, open study of 8 weeks pantoprazole treatment, 40 mg daily. Response was assessed by using the ReQuest™ questionnaire, by the investigator making conventional clinical enquiry and by asking patients about their satisfaction with symptom control. Factors including pre-treatment oesophagitis, gender, age, body mass index (BMI, Helicobacter pylori status, anxiety and depression, and concurrent IBS symptoms were examined using logistic regression to determine if they were related to response, judged from the ReQuest™-GI score. Results Poorer treatment responses were associated with non-erosive reflux disease, female gender, lower BMI, anxiety and concurrent irritable bowel syndrome symptoms before treatment. No association was found with age, Helicobacter pylori status or oesophagitis grade. Some reflux-related symptoms were still present in 14% of patients who declared themselves 'well-satisfied' with their symptom control. Conclusions Some readily identifiable features help to predict symptomatic responses to a PPI and consequently may help in managing patient expectation. ClinicalTrial.gov identifier: NCT00312806.

  10. RADAR PPI Scope Overlay

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — RADAR PPI Scope Overlays are used to position a RADAR image over a station at the correct resolution. The archive maintains several different RADAR resolution types,...

  11. A Comparison of Alkaline Water and Mediterranean Diet vs Proton Pump Inhibition for Treatment of Laryngopharyngeal Reflux.

    Science.gov (United States)

    Zalvan, Craig H; Hu, Shirley; Greenberg, Barbara; Geliebter, Jan

    2017-10-01

    Laryngopharyngeal reflux (LPR) is a common disorder with protean manifestations in the head and neck. In this retrospective study, we report the efficacy of a wholly dietary approach using alkaline water, a plant-based, Mediterranean-style diet, and standard reflux precautions compared with that of the traditional treatment approach of proton pump inhibition (PPI) and standard reflux precautions. To determine whether treatment with a diet-based approach with standard reflux precautions alone can improve symptoms of LPR compared with treatment with PPI and standard reflux precautions. This was a retrospective medical chart review of 2 treatment cohorts. From 2010 to 2012, 85 patients with LPR that were treated with PPI and standard reflux precautions (PS) were identified. From 2013 to 2015, 99 patients treated with alkaline water (pH >8.0), 90% plant-based, Mediterranean-style diet, and standard reflux precautions (AMS) were identified. The outcome was based on change in Reflux Symptom Index (RSI). Recorded change in the RSI after 6 weeks of treatment. Of the 184 patients identified in the PS and AMS cohorts, the median age of participants in each cohort was 60 years (95% CI, 18-82) and 57 years (95% CI, 18-93), respectively (47 [56.3%] and 61 [61.7%] were women, respectively). The percentage of patients achieving a clinically meaningful (≥6 points) reduction in RSI was 54.1% in PS-treated patients and 62.6% in AMS-treated patients (difference between the groups, 8.05; 95% CI, -5.74 to 22.76). The mean reduction in RSI was 27.2% for the PS group and 39.8% in the AMS group (difference, 12.10; 95% CI, 1.53 to 22.68). Our data suggest that the effect of PPI on the RSI based on proportion reaching a 6-point reduction in RSI is not significantly better than that of alkaline water, a plant-based, Mediterranean-style diet, and standard reflux precautions, although the difference in the 2 treatments could be clinically meaningful in favor of the dietary approach. The

  12. Meta-analyses: does long-term PPI use increase the risk of gastric premalignant lesions?

    Science.gov (United States)

    Eslami, Layli; Nasseri-Moghaddam, Siavosh

    2013-08-01

    Proton pump inhibitors (PPIs) are the most effective agents available for reducing acid secretion. They are used for medical treatment of various acid-related disorders. PPIs are used extensively and for extended periods of time in gastroesophageal reflux disease (GERD). A troublesome issue regarding maintenance therapy has been the propensity of PPI-treated patients to develop chronic atrophic gastritis while on therapy that could theoretically lead to an increased incidence of gastric cancer. In addition, animal studies have raised concern for development of enterochromaffin-like cell hyperplasia and carcinoid tumors in the stomachs of mice receiving high dose PPIs. Current literature does not provide a clear-cut conclusion on the subject and the reports are sometimes contradictory. Therefore, this study is a systematic review of the available literature to address the safety of long-term PPI use and its relation to the development of malignant/premalignant gastric lesions. A literature search of biomedical databases was performed. The reference lists of retrieved articles were reviewed to further identify relevant trials. We hand-searched the abstracts of the American Digestive Disease Week (DDW) and the United European Gastroenterology Week (UEGW) from 1995 to 2013. Only randomized clinical trials (RCTs) that used PPIs as the primary treatment for at least six month versus no treatment, placebo, antacid or anti-reflux surgery (ARS) were included. Two reviewers independently extracted the data. Discrepancies in the interpretation were resolved by consensus. All analyses of outcomes were based on the intention-to-treat principle. We performed statistical analysis using Review Manager software. The effect measure of choice was relative risk (RR) for dichotomous data. Six RCTs with a total of 785 patients met the inclusion criteria. Two multicenter RCTs compared Esomeprazole with placebo. One RCT compared omeprazole with ARS. Two RCTs compared omeprazole with

  13. Nitric oxide contributes to minerals absorption, proton pumps and hormone equilibrium under cadmium excess in Trifolium repens L. plants.

    Science.gov (United States)

    Liu, Shiliang; Yang, Rongjie; Pan, Yuanzhi; Ma, Mingdong; Pan, Jiang; Zhao, Yan; Cheng, Qingsu; Wu, Mengxi; Wang, Maohua; Zhang, Lin

    2015-09-01

    Nitric oxide (NO) is a stress-signaling molecule in plants that mediates a wide range of physiological processes and responses to metal toxicity. In this work, various NO modulators (NO donor: SNP; NO scavenger: cPTIO; NO synthase inhibitor: l-NAME; and SNP analogs: sodium nitrite/nitrate and sodium ferrocyanide) were investigated to determine the role of NO in Trifolium repens L. plants exposed to Cd. Cd (100μM) markedly reduced biomass, NO production and chlorophyll (Chl a, Chl b and total Chl) concentration but stimulated reactive oxygen species (ROS) and Cd accumulation in plants. SNP (50μM) substantially attenuated growth inhibition, reduced hydrogen peroxide (H2O2) and malonyldialdehyde (MDA) levels, stimulated ROS-scavenging enzymes/agents, and mitigated the H(+)-ATPase inhibition in proton pumps. Interestingly, SNP considerably up-regulated the levels of jasmonic acid (JA) and proline in plant tissues but down-regulated the levels of ethylene (ET) in both shoots and roots and the level of salicylic acid (SA) in roots only, which might be related to the elevated NO synthesis. Additionally, SNP (25-200μM) regulated mineral absorption and, particularly at 50μM, significantly enhanced the uptake of shoot magnesium (Mg) and copper (Cu) and of root calcium (Ca), Mg and iron (Fe). Nevertheless, the effects of SNP on plant growth were reversed by cPTIO and l-NAME, suggesting that the protective effect of SNP might be associated with NO synthesis in vivo. Moreover, SNP analogs did not display roles similar to that of SNP. These results indicated that NO depleted Cd toxicity by eliminating oxidative damage, enhancing minerals absorption, regulating proton pumps, and maintaining hormone equilibrium. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Optical silencing of C. elegans cells with light-driven proton pumps.

    Science.gov (United States)

    Okazaki, Ayako; Takahashi, Megumi; Toyoda, Naoya; Takagi, Shin

    2014-08-01

    Recent development of optogenetic techniques, which utilize light-driven ion channels or ion pumps for controlling the activity of excitable cells, has greatly facilitated the investigation of nervous systems in vivo. A new generation of optical silencers includes outward-directed proton pumps, such as Arch, which have several advantages over currently widely used halorhodopsin (NpHR). These advantages include the resistance to inactivation during prolonged illumination and the ability to generate a larger optical current from low intensity light. C. elegans, with its small transparent body and well-characterized neural circuits, is especially suitable for optogenetic analyses. In this article, we will outline the practical aspects of using of Arch and other proton pumps as optogenetic tools in C. elegans. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Proton Pump for O-2 Reduction Catalyzed by 5,10,15,20-Tetraphenylporphyrinatocobalt(II)

    Czech Academy of Sciences Publication Activity Database

    Partovi-Nia, R.; Su, B.; Li, F.; Gros, C. P.; Barbe, J.-M.; Samec, Zdeněk; Girault, H. H.

    2009-01-01

    Roč. 15, č. 10 (2009), s. 2335-2340 ISSN 0947-6539 R&D Projects: GA MŠk OC 177; GA ČR(CZ) GA203/07/1257 Institutional research plan: CEZ:AV0Z40400503 Keywords : cobalt * ferrocenes * hydrogen peroxide * oxygen reduction * proton pump Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.382, year: 2009

  16. Proton-pumping rhodopsins are abundantly expressed by microbial eukaryotes in a high-Arctic fjord.

    Science.gov (United States)

    Vader, Anna; Laughinghouse, Haywood D; Griffiths, Colin; Jakobsen, Kjetill S; Gabrielsen, Tove M

    2018-02-01

    Proton-pumping rhodopsins provide an alternative pathway to photosynthesis by which solar energy can enter the marine food web. Rhodopsin genes are widely found in marine bacteria, also in the Arctic, and were recently reported from several eukaryotic lineages. So far, little is known about rhodopsin expression in Arctic eukaryotes. In this study, we used metatranscriptomics and 18S rDNA tag sequencing to examine the mid-summer function and composition of marine protists (size 0.45-10 µm) in the high-Arctic Billefjorden (Spitsbergen), especially focussing on the expression of microbial proton-pumping rhodopsins. Rhodopsin transcripts were highly abundant, at a level similar to that of genes involved in photosynthesis. Phylogenetic analyses placed the environmental rhodopsins within disparate eukaryotic lineages, including dinoflagellates, stramenopiles, haptophytes and cryptophytes. Sequence comparison indicated the presence of several functional types, including xanthorhodopsins and a eukaryotic clade of proteorhodopsin. Transcripts belonging to the proteorhodopsin clade were also abundant in published metatranscriptomes from other oceanic regions, suggesting a global distribution. The diversity and abundance of rhodopsins show that these light-driven proton pumps play an important role in Arctic microbial eukaryotes. Understanding this role is imperative to predicting the future of the Arctic marine ecosystem faced by a changing light climate due to diminishing sea-ice. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  17. Functional dissection of the proton pumping modules of mitochondrial complex I.

    Directory of Open Access Journals (Sweden)

    Stefan Dröse

    2011-08-01

    Full Text Available Mitochondrial complex I, the largest and most complicated proton pump of the respiratory chain, links the electron transfer from NADH to ubiquinone to the pumping of four protons from the matrix into the intermembrane space. In humans, defects in complex I are involved in a wide range of degenerative disorders. Recent progress in the X-ray structural analysis of prokaryotic and eukaryotic complex I confirmed that the redox reactions are confined entirely to the hydrophilic peripheral arm of the L-shaped molecule and take place at a remarkable distance from the membrane domain. While this clearly implies that the proton pumping within the membrane arm of complex I is driven indirectly via long-range conformational coupling, the molecular mechanism and the number, identity, and localization of the pump-sites remains unclear. Here, we report that upon deletion of the gene for a small accessory subunit of the Yarrowia complex I, a stable subcomplex (nb8mΔ is formed that lacks the distal part of the membrane domain as revealed by single particle analysis. The analysis of the subunit composition of holo and subcomplex by three complementary proteomic approaches revealed that two (ND4 and ND5 of the three subunits with homology to bacterial Mrp-type Na(+/H(+ antiporters that have been discussed as prime candidates for harbouring the proton pumps were missing in nb8mΔ. Nevertheless, nb8mΔ still pumps protons at half the stoichiometry of the complete enzyme. Our results provide evidence that the membrane arm of complex I harbours two functionally distinct pump modules that are connected in series by the long helical transmission element recently identified by X-ray structural analysis.

  18. Stimulation by ATP of proinsulin to insulin conversion in isolated rat pancreatic islet secretory granules. Association with the ATP-dependent proton pump

    International Nuclear Information System (INIS)

    Rhodes, C.J.; Lucas, C.A.; Mutkoski, R.L.; Orci, L.; Halban, P.A.

    1987-01-01

    Isolated rat pancreatic islets were pulse-labeled for 5 min with [ 3 H]leucine then chased for 25 min, during which time endogenously labeled [ 3 H]proinsulin becomes predominantly compartmented in immature secretory granules. The islets were then homogenized in isotonic sucrose (pH 7.4) and a beta-granule preparation obtained by differential centrifugation and discontinuous sucrose gradient ultracentrifugation. This preparation was enriched 8-fold in beta-granules. Aside from contamination with mitochondria and a limited number of lysosomes, the beta-granule preparation was essentially free of any other organelles involved in proinsulin synthesis and packaging (i.e. microsomal elements and, more particularly, Golgi complex). Conversion of endogenously labeled [ 3 H]proinsulin was followed in this beta-granule fraction for up to 2 h at 37 degrees C in a buffer (pH 7.3) that mimicked the cationic constituents of B-cell cytosol, during which time 92% of the beta-granules remained intact. Proinsulin conversion was analyzed by high performance liquid chromatography. The rate of proinsulin conversion to insulin was stimulated by 2.2 +/- 0.1-fold (n = 6) (at a 60-min incubation) in the presence of ATP (2 mM) and an ATP regenerating system compared to beta-granule preparations incubated without ATP. This ATP stimulation was abolished in the presence of beta-granule proton pump ATPase inhibitors (tributyltin, 2.5 microM, or 1,3-dicyclohexylcarbodiimide, 50 microM). Inhibitors of mitochondrial proton pump ATPases had no effect on the ATP stimulation of proinsulin conversion. When granules were incubated in a more acidic buffer, proinsulin conversion was increased relative to that at pH 7.3. At pH 5.5, ATP no longer stimulated conversion, and tributyltin and 1,3-dicyclohexylcarbodiimide had no effect

  19. Conformational change during photocycle of bacteriorhodopsin and its proton-pumping mechanism.

    Science.gov (United States)

    Chou, K C

    1993-06-01

    Based on the recent finding on the structural difference of seven helix bundles in the all-trans and 13-cis bacteriorhodopsins, the distances among the key groups performing the function of proton translocation as well as their microenvironments have been investigated. Consequently, a pore-gated model was proposed for the light-driven proton-pumping mechanism of bacteriorhodopsin. According to this model, the five double-bounded polyene chain in retinal chromophore can be phenomenologically likened to a molecular "lever," whose one end links to a "piston" (the beta-ionone ring) and the other end to a pump "relay station" (the Schiff base). During the photocycle of bacteriorhodopsin, the molecular "lever" is moving up and down as marked by the position change of the "piston," so as to trigger the gate of pore to open and close alternately. When the "piston" is up, the pore-controlled gate is open so that the water channel from Asp-96 to the Schiff base and that from the Schiff base to Asp-85 is established; when the "piston" is down, the pore-controlled gate is closed and the water channels for proton transportation in both the cytoplasmic half and extracellular half are blocked. The current model allows a consistent interpretation of a great deal of experimental data and also provides a useful basis for further investigating the mechanism of proton pumping by bacteriorhodopsin.

  20. Piston-assisted proton pumping in Complex I of mitochondria membranes

    Science.gov (United States)

    Mourokh, Lev; Filonenko, Ilan

    2014-03-01

    Proton-pumping mechanism of Complex I remains mysterious because its electron and proton paths are well separated and the direct Coulomb interaction seems to be negligible. The structure of this enzyme was resolved very recently and its functionality was connected the shift of the helix HL. We model the helix as a piston oscillating between the protons and electrons. We assume that positive charges are accumulated near the edges of the helix. In the oxidized state, the piston is attracted to electrons, so its distance to the proton sites increases, the energy of these sites decreases and the sites can be populated. When electrons proceed to the drain, elastic forces return the piston to the original position and the energies of populated proton sites increase, so the protons can be transferred to the positive site of the membrane. In this work, we explore a simplified model when the interaction of the piston with electrons is replaced by a periodic force. We derive quantum Heisenberg equations for the proton operators and solve them jointly with the Langevin equation for the piston position. We show that the proton pumping is possible in such structure with parameters closely resembling the real system. We also address the feasibility of using such mechanism in nanoelectronics.

  1. MODULATION OF GROWTH AND PROTON PUMPING ATPase ACTIVITY OF PROBIOTIC Lactobacilli BY DIETARY CUCURBITS

    Directory of Open Access Journals (Sweden)

    Irfan Ahmad

    2013-12-01

    Full Text Available Gastrointestinal tract predominantly harbor probiotic Lactobacilli which exert beneficial effects on human health. Aqueous extracts from fruits of Lagenaria siceraria (Ls, Luffa cylindrica (Lc and Cucurbita maxima (Cm were prepared and lyophilized. Fruit extracts were investigated for their effects on Lactobacillus rhamnosus (L. rhamnosus, Lactobacillus plantarum (L. plantarum and Lactobacillus acidophilus (L. acidophilus. Extracts were found to enhance growth of Lactobacilli without any toxic effect (up to 1000µg/mL concentration. Minimum concentration of extracts at which growth of probiotic strains were found to be enhanced significantly were determined (103.67 µg/mL-118µg/mL and considered as effective concentration (EC or growth stimulatory concentration (GSC. Proton pumping ATPase activity of Lactobacilli were examined and found to be enhanced significantly (29.89- 61.96% in extracts treated probiotics (Lactobacilli as compared to the normal control. Inulin used as positive control and found to enhance the proton efflux activity (28.06-37.72% with respect to the control. These dietary cucurbits enhance metabolic activity of probiotic Lactobacilli by modulating their proton pumping ATPase mechanism. This study suggested that the consumption of cucurbit fruits might be a natural source of enhancing the activities of probiotic Lactobacilli in the gut.

  2. Design and Use of a Proton Pump Inhibitor Case to Integrate Physiology, Pharmacology, and Biochemistry

    Science.gov (United States)

    Lee, Michael W.

    2014-01-01

    The use of drugs to integrate basic and clinical sciences is frequently used in a lecture format, but the availability of alternative pedagogical approaches that address higher-order learning are not widely available. The use of case studies and case-based projects to reinforce lectures can help link basic and clinical disciplines and promote…

  3. Effect of baseline characteristics on response to proton pump inhibitors in patients with peptic ulcer bleeding.

    Science.gov (United States)

    Lau, James; Lind, Tore; Persson, Tore; Eklund, Stefan

    2017-02-01

    The rate of rebleeding from peptic ulcers could differ between Asian and Western populations. This study aimed to determine whether the observed twofold difference in rebleeding rates in two similarly designed clinical trials (one in Hong Kong [n = 240], the other in a predominantly Western population [n = 764, ClinicalTrials.gov identifier: NCT00251979]) can be explained by differences in baseline patient characteristics. Two-factor and multifactor analyses (adjusted by demographics, established risk factors for peptic ulcer and peptic ulcer bleeding, and disease severity variables) were performed using pooled data from the two studies. Cox regression analysis was used to predict the rebleeding risk at 3 days. In the two-factor analysis (placebo vs esomeprazole/omeprazole and Western study vs Hong Kong study), data trended towards a reduced risk of rebleeding in the Western study (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.44-1.07, P = 0.094). The risk of rebleeding was similar in both studies after adjusted for multiple factors (HR 1.10, 95% CI 0.60-1.99, P = 0.767). The strongest predictor of rebleeding (apart from study drug) was a classification of American Society of Anesthesiologists (ASA) grade IV (HR 4.15, 95% CI 1.49-11.56, P = 0.006). When such patients were excluded, the difference in rebleeding rates between the studies reduced. The difference in rebleeding rates between the two studies is explained by the factors in our analysis, most importantly a classification of ASA grade IV, suggesting that other differences, including ethnicity, did not influence the rebleeding rate. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  4. Rapidly increasing prescribing of proton pump inhibitors in primary care despite interventions

    DEFF Research Database (Denmark)

    Haastrup, Peter; Paulsen, Maja Skov; Zwisler, Jon Eik

    2014-01-01

    Background: Guideline and reimbursement modifications have been introduced to optimize prescribing of antisecretory medication in Danish general practice. Impacts of the interventions have not been evaluated. Objectives: To analyse developments in prescribing of antisecretory medication in Denmark...... increased substantially during the past decade. Both number of users and the average individual use have increased. The prescribing of ulcerogenic drugs to the elderly has stagnated in the same time range. Reimbursement modifications and scientific guidelines do not seem to have had a substantial influence...

  5. Use of bicarbonate buffer systems for dissolution characterization of enteric-coated proton pump inhibitor tablets.

    Science.gov (United States)

    Shibata, Hiroko; Yoshida, Hiroyuki; Izutsu, Ken-Ichi; Goda, Yukihiro

    2016-04-01

    The aim of this study was to assess the effects of buffer systems (bicarbonate or phosphate at different concentrations) on the in vitro dissolution profiles of commercially available enteric-coated tablets. In vitro dissolution tests were conducted using an USP apparatus II on 12 enteric-coated omeprazole and rabeprazole tablets, including innovator and generic formulations in phosphate buffers, bicarbonate buffers and a media modified Hanks (mHanks) buffer. Both omeprazole and rabeprazole tablets showed similar dissolution profiles among products in the compendial phosphate buffer system. However, there were large differences between products in dissolution lag time in mHanks buffer and bicarbonate buffers. All formulations showed longer dissolution lag times at lower concentrations of bicarbonate or phosphate buffers. The dissolution rank order of each formulation differed between mHanks buffer and bicarbonate buffers. A rabeprazole formulation coated with a methacrylic acid copolymer showed the shortest lag time in the high concentration bicarbonate buffer, suggesting varied responses depending on the coating layer and buffer components. Use of multiple dissolution media during in vitro testing, including high concentration bicarbonate buffer, would contribute to the efficient design of enteric-coated drug formulations. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

  6. Rapidly increasing use of proton pump inhibitors prescribed in primary care: a nationwide observational study

    DEFF Research Database (Denmark)

    Haastrup, Peter; Hansen, Jane Møller; Jarbøl, Dorte Ejg

    2013-01-01

    Background: Antisecretory drugs (ADs) are often prescribed in primary care for upper gastrointestinal symptoms. Reimbursement modifications have been made in Denmark to minimize costs related to use of ADs. However knowledge about development in use of ADs over the past decade and the impacts...... of the reimbursement modifications is sparse. Research questions: How has use of ADs developed in Denmark 2001-2011? Which impacts have the reimbursement modifications had on the use of ADs? Methods: The Register of Medicinal Product Statistics includes all sales and redeemed prescriptions nationwide covering...... through the years 2001-2011 were used. Data from prescriptions redeemed by persons younger than 20 years were excluded. Prescriptions for ulcerogenic drugs (acetylsalicylic acid and non-steroidal anti-inflammatory drugs) redeemed by persons aged 65 years and older were included since ulcer prophylaxis...

  7. Towards structural and functional analysis of the plant plasma membrane proton pump

    DEFF Research Database (Denmark)

    Justesen, Bo Højen

    The plasma membrane H+-ATPase is a proton pump essential for several physiological important processes in plants. Through the extrusion of protons from the cell, the PM H+-ATPase establishes and maintains a proton gradient used by proton coupled transporters and secondary active transport...... of nutrients and metabolites across the plasma membrane. Additional processes involving the PM H+-ATPase includes plant growth, development, and response to biotic and abiotic stresses. Extensive efforts have been made in attempts to elucidate the detailed physiological role and biochemical characteristics...... of plasma membrane H+-ATPases. Studies on the plasma membrane H+-ATPases have involved both in vivo and in vitro approaches, with the latter employing either solubilisation by detergent micelles, or reconstitution into lipid vesicles. Despite resulting in a large body of information on structure, function...

  8. Receptor kinase-mediated control of primary active proton pumping at the plasma membrane

    DEFF Research Database (Denmark)

    Fuglsang, Anja Thoe; Kristensen, Astrid; Cuin, Tracey A.

    2014-01-01

    Acidification of the cell wall space outside the plasma membrane is required for plant growth and is the result of proton extrusion by the plasma membrane-localized H+-ATPases. Here we show that the major plasma membrane proton pumps in Arabidopsis, AHA1 and AHA2, interact directly in vitro...... and in planta with PSY1R, a receptor kinase of the plasma membrane that serves as a receptor for the peptide growth hormone PSY1. The intracellular protein kinase domain of PSY1R phosphorylates AHA2/AHA1 at Thr-881, situated in the autoinhibitory region I of the C-terminal domain. When expressed in a yeast...... heterologous expression system, the introduction of a negative charge at this position caused pump activation. Application of PSY1 to plant seedlings induced rapid in planta phosphorylation at Thr-881, concomitant with an instantaneous increase in proton efflux from roots. The direct interaction between AHA2...

  9. Phytoremediation potential of Arabidopsis thaliana, expressing ectopically a vacuolar proton pump, for the industrial waste phosphogypsum.

    Science.gov (United States)

    Khoudi, Habib; Maatar, Yafa; Brini, Faïçal; Fourati, Amine; Ammar, Najoua; Masmoudi, Khaled

    2013-01-01

    Phosphogypsum (PG) is a by-product of the phosphorus-fertiliser industry and represents an environmental concern since it contains pollutants such as cadmium (Cd). We have recently shown that the overexpression of a proton pump gene (TaVP1) in transgenic tobacco (Nicotiana tabacum) led to an enhanced Cd tolerance and accumulation. The aim of this study was to evaluate the potential of transgenic Arabidopsis thaliana plants harbouring the TaVP1 gene to phytoremediate phosphogypsum. A pot experiment was carried out under greenhouse conditions. Transgenic A. thaliana plants harbouring the TaVP1 gene were grown on various substrates containing phosphogypsum (0, 25, 50 and 100 %) for 40 days. At the end of the growth period, we examined the growth (germination, root length, fresh weight) and physiological parameters (chlorophyll and protein contents, catalase activity and proteolysis) as well as the cadmium, Mg, Ca, and P contents of the A. thaliana plants. In order to evaluate Cd tolerance of the A. thaliana lines harbouring the TaVP1 gene, an in vitro experiment was also carried out. One week-old seedlings were transferred to Murashige and Skoog agar plates containing various concentrations of cadmium; the germination, total leaf area and root length were determined. The growth and physiological parameters of all A. thaliana plants were significantly altered by PG. The germination capacity, root growth and biomass production of wild-type (WT) plants were more severely inhibited by PG compared with the TaVP1 transgenic A. thaliana lines. In addition, TaVP1 transgenic A. thaliana plants maintained a higher antioxidant capacity than the WT. Interestingly, elemental analysis of leaf material derived from plants grown on PG revealed that the transgenic A. thaliana line accumulated up to ten times more Cd than WT. Despite its higher Cd content, the transgenic A. thaliana line performed better than the WT counterpart. In vitro evaluation of Cd tolerance showed that TaVP1

  10. A new hypothesis on the simultaneous direct and indirect proton pump mechanisms in NADH-quinone oxidoreductase (complex I).

    Science.gov (United States)

    Ohnishi, Tomoko; Nakamaru-Ogiso, Eiko; Ohnishi, S Tsuyoshi

    2010-10-08

    Recently, Sazanov's group reported the X-ray structure of whole complex I [Nature, 465, 441 (2010)], which presented a strong clue for a "piston-like" structure as a key element in an "indirect" proton pump. We have studied the NuoL subunit which has a high sequence similarity to Na(+)/H(+) antiporters, as do the NuoM and N subunits. We constructed 27 site-directed NuoL mutants. Our data suggest that the H(+)/e(-) stoichiometry seems to have decreased from (4H(+)/2e(-)) in the wild-type to approximately (3H(+)/2e(-)) in NuoL mutants. We propose a revised hypothesis that each of the "direct" and the "indirect" proton pumps transports 2H(+) per 2e(-). Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  11. Structure of a Prokaryotic Virtual Proton Pump at 3.2 Astroms Resolution

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Y.; Jayaram, H; Shane, T; Partensky, L; Wu, F; williams, C; Xiong, Y; Miller, C

    2009-01-01

    To reach the mammalian gut, enteric bacteria must pass through the stomach. Many such organisms survive exposure to the harsh gastric environment (pH 1.5-4) by mounting extreme acid-resistance responses, one of which, the arginine-dependent system of Escherichia coli, has been studied at levels of cellular physiology, molecular genetics and protein biochemistry. This multiprotein system keeps the cytoplasm above pH 5 during acid challenge by continually pumping protons out of the cell using the free energy of arginine decarboxylation. At the heart of the process is a 'virtual proton pump' in the inner membrane, called AdiC, that imports L-arginine from the gastric juice and exports its decarboxylation product agmatine. AdiC belongs to the APC superfamily of membrane proteins, which transports amino acids, polyamines and organic cations in a multitude of biological roles, including delivery of arginine for nitric oxide synthesis, facilitation of insulin release from pancreatic beta-cells, and, when inappropriately overexpressed, provisioning of certain fast-growing neoplastic cells with amino acids. High-resolution structures and detailed transport mechanisms of APC transporters are currently unknown. Here we describe a crystal structure of AdiC at 3.2 A resolution. The protein is captured in an outward-open, substrate-free conformation with transmembrane architecture remarkably similar to that seen in four other families of apparently unrelated transport proteins.

  12. Structure of a prokaryotic virtual proton pump at 3.2 Å resolution

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Yiling; Jayaram, Hariharan; Shane, Tania; Kolmakova-Partensky, Ludmila; Wu, Fang; Williams, Carole; Xiong, Yong; Miller, Christopher; (Yale); (Brandeis)

    2009-09-15

    To reach the mammalian gut, enteric bacteria must pass through the stomach. Many such organisms survive exposure to the harsh gastric environment (pH 1.5-4) by mounting extreme acid-resistance responses, one of which, the arginine-dependent system of Escherichia coli, has been studied at levels of cellular physiology, molecular genetics and protein biochemistry. This multiprotein system keeps the cytoplasm above pH 5 during acid challenge by continually pumping protons out of the cell using the free energy of arginine decarboxylation. At the heart of the process is a 'virtual proton pump' in the inner membrane, called AdiC, that imports L-arginine from the gastric juice and exports its decarboxylation product agmatine. AdiC belongs to the APC superfamily of membrane proteins, which transports amino acids, polyamines and organic cations in a multitude of biological roles, including delivery of arginine for nitric oxide synthesis, facilitation of insulin release from pancreatic {beta}-cells, and, when inappropriately overexpressed, provisioning of certain fast-growing neoplastic cells with amino acids. High-resolution structures and detailed transport mechanisms of APC transporters are currently unknown. Here we describe a crystal structure of AdiC at 3.2 {angstrom} resolution. The protein is captured in an outward-open, substrate-free conformation with transmembrane architecture remarkably similar to that seen in four other families of apparently unrelated transport proteins.

  13. Crystallographic Structure of Xanthorhodopsin, the Light-Driven Proton Pump With a Dual Chromophore

    International Nuclear Information System (INIS)

    Luecke, H.; Schobert, B.; Stagno, J.; Imasheva, E.S.; Wang, J.M.; Balashov, S.P.; Lanyi, J.K

    2008-01-01

    Homologous to bacteriorhodopsin and even more to proteorhodopsin, xanthorhodopsin is a light-driven proton pump that, in addition to retinal, contains a noncovalently bound carotenoid with a function of a light-harvesting antenna. We determined the structure of this eubacterial membrane protein-carotenoid complex by X-ray diffraction, to 1.9-(angstrom) resolution. Although it contains 7 transmembrane helices like bacteriorhodopsin and archaerhodopsin, the structure of xanthorhodopsin is considerably different from the 2 archaeal proteins. The crystallographic model for this rhodopsin introduces structural motifs for proton transfer during the reaction cycle, particularly for proton release, that are dramatically different from those in other retinal-based transmembrane pumps. Further, it contains a histidine-aspartate complex for regulating the pK a of the primary proton acceptor not present in archaeal pumps but apparently conserved in eubacterial pumps. In addition to aiding elucidation of a more general proton transfer mechanism for light-driven energy transducers, the structure defines also the geometry of the carotenoid and the retinal. The close approach of the 2 polyenes at their ring ends explains why the efficiency of the excited-state energy transfer is as high as ∼45%, and the 46 o angle between them suggests that the chromophore location is a compromise between optimal capture of light of all polarization angles and excited-state energy transfer

  14. Chimeric Proton-Pumping Rhodopsins Containing the Cytoplasmic Loop of Bovine Rhodopsin

    Science.gov (United States)

    Sasaki, Kengo; Yamashita, Takahiro; Yoshida, Kazuho; Inoue, Keiichi; Shichida, Yoshinori; Kandori, Hideki

    2014-01-01

    G-protein-coupled receptors (GPCRs) transmit stimuli to intracellular signaling systems. Rhodopsin (Rh), which is a prototypical GPCR, possesses an 11-cis retinal. Photoisomerization of 11-cis to all-trans leads to structural changes in the protein of cytoplasmic loops, activating G-protein. Microbial rhodopsins are similar heptahelical membrane proteins that function as bacterial sensors, light-driven ion-pumps, or light-gated channels. They possess an all-trans retinal, and photoisomerization to 13-cis triggers structural changes in protein. Despite these similarities, there is no sequence homology between visual and microbial rhodopsins, and microbial rhodopsins do not activate G-proteins. In this study, new chimeric proton-pumping rhodopsins, proteorhodopsin (PR) and Gloeobacter rhodopsin (GR) were designed by replacing cytoplasmic loops with bovine Rh loops. Although G-protein was not activated by the PR chimeras, all 12 GR chimeras activated G-protein. The GR chimera containing the second cytoplasmic loop of bovine Rh did not activate G-protein. However, the chimera with a second and third double-loop further enhanced G-protein activation. Introduction of an E132Q mutation slowed the photocycle 30-fold and enhanced activation. The highest catalytic activity of the GR chimera was still 3,200 times lower than bovine Rh but only 64 times lower than amphioxus Go-rhodopsin. This GR chimera showed a strong absorption change of the amide-I band on a light-minus-dark difference FTIR spectrum which could represent a larger helical opening, important for G-protein activation. The light-dependent catalytic activity of this GR chimera makes it a potential optogenetic tool for enzymatic activation by light. PMID:24621599

  15. Proton Pumping and Slippage Dynamics of a Eukaryotic P-Type ATPase Studied at the Single-Molecule Level

    DEFF Research Database (Denmark)

    Veshaguri, Salome

    In all eukaryotes the plasma membrane potential and secondary transport systems are energized by P-type ATPases whose regulation however remains poorly understood. Here we monitored at the single-molecule level the activity of the prototypic proton pumping P-type ATPase Arabidopsis thaliana isoform....... We propose that variable ATP/H+ stoichiometry emerges as a novel mechanism for adaptation when challenged with depletion of ATP that is likely relevant for other ATPases. Such measurements will provide indispensable insights into the mechanisms of function and regulation of many other ion...

  16. [Prevention of NSAID gastropathy: the difference between a coxibs and the addition of a PPI].

    Science.gov (United States)

    Lems, Willem F; Kuipers, Ernst J

    2010-01-01

    Several strategies are available for the prevention of NSAID gastropathy: the addition of misoprostol or proton pump inhibitors (PPIs) to conventional NSAIDs, or selective use of cyclo-oxygenase 2 inhibitors, the 'coxibs'. The recently published CONDOR study was a randomized trial comparing celecoxib with omeprazole in patients at high risk for NSAID gastropathy. A statistically significant reduction in the primary endpoint was found: hazard ratio: 4.3 (95% CI: 2.6-6.7; p < 0.0001). However, the reduction was largely based on a higher incidence of anaemia in the diclofenac plus omeprazole group. The study has strengths and weaknesses. The most important conclusion is that the nature of the gastro-protective effects of celecoxib and diclofenac/misoprostol are different.

  17. Active glucose transport and proton pumping in tonoplast membrane of Zea mays L. coleoptiles are inhibited by anti-H+-ATPase antibodies

    International Nuclear Information System (INIS)

    Rausch, T.; Butcher, D.N.; Taiz, L.

    1987-01-01

    A tonoplast enriched fraction was obtained from Zea mays L. coleoptiles by isopycnic centrifugation of microsomal membranes in a sucrose step gradient. At the 18/26% interface chloride-stimulated and nitrate-inhibited proton pumping activity coincided with a Mg 2+ -ATP dependent accumulation of 3-O-methyl-D-glucose (OMG) as determined by a membrane filtration technique using 14 C-labeled substrate. OMG transport showed an apparently saturable component with a K/sub m/ of 110 micromolar, and was completely inhibited by 10 micromolar carbonyl cyanide m-chlorophenylhydrazone. Polyclonal antibodies against solubilized native tonoplast H + -ATPase and its 62 and 72 kilodalton subunits were assayed for their ability to inhibit proton pumping and OMG accumulation. Antibodies against both the native enzyme and the putative catalytic subunit strongly inhibited proton pumping and OMG transport whereas antibodies against the 62 kilodalton subunit had only a slight effect on both processes

  18. Positive Darwinian selection in the piston that powers proton pumps in complex I of the mitochondria of Pacific salmon.

    Directory of Open Access Journals (Sweden)

    Michael R Garvin

    Full Text Available The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.

  19. Positive Darwinian selection in the piston that powers proton pumps in complex I of the mitochondria of Pacific salmon.

    Science.gov (United States)

    Garvin, Michael R; Bielawski, Joseph P; Gharrett, Anthony J

    2011-01-01

    The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.

  20. Positive Darwinian Selection in the Piston That Powers Proton Pumps in Complex I of the Mitochondria of Pacific Salmon

    Science.gov (United States)

    Garvin, Michael R.; Bielawski, Joseph P.; Gharrett, Anthony J.

    2011-01-01

    The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm. PMID:21969854

  1. Reduced susceptibility of Enterococcus spp. isolates from Cairo University Hospital to tigecycline: Highlight on the influence of proton pump inhibitors.

    Science.gov (United States)

    Hassan, Reem Mostafa; Ghaith, Doaa Mohammad; Ismail, Dalia Kadry; Zafer, Mai Mahmoud

    2018-03-01

    The incidence of reduced susceptibility to tigecycline (TIG) is increasing. This study aimed to analyse the in vitro activity of TIG against Enterococcus spp. isolates recovered from hospitalised patients and to evaluate the effect of omeprazole on the in vitro antimicrobial activity of TIG against several enterococcal species. A total of 67 Enterococcus clinical isolates were identified by MALDI-TOF/MS and multiplex PCR. Minimum inhibitory concentrations (MICs) of TIG alone and in combination with omeprazole (10, 30 and 60mg/L) were determined by broth microdilution. Antibiotic susceptibility to other antibiotics was determined by disk diffusion. The presence of van, tet(X) and tet(X1) genes was tested by multiplex PCR. Of the 67 Enterococcus isolates, 2 (3.0%) were resistant to TIG and 13 (19.4%) were intermediate-resistant according to EUCAST. The frequencies of resistance to norfloxacin (80.6%), doxycycline (80.6%), levofloxacin (74.6%) and ciprofloxacin (71.6%) were highest, whilst that of vancomycin (25.4%) was lowest. The vanA gene was detected in 11 Enterococcus isolates (8 Enterococcus faecalis, 3 Enterococcus faecium), vanB in 3 Enterococcus isolates (2 E. faecium, 1 E. faecalis) and vanC-2/3 in 3 Enterococcus casseliflavus. Nine isolates (13.4%) were positive for tet(X1). TIG resistance occurred both in patients receiving or not TIG and/or omeprazole. Omeprazole increased TIG MICs by 4-128-fold. The possibility of selection of TIG-non-susceptible Enterococcus in the gut may occur with long-term use of omeprazole. Omeprazole influenced TIG activity in a concentration-dependent manner. To our knowledge; this is the first report of TIG-non-susceptible Enterococcus spp. in Egypt. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  2. The comparison between proton pump inhibitors and sucralfate in incidence of ventilator associated pneumonia in critically ill patients.

    Science.gov (United States)

    Khorvash, Farzin; Abbasi, Saeed; Meidani, Mohsen; Dehdashti, Fatemeh; Ataei, Behrooz

    2014-01-01

    Ventilator associated pneumonia (VAP) are one of the most common nosocomial infections in intensive care unit (ICU). The ICU patients are at risk of stress ulcer and gastrointestinal bleeding for different reasons. In order to prevent this complication, anti acids are used for patients. This study compared pantoprazole with sucralfate in incidence of ventilator associated pneumonia. This randomized clinical trial was carried out on ICU patients with mechanical ventilation in Alzahra university hospital in Isfahan from 2010 to 2011. One hundred forty eight ventilated patients were randomly allocated in two groups. The first group was treated with sucralfate and the second group was treated with pantoprazole for stress ulcer prophylaxis and followed up during hospitalization in ICU for nosocomial pneumonia. Data analyzed by SPSS software. One hundred thirty seven patients were selected for study. During the study period, 34 cases (24.8%) acquired pneumonia, of which 10 were in the sucralfate group and 24 were in the pantoprazole group (14.1% vs. 36.4%). According to Chi-square test, rate of pneumonia was significantly lower in patients receiving sucralfate than the pantoprazole group (P < 0.001). On the basis of the results, there is a significant relationship between the kind of drug used for stress ulcer and ventilator associated pneumonia. According to this article, rate of pneumonia was significantly lower in patients receiving sucralfate than the pantoprazole group.

  3. The comparison between proton pump inhibitors and sucralfate in incidence of ventilator associated pneumonia in critically ill patients

    Directory of Open Access Journals (Sweden)

    Farzin Khorvash

    2014-01-01

    Full Text Available Background: Ventilator associated pneumonia (VAP are one of the most common nosocomial infections in intensive care unit (ICU. The ICU patients are at risk of stress ulcer and gastrointestinal bleeding for different reasons. In order to prevent this complication, anti acids are used for patients. This study compared pantoprazole with sucralfate in incidence of ventilator associated pneumonia. Materials and Methods: This randomized clinical trial was carried out on ICU patients with mechanical ventilation in Alzahra university hospital in Isfahan from 2010 to 2011. One hundred forty eight ventilated patients were randomly allocated in two groups. The first group was treated with sucralfate and the second group was treated with pantoprazole for stress ulcer prophylaxis and followed up during hospitalization in ICU for nosocomial pneumonia. Data analyzed by SPSS software. Results: One hundred thirty seven patients were selected for study. During the study period, 34 cases (24.8% acquired pneumonia, of which 10 were in the sucralfate group and 24 were in the pantoprazole group (14.1% vs. 36.4%. According to Chi-square test, rate of pneumonia was significantly lower in patients receiving sucralfate than the pantoprazole group ( P < 0.001. Conclusion: On the basis of the results, there is a significant relationship between the kind of drug used for stress ulcer and ventilator associated pneumonia. According to this article, rate of pneumonia was significantly lower in patients receiving sucralfate than the pantoprazole group.

  4. Acid and non-acid reflux in patients refractory to proton pump inhibitor therapy: is gastroparesis a factor?

    Science.gov (United States)

    Tavakkoli, Anna; Sayed, Bisma A; Talley, Nicholas J; Moshiree, Baharak

    2013-10-07

    To determine whether an increased number and duration of non-acid reflux events as measured using the multichannel intraluminal impedance pH (MII-pH) is linked to gastroparesis (GP). A case control study was conducted in which 42 patients undergoing clinical evaluation for continued symptoms of gastroesophageal reflux disease (both typical and atypical symptoms) despite acid suppression therapy. MII-pH technology was used over 24 h to detect reflux episodes and record patients' symptoms. Parameters evaluated in patients with documented GP and controls without GP by scintigraphy included total, upright, and supine number of acid and non-acid reflux episodes (pH 4, respectively), the duration of acid and non-acid reflux in a 24-h period, and the number of reflux episodes lasting longer than 5 min. No statistical difference was seen between the patients with GP and controls with respect to the total number or duration of acid reflux events, total number and duration of non-acid reflux events or the duration of longest reflux episodes. The number of non-acid reflux episodes with a pH > 7 was higher in subjects with GP than in controls. In addition, acid reflux episodes were more prolonged (lasting longer than 5 min) in the GP patients than in controls; however, these values did not reach statistical significance. Thirty-five patients had recorded symptoms during the 24 h study and of the 35 subjects, only 9% (n = 3) had a positive symptom association probability (SAP) for acid/non-acid reflux and 91% had a negative SAP. The evaluation of patients with a documented history of GP did not show an association between GP and more frequent episodes of non-acid reflux based on MII-pH testing.

  5. Superhigh-resolution 200ppi series TFT-LCDs; Chokoseisai 200ppi ekisho display series

    Energy Technology Data Exchange (ETDEWEB)

    Kawamata, K.; Hirai, H. [Toshiba Corp., Tokyo (Japan)

    2000-02-01

    We have developed a 202 pixels per inch (ppi) thin-film transistor liquid crystal display (TFT-LCD) using low-temperature polycrystalline silicon (LTPS) technology. The superhigh resolution of 202 ppi offers the same image quality as printed matter such as magazines. The 200 ppi series TFT-LCDs are expected to support further developments in such areas as electronic books (e-books) and personal digital-picture viewers. Our lineup of 200 ppi TFT-LCDs includes a 4-inch display with VGA resolution, which is suitable for palmtop-size applications, and a 6.3-inch display with XGA resolution, which is suitable for typical photograph or paperback book-size applications. Larger size LCDs with 200 ppi resolution will be developed. (author)

  6. Circulating aldosterone induces the apical accumulation of the proton pumping V-ATPase and increases proton secretion in clear cells in the caput epididymis.

    Science.gov (United States)

    Roy, Jeremy W; Hill, Eric; Ruan, Ye Chun; Vedovelli, Luca; Păunescu, Teodor G; Brown, Dennis; Breton, Sylvie

    2013-08-15

    Clear cells express the vacuolar proton-pumping H(+)-ATPase (V-ATPase) and acidify the lumen of the epididymis, a process that is essential for male fertility. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance in the epididymis, and a previous study showed binding of aldosterone exclusively to epididymal clear cells (Hinton BT, Keefer DA. Steroid Biochem 23: 231-233, 1985). We examined here the role of aldosterone in the regulation of V-ATPase in the epididymis. RT-PCR showed expression of the mineralocorticoid receptor [MR; nuclear receptor subfamily 3, group C member 2 (NR3C2)] and 11-β-dehydrogenase isozyme 2 (HSD11β2) mRNAs specifically in clear cells, isolated by fluorescence-activated cell sorting from B1-enhanced green fluorescent protein (EGFP) mice. Tail vein injection of adult rats with aldosterone, 1,2-dioctanoyl-sn-glycerol (DOG), or 8-(4-chlorophenylthio)-cAMP (cpt-cAMP) induced V-ATPase apical membrane accumulation and extension of V-ATPase-labeled microvilli in clear cells in the caput epididymis but not in the cauda. V-ATPase activity was measured in EGFP-expressing clear cells using the intracellular pH (pHi)-sensing dye seminaphthorhodafluor-5F-5-(and 6)-carboxylic acid, acetoxymethyl ester acetate (SNARF-5F). Aldosterone induced a rapid increase in the rate of Na(+)- and bicarbonate-independent pHi recovery following an NH4Cl-induced acid load in clear cells isolated from the caput but not the cauda. This effect was abolished by concanamycin A, spironolactone, and chelerythrine but not myristoylated-protein kinase inhibitor (mPKI) or mifepristone. Thus aldosterone increases V-ATPase-dependent proton secretion in clear cells in the caput epididymis via MR/NR3C2 and PKC activation. This study, therefore, identifies aldosterone as an active member of the RAAS for the regulation of luminal acidification in the proximal epididymis.

  7. Molecular cloning and sequence of cDNA encoding the plasma membrane proton pump (H+-ATPase) of Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Harper, J.F.; Surowy, T.K.; Sussman, M.R.

    1989-01-01

    In plants, the transport of solutes across the plasma membrane is driven by a proton pump (H + -ATPase) that produces an electric potential and pH gradient. The authors isolated and sequenced a full-length cDNA clone that encodes this enzyme in Arabidopsis thaliana. The protein predicted from its nucleotide sequence encodes 959 amino acids and has a molecular mass of 104,207 Da. The plant protein shows structural features common to a family of cation-translocating ATPases found in the plasma membrane of prokaryotic and eukaryotic cells, with the greatest overall identity in amino acid sequence (36%) to the H + -ATPase observed in the plasma membrane of fungi. The structure predicted from a hydropathy plant contains at least eight transmembrane segments, with most of the protein (73%) extending into the cytoplasm and only 5% of the residues exposed on the external surface. Unique features of the plant enzyme include diverged sequences at the amino and carboxyl termini as well as greater hydrophilic character in three extracellular loops

  8. Effects of membrane curvature and pH on proton pumping activity of single cytochrome bo3 enzymes

    DEFF Research Database (Denmark)

    Li, Mengqiu; Khan, Sanobar; Rong, Honglin

    2017-01-01

    The molecular mechanism of proton pumping by heme-copper oxidases (HCO) has intrigued the scientific community since it was first proposed. We have recently reported a novel technology that enables the continuous characterisation of proton transport activity of a HCO and ubiquinol oxidase from...... Escherichia coli, cytochrome bo3, for hundreds of seconds on the single enzyme level (Li et al. J Am Chem Soc 137 (2015) 16055–16063). Here, we have extended these studies by additional experiments and analyses of the proton transfer rate as a function of proteoliposome size and pH at the N- and P......-side of single HCOs. Proton transport activity of cytochrome bo3 was found to decrease with increased curvature of the membrane. Furthermore, proton uptake at the N-side (proton entrance) was insensitive to pH between pH 6.4–8.4, while proton release at the P-side had an optimum pH of ~ 7.4, suggesting...

  9. PPI, paradoxes and Plato: who's sailing the ship?

    Science.gov (United States)

    Ives, Jonathan; Damery, Sarah; Redwod, Sabi

    2013-03-01

    Over the last decade, patient and public involvement (PPI) has become a requisite in applied health research. Some funding bodies demand explicit evidence of PPI, while others have made a commitment to developing PPI in the projects they fund. Despite being commonplace, there remains a dearth of engagement with the ethical and theoretical underpinnings of PPI processes and practices. More specifically, while there is a small (but growing) body of literature examining the effectiveness and impact of PPI, there has been relatively little reflection on whether the concept/practice of PPI is internally coherent. Here, the authors unpick a 'paradox' within PPI, which highlights a tension between its moral and pragmatic motivations and its implementation. The authors argue that this 'professionalisation paradox' means we need to rethink the practice, and purpose, of PPI in research.

  10. 32 CFR 701.115 - Protected personal information (PPI).

    Science.gov (United States)

    2010-07-01

    ... Section 701.115 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY UNITED STATES... information (PPI). (a) Access/disclosure. Access to and disclosure of PPI such as SSN, date of birth, home... notice and understand PA rules. DON activities shall ensure that PPI (e.g., home address, date of birth...

  11. Inhibitors

    Science.gov (United States)

    ... JM, and the Hemophilia Inhibitor Research Study Investigators. Validation of Nijmegen-Bethesda assay modifications to allow inhibitor ... webinars on blood disorders Language: English (US) Español (Spanish) File Formats Help: How do I view different ...

  12. Plant proton pumps

    DEFF Research Database (Denmark)

    Gaxiola, Roberto A.; Palmgren, Michael Gjedde; Schumacher, Karin

    2007-01-01

    Chemiosmotic circuits of plant cells are driven by proton (H+) gradients that mediate secondary active transport of compounds across plasma and endosomal membranes. Furthermore, regulation of endosomal acidification is critical for endocytic and secretory pathways. For plants to react...

  13. Modulation of proton pumping across proteoliposome membranes reconstituted with tonoplast H(+)-ATPase from cultured rice (Oryza sativa L. var. Boro) cells by acyl steryl glucoside and steryl glucoside.

    Science.gov (United States)

    Yamaguchi, Mineo; Kasamo, Kunihiro

    2002-07-01

    Tonoplast H(+)-ATPase purified from cultured rice cells (Oryza sativa L. var. Boro) was reconstituted into asolectin liposomes containing steryl glucoside (SG) or acyl steryl glucoside (ASG), and the effects of SG and ASG on proton pumping, ATP-hydrolysis activity and proton permeability of the proteoliposome membranes were investigated. In the proteoliposomes containing 10 mol% SG, proton pumping and ATP-hydrolysis activity were increased to around 140% of those in SG-free proteoliposomes. In the proteoliposomes containing ASG, proton pumping and ATP-hydrolysis activity were decreased to one-tenth of those in ASG-free proteoliposomes at 15 mol% ASG; however, activity increased again slightly in the range between 20 and 40 mol% ASG. The change in proton pumping across the proteoliposome membrane is not due to a change of proteoliposome size nor to the location of the catalytic site of the tonoplast H(+)-ATPase in the proteoliposomes. SG and ASG also reduced the passive proton permeability of the proteoliposomes. These results show that SG and ASG modulate proton pumping across the tonoplast toward stimulation and depression, respectively, and they reduce the passive proton permeability of the tonoplast.

  14. Acidic digestion in a teleost: postprandial and circadian pattern of gastric pH, pepsin activity, and pepsinogen and proton pump mRNAs expression.

    Science.gov (United States)

    Yúfera, Manuel; Moyano, Francisco J; Astola, Antonio; Pousão-Ferreira, Pedro; Martínez-Rodríguez, Gonzalo

    2012-01-01

    Two different modes for regulation of stomach acid secretion have been described in vertebrates. Some species exhibit a continuous acid secretion maintaining a low gastric pH during fasting. Others, as some teleosts, maintain a neutral gastric pH during fasting while the hydrochloric acid is released only after the ingestion of a meal. Those different patterns seem to be closely related to specific feeding habits. However, our recent observations suggest that this acidification pattern could be modified by changes in daily feeding frequency and time schedule. The aim of this study was to advance in understanding the regulation mechanisms of stomach digestion and pattern of acid secretion in teleost fish. We have examined the postprandial pattern of gastric pH, pepsin activity, and mRNA expression for pepsinogen and proton pump in white seabream juveniles maintained under a light/dark 12/12 hours cycle and receiving only one morning meal. The pepsin activity was analyzed according to the standard protocol buffering at pH 2 and using the actual pH measured in the stomach. The results show how the enzyme precursor is permanently available while the hydrochloric acid, which activates the zymogen fraction, is secreted just after the ingestion of food. Results also reveal that analytical protocol at pH 2 notably overestimates true pepsin activity in fish stomach. The expression of the mRNA encoding pepsinogen and proton pump exhibited almost parallel patterns, with notable increases during the darkness period and sharp decreases just before the morning meal. These results indicate that white seabream uses the resting hours for recovering the mRNA stock that will be quickly used during the feeding process. Our data clearly shows that both daily illumination pattern and feeding time are involved at different level in the regulation of the secretion of digestive juices.

  15. Acidic digestion in a teleost: postprandial and circadian pattern of gastric pH, pepsin activity, and pepsinogen and proton pump mRNAs expression.

    Directory of Open Access Journals (Sweden)

    Manuel Yúfera

    Full Text Available Two different modes for regulation of stomach acid secretion have been described in vertebrates. Some species exhibit a continuous acid secretion maintaining a low gastric pH during fasting. Others, as some teleosts, maintain a neutral gastric pH during fasting while the hydrochloric acid is released only after the ingestion of a meal. Those different patterns seem to be closely related to specific feeding habits. However, our recent observations suggest that this acidification pattern could be modified by changes in daily feeding frequency and time schedule. The aim of this study was to advance in understanding the regulation mechanisms of stomach digestion and pattern of acid secretion in teleost fish. We have examined the postprandial pattern of gastric pH, pepsin activity, and mRNA expression for pepsinogen and proton pump in white seabream juveniles maintained under a light/dark 12/12 hours cycle and receiving only one morning meal. The pepsin activity was analyzed according to the standard protocol buffering at pH 2 and using the actual pH measured in the stomach. The results show how the enzyme precursor is permanently available while the hydrochloric acid, which activates the zymogen fraction, is secreted just after the ingestion of food. Results also reveal that analytical protocol at pH 2 notably overestimates true pepsin activity in fish stomach. The expression of the mRNA encoding pepsinogen and proton pump exhibited almost parallel patterns, with notable increases during the darkness period and sharp decreases just before the morning meal. These results indicate that white seabream uses the resting hours for recovering the mRNA stock that will be quickly used during the feeding process. Our data clearly shows that both daily illumination pattern and feeding time are involved at different level in the regulation of the secretion of digestive juices.

  16. Arabidopsis type I proton-pumping pyrophosphatase expresses strongly in phloem, where it is required for pyrophosphate metabolism and photosynthate partitioning.

    Science.gov (United States)

    Pizzio, Gaston A; Paez-Valencia, Julio; Khadilkar, Aswad S; Regmi, Kamesh; Patron-Soberano, Araceli; Zhang, Shangji; Sanchez-Lares, Jonathan; Furstenau, Tara; Li, Jisheng; Sanchez-Gomez, Concepcion; Valencia-Mayoral, Pedro; Yadav, Umesh P; Ayre, Brian G; Gaxiola, Roberto A

    2015-04-01

    Phloem loading is a critical process in plant physiology. The potential of regulating the translocation of photoassimilates from source to sink tissues represents an opportunity to increase crop yield. Pyrophosphate homeostasis is crucial for normal phloem function in apoplasmic loaders. The involvement of Arabidopsis (Arabidopsis thaliana) type I proton-pumping pyrophosphatase (AVP1) in phloem loading was analyzed at genetic, histochemical, and physiological levels. A transcriptional AVP1 promoter::GUS fusion revealed phloem activity in source leaves. Ubiquitous AVP1 overexpression (35S::AVP1 cassette) enhanced shoot biomass, photoassimilate production and transport, rhizosphere acidification, and expression of sugar-induced root ion transporter genes (POTASSIUM TRANSPORTER2 [KUP2], NITRATE TRANSPORTER2.1 [NRT2.1], NRT2.4, and PHOSPHATE TRANSPORTER1.4 [PHT1.4]). Phloem-specific AVP1 overexpression (Commelina Yellow Mottle Virus promoter [pCOYMV]::AVP1) elicited similar phenotypes. By contrast, phloem-specific AVP1 knockdown (pCoYMV::RNAiAVP1) resulted in stunted seedlings in sucrose-deprived medium. We also present a promoter mutant avp1-2 (SALK046492) with a 70% reduction of expression that did not show severe growth impairment. Interestingly, AVP1 protein in this mutant is prominent in the phloem. Moreover, expression of an Escherichia coli-soluble pyrophosphatase in the phloem (pCoYMV::pyrophosphatase) of avp1-2 plants resulted in severe dwarf phenotype and abnormal leaf morphology. We conclude that the Proton-Pumping Pyrophosphatase AVP1 localized at the plasma membrane of the sieve element-companion cell complexes functions as a synthase, and that this activity is critical for the maintenance of pyrophosphate homeostasis required for phloem function. © 2015 American Society of Plant Biologists. All Rights Reserved.

  17. Super high precision 200 ppi liquid crystal display series; Chokoseido 200 ppi ekisho display series

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    In mobile equipment, in demand is a high precision liquid crystal display (LCD) having the power of expression equivalent to printed materials like magazines because of the necessity of displaying a large amount of information on a easily potable small screen. In addition, with the spread and high-quality image of digital still cameras, it is strongly desired to display photographed digital image data in high quality. Toshiba Corp., by low temperature polysilicone (p-Si) technology, commercialized the liquid crystal display series of 200 ppi (pixels per inch) precision dealing with the rise of the high-precision high-image quality LCD market. The super high precision of 200 ppi enables the display of smooth beautiful animation comparable to printed sheets of magazines and photographs. The display series are suitable for the display of various information services such as electronic books and electronic photo-viewers including internet. The screen sizes lined up are No. 4 type VGA (640x480 pixels) of a small pocket notebook size and No. 6.3 type XGA (1,024x768 pixels) of a paperback size, with a larger screen to be furthered. (translated by NEDO)

  18. A designated centre for people with disabilities operated by Health Service Executive, Wexford

    LENUS (Irish Health Repository)

    Cahir, Caitriona

    2012-01-01

    There are concerns that proton pump inhibitors (PPI) are being over prescribed in both primary and secondary care. This study aims to establish potential cost savings in a community drug scheme for a one year period according to published clinical and cost-effective guidelines for PPI prescribing.

  19. Ionic motion in PEDOT and PPy conducting polymer bilayers

    DEFF Research Database (Denmark)

    Zainudeen, Umer L.; Careem, M.A.; Skaarup, Steen

    2006-01-01

    Conducting polymer bilayers with poly(3,4-ethylenedioxythiophene) (PEDOT) and polypyrrole (PPy), each containing dodecyl benzenesulfonate (DBS) as immobile dopant species, were synthesized galvanostatically. The electrochemical behaviour of the bilayers was investigated using cyclic voltammetry...

  20. Sensitivity of PPI analysis to differences in noise reduction strategies.

    Science.gov (United States)

    Barton, M; Marecek, R; Rektor, I; Filip, P; Janousova, E; Mikl, M

    2015-09-30

    In some fields of fMRI data analysis, using correct methods for dealing with noise is crucial for achieving meaningful results. This paper provides a quantitative assessment of the effects of different preprocessing and noise filtering strategies on psychophysiological interactions (PPI) methods for analyzing fMRI data where noise management has not yet been established. Both real and simulated fMRI data were used to assess these effects. Four regions of interest (ROIs) were chosen for the PPI analysis on the basis of their engagement during two tasks. PPI analysis was performed for 32 different preprocessing and analysis settings, which included data filtering with RETROICOR or no such filtering; different filtering of the ROI "seed" signal with a nuisance data-driven time series; and the involvement of these data-driven time series in the subsequent PPI GLM analysis. The extent of the statistically significant results was quantified at the group level using simple descriptive statistics. Simulated data were generated to assess statistical improvement of different filtering strategies. We observed that different approaches for dealing with noise in PPI analysis yield differing results in real data. In simulated data, we found RETROICOR, seed signal filtering and the addition of data-driven covariates to the PPI design matrix significantly improves results. We recommend the use of RETROICOR, and data-driven filtering of the whole data, or alternatively, seed signal filtering with data-driven signals and the addition of data-driven covariates to the PPI design matrix. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Synthesis and microwave absorption properties of PPy/Co nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Juhua, E-mail: luojuhua@163.com [School of Materials Engineering, Yancheng Institute of Technology, Yancheng 224051 (China); Gao, Duoduo [School of Material Science and Engineering, Changzhou University, Changzhou 213164 (China)

    2014-11-15

    Polypyrrole (PPy)/cobalt (Co) nanocomposites were successfully prepared by an in-situ polymerization of pyrrole in the presence of synthesized Co nanoparticles. Characterization of the product was accomplished by XRD, TEM, FT-IR, VSM, and vector network analyzer techniques. XRD analysis revealed that characteristic diffraction peaks of polypyrrole and Co appeared at the same time in nanocomposites. FT-IR analysis indicated a successful conjugation of Co particles with polypyrrole. TEM confirmed the formation of a core-shell structure with a wide particle size distribution. Magnetization measurements showed that polypyrrole coating decreased the saturation magnetization of Co significantly. With the increase of the matching thickness, the absorption peak varied towards low frequency direction. When the matching thickness was 3.0 mm, the value of the maximum reflection loss (RL) was −20.0 dB at 13.8 GHz with the 7.2 GHz bandwidth. - Highlights: • The influence of PPy on the structure of Co is discussed. • The influence of PPy on the magnetic properties of Co is discussed. • The influence of PPy on the absorption property of Co is discussed. • PPy/Co possessed the excellent absorption property.

  2. Proton-Pump inhibitors decrease the risk of bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: A nested case-control study

    NARCIS (Netherlands)

    Vonkeman, Harald Erwin; Fernandes, Robert W.; van der Palen, Jacobus Adrianus Maria; van Roon, Eric N.; van de Laar, Mart A F J

    2006-01-01

    Purpose: To determine which patients are especially at risk for serious NSAID attributable gastroduodenal ulcers and to compare the effectiveness of different preventive strategies in these patients. Methods: A case - control study was conducted in a large teaching hospital serving a population of

  3. Early stellate cell activation and veno-occlusive-disease (VOD)-like hepatotoxicity in dogs treated with AR-H047108, an imidazopyridine proton pump inhibitor.

    Science.gov (United States)

    Berg, Anna-Lena; Böttcher, Gerhard; Andersson, Kjell; Carlsson, Enar; Lindström, Anna-Karin; Huby, Russell; Håkansson, Helen; Skånberg-Wilhelmsson, Inger; Hellmold, Heike

    2008-07-01

    Dogs treated with AR-H047108, an imidazopyridine potassium competitive acid blocker (P-CAB), developed clinical signs of hepatic dysfunction as well as morphologically manifest hepatotoxicity in repeat-dose toxicity studies. An investigative one-month study was performed, with interim euthanasia after one and two weeks. A detailed histopathological and immunohistochemical characterization of the liver lesions was conducted, including markers for fibrosis, Kupffer cell activation, apoptosis, and endothelial injury. In addition, hepatic retinoid and procollagen 1alpha2 mRNA levels in livers of dogs treated with AR-H047108 were analyzed. The results showed an early inflammatory process in central veins and centrilobular areas, present after one week of treatment. This inflammatory reaction was paralleled by activation of stellate/Ito cells to myofibroblasts and was associated with sinusoidal and centrivenular fibrosis. The early activation of stellate cells coincided with a significant decrease in retinyl ester levels, and a significant increase in procollagen 1alpha2 mRNA levels, in the liver. At later time points (three and six months), there was marked sinusoidal fibrosis in centrilobular areas, as well as occlusion of central veins resulting from a combination of fibrosis and increased thickness of smooth muscle bundles in the vessel wall. The pattern of lesions suggests a veno-occlusive-disease (VOD)-like scenario, possibly linked to the imidazopyridine chemical structure of the compound facilitated by specific morphological features of the dog liver.

  4. Two-week, high-dose proton pump inhibitor, moxifloxacin triple Helicobacter pylori therapy after failure of standard triple or non-bismuth quadruple treatments.

    Science.gov (United States)

    Gisbert, Javier P; Romano, Marco; Molina-Infante, Javier; Lucendo, Alfredo J; Medina, Enrique; Modolell, Inés; Rodríguez-Tellez, Manuel; Gomez, Blas; Barrio, Jesús; Perona, Monica; Ortuño, Juan; Ariño, Inés; Domínguez-Muñoz, Juan Enrique; Perez-Aisa, Ángeles; Bermejo, Fernando; Domínguez, Jose Luis; Almela, Pedro; Gomez-Camarero, Judith; Millastre, Judith; Martin-Noguerol, Elisa; Gravina, Antonietta G; Martorano, Marco; Miranda, Agnese; Federico, Alessandro; Fernandez-Bermejo, Miguel; Angueira, Teresa; Ferrer-Barcelo, Luis; Fernández, Nuria; Marín, Alicia C; McNicholl, Adrián G

    2015-02-01

    Aim was to evaluate the efficacy and tolerability of a moxifloxacin-containing second-line triple regimen in patients whose previous Helicobacter pylori eradication treatment failed. Prospective multicentre study including patients in whom a triple therapy or a non-bismuth-quadruple-therapy failed. Moxifloxacin (400mg qd), amoxicillin (1g bid), and esomeprazole (40 mg bid) were prescribed for 14 days. Eradication was confirmed by (13)C-urea-breath-test. Compliance was determined through questioning and recovery of empty medication envelopes. 250 patients were consecutively included (mean age 48 ± 15 years, 11% with ulcer). Previous (failed) therapy included: standard triple (n = 179), sequential (n = 27), and concomitant (n = 44); 97% of patients took all medications, 4 were lost to follow-up. Intention-to-treat and per-protocol eradication rates were 82.4% (95% CI, 77-87%) and 85.7% (95% CI, 81-90%). Cure rates were similar independently of diagnosis (ulcer, 77%; dyspepsia, 82%) and previous treatment (standard triple, 83%; sequential, 89%; concomitant, 77%). At multivariate analysis, only age was associated with eradication (OR = 0.957; 95% CI, 0.933-0.981). Adverse events were reported in 25.2% of patients: diarrhoea (9.6%), abdominal pain (9.6%), and nausea (9.2%). 14-day moxifloxacin-containing triple therapy is an effective and safe second-line strategy in patients whose previous standard triple therapy or non-bismuth quadruple (sequential or concomitant) therapy has failed, providing a simple alternative to bismuth quadruple regimen. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  5. Partial response to proton pump inhibitor therapy for GERD: observational study of patient characteristics, burden of disease, and costs in the USA

    OpenAIRE

    St?lhammar, Nils-Olov; Spiegel, Brennan M; Granstedt L?fman, Helena; Karlsson, Maria; Wahlqvist, Peter; N?sdal, J?rgen; Nelson, M Todd; Despi?gel, Nicolas

    2012-01-01

    Nils-Olov Stålhammar,1 Brennan M Spiegel,2,3 Helena Granstedt Löfman,1 Maria Karlsson,1 Peter Wahlqvist,1 Jørgen Næsdal,4 M Todd Nelson,5 Nicolas Despiégel61Payer Evidence, AstraZeneca R&D, Mölndal, Sweden; 2Department of Gastroenterology, VA Greater Los Angeles Healthcare System, 3David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 4Medical Department, AstraZeneca R&D, Mölndal, Sweden; 5Late Phase...

  6. Hopping conduction on PPy/SiO2 nanocomposites obtained via in situ emulsion polymerization

    NARCIS (Netherlands)

    Rubinger, C.P.L.; Costa, L.C.; Carvalho Esteves, de A.C.; Barros-Timmons, A.M.M.V.

    2008-01-01

    This work describes the preparation and electrical characterization of conducting polypyrrole (PPy) and silica nanocomposites. Four samples were investigated: (i) pure PPy, (ii) PPy-covered SiO2 spherical nanoparticles, (iii) PPy-covered SiO2 spherical nanoparticles modified with

  7. A quantum chemical study of the mechanism for proton-coupled electron transfer leading to proton pumping in cytochrome c oxidase

    Science.gov (United States)

    Blomberg, Margareta R. A.; Siegbahn, Per E. M.

    2010-10-01

    The proton pumping mechanism in cytochrome c oxidase, the terminal enzyme in the respiratory chain, has been investigated using hybrid DFT with large chemical models. In previous studies, a gating mechanism was suggested based on electrostatic interpretations of kinetic experiments. The predictions from that analysis are tested here. The main result is that the suggestion of a positively charged transition state for proton transfer is confirmed, while some other suggestions for the gating are not supported. It is shown that a few critical relative energy values from the earlier studies are reproduced with quite high accuracy using the present model calculations. Examples are the forward barrier for proton transfer from the N-side of the membrane to the pump-loading site when the heme a cofactor is reduced, and the corresponding back leakage barrier when heme a is oxidised. An interesting new finding is an unexpected double-well potential for proton transfer from the N-side to the pump-loading site. In the intermediate between the two transition states found, the proton is bound to PropD on heme a. A possible purpose of this type of potential surface is suggested here. The accuracy of the present values are discussed in terms of their sensitivity to the choice of dielectric constant. Only one energy value, which is not critical for the present mechanism, varies significantly with this choice and is therefore less certain.

  8. FMFinder: A Functional Module Detector for PPI Networks

    Directory of Open Access Journals (Sweden)

    M. Modi

    2017-10-01

    Full Text Available Bioinformatics is an integrated area of data mining, statistics and computational biology. Protein-Protein Interaction (PPI network is the most important biological process in living beings. In this network a protein module interacts with another module and so on, forming a large network of proteins. The same set of proteins which takes part in the organic courses of biological actions is detected through the Function Module Detection method. Clustering process when applied in PPI networks is made of proteins which are part of a larger communication network. As a result of this, we can define the limits for module detection as well as clarify the construction of a PPI network. For understating the bio-mechanism of various living beings, a detailed study of FMFinder detection by clustering process is called for.

  9. The feasibility and application of PPy in cathodic polarization antifouling.

    Science.gov (United States)

    Jia, Meng-Yang; Zhang, Zhi-Ming; Yu, Liang-Min; Wang, Jia; Zheng, Tong-Tong

    2018-04-01

    Cathodic polarization antifouling deserves attention because of its environmentally friendly nature and good sustainability. It has been proven that cathodic voltages applied on metal substrates exhibit outstanding antifouling effects. However, most metals immersed in marine environment are protected by insulated anticorrosive coatings, restricting the cathodic polarization applied on metals. This study developed a conducting polypyrrole (PPy)/acrylic resin coating (σ = 0.18 Scm -1 ), which can be applied in cathodic polarization antifouling. The good stability and electro-activity of PPy in the negative polarity zone in alkalescent NaCl solution were verified by linear sweep voltammetry (LSV), chronoamperometry (CA), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), demonstrating the feasibility of PPy as cathodic polarization material. Furthermore, the antifouling effects of PPy/acrylicresin coating on 24-h old Escherichia coli bacteria (E. coli) which formed on PPy/acrylic resin-coated plastic plate were measured under different cathodic potentials and treatment time, characterized by fluorescent microscope. The results suggest that at cathodic potential around -0.5 V (vs. saturated calomel electrode (SCE)), there was little trace of attached bacteria on the substrate after 20 min of treatment. PPy/acrylicresin-coated substrates were also subjected to repeated cycles of biofilm formation and electrochemical removal, where high removal efficiencies were maintained throughout the total polarization process. Under these conditions, the generation of hydrogen peroxide is believed to be responsible for the antifouling effects because of causing oxidative damage to cells, suggesting the potential of the proposed technology for application on insulated surfaces in various industrial settings. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Photocurrent and photothermal current of polypyrrole (PPy) film

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Chongjun; Wang Haihong; Jiang Zhiyu

    2003-02-28

    The photoelectrochemical properties of polypyrrole (PPy) film in aqueous solutions in the potential region of -0.7 to 0.5 V (versus Ag/AgCl) were investigated by using photocurrent, photothermal and photothermal current methods under the irradiation of laser beams with wavelength of 532 and 632.8 nm, respectively. It was found that the photocurrent at more negative potential was caused by the p-type semiconductor properties, while the photocurrent at more positive potential was caused by the local temperature rather than the semiconductor properties of the films. The effect of the film thickness on the photocurrent of PPy films was studied in detail.

  11. Photocurrent and photothermal current of polypyrrole (PPy) film

    International Nuclear Information System (INIS)

    Zhao Chongjun; Wang Haihong; Jiang Zhiyu

    2003-01-01

    The photoelectrochemical properties of polypyrrole (PPy) film in aqueous solutions in the potential region of -0.7 to 0.5 V (versus Ag/AgCl) were investigated by using photocurrent, photothermal and photothermal current methods under the irradiation of laser beams with wavelength of 532 and 632.8 nm, respectively. It was found that the photocurrent at more negative potential was caused by the p-type semiconductor properties, while the photocurrent at more positive potential was caused by the local temperature rather than the semiconductor properties of the films. The effect of the film thickness on the photocurrent of PPy films was studied in detail

  12. A review on comparative study of PPI and PAMAM dendrimers

    International Nuclear Information System (INIS)

    Kaur, Daljeet; Jain, Keerti; Mehra, Neelesh Kumar; Kesharwani, Prashant; Jain, Narendra K.

    2016-01-01

    Dendrimers are hyperbranched, monodispersed macromolecules with multivalent functional end groups. Dendrimers have been explored as carrier for many drugs like anticancer, antiviral, antimalarial, antiprotozoal, anti tubercular drugs. Although a number of different types of dendrimers containing different core molecules, branching monomers and surface functional groups have been designed till date for drug delivery applications, yet the poly(propyleneimine) (PPI) and poly(amidoamine) (PAMAM) dendrimers have been the most explored dendrimers in this regard. In this review, we have summarized a comparative data on PPI and PAMAM dendrimers particularly relevant to their properties, synthesis, toxicity, biomedical applications and drug delivery attributes.

  13. A review on comparative study of PPI and PAMAM dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Daljeet; Jain, Keerti, E-mail: keertijain02@gmail.com; Mehra, Neelesh Kumar [ISF College of Pharmacy, Pharmaceutical Nanotechnology Research Laboratory (India); Kesharwani, Prashant [Wayne State University, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences (United States); Jain, Narendra K., E-mail: jnarendr@yahoo.co.in, E-mail: dr.jnarendr@gmail.com [ISF College of Pharmacy, Pharmaceutical Nanotechnology Research Laboratory (India)

    2016-06-15

    Dendrimers are hyperbranched, monodispersed macromolecules with multivalent functional end groups. Dendrimers have been explored as carrier for many drugs like anticancer, antiviral, antimalarial, antiprotozoal, anti tubercular drugs. Although a number of different types of dendrimers containing different core molecules, branching monomers and surface functional groups have been designed till date for drug delivery applications, yet the poly(propyleneimine) (PPI) and poly(amidoamine) (PAMAM) dendrimers have been the most explored dendrimers in this regard. In this review, we have summarized a comparative data on PPI and PAMAM dendrimers particularly relevant to their properties, synthesis, toxicity, biomedical applications and drug delivery attributes.

  14. Two cases of esophageal eosinophilia: eosinophilic esophagitis or gastro-esophageal reflux disease?

    Directory of Open Access Journals (Sweden)

    Ozlem Yilmaz

    2014-06-01

    Full Text Available Eosinophilic esophagitis (EoE and gastro-esophageal reflux disease are among the major causes of isolated esophageal eosinophilia. Isolated esophageal eosinophilia meeting criteria for EoE may respond to proton pump inhibitor (PPI treatment. This entity is termed proton pumps inhibitor responsive esophageal eosinophilia (PPI-REE. Gastro-esophageal reflux is thought to comprise a subgroup of patients with PPI-REE. According to the latest guidelines, PPI responsiveness distinguishes people with PPI-REE from patients having EoE (non-responders. In this report, two unusual cases with findings belonging to both EoE and PPI-REE are discussed with known and unknown facts.

  15. Electrochemomechanical constrained multiobjective optimization of PPy/MWCNT actuators

    International Nuclear Information System (INIS)

    Khalili, N; Naguib, H E; Kwon, R H

    2014-01-01

    Polypyrrole (PPy) conducting polymers have shown a great potential for the fabrication of conjugated polymer-based actuating devices. Consequently, they have been a key point in developing many advanced emerging applications such as biomedical devices and biomimetic robotics. When designing an actuator, taking all of the related decision variables, their roles and relationships into consideration is of pivotal importance to determine the actuator’s final performance. Therefore, the central focus of this study is to develop an electrochemomechanical constrained multiobjective optimization model of a PPy/MWCNTs trilayer actuator. For this purpose, the objective functions are designed to capture the three main characteristics of these actuators, namely their tip vertical displacement, blocking force and response time. To obtain the optimum range of the designated decision variables within the feasible domain, a multiobjective optimization algorithm is applied while appropriate constraints are imposed. The optimum points form a Pareto surface on which they are consistently spread. The numerical results are presented; these results enable one to design an actuator with consideration to the desired output performances. For the experimental analysis, a multilayer bending-type actuator is fabricated, which is composed of a PVDF layer and two layers of PPy with an incorporated layer of multi-walled carbon nanotubes deposited on each side of the PVDF membrane. The numerical results are experimentally verified; in order to determine the performance of the fabricated actuator, its outputs are compared with a neat PPy actuator’s experimental and numerical counterparts. (paper)

  16. [Study on the land use optimization based on PPI].

    Science.gov (United States)

    Wu, Xiao-Feng; Li, Ting

    2012-03-01

    Land use type and managing method which is greatly influenced by human activities, is one of the most important factors of non-point pollution. Based on the collection and analysis of non-point pollution control methods and the concept of the three ecological fronts, 9 land use optimized scenarios were designed according to rationality analysis of the current land use situation in the 3 typed small watersheds in Miyun reservoir basin. Take Caojialu watershed for example to analyze and compare the influence to environment of different scenarios based on potential pollution index (PPI) and river section potential pollution index (R-PPI) and the best combination scenario was found. Land use scenario designing and comparison on basis of PPI and R-PPI could help to find the best combination scenario of land use type and managing method, to optimize space distribution and managing methods of land use in basin, to reduce soil erosion and to provide powerful support to formulation of land use planning and pollution control project.

  17. Pedot and PPy Conducting Polymer Bilayer and Trilayer Actuators

    DEFF Research Database (Denmark)

    Zainudeen, Umer Lebbe; Careem, Mohamed Abdul; Skaarup, Steen

    2008-01-01

    attempts have been made to improve the actuator performance. We report electromechanical measurements on actuators of bilayer and trilayer free standing films prepared with polypyrrole (PPy) and poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymers. Both types of conducting polymer are pre...

  18. The mechanism of electron gating in proton pumping cytochrome c oxidase: the effect of pH and temperature on internal electron transfer.

    Science.gov (United States)

    Brzezinski, P; Malmström, B G

    1987-10-29

    Electron-transfer reactions following flash photolysis of the mixed-valence cytochrome oxidase-CO complex have been measured at 445, 598 and 830 nm between pH 5.2 and 9.0 in the temperature range of 0-25 degrees C. There is a rapid electron transfer from the cytochrome a3-CuB pair to CuA (time constant: 14200 s-1), which is followed by a slower electron transfer to cytochrome a. Both the rate and the amplitude of the rapid phase are independent of pH, and the rate in the direction from CuA to cytochrome a3-CuB is practically independent of temperature. The second phase depends strongly on pH due to the titration of an acid-base group with pKa = 7.6. The equilibrium at pH 7.4 corresponds to reduction potentials of 225 and 345 mV for cytochrome a and a3, respectively, from which it is concluded that the enzyme is in a different conformation compared to the fully oxidized form. The results have been used to suggest a series of reaction steps in a cycle of the oxidase as a proton pump. Application of the electron-transfer theory to the temperature-dependence data suggests a mechanism for electron gating in the pump. Reduction of both cytochrome a and CuA leads to a conformational change, which changes the structure of cytochrome a3-CuB in such a way that the reorganizational barrier for electron transfer is removed and the driving force is increased.

  19. Inhibition of the coated vesicle proton pump and labeling of a 17,000-dalton polypeptide by N,N'-dicyclohexylcarbodiimide

    International Nuclear Information System (INIS)

    Arai, H.; Berne, M.; Forgac, M.

    1987-01-01

    N,N'-Dicyclohexylcarbodiimide (DCCD) inhibits 100% of proton transport and 80-85% of (Mg2+)-ATPase activity in clathrin-coated vesicles. Half-maximum inhibition of proton transport is observed at 10 microM DCCD after 30 min. Although treatment of the coated vesicle (H+)-ATPase with DCCD has no effect on ATP hydrolysis in the detergent-solubilized state, sensitivity of proton transport and ATPase activity to DCCD is restored following reconstitution into phospholipid vesicles. In addition, treatment of the detergent-solubilized enzyme with DCCD followed by reconstitution gives a preparation that is blocked in both proton transport and ATP hydrolysis. These results suggest that although the coated vesicle (H+)-ATPase can react with DCCD in either a membrane-bound or detergent-solubilized state, inhibition of ATPase activity is only manifested when the pump is present in sealed membrane vesicles. To identify the subunit responsible for inhibition of the coated vesicle (H+)-ATPase by DCCD, we have labeled the partially purified enzyme with [ 14 C]DCCD. A single polypeptide of molecular weight 17,000 is labeled. The extremely hydrophobic nature of this polypeptide is indicated by its extraction with chloroform:methanol. The 17,000-dalton protein can be labeled to a maximum stoichiometry of 0.99 mol of DCCD/mol of protein with 100% inhibition of proton transport occurring at a stoichiometry of 0.15-0.20 mol of DCCD/mol of protein. Amino acid analysis of the chloroform:methanol extracted 17,000-dalton polypeptide reveals a high percentage of nonpolar amino acids. The similarity in properties of this protein and the DCCD-binding subunit of the coupling factor (H+)-ATPases suggests that the 17,000-dalton polypeptide may function as part of a proton channel in the coated vesicle proton pump

  20. The innovative potential of Lactobacillus rhamnosus LR06, Lactobacillus pentosus LPS01, Lactobacillus plantarum LP01, and Lactobacillus delbrueckii Subsp. delbrueckii LDD01 to restore the "gastric barrier effect" in patients chronically treated with PPI: a pilot study.

    Science.gov (United States)

    Del Piano, Mario; Anderloni, Andrea; Balzarini, Marco; Ballarè, Marco; Carmagnola, Stefania; Montino, Franco; Orsello, Marco; Pagliarulo, Michela; Tari, Roberto; Soattini, Liliana; Sforza, Filomena; Mogna, Luca; Mogna, Giovanni

    2012-10-01

    Gastroesophageal reflux disease is a very widespread condition. In Europe, it is estimated that about 175 million people suffer from this disease and have to chronically take drugs to increase gastric pH. The proton pump inhibitors (PPIs) such as omeprazole, lansoprazole, and esomeprazole are the most widely used drug typology in this regard. However, the inhibition of normal gastric acid secretion has important side effects, the most important being bacterial overgrowth in the stomach and duodenum with a concentration of >10⁵ viable cells/mL. As a major consequence of this, many harmful or even pathogenic bacteria contained in some foods could survive the gastric transit and colonize either the stomach itself, the duodenum, or the gut, where they could establish acute and even chronic infections with unavoidable consequences for the host's health. In other words, the "gastric barrier effect" is strongly reduced or even disrupted. To date, there are no real strategies to deal with this widespread, although still relatively little known, problem. The aim of this study was to confirm the gastric bacterial overgrowth in long-term PPI consumers and to assess the efficacy of some probiotic bacteria, belonging to both genera Lactobacillus and Bifidobacterium, in the reduction of gastric and duodenal bacterial overgrowth, therefore partially restoring the gastric barrier effect against foodborne pathogenic bacteria. For this purpose, probiotics with a strong demonstrated inhibitory activity on gram-negative bacteria, such as Escherichia coli, were tested in a human intervention trial involving a total of 30 subjects treated with PPIs for either 3 to 12 consecutive months (short-term) or >12 consecutive months (long-term). An additional 10 subjects not taking PPIs were enrolled and used as a control group representing the general population. Four selected probiotics Probiotical SpA (Novara, Italy), namely Lactobacillus rhamnosus LR06 (DSM 21981), Lactobacillus pentosus

  1. 77 FR 76303 - Notice of Availability of Producer Price Index (PPI) Data Users Survey

    Science.gov (United States)

    2012-12-27

    ...) Data Users Survey AGENCY: Bureau of Labor Statistics, Labor. ACTION: Notice of availability of survey... Index (PPI) data users. The survey is necessary to: Identify PPI data users, see how they use our data... conducted a survey of PPI data users in late 1976 through early 1977. Since that time, numerous new time...

  2. Dielectric and AC Conductivity Studies in PPy-Ag Nanocomposites

    OpenAIRE

    Praveenkumar, K.; Sankarappa, T.; Ashwajeet, J. S.; Ramanna, R.

    2015-01-01

    Polypyrrole and silver nanoparticles have been synthesized at 277 K by chemical route. Nanoparticles of polypyrrole-silver (PPy-Ag) composites were prepared by mixing polypyrrole and silver nanoparticles in different weight percentages. Dielectric properties as a function of temperature in the range from 300 K to 550 K and frequency in the range from 50 Hz to 1 MHz have been measured. Dielectric constant decreased with increase in frequency and temperature. Dielectric loss decreased with incr...

  3. Packaged Au-PPy valves for drug delivery systems

    Science.gov (United States)

    Tsai, Han-Kuan A.; Ma, Kuo-Sheng; Zoval, Jim; Kulinsky, Lawrence; Madou, Marc

    2006-03-01

    The most common methods for the drug delivery are swallowing pills or receiving injections. However, formulations that control the rate and period of medicine (i.e., time-release medications) are still problematic. The proposed implantable devices which include batteries, sensors, telemetry, valves, and drug storage reservoirs provide an alternative method for the responsive drug delivery system [1]. Using this device, drug concentration can be precisely controlled which enhances drug efficiency and decreases the side effects. In order to achieve responsive drug delivery, a reliable release valve has to be developed. Biocompatibility, low energy consumption, and minimized leakage are the main requirements for such release method. A bilayer structure composed of Au/PPy film is fabricated as a flap to control the release valve. Optimized potentiostatic control to synthesize polypyrrole (PPy) is presented. The release of miniaturize valve is tested and showed in this paper. A novel idea to simultaneously fabricate the device reservoirs as well as protective packaging is proposed in this paper. The solution of PDMS permeability problem is also mentioned in this article.

  4. Preparation and characterization of visible light-driven AgCl/PPy photocatalyst

    International Nuclear Information System (INIS)

    Gu Shuna; Li Bing; Zhao Chongjun; Xu Yunlong; Qian Xiuzhen; Chen, Guorong

    2011-01-01

    Graphical abstract: AgCl/PPy composite exhibits improved photocatalytic performance and high stability under visible light. Display Omitted Highlights: → AgCl/(PPy) nanocomposites as visible light driven photocatalyst. → Composites exhibited high visible light-driven photocatalytic activity and stability. → Photocatalytic process on MO followed photoreduction mechanisms. → Used photocatalyst can be regenerated in aqueous FeCl 3 solution. - Abstract: Visible light photoactive AgCl/polypyrrole (PPy) composites were prepared via the reaction between excessive Ag + and Cl - ions in the presence of PPy . The AgCl/PPy composites were systematically characterized using Fourier transform infrared (FTIR) spectroscopy, Raman spectra, X-ray diffraction (XRD), Scanning electron microscope (SEM), Transmission electron microscope (TEM) and Thermal gravity analysis (TGA). It was found that face-centered cubic AgCl nanocrystallite and 0.2 wt% PPy component existed in the composite and spherical AgCl/PPy nanoparticles were in the range of 200-600 nm. The AgCl/PPy composites showed higher visible light-driven photocatalytic activity and stability than that of AgCl. A photoreduction mechanism was postulated for AgCl/PPy photocatalyst on dye methyl orange (MO). The used AgCl/PPy photocatalyst was facilely regenerated by an oxidation process in aqueous FeCl 3 solution.

  5. Preparation and characterization of visible light-driven AgCl/PPy photocatalyst

    Energy Technology Data Exchange (ETDEWEB)

    Gu Shuna; Li Bing [Key Laboratory for Ultrafine Materials of Ministry of Education, Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Zhao Chongjun, E-mail: chongjunzhao@ecust.edu.cn [Key Laboratory for Ultrafine Materials of Ministry of Education, Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Xu Yunlong; Qian Xiuzhen; Chen, Guorong [Key Laboratory for Ultrafine Materials of Ministry of Education, Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2011-05-05

    Graphical abstract: AgCl/PPy composite exhibits improved photocatalytic performance and high stability under visible light. Display Omitted Highlights: > AgCl/(PPy) nanocomposites as visible light driven photocatalyst. > Composites exhibited high visible light-driven photocatalytic activity and stability. > Photocatalytic process on MO followed photoreduction mechanisms. > Used photocatalyst can be regenerated in aqueous FeCl{sub 3} solution. - Abstract: Visible light photoactive AgCl/polypyrrole (PPy) composites were prepared via the reaction between excessive Ag{sup +} and Cl{sup -} ions in the presence of PPy{sub .} The AgCl/PPy composites were systematically characterized using Fourier transform infrared (FTIR) spectroscopy, Raman spectra, X-ray diffraction (XRD), Scanning electron microscope (SEM), Transmission electron microscope (TEM) and Thermal gravity analysis (TGA). It was found that face-centered cubic AgCl nanocrystallite and 0.2 wt% PPy component existed in the composite and spherical AgCl/PPy nanoparticles were in the range of 200-600 nm. The AgCl/PPy composites showed higher visible light-driven photocatalytic activity and stability than that of AgCl. A photoreduction mechanism was postulated for AgCl/PPy photocatalyst on dye methyl orange (MO). The used AgCl/PPy photocatalyst was facilely regenerated by an oxidation process in aqueous FeCl{sub 3} solution.

  6. Protein complex detection in PPI networks based on data integration and supervised learning method.

    Science.gov (United States)

    Yu, Feng; Yang, Zhi; Hu, Xiao; Sun, Yuan; Lin, Hong; Wang, Jian

    2015-01-01

    Revealing protein complexes are important for understanding principles of cellular organization and function. High-throughput experimental techniques have produced a large amount of protein interactions, which makes it possible to predict protein complexes from protein-protein interaction (PPI) networks. However, the small amount of known physical interactions may limit protein complex detection. The new PPI networks are constructed by integrating PPI datasets with the large and readily available PPI data from biomedical literature, and then the less reliable PPI between two proteins are filtered out based on semantic similarity and topological similarity of the two proteins. Finally, the supervised learning protein complex detection (SLPC), which can make full use of the information of available known complexes, is applied to detect protein complex on the new PPI networks. The experimental results of SLPC on two different categories yeast PPI networks demonstrate effectiveness of the approach: compared with the original PPI networks, the best average improvements of 4.76, 6.81 and 15.75 percentage units in the F-score, accuracy and maximum matching ratio (MMR) are achieved respectively; compared with the denoising PPI networks, the best average improvements of 3.91, 4.61 and 12.10 percentage units in the F-score, accuracy and MMR are achieved respectively; compared with ClusterONE, the start-of the-art complex detection method, on the denoising extended PPI networks, the average improvements of 26.02 and 22.40 percentage units in the F-score and MMR are achieved respectively. The experimental results show that the performances of SLPC have a large improvement through integration of new receivable PPI data from biomedical literature into original PPI networks and denoising PPI networks. In addition, our protein complexes detection method can achieve better performance than ClusterONE.

  7. NSAID Use after Bariatric Surgery : a Randomized Controlled Intervention Study

    NARCIS (Netherlands)

    Yska, Jan Peter; Gertsen, Sanneke; Flapper, Gerbrich; Emous, Marloes; Wilffert, Bob; van Roon, Eric N.

    2016-01-01

    Background Use of nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided in bariatric surgery patients. If use of an NSAID is inevitable, a proton pump inhibitor (PPI) should also be used. Aim To determine the effect of an, compared to care-as-usual, additional intervention to reduce NSAID

  8. Laparoscopic anti-reflux surgery : indications, techniques and physiological effects

    NARCIS (Netherlands)

    Broeders, J.A.J.L.

    2011-01-01

    Gastro-oesophageal reflux disease (GORD) is a highly prevalent chronic disorder in which retrograde flow of gastric contents into the oesophagus causes troublesome symptoms or lesions. Proton pump inhibitor (PPI) therapy controls reflux disease in 95% of the patients and the remaining 5% have

  9. Emerging drugs for gastroesophageal reflux disease

    NARCIS (Netherlands)

    Boeckxstaens, G. E.

    2009-01-01

    Proton pump inhibitors (PPIs) are very effective and safe drugs for the treatment of erosive and non-erosive gastroesophageal reflux disease (GERD). Nevertheless, a significant proportion of GERD patients (30 - 40%) continue to suffer from symptoms during PPI treatment, which has stimulated the

  10. Esophageal acid exposure decreases intraluminal baseline impedance levels

    NARCIS (Netherlands)

    Kessing, Boudewijn F.; Bredenoord, Albert J.; Weijenborg, Pim W.; Hemmink, Gerrit J. M.; Loots, Clara M.; Smout, A. J. P. M.

    2011-01-01

    Intraluminal baseline impedance levels are determined by the conductivity of the esophageal wall and can be decreased in gastroesophageal reflux disease (GERD) patients. The aim of this study was to investigate the baseline impedance in GERD patients, on and off proton pump inhibitor (PPI), and in

  11. Bleeding peptic ulcer. Prevalence of Helicobacter pylori and use of nonsteroidal anti-inflammatory drugs/acetylsalicylic acid

    DEFF Research Database (Denmark)

    Vestergard, A.; Bredahl, K.; Muckadell, O.B. de

    2009-01-01

    INTRODUCTION: Helicobacter pylori (HP) infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs)/acetyl salicylic acid (ASA) are risk factors for bleeding peptic ulcer. HP eradication reduces the risk of rebleeding. Antibiotics, proton pump inhibitors (PPI) and presence of blood...

  12. Blødende peptisk ulcus. Helicobacter pylori -praevalens og forbrug af non-steroide antiinflammatoriske stoffer/acetylsalicylsyre

    DEFF Research Database (Denmark)

    Vestergaard, Anders; Bredahl, Kim; de Muckadell, Ove B Schaffalitzky

    2009-01-01

    INTRODUCTION: Helicobacter pylori (HP) infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs)/acetyl salicylic acid (ASA) are risk factors for bleeding peptic ulcer. HP eradication reduces the risk of rebleeding. Antibiotics, proton pump inhibitors (PPI) and presence of blood...

  13. Risk of gastrointestinal adverse effects of dabigatran compared with warfarin among patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Staerk, Laila; Gislason, Gunnar H.; Lip, Gregory Y.H.

    2015-01-01

    Danish nationwide registries from 22 August 2011 until 31 December 2012. Patients were classified as naive or experienced users, according to prior use of oral anticoagulant (OAC) therapy. The risk of subsequent proton pump inhibitor (PPI) use, upper dyspepsia-like diagnoses (gastroesophageal reflux...

  14. PPI versus Histamine H2 Receptor Antagonists for Prevention of Upper Gastrointestinal Injury Associated with Low-Dose Aspirin: Systematic Review and Meta-analysis.

    Directory of Open Access Journals (Sweden)

    Chen Mo

    Full Text Available This study compared proton pump inhibitors (PPIs and histamine H2 receptor antagonists (H2RAs for prevention of low-dose aspirin (LDA-related gastrointestinal (GI erosion, ulcer and bleeding. Electronic databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and WanFang Data were searched from the date of their establishment to December 31, 2013. Randomized controlled trials comparing PPIs and H2RAs for prevention of GI injury associated with low-dose aspirin (LDA were collected. Two reviewers independently abstracted studies and patient characteristics and appraised study quality using the Cochrane risk-of-bias tool. Meta-analysis was performed using RevMan 5.1 software. We included nine RCTs involving 1047 patients. The meta-analysis showed that PPIs were superior to H2RAs for prevention of LDA-associated GI erosion/ulcer [odds ratio (OR=0.28, 95% confidence interval (CI: 0.16-0.50] and bleeding (OR=0.28, 95% CI: 0.14-0.59. In conclusion, PPIs were superior to H2RAs for prevention of LDA-related GI erosion/ulcer and bleeding. Higher quality, large, multicenter RCTs are needed to demonstrate the preventive effect of the two acid-suppressive drugs.

  15. Chemically designed Pt/PPy nano-composite for effective LPG gas sensor.

    Science.gov (United States)

    Gaikwad, Namrata; Bhanoth, Sreenu; More, Priyesh V; Jain, G H; Khanna, P K

    2014-03-07

    Simultaneous in situ reduction of hexachloroplatinic acid by the amine group in the pyrrole monomer and oxidation of pyrrole to form polypyrrole (PPy) was examined. The reactions were performed at various temperatures to understand the degree of reduction of platinum precursor as well as doping of polypyrrole with Pt(II) chloro-complex. Spectroscopic images revealed different morphologies for the Pt/PPy nano-composite prepared at various temperatures. The as-prepared Pt/PPy nano-composite samples were tested for their ability to sense liquefied petroleum gas (LPG) which resulted in excellent sensing at relatively low temperature. The porous nature and ohmic contact between the PPy and platinum nanoparticles makes the as-prepared Pt/PPy nano-composite highly useful for sensors as well as electronic applications.

  16. Does the Sustainable PPI Investments Promote Financial Market’s Sustainable Development?

    Directory of Open Access Journals (Sweden)

    Tong Fu

    2016-01-01

    Full Text Available Since the late 1980s, most developing countries adopt a policy of attracting investments for Private Participation in Infrastructure (PPI projects. With a perspective of sustainability, this paper offers a first attempt to examine whether the sustainable PPI investments promote financial market development. First, we demonstrate how the PPI policy enlargers the size of financial markets and then fosters the liquidity of financial markets in the static and dynamic conditions. Using the data from 33 developing countries during 1997–2012, we discover the significant promotion effect of PPI investments on the development of financial markets in the dimensions of size and liquidity. Additionally, we confirm the significant mediator effect of financial market size for the positive relationship between PPI investments and financial market liquidity. Both the promotion effect and mediation effect are robust to different control variables and estimation techniques used.

  17. SnO2/PPy Screen-Printed Multilayer CO2 Gas Sensor

    Directory of Open Access Journals (Sweden)

    S.A. WAGHULEY

    2007-05-01

    Full Text Available Tin dioxide (SnO2 plays a dominant role in solid state gas sensors and exhibit sensitivity towards oxidizing and reducing gases by a variation of its electrical properties. The electrical conducting polymer-polypyrrole (PPy has high anisotropy of electrical conduction and used as a gas sensor. SnO2/PPy multilayer, pure SnO2, pure PPy sensors were prepared by screen-printing method on Al2O3 layer followed by glass substrate. The sensors were used for different concentration (ppm of CO2 gas investigation at room temperature (303 K. The sensitivity of SnO2/PPy multilayer sensor was found to be higher, compared with pure SnO2 and pure PPy sensors. The multilayer sensor exhibited improved stability. The response and recovery time of multilayer sensor were found to be ~2 min and ~10 min respectively.

  18. Status of PPI (Pohang Photo-Injector) for PAL XFEL

    CERN Document Server

    Park, Sung-Ju; Oh, Jong-Seok; Park, Chong-Do; Park Jang Ho; Soo Ko In; Wang, Xijie; Woon Parc, Yong

    2005-01-01

    A X-Ray Free Electron Laser (XFEL) project based on the Self-Amplified Spontaneous Emission (SASE) is under progress at the Pohang Accelerator Laboratory (PAL). One of the critical R&D for the PAL XFEL* is to develop the Pohang Photo-Injector (PPI) which is required to deliver electron beams with normalized emittance < 1.5 mm-mrad. In order to achieve the required beam quality with high stability and reliability, we will use photocathode with quantum efficiency > 0.1 % and long lifetime. This will greatly lessen the laser energy requirement for producing flat-top UV pulses, and open the possibility of using only regenerative amplifiers (RGAs) to drive the photocathode RF gun. The RGAs can produce mJs output with much better stability than multi-pass amplifiers. Both the Cs2Te and Mg are under consideration for the possible photo-cathode. To demonstrate the suitability of the Mg and Cs2Te for the future 4th generation light source application, an improved BNL-type S-band RF gun with a high-pe...

  19. Hot spot-based design of small-molecule inhibitors for protein-protein interactions.

    Science.gov (United States)

    Guo, Wenxing; Wisniewski, John A; Ji, Haitao

    2014-06-01

    Protein-protein interactions (PPIs) are important targets for the development of chemical probes and therapeutic agents. From the initial discovery of the existence of hot spots at PPI interfaces, it has been proposed that hot spots might provide the key for developing small-molecule PPI inhibitors. However, there has been no review on the ways in which the knowledge of hot spots can be used to achieve inhibitor design, nor critical examination of successful examples. This Digest discusses the characteristics of hot spots and the identification of druggable hot spot pockets. An analysis of four examples of hot spot-based design reveals the importance of this strategy in discovering potent and selective PPI inhibitors. A general procedure for hot spot-based design of PPI inhibitors is outlined. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Influence of disordered morphology on electrochromic stability of WO{sub 3}/PPy

    Energy Technology Data Exchange (ETDEWEB)

    Gaikwad, Digambar K. [D. Y. Patil College of Engineering & Technology, Kasaba Bawada, Kolhapur, 416006, Maharashtra (India); Mali, Sawanta S.; Hong, Chang K. [Polymer Energy Materials Laboratory, Department of Advanced Chemical Engineering, Chonnam National University, Gwangju, 500-757 (Korea, Republic of); Kadam, Anamika V., E-mail: anamikasonavane@rediff.com [D. Y. Patil College of Engineering & Technology, Kasaba Bawada, Kolhapur, 416006, Maharashtra (India); D.Y. Patil Medical University, Kasaba Bawada, Kolhapur, 416006, Maharashtra (India)

    2016-06-05

    Tungsten oxide (WO{sub 3}) films are critical for smart windows because of their capacity of varying the throughput of visible light and solar energy. This study highlights the evolution of structural and morphological changes of electrodeposited WO{sub 3} thin films coated with polypyrrole (PPy) by using chemical bath deposition. The structural and surface properties of WO{sub 3} thin films were studied using X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and transmission electron microscopy. The electrochemical stability was inspected using repetitive cyclic voltammetry (CV) cycles for each sample in LiClO{sub 4}-PC electrolyte for prolonged periods. The results showed an improvement in the electrochemical stability after the CV study. - Graphical abstract: Mechanism: A schematic of the mechanism is proposed in above fig. The mechanism is based on three step process: (i) WO{sub 3} coated on ITO by electrodeposition followed by thermal treatment. It produces ordered nanoarrayed morphology. (ii) A second step involving deposition of PPy by chemical bath deposition on ITO. It possesses globular morphology. (iii) When PPy coated on WO{sub 3}, PPy applies shearing force on WO{sub 3} and produces disordered nanoarrayed morphology. - Highlights: • Nanoarrayed WO{sub 3}/PPy composite was synthesized. • Interplanar spacing enhances due to PPy coating. • PPy applies shearing force on WO{sub 3} produces disordered morphology. • Nanocomposite showed high stability in LiClO{sub 4}-PC.

  1. Easily fabricated and lightweight PPy/PDA/AgNW composites for excellent electromagnetic interference shielding.

    Science.gov (United States)

    Wang, Yan; Gu, Fu-Qiang; Ni, Li-Juan; Liang, Kun; Marcus, Kyle; Liu, Shu-Li; Yang, Fan; Chen, Jin-Ju; Feng, Zhe-Sheng

    2017-11-30

    Conductive polymer composites (CPCs) containing nanoscale conductive fillers have been widely studied for their potential use in various applications. In this paper, polypyrrole (PPy)/polydopamine (PDA)/silver nanowire (AgNW) composites with high electromagnetic interference (EMI) shielding performance, good adhesion ability and light weight are successfully fabricated via a simple in situ polymerization method followed by a mixture process. Benefiting from the intrinsic adhesion properties of PDA, the adhesion ability and mechanical properties of the PPy/PDA/AgNW composites are significantly improved. The incorporation of AgNWs endows the functionalized PPy with tunable electrical conductivity and enhanced EMI shielding effectiveness (SE). By adjusting the AgNW loading degree in the PPy/PDA/AgNW composites from 0 to 50 wt%, the electrical conductivity of the composites greatly increases from 0.01 to 1206.72 S cm -1 , and the EMI SE of the composites changes from 6.5 to 48.4 dB accordingly (8.0-12.0 GHz, X-band). Moreover, due to the extremely low density of PPy, the PPy/PDA/AgNW (20 wt%) composites show a superior light weight of 0.28 g cm -3 . In general, it can be concluded that the PPy/PDA/AgNW composites with tunable electrical conductivity, good adhesion properties and light weight can be used as excellent EMI shielding materials.

  2. Electrochemical Behaviour of a PPy(DBS)/Polyacrylonitrile (PAN):LITF:EC:PC/ Li Cell

    DEFF Research Database (Denmark)

    Vidanapathirana, K.; Careem, M.A.; Skaarup, Steen

    2006-01-01

    The electrochemical behaviour of Li rechargeable cells with Polypyrrole (PPy) as the cathode material was investigated using cyclic voltammetry. The PPy used was doped with the large surfactant anion dodecyl benzenesulphonate (DBS-). The cells were constructed with PAN:LiTF:EC:PC gel electrolyte...... with Li as anode. The results indicate that during the first reduction, cations are inserted into the PPy film forming LiDBS neutral salt. During the next oxidation/reduction cycles, the mechanism then switches to anion movement. Cyclic voltammetry studies also verified that complete electrochemical...

  3. HomPPI: a class of sequence homology based protein-protein interface prediction methods

    Directory of Open Access Journals (Sweden)

    Dobbs Drena

    2011-06-01

    Full Text Available Abstract Background Although homology-based methods are among the most widely used methods for predicting the structure and function of proteins, the question as to whether interface sequence conservation can be effectively exploited in predicting protein-protein interfaces has been a subject of debate. Results We studied more than 300,000 pair-wise alignments of protein sequences from structurally characterized protein complexes, including both obligate and transient complexes. We identified sequence similarity criteria required for accurate homology-based inference of interface residues in a query protein sequence. Based on these analyses, we developed HomPPI, a class of sequence homology-based methods for predicting protein-protein interface residues. We present two variants of HomPPI: (i NPS-HomPPI (Non partner-specific HomPPI, which can be used to predict interface residues of a query protein in the absence of knowledge of the interaction partner; and (ii PS-HomPPI (Partner-specific HomPPI, which can be used to predict the interface residues of a query protein with a specific target protein. Our experiments on a benchmark dataset of obligate homodimeric complexes show that NPS-HomPPI can reliably predict protein-protein interface residues in a given protein, with an average correlation coefficient (CC of 0.76, sensitivity of 0.83, and specificity of 0.78, when sequence homologs of the query protein can be reliably identified. NPS-HomPPI also reliably predicts the interface residues of intrinsically disordered proteins. Our experiments suggest that NPS-HomPPI is competitive with several state-of-the-art interface prediction servers including those that exploit the structure of the query proteins. The partner-specific classifier, PS-HomPPI can, on a large dataset of transient complexes, predict the interface residues of a query protein with a specific target, with a CC of 0.65, sensitivity of 0.69, and specificity of 0.70, when homologs of

  4. Surprising volume change in PPy(DBS): An atomic force microscopy study

    DEFF Research Database (Denmark)

    Smela, E.; Gadegaard, N.

    1999-01-01

    Communication: Conjugated polymers such as polypyrrole (PPy) have potential use as artificial muscles or in microsystems such as valves for micro-fluid handling. One of the most important parameters in such uses is the magnitude of volume change during associated redox processes; however, until now...... estimates have varied greatly. Atomic force microscopy is reported here as allowing direct measurement of the in situ thickness change during oxidation and reduction of thin films of PPy doped with dodecylbenzenesulfonate....

  5. Luminescent Immunoprecipitation System (LIPS) for Detection of Autoantibodies Against ATP4A and ATP4B Subunits of Gastric Proton Pump H+,K+-ATPase in Atrophic Body Gastritis Patients

    Science.gov (United States)

    Lahner, Edith; Brigatti, Cristina; Marzinotto, Ilaria; Carabotti, Marilia; Scalese, Giulia; Davidson, Howard W; Wenzlau, Janet M; Bosi, Emanuele; Piemonti, Lorenzo; Annibale, Bruno; Lampasona, Vito

    2017-01-01

    Objectives: Circulating autoantibodies targeting the H+/K+-ATPase proton pump of gastric parietal cells are considered markers of autoimmune gastritis, whose diagnostic accuracy in atrophic body gastritis, the pathological lesion of autoimmune gastritis, remains unknown. This study aimed to assess autoantibodies against ATP4A and ATP4B subunits of parietal cells H+, K+-ATPase in atrophic body gastritis patients and controls. Methods: One-hundred and four cases with atrophic body gastritis and 205 controls were assessed for serological autoantibodies specific for ATP4A or ATP4B subunits using luminescent immunoprecipitation system (LIPS). Recombinant luciferase-reporter-fused-antigens were expressed by in vitro transcription-translation (ATP4A) or after transfection in Expi293F cells (ATP4B), incubated with test sera, and immune complexes recovered using protein-A-sepharose. LIPS assays were compared with a commercial enzyme immunoassay (EIA) for parietal cell autoantibodies. Results: ATP4A and ATP4B autoantibody titers were higher in cases compared to controls (Pgastritis. Both assays had the highest sensitivity, at the cost of diagnostic accuracy (89 and 90% specificity), outperforming traditional EIA. Once validated, these LIPS assays should be valuable screening tools for detecting biomarkers of damaged atrophic oxyntic mucosa. PMID:28102858

  6. Designing Focused Chemical Libraries Enriched in Protein-Protein Interaction Inhibitors using Machine-Learning Methods

    Science.gov (United States)

    Reynès, Christelle; Host, Hélène; Camproux, Anne-Claude; Laconde, Guillaume; Leroux, Florence; Mazars, Anne; Deprez, Benoit; Fahraeus, Robin; Villoutreix, Bruno O.; Sperandio, Olivier

    2010-01-01

    Protein-protein interactions (PPIs) may represent one of the next major classes of therapeutic targets. So far, only a minute fraction of the estimated 650,000 PPIs that comprise the human interactome are known with a tiny number of complexes being drugged. Such intricate biological systems cannot be cost-efficiently tackled using conventional high-throughput screening methods. Rather, time has come for designing new strategies that will maximize the chance for hit identification through a rationalization of the PPI inhibitor chemical space and the design of PPI-focused compound libraries (global or target-specific). Here, we train machine-learning-based models, mainly decision trees, using a dataset of known PPI inhibitors and of regular drugs in order to determine a global physico-chemical profile for putative PPI inhibitors. This statistical analysis unravels two important molecular descriptors for PPI inhibitors characterizing specific molecular shapes and the presence of a privileged number of aromatic bonds. The best model has been transposed into a computer program, PPI-HitProfiler, that can output from any drug-like compound collection a focused chemical library enriched in putative PPI inhibitors. Our PPI inhibitor profiler is challenged on the experimental screening results of 11 different PPIs among which the p53/MDM2 interaction screened within our own CDithem platform, that in addition to the validation of our concept led to the identification of 4 novel p53/MDM2 inhibitors. Collectively, our tool shows a robust behavior on the 11 experimental datasets by correctly profiling 70% of the experimentally identified hits while removing 52% of the inactive compounds from the initial compound collections. We strongly believe that this new tool can be used as a global PPI inhibitor profiler prior to screening assays to reduce the size of the compound collections to be experimentally screened while keeping most of the true PPI inhibitors. PPI-HitProfiler is

  7. Designing focused chemical libraries enriched in protein-protein interaction inhibitors using machine-learning methods.

    Directory of Open Access Journals (Sweden)

    Christelle Reynès

    2010-03-01

    Full Text Available Protein-protein interactions (PPIs may represent one of the next major classes of therapeutic targets. So far, only a minute fraction of the estimated 650,000 PPIs that comprise the human interactome are known with a tiny number of complexes being drugged. Such intricate biological systems cannot be cost-efficiently tackled using conventional high-throughput screening methods. Rather, time has come for designing new strategies that will maximize the chance for hit identification through a rationalization of the PPI inhibitor chemical space and the design of PPI-focused compound libraries (global or target-specific. Here, we train machine-learning-based models, mainly decision trees, using a dataset of known PPI inhibitors and of regular drugs in order to determine a global physico-chemical profile for putative PPI inhibitors. This statistical analysis unravels two important molecular descriptors for PPI inhibitors characterizing specific molecular shapes and the presence of a privileged number of aromatic bonds. The best model has been transposed into a computer program, PPI-HitProfiler, that can output from any drug-like compound collection a focused chemical library enriched in putative PPI inhibitors. Our PPI inhibitor profiler is challenged on the experimental screening results of 11 different PPIs among which the p53/MDM2 interaction screened within our own CDithem platform, that in addition to the validation of our concept led to the identification of 4 novel p53/MDM2 inhibitors. Collectively, our tool shows a robust behavior on the 11 experimental datasets by correctly profiling 70% of the experimentally identified hits while removing 52% of the inactive compounds from the initial compound collections. We strongly believe that this new tool can be used as a global PPI inhibitor profiler prior to screening assays to reduce the size of the compound collections to be experimentally screened while keeping most of the true PPI inhibitors. PPI

  8. Designing focused chemical libraries enriched in protein-protein interaction inhibitors using machine-learning methods.

    Science.gov (United States)

    Reynès, Christelle; Host, Hélène; Camproux, Anne-Claude; Laconde, Guillaume; Leroux, Florence; Mazars, Anne; Deprez, Benoit; Fahraeus, Robin; Villoutreix, Bruno O; Sperandio, Olivier

    2010-03-05

    Protein-protein interactions (PPIs) may represent one of the next major classes of therapeutic targets. So far, only a minute fraction of the estimated 650,000 PPIs that comprise the human interactome are known with a tiny number of complexes being drugged. Such intricate biological systems cannot be cost-efficiently tackled using conventional high-throughput screening methods. Rather, time has come for designing new strategies that will maximize the chance for hit identification through a rationalization of the PPI inhibitor chemical space and the design of PPI-focused compound libraries (global or target-specific). Here, we train machine-learning-based models, mainly decision trees, using a dataset of known PPI inhibitors and of regular drugs in order to determine a global physico-chemical profile for putative PPI inhibitors. This statistical analysis unravels two important molecular descriptors for PPI inhibitors characterizing specific molecular shapes and the presence of a privileged number of aromatic bonds. The best model has been transposed into a computer program, PPI-HitProfiler, that can output from any drug-like compound collection a focused chemical library enriched in putative PPI inhibitors. Our PPI inhibitor profiler is challenged on the experimental screening results of 11 different PPIs among which the p53/MDM2 interaction screened within our own CDithem platform, that in addition to the validation of our concept led to the identification of 4 novel p53/MDM2 inhibitors. Collectively, our tool shows a robust behavior on the 11 experimental datasets by correctly profiling 70% of the experimentally identified hits while removing 52% of the inactive compounds from the initial compound collections. We strongly believe that this new tool can be used as a global PPI inhibitor profiler prior to screening assays to reduce the size of the compound collections to be experimentally screened while keeping most of the true PPI inhibitors. PPI-HitProfiler is

  9. PpiA, a surface PPIase of the cyclophilin family in Lactococcus lactis.

    Directory of Open Access Journals (Sweden)

    Nicolas Trémillon

    Full Text Available BACKGROUND: Protein folding in the envelope is a crucial limiting step of protein export and secretion. In order to better understand this process in Lactococcus lactis, a lactic acid bacterium, genes encoding putative exported folding factors like Peptidyl Prolyl Isomerases (PPIases were searched for in lactococcal genomes. RESULTS: In L. lactis, a new putative membrane PPIase of the cyclophilin subfamily, PpiA, was identified and characterized. ppiA gene was found to be constitutively expressed under normal and stress (heat shock, H(2O(2 conditions. Under normal conditions, PpiA protein was synthesized and released from intact cells by an exogenously added protease, showing that it was exposed at the cell surface. No obvious phenotype could be associated to a ppiA mutant strain under several laboratory conditions including stress conditions, except a very low sensitivity to H(2O(2. Induction of a ppiA copy provided in trans had no effect i on the thermosensitivity of an mutant strain deficient for the lactococcal surface protease HtrA and ii on the secretion and stability on four exported proteins (a highly degraded hybrid protein and three heterologous secreted proteins in an otherwise wild-type strain background. However, a recombinant soluble form of PpiA that had been produced and secreted in L. lactis and purified from a culture supernatant displayed both PPIase and chaperone activities. CONCLUSIONS: Although L. lactis PpiA, a protein produced and exposed at the cell surface under normal conditions, displayed a very moderate role in vivo, it was found, as a recombinant soluble form, to be endowed with folding activities in vitro.

  10. A patient and public involvement (PPI) toolkit for meaningful and flexible involvement in clinical trials - a work in progress.

    Science.gov (United States)

    Bagley, Heather J; Short, Hannah; Harman, Nicola L; Hickey, Helen R; Gamble, Carrol L; Woolfall, Kerry; Young, Bridget; Williamson, Paula R

    2016-01-01

    Funders of research are increasingly requiring researchers to involve patients and the public in their research. Patient and public involvement (PPI) in research can potentially help researchers make sure that the design of their research is relevant, that it is participant friendly and ethically sound. Using and sharing PPI resources can benefit those involved in undertaking PPI, but existing PPI resources are not used consistently and this can lead to duplication of effort. This paper describes how we are developing a toolkit to support clinical trials teams in a clinical trials unit. The toolkit will provide a key 'off the shelf' resource to support trial teams with limited resources, in undertaking PPI. Key activities in further developing and maintaining the toolkit are to: ● listen to the views and experience of both research teams and patient and public contributors who use the tools; ● modify the tools based on our experience of using them; ● identify the need for future tools; ● update the toolkit based on any newly identified resources that come to light; ● raise awareness of the toolkit and ● work in collaboration with others to either develop or test out PPI resources in order to reduce duplication of work in PPI. Background Patient and public involvement (PPI) in research is increasingly a funder requirement due to the potential benefits in the design of relevant, participant friendly, ethically sound research. The use and sharing of resources can benefit PPI, but available resources are not consistently used leading to duplication of effort. This paper describes a developing toolkit to support clinical trials teams to undertake effective and meaningful PPI. Methods The first phase in developing the toolkit was to describe which PPI activities should be considered in the pathway of a clinical trial and at what stage these activities should take place. This pathway was informed through review of the type and timing of PPI activities within

  11. A Generalized Form of Context-Dependent Psychophysiological Interactions (gPPI): A Comparison to Standard Approaches

    Science.gov (United States)

    McLaren, Donald G.; Ries, Michele L.; Xu, Guofan; Johnson, Sterling C.

    2012-01-01

    Functional MRI (fMRI) allows one to study task-related regional responses and task-dependent connectivity analysis using psychophysiological interaction (PPI) methods. The latter affords the additional opportunity to understand how brain regions interact in a task-dependent manner. The current implementation of PPI in Statistical Parametric Mapping (SPM8) is configured primarily to assess connectivity differences between two task conditions, when in practice fMRI tasks frequently employ more than two conditions. Here we evaluate how a generalized form of context-dependent PPI (gPPI; http://www.nitrc.org/projects/gppi), which is configured to automatically accommodate more than two task conditions in the same PPI model by spanning the entire experimental space, compares to the standard implementation in SPM8. These comparisons are made using both simulations and an empirical dataset. In the simulated dataset, we compare the interaction beta estimates to their expected values and model fit using the Akaike Information Criterion (AIC). We found that interaction beta estimates in gPPI were robust to different simulated data models, were not different from the expected beta value, and had better model fits than when using standard PPI (sPPI) methods. In the empirical dataset, we compare the model fit of the gPPI approach to sPPI. We found that the gPPI approach improved model fit compared to sPPI. There were several regions that became non-significant with gPPI. These regions all showed significantly better model fits with gPPI. Also, there were several regions where task-dependent connectivity was only detected using gPPI methods, also with improved model fit. Regions that were detected with all methods had more similar model fits. These results suggest that gPPI may have greater sensitivity and specificity than standard implementation in SPM. This notion is tempered slightly as there is no gold standard; however, data simulations with a known outcome support our

  12. PPI finder: a mining tool for human protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Min He

    Full Text Available BACKGROUND: The exponential increase of published biomedical literature prompts the use of text mining tools to manage the information overload automatically. One of the most common applications is to mine protein-protein interactions (PPIs from PubMed abstracts. Currently, most tools in mining PPIs from literature are using co-occurrence-based approaches or rule-based approaches. Hybrid methods (frame-based approaches by combining these two methods may have better performance in predicting PPIs. However, the predicted PPIs from these methods are rarely evaluated by known PPI databases and co-occurred terms in Gene Ontology (GO database. METHODOLOGY/PRINCIPAL FINDINGS: We here developed a web-based tool, PPI Finder, to mine human PPIs from PubMed abstracts based on their co-occurrences and interaction words, followed by evidences in human PPI databases and shared terms in GO database. Only 28% of the co-occurred pairs in PubMed abstracts appeared in any of the commonly used human PPI databases (HPRD, BioGRID and BIND. On the other hand, of the known PPIs in HPRD, 69% showed co-occurrences in the literature, and 65% shared GO terms. CONCLUSIONS: PPI Finder provides a useful tool for biologists to uncover potential novel PPIs. It is freely accessible at http://liweilab.genetics.ac.cn/tm/.

  13. Oxadiazole-carbazole polymer (POC)-Ir(ppy)3 tunable emitting composites

    Science.gov (United States)

    Bruno, Annalisa; Borriello, Carmela; Di Luccio, Tiziana; Sessa, Lucia; Concilio, Simona; Haque, Saif A.; Minarini, Carla

    2017-04-01

    POC polymer is an oxadiazole-carbazole copolymer we have previously synthetized and established as light emitting material in Organic Light Emitting Devices (OLEDs), although POC quantum yield emission efficiency and color purity still need to be enhanced. On the other hand, tris[2-phenylpyridinato-C2,N]iridium(III) (Ir(ppy)3) complexes, namely Ir(ppy)3 are among the brightest luminophores employed in green light emitting devices. Our aim, in this work, is to take advantage of Ir(ppy)3 bright emission by combining the Ir complex with blue emitting POC to obtain tunable light emitting composites over a wide range of the visible spectrum. Here we have investigated the optical proprieties POC based nanocomposites with different concentrations of Ir(ppy)3, ranging from 1 to 10 wt%. Both spectral and time resolved fluorescence measurements show an efficient energy transfer from the polymer to the dopants, resulting in white-emitting composites. The most intense and stable emission has been found when POC was doped with about 5 wt% concentration of Ir(ppy)3.

  14. Randomised clinical trial

    DEFF Research Database (Denmark)

    Coyle, C; Crawford, G; Wilkinson, J

    2017-01-01

    BACKGROUND: Symptomatic breakthrough in proton pump inhibitor (PPI)-treated gastro-oesophageal reflux disease (GERD) patients is a common problem with a range of underlying causes. The nonsystemic, raft-forming action of alginates may help resolve symptoms. AIM: To assess alginate-antacid (Gaviscon...... Double Action, RB, Slough, UK) as add-on therapy to once-daily PPI for suppression of breakthrough reflux symptoms. METHODS: In two randomised, double-blind studies (exploratory, n=52; confirmatory, n=262), patients taking standard-dose PPI who had breakthrough symptoms, assessed by Heartburn Reflux...

  15. TO COMPARE THE SAFETY AND EFFICACY OF THREE DIFFERENT, PROTON PUMP INHIBITORS OMEPRAZOLE, ESO M EPRAZOLE AND RABEPRAZOLE IN A TRIPLE DRUG REGIMEN IN PATIENTS WITH PEPTIC ULCER DISEASE IN THE ERADICATION OF H. PYLORI INFECTION

    Directory of Open Access Journals (Sweden)

    Margaret Viola

    2015-03-01

    Full Text Available Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world. Helicobacter pylori ( H. pylori infection associated duodenal ulcers should undergo eradication therapy. There are many regimens offered for H. pylori eradication which include triple , quadruple , or sequential therapy regimens. In our study we planned to see whether these differences in pharmacokinetic properties show any difference in t he efficacy and safety parameters between treatment with omeprazole rabeprazole and esomeprazole in the triple drug regimen for eradication of H.pylori infection in peptic ulcer patients in our hospital Osmania General Hospital / Osmania Medical College , Hyderabad. MATERIALS AND METHODS: A total number of 45 patients were enrolled in the study. Patients with either sex suffering from peptic ulcer defined as ulcer crater of >2.5mm in size by endoscopy. Study Design : It was a randomized double blind , paralle l and comparative study. CONCLUSION: Two weeks after triple drug treatment , H.pylori was negative in 66.7% , 73% and 80% and Rapid urease test was negative in 53% , 60% and 66% in group A , B and C respectively. Endoscopy findings showed significant reduction in size and healing of ulcers in group A , B and C. There was improvement in signs and symptoms by 53 to 80% , after 2 weeks. Hence after therapy with triple drug regimen H.pylori eradication was 66 - 80% and healing of ulcers was 83 – 100% which was higher in Rabeprazole group. At 6 weeks , there was complete relief of signs and symptoms. At the follow up of 10 weeks there was no ulcer recurrence. No adverse effects were noted in all the groups. In conclusion , Triple drug regimen had shown to eradicate H.pylori infection in the treatment of Peptic ulcer. There was healing of ulcers in all the groups which was highly significant. There was no recurrence of peptic ulcer with these regimens in all the groups. However Rabeprazole group patients became asymptomatic ra pidly than other groups with better H.pylori eradication.

  16. Evolutionary, kinetic and thermodynamic aspects on the bioenergetics of inorganic pyrophosphate (PPi) and adenosine triphosphate (ATP)

    International Nuclear Information System (INIS)

    Baltscheffsky, H.; Baltscheffsky, M.

    1995-01-01

    Energy barriers for energy carriers are of fundamental significance for the successful operation of the bioenergetic reactions in living cells. PPi and ATP are outstanding ''energy-rich'' examples of molecular ''energy currencies'' in biological systems, with kinetic barriers preventing excessively fast thermodynamically feasible hydrolysis from occurring. The barriers may be considered to facilitate the energy coupling roles of these phosphate compounds, which are to secure growth and maintain numerous other energy requiring functions. The enzymes involved in overcoming the energies of activation of the bioenergetic reactions have evolved to be very well tuned for their roles. Three aspects will be discussed in some detail. The first is the fact that ATP at neutral pH is considerably more energy-rich than PPi, which thus has been called a ''poor man's ATP''. This is exemplified by the kinetic and thermodynamic differences observed between the requirements for the photosynthetic formation of PPi and ATP in certain photobacterial chromatophores by varying levels of energy supply. At lower pH, PPi and ATP are equally energy-rich, which may be of significance for acidophiles. The second concerns the possible evolutionary significance of the finding that, in the dark, a pH gradient suffices to drive extensive PPi synthesis, whereas ATP synthesis requires both a pH gradient and a membrane potential (Strid et al, Biochim. Biophys. Acta 892 (1987) 236-244). Thirdly, PPi as the most plausible predecessor to ATP in the origin and early evolution of life, will be discussed. (author). Abstract only

  17. A solid state actuator based on polypyrrole (PPy) and a solid electrolyte NBR working in air

    Science.gov (United States)

    Cho, Misuk; Nam, Jaedo; Choi, Hyouk Ryeol; Koo, Jachoon; Lee, Youngkwan

    2005-05-01

    The solid polymer electrolyte based conducting polymer actuator was presented. In the preparation of acutuator module, an ionic liquid impregnated a synthetic rubber (NBR) and PPy were used as a solid polymer electrolyte and conducting polymer, respectively. An ionic liquid, 1-butyl-3-methylimidazolium bis (trifluoromethyl sulfonyl)imide (BMITFSI) is gradually dispersed into the NBR film and the conducting polymer, PPy was synthesized on the surface of NBR. The ionic conductivity of new type solid polymer electrolyte as a function of the immersion time was investigated. The cyclic voltammetry responsed and the redox switching dynamics of PEDOT in NBR matrix were studied. The displacement of the actuator was measured by laser beam.

  18. Electrochemomechanical Behaviour of Bilayer and Trilayer Films with PEDOT and PPY Conducting Polymers

    DEFF Research Database (Denmark)

    Zainudeen, Umer L.; Careem, M.A.; Skaarup, Steen

    2008-01-01

    a constant load of 1.5 g. The cyclic voltammograms as well as the UV-visible spectra of PEDOT and PPy are very different, pointing towards the possibility of being able to separate the two layers experimentally – even when combined in a single film. Bilayer results show combined characteristics of each...... layer is very thin compared to that of the PPy layer, and characterized using cyclic voltammetry, optical absorption spectroscopy and electrochemical quartz crystal microbalance (EQCM) techniques. Actuators of bilayer and trilayer free standing films were characterized electromechanically under...

  19. Seven-day PPI-triple therapy with levofloxacin is very effective for Helicobacter pylori eradication.

    NARCIS (Netherlands)

    Schrauwen, R.W.; Janssen, M.J.R.; Boer, W.A. de

    2009-01-01

    BACKGROUND: Helicobacter pylori infection causes lifelong gastritis and is associated with the development of peptic ulcer disease, MALT lymphoma and gastric cancer. Many patients benefit from H. pylori eradication therapy. PPI-triple therapy is recommended as initial therapy. Quadruple therapy,

  20. Identifying protein complex by integrating characteristic of core-attachment into dynamic PPI network.

    Directory of Open Access Journals (Sweden)

    Xianjun Shen

    Full Text Available How to identify protein complex is an important and challenging task in proteomics. It would make great contribution to our knowledge of molecular mechanism in cell life activities. However, the inherent organization and dynamic characteristic of cell system have rarely been incorporated into the existing algorithms for detecting protein complexes because of the limitation of protein-protein interaction (PPI data produced by high throughput techniques. The availability of time course gene expression profile enables us to uncover the dynamics of molecular networks and improve the detection of protein complexes. In order to achieve this goal, this paper proposes a novel algorithm DCA (Dynamic Core-Attachment. It detects protein-complex core comprising of continually expressed and highly connected proteins in dynamic PPI network, and then the protein complex is formed by including the attachments with high adhesion into the core. The integration of core-attachment feature into the dynamic PPI network is responsible for the superiority of our algorithm. DCA has been applied on two different yeast dynamic PPI networks and the experimental results show that it performs significantly better than the state-of-the-art techniques in terms of prediction accuracy, hF-measure and statistical significance in biology. In addition, the identified complexes with strong biological significance provide potential candidate complexes for biologists to validate.

  1. True-color 640 ppi OLED arrays patterned by CA i-line photolithography

    NARCIS (Netherlands)

    Malinowski, P.E.; Ke, T.; Nakamura, A.; Chang, T.-Y.; Gokhale, P.; Steudel, S.; Janssen, D.; Kamochi, Y.; Koyama, I.; Iwai,Y.; Heremans, P.

    2015-01-01

    In this paper, side-by-side patterning of red, green and blue OLEDs is demonstrated. To achieve 640 ppi arrays with 20 µm subpixel pitch, chemically amplified, i-line photoresist system with submicron resolution was used. These results show feasibility of obtaining full-color displays with

  2. 44-1: Invited Paper: Photolithography as Enabler of AMOLED Displays Beyond 1000 ppi

    NARCIS (Netherlands)

    Malinowski, P.E.; Ke, T.; Nakamura, A.; Vicca, P.; Kronemeijer, A.J.; Ameys, M.; Steen, J.L. van der; Steudel, S.; Kamochi, Y.; Iwai, Y.; Gelinck, G.; Heremans, P.

    2017-01-01

    This paper describes the potential of hi-res display fabrication using OLED photolithography. We demonstrate 1250 ppi multicolor arrays, pixel scaling down to 3 μm pitch, integration in active displays, and improving lifetime after patterning (200 hours T75, smOLEDs). Photolithography can enable

  3. Pancreatic bicarbonate secretion involves two proton pumps

    DEFF Research Database (Denmark)

    Novak, Ivana; Wang, Jing; Henriksen, Katrine L.

    2011-01-01

    Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium expres...

  4. Structural aspects of proton-pumping ATPases

    NARCIS (Netherlands)

    Walker, J. E.; Fearnley, I. M.; Lutter, R.; Todd, R. J.; Runswick, M. J.

    1990-01-01

    ATP synthase is found in bacteria, chloroplasts and mitochondria. The simplest known example of such an enzyme is that in the eubacterium Escherichia coli; it is a membrane-bound assembly of eight different polypeptides assembled with a stoichiometry of alpha 3 beta 3 gamma 1 delta 1 epsilon 1

  5. Feasibility of MR Imaging/MR Spectroscopy-Planned Focal Partial Salvage Permanent Prostate Implant (PPI) for Localized Recurrence After Initial PPI for Prostate Cancer

    International Nuclear Information System (INIS)

    Hsu, Charles C.; Hsu, Howard; Pickett, Barby; Crehange, Gilles; Hsu, I-Chow Joe; Dea, Ryan; Weinberg, Vivian; Gottschalk, Alexander R.; Kurhanewicz, John; Shinohara, Katsuto; Roach, Mack

    2013-01-01

    Purpose: To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease. Methods and Materials: From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Results: At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or ≥7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound

  6. Feasibility of MR Imaging/MR Spectroscopy-Planned Focal Partial Salvage Permanent Prostate Implant (PPI) for Localized Recurrence After Initial PPI for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Charles C., E-mail: hsucc@radonc.ucsf.edu [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Hsu, Howard [Department of Radiation Oncology, New York University, New York, New York (United States); Pickett, Barby [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Crehange, Gilles [Department of Radiation Oncology, Dijon University, Dijon (France); Hsu, I-Chow Joe; Dea, Ryan [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Weinberg, Vivian [Biostatistics and Computational Biology Core, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Gottschalk, Alexander R. [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Kurhanewicz, John [Department of Radiology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Shinohara, Katsuto [Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Roach, Mack [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States)

    2013-02-01

    Purpose: To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease. Methods and Materials: From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Results: At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or {>=}7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound

  7. Nano-silver mediated polymerization of pyrrole: synthesis and gas sensing properties of polypyrrole (PPy)/Ag nano-composite.

    Science.gov (United States)

    Kate, Kunal H; Damkale, Shubhangi R; Khanna, P K; Jain, G H

    2011-09-01

    Thermal polymerization of pyrrole was performed using silver nitrate as source of silver ions followed by its conversion to Polypyrrole (PPy)/Ag nano-comoposites without using any external oxidizing agent or solvent. The formation of PPy was monitored by UV-Visible absorption spectroscopy showing a band at approximately 464 nm. XRD measurement confirmed characteristic peaks for face centered cubic (fcc) silver and presence of PPy at 2 theta of approximately 23 degrees suggesting the formation of PPy/Ag nanocomposite. Transmission electron microscopy (TEM) images showed non-aggregated spherical Ag nano-particles of about 5-10 nm. PPy/Ag thick film acts as a NH3 sensor at 100 degrees C, a H2S sensor at 250 degrees C and CO2 sensor at 350 degrees C. The thick films showed capability to recognize various gases at different operating temperature.

  8. Significant enhancement in volumetric and gravimetric capacitance of Cu-TiO2/PPY composite for supercapacitor application

    Science.gov (United States)

    Purty, B.; Choudhary, R. B.

    2018-04-01

    Copper doped titanium dioxide-polypyrrole (Cu-TiO2/PPY) composite was successfully synthesized via chemical oxidative in-situ polymerization process. The structural and morphological properties of Cu-TiO2/PPY composite were investigated using X-ray diffractometer (XRD), field emission electron microscopy (FESEM) and transmission electron microscopy(TEM) techniques. The electrochemical properties of as-synthesized composite were studied using cyclic voltammetry (CV), galvanostatic charge discharge (GCD) and electrochemical impedance spectroscopic (EIS) techniques. The novel Cu-TiO2/PPY composite showed enhanced volumetric capacitance ˜714 F cm-1 and gravimetric capacitance ˜674 F g-1 at 1 A g-1. In addition an excellent coulombic efficiency and comparabley low charge transfer resistance than pure PPY suggests improved supercapacitive performance of Cu-TiO2/PPY composite as an electrode material.

  9. Selective Phosphonylation of 5'-Adenosine Monophosphate (5'-AMP) via Pyrophosphite [PPi(III)].

    Science.gov (United States)

    Kaye, Karl; Bryant, David E; Marriott, Katie E R; Ohara, Shohei; Fishwick, Colin W G; Kee, Terence P

    2016-11-01

    We describe here experiments which demonstrate the selective phospho-transfer from a plausibly prebiotic condensed phosphorus (P) salt, pyrophosphite [H 2 P 2 O 5 2- ; PPi(III)], to the phosphate group of 5'-adenosine mono phosphate (5'-AMP). We show further that this P-transfer process is accelerated both by divalent metal ions (M 2+ ) and by organic co-factors such as acetate (AcO - ). In this specific case of P-transfer from PPi(III) to 5'-AMP, we show a synergistic enhancement of transfer in the combined presence of M 2+ & AcO - . Isotopic labelling studies demonstrate that hydrolysis of the phosphonylated 5'-AMP, [P(III)P(V)-5'-AMP], proceeds via nuceophilic attack of water at the Pi(III) terminus.

  10. Fabrication, characterization and gas sensing studies of PPy/MWCNT/SLS nanocomposite

    Energy Technology Data Exchange (ETDEWEB)

    Tiwari, D. C., E-mail: dctiwari2001@yahoo.com; Atri, Priyanka, E-mail: dctiwari2001@yahoo.com [SOS Electronics, Jiwaji University, Gwalior (M.P.)-474011 (India); Sharma, R. [CSIR-CEERI, Pilani (Rajasthan)-333031 (India)

    2014-04-24

    Multiwall carbon nanotubes (MWCNT) coated with polypyrrole nanocomposite was prepared by in-situ chemical oxidative polymerization method in the presence of surfactant (SLS). The scanning electron microscope (SEM) pictures indicate the core shell structure of PPy/MWCNT/SLS nanocomposite. Nature of the prepared material was investigated by X-ray diffraction spectroscopy. This nanocomposite shows the excellent gas sensing behaviour for ammonia gas at 150 ppm and 300 ppm levels.

  11. Preparation and Surface Analysis of PPY/SDBS Films on Aluminum Substrates

    Directory of Open Access Journals (Sweden)

    Lisete C. Scienza

    2001-09-01

    Full Text Available Polypyrrole films were generated on high purity aluminum substrates under anodic polarization from aqueous electrolytes comprised of pyrrole and sodium dodecylbenzene sulfonate. The methods employed to characterize the polymer films included scanning electron microscopy, Fourier-transform infrared and X-photoelectron spectroscopy and X-ray diffraction. PPY/SDBS films revealed nodular morphology with occasional appearing of "dendrites", high level of protonation, excess of counter-anions ([S]/[N] > [N+]/[N] and high degrees of disorder.

  12. High Operating Voltage Supercapacitor Using PPy/AC Composite Electrode Based on Simple Dipping Method

    Directory of Open Access Journals (Sweden)

    Kyoungho Kim

    2015-01-01

    Full Text Available As various wearable devices are emerging, self-generated power sources, such as piezoelectric generators, triboelectric generators, and thermoelectric generators, are of interest. To adapt self-generated power sources for application devices, a supercapacitor is necessary because of the short generation times (1–10 ms and low generated power (1–100 μW of self-generated power sources. However, to date, supercapacitors are too large to be adapted for wearable devices. There have been many efforts to reduce the size of supercapacitors by using polypyrrole (PPy for high energy supercapacitor electrodes. However, these supercapacitors have several disadvantages, such as a low operating voltage due to the use of an aqueous electrolyte, and complex manufacturing methods, such as the hydrogel and aerosol methods. In particular, the low operating voltage (~1.0 V is a significant issue because most electronic components operate above 3.0 V. In this study, we successfully demonstrated the high operating voltage (3.0 V of a supercapacitor using a PPy/activated carbon (AC composite electrode based on the chemical polymerization of the PPy by simple dipping. In addition, a twofold enhancement of its energy density was achieved compared with conventional supercapacitors using AC electrodes.

  13. Tautomeric forms of PPI dendrimers functionalized with 4-(4′-ethoxybenzoyloxy)salicylaldehyde chromophores

    International Nuclear Information System (INIS)

    Franckevičius, M.; Vaišnoras, R.; Marcos, M.; Serrano, J.L.; Gruodis, A.; Galikova, N.; Gulbinas, V.

    2012-01-01

    Highlights: ► SA chromophore groups are formed by bonding terminal groups to PPI dendrimers. ► SA chromophore groups reveal four most stable tautomeric forms. ► Tautomeric properties of SA groups depend on the dendrimer generation and solvent. ► Aggregation of SA chromophores facilitates formation of the trans-keto tautomers. ► Fluorescence of PPI SA dendrimers is attributed to nπ ∗ states of keto tautomers. -- Abstract: Bonding of the promesogenic unit derived from 4-(4′-ethoxybenzoyloxy)salicylaldehyde to the amino terminated PPI dendrimer chains results in formation of the salicylidenimine chromophore groups. Absorption and fluorescence investigations of the dendrimer solutions supported by the quantum chemistry calculations revealed that the chromophore groups may exist in enol and keto tautomeric forms with relative concentrations depending on the dendrimer generation and solvent. The dendrimer fluorescence is attributed to nπ ∗ states of keto tautomers which may also be formed from excited enol tautomers.

  14. A validity assessment of the Progress out of Poverty Index (PPI)™.

    Science.gov (United States)

    Desiere, Sam; Vellema, Wytse; D'Haese, Marijke

    2015-04-01

    Development organisations need easy-to-use and quick-to-implement indicators to quantify poverty when requested to measure program impact. In this paper we assess the validity of the Progress out of Poverty Index (PPI)™, a country-specific indicator based on ten closed questions on directly observable household characteristics, by its compliance to the SMART criteria. Each response receives a pre-determined score, such that the sum of these scores can be converted into the likelihood the household is living below the poverty line. We focus on the PPI scorecard for Rwanda, which was validated using two national household surveys conducted in 2005/06 and 2010/11. The PPI is Specific, Measurable, Available cost effectively, and Timely available. Yet, its Relevance depends on the way it is used. Although it accurately distinguishes poor from non-poor households, making it a useful reporting tool, its limited sensitivity to changes in poverty status restricts its usefulness for evaluating the impact of development projects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Pantoprazole-Induced Delirium: Review of a Case and Associated Literature.

    Science.gov (United States)

    Razdan, Anupriya; Viswanathan, Ramaswamy; Tusher, Alan

    2018-01-01

    Proton pump inhibitors (PPIs) are frequently prescribed antiulcer agents in hospitals and are shown to be safer than H-2 blockers. We present a case report of PPI-induced delirium, regarding which not much has been written in the literature. We present a case of a 93-year-old woman with no known past psychiatric history, who was hospitalized for syncope workup and who developed delirium after a double dose of pantoprazole. Very few reports of PPI-induced delirium exist in the literature. In this case report, we attempt to highlight the mechanism of PPI induced delirium which in our case was most likely due to the primary effects of PPI and drug-drug interactions. Given the paucity of literature on this topic, we encourage further research into relationship between PPI and delirium and urge caution while using PPIs in geriatric population.

  16. The Arabidopsis ppi1 Mutant Is Specifically Defective in the Expression, Chloroplast Import, and Accumulation of Photosynthetic ProteinsW⃞

    Science.gov (United States)

    Kubis, Sybille; Baldwin, Amy; Patel, Ramesh; Razzaq, Azam; Dupree, Paul; Lilley, Kathryn; Kurth, Joachim; Leister, Dario; Jarvis, Paul

    2003-01-01

    The import of nucleus-encoded proteins into chloroplasts is mediated by translocon complexes in the envelope membranes. A component of the translocon in the outer envelope membrane, Toc34, is encoded in Arabidopsis by two homologous genes, atTOC33 and atTOC34. Whereas atTOC34 displays relatively uniform expression throughout development, atTOC33 is strongly upregulated in rapidly growing, photosynthetic tissues. To understand the reason for the existence of these two related genes, we characterized the atTOC33 knockout mutant ppi1. Immunoblotting and proteomics revealed that components of the photosynthetic apparatus are deficient in ppi1 chloroplasts and that nonphotosynthetic chloroplast proteins are unchanged or enriched slightly. Furthermore, DNA array analysis of 3292 transcripts revealed that photosynthetic genes are moderately, but specifically, downregulated in ppi1. Proteome differences in ppi1 could be correlated with protein import rates: ppi1 chloroplasts imported the ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit and 33-kD oxygen-evolving complex precursors at significantly reduced rates, but the import of a 50S ribosomal subunit precursor was largely unaffected. The ppi1 import defect occurred at the level of preprotein binding, which is consistent with a role for atToc33 during preprotein recognition. The data suggest that atToc33 is involved preferentially in the import of photosynthetic proteins and, by extension, that atToc34 is involved in the import of nonphotosynthetic chloroplast proteins. PMID:12897258

  17. Preparation of stable magnetic nanofluids containing Fe3O4@PPy nanoparticles by a novel one-pot route

    Directory of Open Access Journals (Sweden)

    Zhao Baobao

    2011-01-01

    Full Text Available Abstract Stable magnetic nanofluids containing Fe3O4@Polypyrrole (PPy nanoparticles (NPs were prepared by using a facile and novel method, in which one-pot route was used. FeCl3·6H2O was applied as the iron source, and the oxidizing agent to produce PPy. Trisodium citrate (Na3cit was used as the reducing reagent to form Fe3O4 NPs. The as-prepared nanofluid can keep long-term stability. The Fe3O4@PPy NPs can still keep dispersing well after the nanofluid has been standing for 1 month and no sedimentation is found. The polymerization reaction of the pyrrole monomers took place with Fe3+ ions as the initiator, in which these Fe3+ ions remained in the solution adsorbed on the surface of the Fe3O4 NPs. Thus, the core-shell NPs of Fe3O4@PPy were obtained. The particle size of the as-prepared Fe3O4@PPy can be easily controlled from 7 to 30 nm by the polymerization reaction of the pyrrole monomers. The steric stabilization and weight of the NPs affect the stability of the nanofluids. The as-prepared Fe3O4@PPy NPs exhibit superparamagnetic behavior.

  18. Structural and electrochemical studies of PPy/PEG-LiFePO4 cathode material for Li-ion batteries

    International Nuclear Information System (INIS)

    Fedorkova, Andrea; Nacher-Alejos, Ana; Gomez-Romero, Pedro; Orinakova, Renata; Kaniansky, Dusan

    2010-01-01

    A simple chemical oxidative polymerization of pyrrole (Py) directly onto the surface of LiFePO 4 particles was applied to the synthesis of polypyrrole-LiFePO 4 (PPy-LiFePO 4 ) powder. The LiFePO 4 sample without carbon coating was synthesized by a solvothermal method. The polyethylene glycol (PEG) was used as additive during Py polymerization for increasing the PPy-LiFePO 4 conductivity. Properties of resulting LiFePO 4 , PPy-LiFePO 4 and PPy/PEG-LiFePO 4 samples were characterized by XRD, SEM, TGA and galvanostatic charge-discharge measurements. These methods confirmed the presence of polypyrrole on LiFePO 4 particles and its homogeneous distribution in the resulting powder material. The PPy/PEG-LiFePO 4 composites show higher discharge capacity than pure LiFePO 4 , as PPy/PEG network improves the electron conductivity. It presents specific discharge capacity of 153 mAh/g at C/5 rate.

  19. Measurement of the asymmetry parameter for the decay $\\bar\\Lambda \\to \\bar p\\pi^+$

    OpenAIRE

    BES collaboration

    2009-01-01

    Based on a sample of $58\\times10^6J/\\psi$ decays collected with the BESII detector at the BEPC, the $\\bar\\Lambda$ decay parameter $\\alpha_{\\bar\\Lambda}$ for $\\bar\\Lambda\\to \\bar p \\pi^+$ is measured using about 9000 $J/\\psi\\to\\Lambda\\bar\\Lambda\\to p \\bar p \\pi^+\\pi^-$ decays. A fit to the joint angular distributions yields $\\alpha_{\\bar\\Lambda}(\\bar\\Lambda\\to \\bar p\\pi^+)=-0.755\\pm0.083\\pm0.063$, where the first error is statistical, and the second systematic.

  20. Alzheimer Europe's position on involving people with dementia in research through PPI (patient and public involvement)

    DEFF Research Database (Denmark)

    Gove, Dianne; Diaz-Ponce, Ana; Georges, Jean

    2018-01-01

    This paper reflects Alzheimer Europe's position on PPI (patient and public involvement) in the context of dementia research and highlights some of the challenges and potential risks and benefits associated with such meaningful involvement. The paper was drafted by Alzheimer Europe in collaboration...... with members of INTERDEM and the European Working Group of People with Dementia. It has been formally adopted by the Board of Alzheimer Europe and endorsed by the Board of INTERDEM and by the JPND working group 'Dementia Outcome Measures - Charting New Territory'. Alzheimer Europe is keen to promote...

  1. Discovering functional interdependence relationship in PPI networks for protein complex identification.

    Science.gov (United States)

    Lam, Winnie W M; Chan, Keith C C

    2012-04-01

    Protein molecules interact with each other in protein complexes to perform many vital functions, and different computational techniques have been developed to identify protein complexes in protein-protein interaction (PPI) networks. These techniques are developed to search for subgraphs of high connectivity in PPI networks under the assumption that the proteins in a protein complex are highly interconnected. While these techniques have been shown to be quite effective, it is also possible that the matching rate between the protein complexes they discover and those that are previously determined experimentally be relatively low and the "false-alarm" rate can be relatively high. This is especially the case when the assumption of proteins in protein complexes being more highly interconnected be relatively invalid. To increase the matching rate and reduce the false-alarm rate, we have developed a technique that can work effectively without having to make this assumption. The name of the technique called protein complex identification by discovering functional interdependence (PCIFI) searches for protein complexes in PPI networks by taking into consideration both the functional interdependence relationship between protein molecules and the network topology of the network. The PCIFI works in several steps. The first step is to construct a multiple-function protein network graph by labeling each vertex with one or more of the molecular functions it performs. The second step is to filter out protein interactions between protein pairs that are not functionally interdependent of each other in the statistical sense. The third step is to make use of an information-theoretic measure to determine the strength of the functional interdependence between all remaining interacting protein pairs. Finally, the last step is to try to form protein complexes based on the measure of the strength of functional interdependence and the connectivity between proteins. For performance evaluation

  2. Dielectric and electrical study of PPy doped PVA-PVP films

    Science.gov (United States)

    Jha, Sushma; Tripathi, Deepti

    2018-05-01

    Dielectric parameters of free standing films of pure PVA (PolyvinylAlcohol) and PVA with varying concentrations of PVP(Polyvinylpyrrolidone) and Polypyrrole were prepared and studied in low frequency range (100Hz - 2MHz). The results show that dielectric constant, loss tangent and conductivity increase sharply on increasing the concentration of PVP above 50wt% in polymer matrix. PVA-PVP film with low concentration of PPy showed improvement in the values of complex permittivity, loss tangent and ac conductivity within the experimental frequency range. This eco - friendly polymeric material will be studied for its probable application for RFI/EMI shielding, biosensors, capacitors & insulation purposes.

  3. Search for $B_c^+$ decays to the $p\\overline p\\pi^+$ final state

    CERN Document Server

    Aaij, Roel; Adeva, Bernardo; Adinolfi, Marco; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; d'Argent, Philippe; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baker, Sophie; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Bellee, Violaine; Belloli, Nicoletta; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Betti, Federico; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bifani, Simone; Billoir, Pierre; Bird, Thomas; Birnkraut, Alex; Bizzeti, Andrea; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borgheresi, Alessio; Borghi, Silvia; Borisyak, Maxim; Borsato, Martino; Boubdir, Meriem; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Buchanan, Emma; Burr, Christopher; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chatzikonstantinidis, Georgios; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dall'Occo, Elena; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Aguiar Francisco, Oscar; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Demmer, Moritz; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Di Ruscio, Francesco; Dijkstra, Hans; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Dungs, Kevin; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farley, Nathanael; Farry, Stephen; Fay, Robert; Fazzini, Davide; Ferguson, Dianne; Fernandez Albor, Victor; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fleuret, Frederic; Fohl, Klaus; Fontana, Marianna; Fontanelli, Flavio; Forshaw, Dean Charles; Forty, Roger; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Garsed, Philip John; Gascon, David; Gaspar, Clara; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heister, Arno; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hongming, Li; Hulsbergen, Wouter; Humair, Thibaud; Hushchyn, Mikhail; Hussain, Nazim; Hutchcroft, David; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kecke, Matthieu; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khairullin, Egor; Khanji, Basem; Khurewathanakul, Chitsanu; Kirn, Thomas; Klaver, Suzanne; Klimaszewski, Konrad; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Kozeiha, Mohamad; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kurek, Krzysztof; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Xuesong; Loh, David; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusardi, Nicola; Lusiani, Alberto; Lyu, Xiao-Rui; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Maguire, Kevin; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massacrier, Laure Marie; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Melnychuk, Dmytro; Merk, Marcel; Merli, Andrea; Michielin, Emanuele; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Molina Rodriguez, Josue; Monroy, Ignacio Alberto; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen-Mau, Chung; Niess, Valentin; Nieswand, Simon; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Osorio Rodrigues, Bruno; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Pappenheimer, Cheryl; Parker, William; Parkes, Christopher; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pikies, Malgorzata; Pinci, Davide; Pistone, Alessandro; Piucci, Alessio; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rama, Matteo; Ramos Pernas, Miguel; Rangel, Murilo; Raniuk, Iurii; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; dos Reis, Alberto; Renaudin, Victor; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Rogozhnikov, Alexey; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Ruf, Thomas; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schael, Stefan; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sergi, Antonino; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefkova, Slavomira; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szumlak, Tomasz; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Traill, Murdo; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valat, Sebastien; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; van Veghel, Maarten; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Volkov, Vladimir; Vollhardt, Achim; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wicht, Jean; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wraight, Kenneth; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xu, Zhirui; Yang, Zhenwei; Yin, Hang; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhelezov, Alexey; Zheng, Yangheng; Zhokhov, Anatoly; Zhong, Liang; Zhukov, Valery; Zucchelli, Stefano

    2016-08-10

    A search for the decays of the $B_c^+$ meson to $p\\overline p\\pi^+$ is performed for the first time using a data sample corresponding to an integrated luminosity of 3.0 $\\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. No signal is found and an upper limit, at 95$\\%$ confidence level, is set, $\\frac{f_c}{f_u}\\times\\mathcal{B}(B_c^+\\to p\\overline p\\pi^+)<3.6\\times10^{-8}$ in the kinematic region $m(p\\overline p)<2.85\\mathrm{\\,Ge\\kern -0.1em V\\!/}c^2$, $p_{\\rm T}(B)<20\\mathrm{\\,Ge\\kern -0.1em V\\!/}c$ and $2.0< {y}(B)<4.5$, where $\\mathcal{B}$ is the branching fraction and $f_c$ ($f_u$) is the fragmentation fraction of the $b$ quark into a $B_c^+$ ($B^+$) meson.

  4. Dual emitter IrQ(ppy)2 for OLED applications: Synthesis and spectroscopic analysis

    International Nuclear Information System (INIS)

    Ciobotaru, I.C.; Polosan, S.; Ciobotaru, C.C.

    2014-01-01

    The synthesis of organometallic compound with iridium and two types of ligands, quinoline and phenylpyridine, was done successfully. The absorption spectra of this compound have shown broad peaks in a visible region assigned to metal-to-ligands charge transfer and in UV region assigned to intraligand absorptions. The photoluminescence spectra exhibit dual character in which the red emission is more intense than the green one. In cathodoluminescence measurements, under electron beam, the powder obtained after recrystallization from dichloromethane, shows similar behaviors with photoluminescence spectra. The cathodoluminescence images have shown a luminescent crystalline powder with triclinic structure. This compound exhibits combined vibrational modes, which proves the presence in the same molecule of both ligands. Density Functional Theory calculation was involved in order to identify the main vibrations of this compound. Highlights: • Mixed-ligand of IrQ(ppy) 2 synthesis which gives green and red phosphorescence due to the MCLT processes coming from two types of ligands. • Absorption, photoluminescence, infrared spectroscopy and cathodoluminescence measurements for characterization of IrQ(ppy) 2 organometallic compound. • Experimental results have been compared with the output files obtained from Density Functional Theory by using the Gaussian 03W software

  5. msiDBN: A Method of Identifying Critical Proteins in Dynamic PPI Networks

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    2014-01-01

    Full Text Available Dynamics of protein-protein interactions (PPIs reveals the recondite principles of biological processes inside a cell. Shown in a wealth of study, just a small group of proteins, rather than the majority, play more essential roles at crucial points of biological processes. This present work focuses on identifying these critical proteins exhibiting dramatic structural changes in dynamic PPI networks. First, a comprehensive way of modeling the dynamic PPIs is presented which simultaneously analyzes the activity of proteins and assembles the dynamic coregulation correlation between proteins at each time point. Second, a novel method is proposed, named msiDBN, which models a common representation of multiple PPI networks using a deep belief network framework and analyzes the reconstruction errors and the variabilities across the time courses in the biological process. Experiments were implemented on data of yeast cell cycles. We evaluated our network construction method by comparing the functional representations of the derived networks with two other traditional construction methods. The ranking results of critical proteins in msiDBN were compared with the results from the baseline methods. The results of comparison showed that msiDBN had better reconstruction rate and identified more proteins of critical value to yeast cell cycle process.

  6. Rilpivirine: a new non-nucleoside reverse transcriptase inhibitor.

    Science.gov (United States)

    Sharma, Mamta; Saravolatz, Louis D

    2013-02-01

    Rilpivirine is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) that is approved for HIV-1 treatment-naive adult patients in combination with other antiretroviral agents. The recommended dose is a 25 mg tablet once daily taken orally with a meal. Due to cytochrome P450 3A4 enzyme induction or gastric pH increase, rilpivirine cannot be coadministered with a number of other drugs (anticonvulsants, rifabutin, rifampicin, rifapentine, proton pump inhibitors, systemic dexamethasone and St John's wort). Rilpivirine should be used with caution when coadministered with a drug with a known risk for torsade de pointes. Rilpivirine has a better tolerability than a comparative NNRTI, efavirenz, in clinical trials, with fewer central nervous system adverse effects, rashes, lipid abnormalities and discontinuation rates. Virological failure occurs more commonly with higher baseline viral loads (>100,000 copies/mL) and lower baseline CD4 counts (<50 cells/mm(3)). Seventeen NNRTI mutations have been associated with decreased susceptibility to rilpivirine: K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C, M230I/L, Y188L and the combination L100I + K103N. Resistance to rilpivirine largely excludes future use of the NNRTI class.

  7. Synthesis and characterization of a novel tube-in-tube nanostructured PPy/MnO2/CNTs composite for supercapacitor

    International Nuclear Information System (INIS)

    Li, Juan; Que, Tingli; Huang, Jianbin

    2013-01-01

    Graphical abstract: A novel tube-in-tube nanostructured PPy/MnO 2 /CNTs composite have been successfully fabricated. Its inner tubules are CNTs and the outer tubules are template-synthesized PPy. Most MnO 2 nanoparticles are sandwiched between the inner and outer wall, some relatively large particles are also latched onto the outside wall of the PPy tube. The composite yields a good electrochemical reversibility through 1000 cycles’ cyclic voltammogram (CV) test and galvanostatic charge–discharge experiments at different current densities. Display Omitted Highlights: ► We fabricate a ternary organic–inorganic complex of PPy/MnO 2 /CNTs composite. ► We characterize its morphological structures and properties by several techniques. ► The composite possesses the typical tube-in-tube nanostructures. ► Most MnO 2 nanoparticles are sandwiched between the inner CNTs and outer PPy wall. ► The composite has good electrochemical reversibility for supercapacitor. -- Abstract: Ternary organic–inorganic complex of polypyrrole/manganese dioxide/carbon nanotubes (PPy/MnO 2 /CNTs) composite was prepared by in situ chemical oxidation polymerization of pyrrole in the host of inorganic matrix of MnO 2 and CNTs, using complex of methyl orange (MO)/FeCl 3 was used as a reactive self-degraded soft-template. The morphological structures of the composite were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopic (HRTEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD), respectively. All the results indicate that the PPy/MnO 2 /CNTs composite possesses the typical tube-in-tube nanostructures: the inner tubules are CNTs and the outer tubules are template-synthesized PPy. MnO 2 nanoparticles may either sandwich the space between the inner and outer tubules or directly latch onto the wall of the PPy tubes. The composite yields a good electrochemical

  8. Oesophageal narrowing on barium oesophagram is more common in adult patients with eosinophilic oesophagitis than PPI-responsive oesophageal eosinophilia.

    Science.gov (United States)

    Podboy, A; Katzka, D A; Enders, F; Larson, J J; Geno, D; Kryzer, L; Alexander, J

    2016-06-01

    To date there have been no clear features that aid in differentiating patients with eosinophilic oesophagitis (EoE) from PPI-responsive oesophageal eosinophilia (PPI-REE). However, barium swallow roentgenography is a more sensitive and specific measure to detect subtle fibrostenotic remodeling changes present in EoE. We aim to characterise any clinical, endoscopic, histiological or barium roentgenographic differences between EoE and PPI-REE. To characterise any clinical, endoscopic, histiological or barium roentgenographic differences between EoE and PPI-REE. We performed a retrospective cohort analysis on data collected from a tertiary referral centre population from 2010 to 2015. Data from 66 patients with EoE and 28 patients with PPI-REE were analysed. Cases were adults who met consensus guidelines for EOE, and had a barium swallow study within 6 months of the index endoscopy. Clinical, endoscopic, histiological and barium swallow findings were collected. Patients with EoE reported similar characteristics as PPI-REE patients, except EoE patients were younger (35.6 vs. 46.6 years; P = 0.011), had earlier symptom onset (29.0 vs. 38.0 years; P = 0.026), and smaller oesophageal diameters on barium swallow (19.5 mm vs. 20; P = 0.042). Patients with EoE were more likely to have distal strictures (EoE 77% vs. 25%; P = 0.02) and, importantly, a greater likelihood of small calibre oesophagus (51.5% vs. 17.9%; P = 0.002). Moreover, EoE patients had a higher probability of developing small calibre oesophagus after 20 years of symptoms (72.3% vs. 30.2%; P = 0.074) compared to PPI-REE patients. When compared with eosinophilic oesophagitis, PPI-REE patients demonstrate findings that suggest PPI-responsive oesophageal eosinophilia to be a later onset, less aggressive form of oesophageal stricturing disease than eosinophilic oesophagitis. © 2016 John Wiley & Sons Ltd.

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... also often take other medicines—such as proton pump inhibitors, anticoagulants, or blood thinners—that may cause iron-deficiency anemia. Proton pump inhibitors interfere with iron absorption, and blood thinners ...

  10. Performance of the Chemical and Electrochemical Composites of PPy/CNT as Electrodes in Type I Supercapacitors

    Directory of Open Access Journals (Sweden)

    S. C. Canobre

    2015-01-01

    Full Text Available Polypyrrole (PPy is one of the most studied conducting polymers and a very promising material for various applications such as lithium-ion secondary batteries, light-emitting devices, capacitors, and supercapacitors, owing to its many advantages, including good processability, easy handling, and high electronic conductivity. In this work, PPy films were chemically and electrochemically synthesized, both in and around carbon nanotubes (CNTs. The cyclic voltammograms of the device, composed of the electrochemically synthesized PPy/CNT composites as working and counter electrodes (Type I supercapacitor with p-type doping, showed a predominantly capacitive profile with low impedance values and good electrochemical stability, with the anodic charge remaining almost constant (11.38 mC, a specific capacitance value of 530 F g−1 after 50 charge and discharge cycles, and a coulombic efficiency of 99.2%. The electrochemically synthesized PPy/CNT composite exhibited better electrochemical properties compared to those obtained for the chemically synthesized composite. Thus, the electrochemically synthesized PPy/CNT composite is a promising material to be used as electrodes in Type I supercapacitors.

  11. Modification of Screen Printed Carbon Electrode (SPCE with Polypyrrole (Ppy-SiO2 for Phenol Determination

    Directory of Open Access Journals (Sweden)

    Ani Mulyasuryani

    2018-01-01

    Full Text Available Electrode modification on screen printed carbon electrode (SPCE with polypyrrole (Ppy-SiO2 was done by electropolymerization. Polypyrrole (Ppy-SiO2 was used for phenol determination. The analysis of this material was done by using Scanning Electron Microscopy (SEM, cyclic voltammetry method and differential pulse voltammetry. In a cyclic voltammetry analysis, we used potential range of -1 to 1 V with Ag/AgCl comparator electrode at scan rate of 100 mV/sec, while in differential pulse voltammetry method the potential range was 0 to 1 V toward Ag/AgCl, the scan rate of 50 mV/sec, the pulse rate is 0,2 V and the pulse width is 50 ms. From the analysis result with SEM, cyclic voltammetry and differential pulse voltammetry method, Polypyrrole (Ppy -SiO2 is the best material and can be used as phenol measurement.

  12. A metal-based inhibitor of NEDD8-activating enzyme.

    Directory of Open Access Journals (Sweden)

    Hai-Jing Zhong

    Full Text Available A cyclometallated rhodium(III complex [Rh(ppy(2(dppz](+ (1 (where ppy=2-phenylpyridine and dppz=dipyrido[3,2-a:2',3'-c]phenazine dipyridophenazine has been prepared and identified as an inhibitor of NEDD8-activating enzyme (NAE. The complex inhibited NAE activity in cell-free and cell-based assays, and suppressed the CRL-regulated substrate degradation and NF-κB activation in human cancer cells with potency comparable to known NAE inhibitor MLN4924. Molecular modeling analysis suggested that the overall binding mode of 1 within the binding pocket of the APPBP1/UBA3 heterodimer resembled that for MLN4924. Complex 1 is the first metal complex reported to suppress the NEDDylation pathway via inhibition of the NEDD8-activating enzyme.

  13. Frequency of reporting on patient and public involvement (PPI) in research studies published in a general medical journal: a descriptive study.

    Science.gov (United States)

    Price, Amy; Schroter, Sara; Snow, Rosamund; Hicks, Melissa; Harmston, Rebecca; Staniszewska, Sophie; Parker, Sam; Richards, Tessa

    2018-03-23

    While documented plans for patient and public involvement (PPI) in research are required in many grant applications, little is known about how frequently PPI occurs in practice. Low levels of reported PPI may mask actual activity due to limited PPI reporting requirements. This research analysed the frequency and types of reported PPI in the presence and absence of a journal requirement to include this information. A before and after comparison of PPI reported in research papers published in The BMJ before and 1 year after the introduction of a journal policy requiring authors to report if and how they involved patients and the public within their papers. Between 1 June 2013 and 31 May 2014, The BMJ published 189 research papers and 1 (0.5%) reported PPI activity. From 1 June 2015 to 31 May 2016, following the introduction of the policy, The BMJ published 152 research papers of which 16 (11%) reported PPI activity. Patients contributed to grant applications in addition to designing studies through to coauthorship and participation in study dissemination. Patient contributors were often not fully acknowledged; 6 of 17 (35%) papers acknowledged their contributions and 2 (12%) included them as coauthors. Infrequent reporting of PPI activity does not appear to be purely due to a failure of documentation. Reporting of PPI activity increased after the introduction of The BMJ 's policy, but activity both before and after was low and reporting was inconsistent in quality. Journals, funders and research institutions should collaborate to move us from the current situation where PPI is an optional extra to one where PPI is fully embedded in practice throughout the research process. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Organization of film data processing in the PPI-SA automated system

    International Nuclear Information System (INIS)

    Ovsov, Yu.V.; Perekatov, V.G.

    1984-01-01

    Organization of processing nuclear interaction images at PUOS - type standard devices using the PPI-SA automated system is considered. The system is made in the form of a complete module comprising two scanning measuring projectors and a scan-ning automatic device which operate in real time on line with the BESM-4-computer. The system comprises: subsystem for photographic film scanning, selection of events for measurements and preliminary encoding; subsystem for formation and generation of libraries with data required for monitoring the scanning automatic device; subsystem for precision measurements separate coordinates on photo images of nuclear particle tracks and ionization losses. The system software comprises monitoring programs for the projectors and scanning automatic device as well as test functional control programs and operating system. The programs are organized a modular concept. By changing the module set the system can be modified and adapted for image processing in different fields of science and technology

  15. Metal Oxides Doped PPY-PVA Blend Thin Films Based Gas Sensor

    Directory of Open Access Journals (Sweden)

    D. B. DUPARE

    2009-02-01

    Full Text Available Synthesis of metal oxides doped polypyrrole–polyvinyl alcohol blend thin films by in situ chemical oxidative polymerization, using microwave oven on glass substrate for development of Ammonia and Trimethyl ammine hazardous gas sensor. The all experimental process carried out at room temperature(304 K. These polymer materials were characterized by Chemical analyses, spectral studies (UV-visible and IR and conductivity measurement by four –probe technique. The surface morphology as observed in the SEM image was observed to be uniformly covering the entire substrate surface. The sensor was used for different concentration (ppm of TMA and Ammonia gas investigation at room temperature (304 k. This study found to possess improved electrical, mechanical and environmental stability metal oxides doped PPY-PVA films.

  16. PPY-PVA Blend Thin Films as a Ammines Gas Sensor

    Directory of Open Access Journals (Sweden)

    D. B. DUPARE

    2009-06-01

    Full Text Available Synthesis of polypyrrole–polyvinyl alcohol blend thin by in situ chemical oxidative polymerization, on glass substrate for development of Ammonia and Trimethyl ammine hazardous gas sensor. The all experimental process carried out at room temperature (304 k. These polymer materials were characterized by Chemical analyses, spectral studies (UV-visible and IR and conductivity measurement by four –probe technique. The surface morphology as seen in the SEM image was observed to be granular, tubular, uniformly covering the entire substrate surface having porous in nature. The current–voltage characterization show that these thin films have conducting in nature having ohmic behaviors. The sensor was used for different concentration (ppm of TMA and Ammonia gas investigation at room temperature (304 k. This study found to possess improved electrical, mechanical and environmental stability PPY-PVA films.

  17. Evaluation of a New Biosensor Based on in Situ Synthesized PPy-Ag-PVP Nanohybrid for Selective Detection of Dopamine.

    Science.gov (United States)

    Vellaichamy, Balakumar; Periakaruppan, Prakash; Paulmony, Tharmaraj

    2017-02-09

    In the present work, in situ synthesis of polypyrrole-silver-polyvinylpyrrolidone (PPy-Ag-PVP) nanohybrid using AgNO 3 as an oxidant and polyvinylpyrrolidone (PVP) as a stabilizer and surfactant is demonstrated. The obtained ternary PPy-Ag-PVP nanohybrid was characterized by UV-vis, FT-IR, XRD, Raman, TGA, SEM, and HR-TEM analysis. Further the synthesized PPy-Ag-PVP has been investigated for its selective and sensitive sensing of dopamine (DA). The PPy-Ag-PVP modified glassy carbon electrode shows a reversible electrochemical behavior with superior response for DA. The limit of detection and limit of quantification are found to be 0.0126 and 0.042 μM (S/N = 3 and 10), respectively, with remarkable sensitivity (7.26 μA mM -1 cm -2 ). The practical application of the present modified electrode has been validated by determining the concentration of DA in human urine samples of different age group.

  18. Delocalization of π electrons and trapping action of ZnO nanoparticles in PPY matrix for hybrid solar cell application

    Science.gov (United States)

    Singh, Rajinder; Choudhary, Ram Bilash; Kandulna, Rohit

    2018-03-01

    Polypyrrole (PPY)-Zinc Oxide (ZnO) nanocomposites with varying concentration of ZnO (1:1-1:4) were prepared via in-situ polymerization technique by using pyrrole monomer in the presence of ammonium persulphate (APS) as oxidant. Globular morphology of PPY and sheet like structure of ZnO was examined using FESEM and EDAX. FTIR showed the presence of vibration modes in fingerprint region (1500 cm-1-500 cm-1) for metal oxides confirming the presence and interaction of ZnO with the polymer matrix in nanocomposites. Amorphous nature of PPY and hexagonal wurtzite structure of ZnO was confirmed using XRD with average crystallite size within 20 nm-30 nm. PANI-ZnO (1:1) exhibited blue shift in comparison to PPY (neat) and optimized optical band gap ∼ 1.81 eV. The effect of carrier concentration was investigated using electrochemical analyzer and maximum current was recorded for PANI-ZnO (1:1). The highest conductance was calculated for PANI-ZnO (1:1) ∼ 7.3242 × 10-3 S using current -voltage characteristics. Thermal stability was found to be increasing with the increase in ZnO concentration PANI-ZnO nanocomposite.

  19. PPI-IRO: A two-stage method for protein-protein interaction extraction based on interaction relation ontology

    KAUST Repository

    Li, Chuanxi

    2014-01-01

    Mining Protein-Protein Interactions (PPIs) from the fast-growing biomedical literature resources has been proven as an effective approach for the identifi cation of biological regulatory networks. This paper presents a novel method based on the idea of Interaction Relation Ontology (IRO), which specifi es and organises words of various proteins interaction relationships. Our method is a two-stage PPI extraction method. At fi rst, IRO is applied in a binary classifi er to determine whether sentences contain a relation or not. Then, IRO is taken to guide PPI extraction by building sentence dependency parse tree. Comprehensive and quantitative evaluations and detailed analyses are used to demonstrate the signifi cant performance of IRO on relation sentences classifi cation and PPI extraction. Our PPI extraction method yielded a recall of around 80% and 90% and an F1 of around 54% and 66% on corpora of AIMed and Bioinfer, respectively, which are superior to most existing extraction methods. Copyright © 2014 Inderscience Enterprises Ltd.

  20. Three-dimensional (3D α-Fe2O3/polypyrrole (PPy nanocomposite for effective electromagnetic absorption

    Directory of Open Access Journals (Sweden)

    Wanchun Jiang

    2016-06-01

    Full Text Available The lightweight and 3-dimensional reticulated α-Fe2O3/PPy hybrids were successfully fabricated via a facile one-pot polyreaction. The measured complex permittivity and microwave attenuation performance suggest that the dielectric properties of PPy can be regulated by the mass ratio of added α-Fe2O3. The two dielectric resonance peaks of complex permittivity can be ascribed to the interface capacitor-like structure. An equivalent circuit model was established to explain the nonlinear resonance behavior of the α-Fe2O3/PPy wax composites. The addition of α-Fe2O3 properly tuned the dielectric constant to endow the composites with highly efficient microwave absorption. The minimum reflection loss of α-Fe2O3/PPy wax composites were enhanced to nearly −29dB with an effective bandwidth (RL≤ − 10dB up to 5.0GHz. The numerical method was proposed to calculate the optimum thickness for minimum RL at expected frequency by detailed investigation on the transmission formula. Moreover, the required thickness for optimum absorption efficiency at expected frequency can be obtained directly.

  1. Experimental analysis of R134a flow boiling inside a 5 PPI copper foam

    Science.gov (United States)

    Diani, A.; Mancin, S.; Rossetto, L.

    2014-04-01

    Heat dissipation is one of the most important issues for the reliability of electronic equipment. Boiling can be a very efficient heat transfer mechanism when used to face with the electronic technology needs of efficient and compact heat sinks. Recently, cellular structured materials both stochastic and periodic, particularly open cell metal foams, have been proposed as possible enhanced surfaces to lower the junction temperatures at high heat fluxes. Up today, most of the research on metal foams only regards single phase flow, whereas the two phase flow is still almost unexplored. This paper presents an experimental study on the heat transfer of R134a during flow boiling inside a 5 PPI (Pores Per linear Inch) copper foam, which is 5 mm high, 10 mm wide and 200 mm long, and it is brazed on a 10 mm thick copper plate. The experimental measurements were carried out by imposing three different heat fluxes (50, 75, and 100 kW m-2) and by varying the refrigerant mass velocity between 50 and 200 kg m-2 s-1 and the vapour quality from 0.2 to 0.90, at constant saturation temperature (30°C). The effects of the refrigerant mass flow rate, heat flux and vapour quality on the heat transfer coefficient, dry out phenomenon, and pressure drop are studied.

  2. Nature-inspired multifunctional membrane fabricated by adaptive hybridization of PNIPAm and PPy

    Science.gov (United States)

    Kim, Hyejeong; Kim, Kiwoong; Lee, Sang Joon

    2017-11-01

    Specialized plant organs, such as guard cells of stomata, consist of soft materials with deformability and electrochemical properties in response to various environmental stimuli. Stimulus-responsive hydrogels with electrochemical properties are good candidates for imitating such functionalities having great potential in a wide range of applications. However, conductive hydrogels are usually mechanically rigid and the fabrication technology of structured hydrogels has low reproducibility. Here, inspired by stimulus-responsive functionalities of plants, a thermo-responsive multifunctional hybrid membrane (HM) is synthesized through the in situ hybridization of conductive poly(pyrrole)(PPy) on a photopolymerized poly(N-isopropylacrylamide)(PNIPAm) membrane. The various properties of the HM are investigated to characterize its multiple functions. In terms of morphology, the HM can be easily fabricated into various structures, and exhibits thermo-responsive deformability. In terms of functionality, it exhibits various electrical and charge responses to thermal stimuli. This simple and efficient fabrication method can be used as a promising platform for fabricating a variety of functional devices, such as actuators, biosensors, and filtration membranes. This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (No. 2017R1A2B3005415).

  3. Oral bioavailability of the ether lipid plasmalogen precursor, PPI-1011, in the rabbit: a new therapeutic strategy for Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Wood Paul L

    2011-12-01

    Full Text Available Abstract Introduction Docosahexaenoic acid (DHA and DHA-containing ethanolamine plasmalogens (PlsEtn are decreased in the brain, liver and the circulation in Alzheimer's disease. Decreased supply of plasmalogen precursors to the brain by the liver, as a result of peroxisomal deficits is a process that probably starts early in the AD disease process. To overcome this metabolic compromise, we have designed an orally bioavailable DHA-containing ether lipid precursor of plasmalogens. PPI-1011 is an alkyl-diacyl plasmalogen precursor with palmitic acid at sn-1, DHA at sn-2 and lipoic acid at sn-3. This study outlines the oral pharmacokinetics of this precursor and its conversion to PlsEtn and phosphatidylethanolamines (PtdEtn. Methods Rabbits were dosed orally with PPI-1011 in hard gelatin capsules for time-course and dose response studies. Incorporation into PlsEtn and PtdEtn was monitored by LC-MS/MS. Metabolism of released lipoic acid was monitored by GC-MS. To monitor the metabolic fate of different components of PPI-1011, we labeled the sn-1 palmitic acid, sn-2 DHA and glycerol backbone with13C and monitored their metabolic fates by LC-MS/MS. Results PPI-1011 was not detected in plasma suggesting rapid release of sn-3 lipoic acid via gut lipases. This conclusion was supported by peak levels of lipoic acid metabolites in the plasma 3 hours after dosing. While PPI-1011 did not gain access to the plasma, it increased circulating levels of DHA-containing PlsEtn and PtdEtn. Labeling experiments demonstrated that the PtdEtn increases resulted from increased availability of DHA released via remodeling at sn-2 of phospholipids derived from PPI-1011. This release of DHA peaked at 6 hrs while increases in phospholipids peaked at 12 hr. Increases in circulating PlsEtn were more complex. Labeling experiments demonstrated that increases in the target PlsEtn, 16:0/22:6, consisted of 2 pools. In one pool, the intact precursor received a sn-3

  4. Synthesis and characterization of LDH/Ppi composite and its application as adsorbent of 2,4-dichlorophenoxyacetic (herbicide); Sintese e caracterizacao do composito HDL/Ppi e sua aplicacao como adsorvente do 2,4-diclorofenoxiacetico (herbicida)

    Energy Technology Data Exchange (ETDEWEB)

    Pacheco, I.S.; Oliveira, R.S.; Girotto, L.G.; Freitas, L.L. de; Amaral, F.A. do; Canobre, S.C., E-mail: ingrid_1194@hotmail.com [Universidade Federal de Uberlandia (UFU), MG (Brazil). Instituto de Quimica

    2016-07-01

    This work had as main objective the synthesis and characterization of LDH [Co-Al-Cl] method by hydrolysis of urea and then its synthesized polypyrrole coating by chemically targeting the application as adsorbent dichlorophenoxyacetic acid (2,4-D). The x-ray diffractogram of well defined showed diffraction peaks corresponding to the planes 003, 006, 009 and 110 which allow them to rhombohedral indexes and lamellar structure. The composite LDH / Ppi had a percentage of 49% herbicide retention in aqueous solution. From the investigated adsorption isotherm models that more fit the experimental data was the Freundlich, so it could be inferred that the interaction between the LDH / Ppi and the herbicide was physical, ie an rapid, reversible adsorption and does not specify. (author)

  5. Synthesis and characterization of LDH/Ppi composite and its application as adsorbent of 2,4-dichlorophenoxyacetic (herbicide)

    International Nuclear Information System (INIS)

    Pacheco, I.S.; Oliveira, R.S.; Girotto, L.G.; Freitas, L.L. de; Amaral, F.A. do; Canobre, S.C.

    2016-01-01

    This work had as main objective the synthesis and characterization of LDH [Co-Al-Cl] method by hydrolysis of urea and then its synthesized polypyrrole coating by chemically targeting the application as adsorbent dichlorophenoxyacetic acid (2,4-D). The x-ray diffractogram of well defined showed diffraction peaks corresponding to the planes 003, 006, 009 and 110 which allow them to rhombohedral indexes and lamellar structure. The composite LDH / Ppi had a percentage of 49% herbicide retention in aqueous solution. From the investigated adsorption isotherm models that more fit the experimental data was the Freundlich, so it could be inferred that the interaction between the LDH / Ppi and the herbicide was physical, ie an rapid, reversible adsorption and does not specify. (author)

  6. Choice vs. voice? PPI policies and the re‐positioning of the state in England and Wales

    Science.gov (United States)

    Hughes, David; Mullen, Caroline; Vincent‐Jones, Peter

    2009-01-01

    Abstract Context and Thesis  Changing patient and public involvement (PPI) policies in England and Wales are analysed against the background of wider National Health Service (NHS) reforms and regulatory frameworks. We argue that the growing divergence of health policies is accompanied by a re‐positioning of the state vis‐à‐vis PPI, characterized by different mixes of centralized and decentralized regulatory instruments. Method  Analysis of legislation and official documents, and interviews with policy makers. Findings  In England, continued hierarchical control is combined with the delegation of responsibilities for the oversight and organization of PPI to external institutions such as the Care Quality Commission and local involvement networks, in support of the government’s policy agenda of increasing marketization. In Wales, which has rejected market reforms and economic regulation, decentralization is occurring through the use of mixed regulatory approaches and networks suited to the small‐country governance model, and seeks to benefit from the close proximity of central and local actors by creating new forms of engagement while maintaining central steering of service planning. Whereas English PPI policies have emerged in tandem with a pluralistic supply‐side market and combine new institutional arrangements for patient ‘choice’ with other forms of involvement, the Welsh policies focus on ‘voice’ within a largely publicly‐delivered service. Discussion  While the English reforms draw on theories of economic regulation and the experience of independent regulation in the utilities sector, the Welsh model of local service integration has been more influenced by reforms in local government. Such transfers of governance instruments from other public service sectors to the NHS may be problematic. PMID:19754688

  7. Choice vs. voice? PPI policies and the re-positioning of the state in England and Wales.

    Science.gov (United States)

    Hughes, David; Mullen, Caroline; Vincent-Jones, Peter

    2009-09-01

    CONTEXT AND THESIS: Changing patient and public involvement (PPI) policies in England and Wales are analysed against the background of wider National Health Service (NHS) reforms and regulatory frameworks. We argue that the growing divergence of health policies is accompanied by a re-positioning of the state vis-à-vis PPI, characterized by different mixes of centralized and decentralized regulatory instruments. Analysis of legislation and official documents, and interviews with policy makers. In England, continued hierarchical control is combined with the delegation of responsibilities for the oversight and organization of PPI to external institutions such as the Care Quality Commission and local involvement networks, in support of the government's policy agenda of increasing marketization. In Wales, which has rejected market reforms and economic regulation, decentralization is occurring through the use of mixed regulatory approaches and networks suited to the small-country governance model, and seeks to benefit from the close proximity of central and local actors by creating new forms of engagement while maintaining central steering of service planning. Whereas English PPI policies have emerged in tandem with a pluralistic supply-side market and combine new institutional arrangements for patient 'choice' with other forms of involvement, the Welsh policies focus on 'voice' within a largely publicly-delivered service. While the English reforms draw on theories of economic regulation and the experience of independent regulation in the utilities sector, the Welsh model of local service integration has been more influenced by reforms in local government. Such transfers of governance instruments from other public service sectors to the NHS may be problematic.

  8. Polypyrrole-poly(3,4-ethylenedioxythiophene)-Ag (PPy-PEDOT-Ag) nanocomposite films for label-free electrochemical DNA sensing.

    Science.gov (United States)

    Radhakrishnan, S; Sumathi, C; Umar, Ahmad; Jae Kim, Sang; Wilson, J; Dharuman, V

    2013-09-15

    The electrochemical DNA hybridization sensing of bipolymer polypyrrole and poly(3,4-ethylenedioxythiophene) (PPy-PEDOT) nanotubes functionalized with Ag nanoparticles has been investigated. The bipolymer nanotubes are prepared by simple chemical route and silver nanoparticles (Ag) further deposited over the PPy-PEDOT nanotubes to form PPy-PEDOT-Ag nanocomposite films. DNA labeled at 5'end using 6-mercapto-1-hexhane (HS-ssDNA) is immobilized on the PPy-PEDOT-Ag surface to form PPy-PEDOT-Ag-S-ssDNA and hybridization sensing is done in phosphate buffer. The presence of Ag nanoparticles (~28±5nm) well dispersed in the polymer composite with high surface area, high electrical conductivity and catalytic activity provides desirable microenvironment for the immobilization of probe DNA with controlled orientation leading to increased hybridization efficiency with target DNA. The morphological and structural characterizations by a scanning electron microscope (SEM) and X-ray diffraction (XRD) confirm the nanotube structure of composite polymer while Raman measurements indicate the efficient interactions between the PPy, PEDOT, Ag and HS-ssDNA. The sensor effectively discriminates different target DNA sequences with PPy-PEDOT-Ag-S-ssDNA substrate. The observed dynamic detection range is found between 1×10(-11)M and 1×10(-14)M with the lowest detection limit (3 σ/b) of 5.4×10(-15)M. This observed value is of higher sensitivity than that for MWCNT-Ag, PANi-Au, MWCNT-PPy-Au and PPy-PANi-Au composites reported previously. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Fabrication of conductive and high-dispersed Ppy@Ag/g-C{sub 3}N{sub 4} composite photocatalysts for removing various pollutants in water

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Zhi; Tang, Xu [School of Chemistry and Chemical Engineering, Jiangsu University (China); Ma, Changchang [School of the Environment and Safety Engineering, Jiangsu University (China); Song, Minshan [School of Mathematics and Physics, Jiangsu University of Science and Technology (China); Gao, Nailing; Wang, Youshan; Huo, Pengwei [School of Chemistry and Chemical Engineering, Jiangsu University (China); Lu, Ziyang, E-mail: mrzhuzhi007@163.com [School of the Environment and Safety Engineering, Jiangsu University (China); Yan, Yongsheng, E-mail: gchxz206@126.com [School of Chemistry and Chemical Engineering, Jiangsu University (China)

    2016-11-30

    Highlights: • The high-dispersed Ag modified g-C{sub 3}N{sub 4} (Ag/g-C{sub 3}N{sub 4}) was successfully synthesized in situ deposited on the surface of g-C{sub 3}N{sub 4} during calcined melamine. • The as-prepared Ppy@Ag/g-C{sub 3}N{sub 4} could remove of various organic pollutants in water. • The enhanced photocatalytic activity of Ppy@Ag/g-C{sub 3}N{sub 4} comes from π conjugated electronic structures of Ppy and Ag species as the electron transfer mediator between Ppy and g-C{sub 3}N{sub 4}. • The Ppy@Ag/g-C{sub 3}N{sub 4} sample also showed a relatively good recycling stability. - Abstract: The ternary conductive Ppy@Ag/g-C{sub 3}N{sub 4} composite photocatalysts was successfully synthesized by polymerization process and surface polymerization technique. And the as-prepared Ppy@Ag/g-C{sub 3}N{sub 4} sample exhibited the higher photocatalytic activity for various pollutant (MO, DM, TC, CIP, GFLX and EH) remove than that of pure g-C{sub 3}N{sub 4} and Ag/g-C{sub 3}N{sub 4} under visible light irradiation. It mainly originated from the Ag nanoparticles anchored between g-C{sub 3}N{sub 4} and Ppy acted as electron transfer mediator that facilitated the charge carrier separation and then expending the lifetime of the carriers. Meanwhile, the obtained Ppy@Ag/g-C{sub 3}N{sub 4} sample also showed a relatively good recycling stability which was the crucial factor for photocatalyst practical application. This work provided a new facile strategy for improving photo-degradation activity of g-C{sub 3}N{sub 4} photocatalyst.

  10. Luminescent sensitization and blue shift emission of Ir(ppy){sub 2}(VPHD) by copolymerization with MMA

    Energy Technology Data Exchange (ETDEWEB)

    An Baoli, E-mail: blan@staff.shu.edu.cn [Department of Chemistry, College of Science, Shanghai University, Shanghai 200444 (China); Dai Fanzeng; Zhang Yanling; Song Jian; Huang, Xiao-Di [Department of Chemistry, College of Science, Shanghai University, Shanghai 200444 (China); Xu, Jia-Qiang, E-mail: xujiaqiang@shu.edu.cn [Department of Chemistry, College of Science, Shanghai University, Shanghai 200444 (China); State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China)

    2011-08-15

    Ir(ppy){sub 2}(VPHD) (ppy=2-phenyl pyridine, VPHD=6-(4-vinylphenyl)-2,4-hexanedione) was copolymerized with methyl methacrylate (MMA). The copolymer had high quantum yield of 52.3{+-}0.5% in dilute ethyl acetate solution, and the yield increased around 45% than that of the iridium monomer. The maximum emission peaks for the copolymers shifted from 515 to 489 nm while the iridium complex content was less than 0.005 mol% in the feed. The blue emission at 489 nm and the green emission at 520 nm were analyzed by Lorenz function. They are attributed to {sup 1}MLCT and {sup 3}MLCT emissions, respectively. - Highlights: > PMMA-Ir(ppy){sub 2}(VPHD) as luminescent material with high yield of 53%. > The blue color emission at 489 nm from {sup 1}MLCT in conformity with Lorenz function. > The quantum yield for the copolymer increases 45% than that of the iridium monomer. > The {sup 3}MLCT Ex. intensity versus the monomer concentration is in conformity with Boltzmann function.

  11. Facile Synthesis of SrCO3-Sr(OH2/PPy Nanocomposite with Enhanced Photocatalytic Activity under Visible Light

    Directory of Open Access Journals (Sweden)

    Alfredo Márquez-Herrera

    2016-01-01

    Full Text Available Pyrrole monomer was chemically polymerized onto SrCO3-Sr(OH2 powders to obtain SrCO3-Sr(OH2/polypyrrole nanocomposite to be used as a candidate for photocatalytic degradation of methylene blue dye (MB. The material was characterized by Fourier transform infrared (FTIR spectroscopy, UV/Vis spectroscopy, and X-ray diffraction (XRD. It was observed from transmission electronic microscopy (TEM analysis that the reported synthesis route allows the production of SrCO3-Sr(OH2 nanoparticles with particle size below 100 nm which were embedded within a semiconducting polypyrrole matrix (PPy. The SrCO3-Sr(OH2 and SrCO3-Sr(OH2/PPy nanocomposites were tested in the photodegradation of MB dye under visible light irradiation. Also, the effects of MB dye initial concentration and the catalyst load on photodegradation efficiency were studied and discussed. Under the same conditions, the efficiency of photodegradation of MB employing the SrCO3-Sr(OH2/PPy nanocomposite increases as compared with that obtained employing the SrCO3-Sr(OH2 nanocomposite.

  12. Fabricate BC/Fe3O4@PPy 3D nanofiber film as flexible electrode for supercapacitor application

    Science.gov (United States)

    Lv, Xvdan; Li, Guohui; Pang, Zengyuan; Li, Dawei; Lei, Luo; Lv, Pengfei; Mushtaq, Muhammad; Wei, Qufu

    2018-05-01

    For flexible film supercapacitor, high areal capacitance is a main evaluating indicator. In this paper, bacterial cellulose (BC) with special three-dimensional structure was used as the natural flexible base material. Fe3O4 nanoparticles with average diameter of 20 nm were synthesized on the surface of BC fibers. The conductive path polypyrrole (PPy) was introduced as shell of BC/Fe3O4 fibers to further improve the pseudo capacitance in 1 mol/L H2SO4 solution. Besides, the BC/Fe3O4@PPy was used for supercapacitor application in acid electrolyte, and delivered higher areal capacitance compared to other Fe3O4 composites in previous reports. The obtained BC/Fe3O4@PPy film showed excellent mechanical strength (tensile strength reached 11 MPa), high areal specific capacitance (5.4 F cm-2 at active mass of 8.4 mg cm-2), and long cycle life (1.95 F cm-2 over 3500 cycles).

  13. Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines

    International Nuclear Information System (INIS)

    Bodewein, Lambert; Schmelter, Frank; Di Fiore, Stefano; Hollert, Henner; Fischer, Rainer; Fenske, Martina

    2016-01-01

    Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96 h and human cancer cell lines for 24 h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7 μM at 24 and 48 hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values ≥ 402 μM (PAMAMs) and ≤ 240 μM (PPIs) for HepG2 and ≤ 13.24 μM (PAMAMs) and ≤ 12.84 μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. - Highlights: • Zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time. • Zebrafish embryo toxicity of cationic dendrimers did not increase with generation. • Cationic dendrimers induced apoptosis in zebrafish embryos. • Toxicity of cationic dendrimers was lower in HepG2 and DU145 than zebrafish embryos.

  14. Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Bodewein, Lambert [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Frankfurt & Aachen (Germany); Institute of Environmental Research (Biology V), RWTH Aachen University (Germany); Schmelter, Frank; Di Fiore, Stefano [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Molecular Biology Division, Aachen (Germany); Hollert, Henner [Institute of Environmental Research (Biology V), RWTH Aachen University (Germany); Fischer, Rainer [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Frankfurt & Aachen (Germany); Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Molecular Biology Division, Aachen (Germany); Fenske, Martina, E-mail: martina.fenske@ime.fraunhofer.de [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Frankfurt & Aachen (Germany)

    2016-08-15

    Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96 h and human cancer cell lines for 24 h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7 μM at 24 and 48 hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values ≥ 402 μM (PAMAMs) and ≤ 240 μM (PPIs) for HepG2 and ≤ 13.24 μM (PAMAMs) and ≤ 12.84 μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. - Highlights: • Zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time. • Zebrafish embryo toxicity of cationic dendrimers did not increase with generation. • Cationic dendrimers induced apoptosis in zebrafish embryos. • Toxicity of cationic dendrimers was lower in HepG2 and DU145 than zebrafish embryos.

  15. Dynamic programming re-ranking for PPI interactor and pair extraction in full-text articles

    Science.gov (United States)

    2011-01-01

    Background Experimentally verified protein-protein interactions (PPIs) cannot be easily retrieved by researchers unless they are stored in PPI databases. The curation of such databases can be facilitated by employing text-mining systems to identify genes which play the interactor role in PPIs and to map these genes to unique database identifiers (interactor normalization task or INT) and then to return a list of interaction pairs for each article (interaction pair task or IPT). These two tasks are evaluated in terms of the area under curve of the interpolated precision/recall (AUC iP/R) score because the order of identifiers in the output list is important for ease of curation. Results Our INT system developed for the BioCreAtIvE II.5 INT challenge achieved a promising AUC iP/R of 43.5% by using a support vector machine (SVM)-based ranking procedure. Using our new re-ranking algorithm, we have been able to improve system performance (AUC iP/R) by 1.84%. Our experimental results also show that with the re-ranked INT results, our unsupervised IPT system can achieve a competitive AUC iP/R of 23.86%, which outperforms the best BC II.5 INT system by 1.64%. Compared to using only SVM ranked INT results, using re-ranked INT results boosts AUC iP/R by 7.84%. Statistical significance t-test results show that our INT/IPT system with re-ranking outperforms that without re-ranking by a statistically significant difference. Conclusions In this paper, we present a new re-ranking algorithm that considers co-occurrence among identifiers in an article to improve INT and IPT ranking results. Combining the re-ranked INT results with an unsupervised approach to find associations among interactors, the proposed method can boost the IPT performance. We also implement score computation using dynamic programming, which is faster and more efficient than traditional approaches. PMID:21342534

  16. Autophagic dedifferentiation induced by cooperation between TOR inhibitor and retinoic acid signals in budding tunicates.

    Science.gov (United States)

    Kawamura, Kaz; Yoshida, Takuto; Sekida, Satoko

    2018-01-15

    Asexual bud development in the budding tunicate Polyandrocarpa misakiensis involves transdifferentiation of multipotent epithelial cells, which is triggered by retinoic acid (RA), and thrives under starvation after bud isolation from the parent. This study aimed to determine cell and molecular mechanisms of dedifferentiation that occur during the early stage of transdifferentiation. During dedifferentiation, the numbers of autophagosomes, lysosomes, and secondary lysosomes increased remarkably. Mitochondrial degradation and exosome discharge also occurred in the atrial epithelium. Autophagy-related gene 7 (Atg7) and lysosomal proton pump A gene (PumpA) were activated during the dedifferentiation stage. When target of rapamycin (TOR) inhibitor was administered to growing buds without isolating them from the parent, phagosomes and secondary lysosomes became prominent. TOR inhibitor induced Atg7 only in the presence of RA. In contrast, when growing buds were treated with RA, lysosomes, secondary lysosomes, and mitochondrial degradation were prematurely induced. RA significantly activated PumpA in a retinoid X receptor-dependent manner. Our results indicate that in P. misakiensis, TOR inhibition and RA signals act in synergy to accomplish cytoplasmic clearance for dedifferentiation. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. A novel EIS field effect structures coated with TESUD-PPy-PVC-dibromoaza[7]helicene matrix for potassium ions detection

    Energy Technology Data Exchange (ETDEWEB)

    Tounsi, Moncef, E-mail: tounsi1981@live.fr [Laboratoire des Interfaces et des Matériaux Avancés (LIMA), Faculté des Sciences de Monastir, Université de Monastir (Tunisia); Université de Lyon, Institut de Sciences Analytiques (ISA) – UMR 5280, 5 rue de la Doua, 69100 Villeurbanne (France); Ben Braiek, Mourad [Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène, Faculté des Sciences, Université de Monastir, Avenue de l' environnement, 5019, Monastir (Tunisia); Barhoumi, Houcine [Laboratoire des Interfaces et des Matériaux Avancés (LIMA), Faculté des Sciences de Monastir, Université de Monastir (Tunisia); Baraket, Abdoullatif; Lee, Michael; Zine, Nadia [Université de Lyon, Institut de Sciences Analytiques (ISA) – UMR 5280, 5 rue de la Doua, 69100 Villeurbanne (France); Maaref, Abderrazak [Laboratoire des Interfaces et des Matériaux Avancés (LIMA), Faculté des Sciences de Monastir, Université de Monastir (Tunisia); Errachid, Abdelhamid, E-mail: abdelhamid.errachid-el-salhi@univ-lyon1.fr [Université de Lyon, Institut de Sciences Analytiques (ISA) – UMR 5280, 5 rue de la Doua, 69100 Villeurbanne (France)

    2016-04-01

    In this work, we describe the development of new Aza[7]helicene-containing PVC-based membranes for the K{sup +} ions quantification. Here, silicon nitride-based structures (Si-p/SiO{sub 2}/Si{sub 3}N{sub 4}) were developed and the surface was activated, functionalized with an aldehyde–silane (11-(Triethoxysilyl)undecanal (TESUD)), functionalized with polypyrrole (PPy), and coated with the polyvinylchloride (PVC)-membrane containing the Aza[7]helicene as ionophore. All stages of functionalization process have been thoroughly studied by contact angle measurements (CAMs) and atomic force microscopy (AFM). The developed ion-selective electrode (ISE) was then applied using electrochemical impedance spectroscopy (EIS) for the detection of potassium ions. A linear range was observed between 1.0 × 10{sup −8} M to 1.0 × 10{sup −3} M and a detection limit of 1.0 × 10{sup −8} M was observed. The EIS results have showed a good sensitivity to potassium ion using this novel technique. The target helicene exhibited good solubility and excellent thermal stability with a high decomposition temperature (Td > 300 °C) and it indicates that helicene may be a promising material as ionophore for ion-selective electrodes (ISEs) elaboration. - Highlights: • Synthesis and characterization of a new derivatives of Aza[7]helicenes • Manufacture of PPy structures on the SiO{sub 2}/Si{sub 3}N{sub 4} surface using the TESUD as cross linking agent. • The PPy fabricated microstructures can be used as support matrix in biosensing. • Impedimetric K{sup +}-ISEs was developed by using dibromoaza[7]helicene as ionophore for K{sup +} ions determination.

  18. Study of the O(N) linear σ model at finite temperature using the 2PPI expansion

    International Nuclear Information System (INIS)

    Verschelde, H.; De Pessemier, J.

    2002-01-01

    We show that a new expansion, which sums seagull and bubble graphs to all orders, can be applied to the O(N) linear σ-model at finite temperature. We prove that this expansion can be renormalized with the usual counterterms in a mass independent scheme and that Goldstone's theorem is satisfied at each order. At the one loop order of this expansion, the Hartree result for the effective potential (daisy and superdaisy graphs) is recovered. We show that at one loop 2PPI order, the self-energy of the σ-meson can be calculated exactly and that diagrams are summed beyond the Hartree approximation. (orig.)

  19. Inhibitors of Ras-SOS Interactions.

    Science.gov (United States)

    Lu, Shaoyong; Jang, Hyunbum; Zhang, Jian; Nussinov,