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Sample records for term proton pump

  1. 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

  2. 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...

  3. 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

  4. 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.

  5. 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.

  6. 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...

  7. 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.

  8. 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....

  9. 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.

  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. 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

  12. 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.

  13. 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.

  14. 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...

  15. 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...

  16. 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.

  17. 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

  18. 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

  19. 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...

  20. [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.

  1. 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.

  2. 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....

  3. 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...

  4. 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.

  5. 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.

  6. Exchangers man the pumps: Functional interplay between proton pumps and proton-coupled Ca exchangers.

    Science.gov (United States)

    Barkla, Bronwyn J; Hirschi, Kendal D; Pittman, Jon K

    2008-05-01

    Tonoplast-localised proton-coupled Ca(2+) transporters encoded by cation/H(+)exchanger (CAX) genes play a critical role in sequestering Ca(2+) into the vacuole. These transporters may function in coordination with Ca(2+) release channels, to shape stimulus-induced cytosolic Ca(2+) elevations. Recent analysis of Arabidopsis CAX knockout mutants, particularly cax1 and cax3, identified a variety of phenotypes including sensitivity to abiotic stresses, which indicated that these transporters might play a role in mediating the plant's stress response. A common feature of these mutants was the perturbation of H(+)-ATPase activity at both the tonoplast and the plasma membrane, suggesting a tight interplay between the Ca(2+)/H(+) exchangers and H(+) pumps. We speculate that indirect regulation of proton flux by the exchangers may be as important as the direct regulation of Ca(2+) flux. These results suggest cautious interpretation of mutant Ca(2+)/H(+) exchanger phenotypes that may be due to either perturbed Ca(2+) or H(+) transport.

  7. 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.

  8. 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...

  9. 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.

  10. 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

  11. 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 ...

  12. 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...

  13. 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)

  14. Sodium and Proton Effects on Inward Proton Transport through Na/K Pumps

    Science.gov (United States)

    Mitchell, Travis J.; Zugarramurdi, Camila; Olivera, J. Fernando; Gatto, Craig; Artigas, Pablo

    2014-01-01

    The Na/K pump hydrolyzes ATP to export three intracellular Na (Nai) as it imports two extracellular K (Ko) across animal plasma membranes. Within the protein, two ion-binding sites (sites I and II) can reciprocally bind Na or K, but a third site (site III) exclusively binds Na in a voltage-dependent fashion. In the absence of Nao and Ko, the pump passively imports protons, generating an inward current (IH). To elucidate the mechanisms of IH, we used voltage-clamp techniques to investigate the [H]o, [Na]o, and voltage dependence of IH in Na/K pumps from ventricular myocytes and in ouabain-resistant pumps expressed in Xenopus oocytes. Lowering pHo revealed that Ho both activates IH (in a voltage-dependent manner) and inhibits it (in a voltage-independent manner) by binding to different sites. Nao effects depend on pHo; at pHo where no Ho inhibition is observed, Nao inhibits IH at all concentrations, but when applied at pHo that inhibits pump-mediated current, low [Na]o activates IH and high [Na]o inhibits it. Our results demonstrate that IH is a property inherent to Na/K pumps, not linked to the oocyte expression environment, explains differences in the characteristics of IH previously reported in the literature, and supports a model in which 1), protons leak through site III; 2), binding of two Na or two protons to sites I and II inhibits proton transport; and 3), pumps with mixed Na/proton occupancy of sites I and II remain permeable to protons. PMID:24940773

  15. 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.

  16. Neutrino proton scattering and the isosinglet term

    International Nuclear Information System (INIS)

    White, D.H.

    1990-01-01

    Elastic neutrino proton scattering is sensitive to the SU(3) axial isosinglet term which is in turn dependent on the strangeness content of the proton. The uncertainties in the analysis of a neutrino proton elastic scattering experiment are discussed, and an experiment which is insensitive to many of the difficulties of the previous experiment is described

  17. 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)

  18. 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.

  19. Exchangers man the pumps: Functional interplay between proton pumps and proton-coupled Ca(2+) exchangers

    Science.gov (United States)

    Tonoplast-localised proton-coupled Ca(2+) transporters encoded by cation/H(+) exchanger (CAX) genes play a critical role in sequestering Ca(2+) into the vacuole. These transporters may function in coordination with Ca(2+) release channels, to shape stimulus-induced cytosolic Ca(2+) elevations. Recen...

  20. Exchangers man the pumps: Functional interplay between proton pumps and proton-coupled Ca2+ exchangers

    OpenAIRE

    Barkla, Bronwyn J; Hirschi, Kendal D; Pittman, Jon K

    2008-01-01

    Tonoplast-localised proton-coupled Ca2+ transporters encoded by cation/H+ exchanger (CAX) genes play a critical role in sequestering Ca2+ into the vacuole. These transporters may function in coordination with Ca2+ release channels, to shape stimulus-induced cytosolic Ca2+ elevations. Recent analysis of Arabidopsis CAX knockout mutants, particularly cax1 and cax3, identified a variety of phenotypes including sensitivity to abiotic stresses, which indicated that these transporters might play a ...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  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. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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/

  15. 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.

  16. 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.

  17. Molecular mechanisms controlling proton pumping by bacteriorhodopsin. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Crouch, Rosalie K.; Ebrey, Thomas G.

    2000-02-10

    Bacteriorhodopsin (bR) is the simplest biological system for the transduction of light energy. Light energy is directly converted to transmembrane proton gradient by a single, small membrane protein. The extraordinary stability of bR makes it an outstanding subject for bioenergetic studies. This project has focused on the role of interactions between key residues of the pigment involved in light-induced proton transfer. Methods to estimate the strength of these interactions and their correlation with the rate and efficiency of proton transfer have been developed. The concept of the coupling of the protonation states of key groups has been applied to individual steps of the proton transfer with the ultimate goal of understanding on the molecular level the driving forces for proton transport and the pathway of the transported proton in bT. The mechanism of light-induced proton release, uptake and the mechanism of recovery of initial state of bT has been examined. The experiments were performed with genetically engineered, site-specific mutants of bR. This has enabled us to characterize the role of individual amino acid residues in bR. Time resolved and low temperature absorption spectroscopy and light-induced photocurrent measurements were used in order to study the photochemical cycle and proton transfer in mutant pigments. Chemical modification and crosslinking of both the specific amino acids to the chromophore or to other amino acids were used to elucidate the role of light-induced conformational changes in the photocycle and the structure of the protein in the ground state. The results of this project provided new knowledge on the architecture of the proton transfer pathways inside the protein, on the mechanism of proton release in bR, and on the role of specific amino acid residues in the structure and function of bR.

  18. 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.

  19. 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.

  20. 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.

  1. [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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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 ...

  9. 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...

  10. 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.

  11. 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.

  12. Development of a tritium monitor combined with an electrochemical tritium pump using a proton conducting oxide

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, M. [National Institute for Fusion Science, Toki, Gifu (Japan); Sugiyama, T. [Nagoya University, Fro-cho, Chikusa-ku, Nagoya (Japan)

    2015-03-15

    The detection of low level tritium is one of the key issues for tritium management in tritium handling facilities. Such a detection can be performed by tritium monitors based on proton conducting oxide technique. We tested a tritium monitoring system composed of a commercial proportional counter combined with an electrochemical hydrogen pump equipped with CaZr{sub 0.9}In{sub 0.1}O{sub 3-α} as proton conducting oxide. The hydrogen pump operated at 973 K under electrolysis conditions using tritiated water vapor (HTO). The proton conducting oxide extracts tritium molecules (HT) from HTO and tritium concentration is measured by the proportional counter. The advantage of the proposed tritium monitoring system is that it is able to convert HTO into molecular hydrogen.

  13. 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...

  14. 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.

  15. 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...

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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...

  19. Optical silencing of C. elegans cells with arch proton pump.

    Directory of Open Access Journals (Sweden)

    Ayako Okazaki

    Full Text Available BACKGROUND: Optogenetic techniques using light-driven ion channels or ion pumps for controlling excitable cells have greatly facilitated the investigation of nervous systems in vivo. A model organism, C. elegans, with its small transparent body and well-characterized neural circuits, is especially suitable for optogenetic analyses. METHODOLOGY/PRINCIPAL FINDINGS: We describe the application of archaerhodopsin-3 (Arch, a recently reported optical neuronal silencer, to C. elegans. Arch::GFP expressed either in all neurons or body wall muscles of the entire body by means of transgenes were localized, at least partially, to the cell membrane without adverse effects, and caused locomotory paralysis of worms when illuminated by green light (550 nm. Pan-neuronal expression of Arch endowed worms with quick and sustained responsiveness to such light. Worms reliably responded to repeated periods of illumination and non-illumination, and remained paralyzed under continuous illumination for 30 seconds. Worms expressing Arch in different subsets of motor neurons exhibited distinct defects in the locomotory behavior under green light: selective silencing of A-type motor neurons affected backward movement while silencing of B-type motor neurons affected forward movement more severely. Our experiments using a heat-shock-mediated induction system also indicate that Arch becomes fully functional only 12 hours after induction and remains functional for more than 24 hour. CONCLUSIONS/SGNIFICANCE: Arch can be used for silencing neurons and muscles, and may be a useful alternative to currently widely used halorhodopsin (NpHR in optogenetic studies of C. elegans.

  20. 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

  1. 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...

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps.

    Science.gov (United States)

    Vedovato, Natascia; Gadsby, David C

    2014-04-01

    A single Na(+)/K(+)-ATPase pumps three Na(+) outwards and two K(+) inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na(+) than K(+) generates outward current across the cell membrane. Less well understood is the ability of Na(+)/K(+) pumps to generate an inward current of protons. Originally noted in pumps deprived of external K(+) and Na(+) ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K(+) and Na(+) concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na(+) release from phosphorylated Na(+)/K(+) pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na(+)/K(+) pumps that enables proton import is not required for completion of the 3 Na(+)/2 K(+) transport cycle. However, the back-step occurs readily during Na(+)/K(+) transport when external K(+) ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na(+)-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na(+) and K(+) ions that passes through binding site II. The inferred occurrence of Na(+)/K(+) exchange and H(+) import during the same conformational cycle of a single molecule identifies the Na(+)/K(+) pump as a hybrid transporter. Whether Na(+)/K(+) pump-mediated proton inflow may have any physiological or

  8. Long-term safety issues associated with mixer pump operation

    International Nuclear Information System (INIS)

    Kubic, W.L. Jr.

    1994-01-01

    In this report, we examine several long-term issues: the effect of pump operation on future gas release events (GREs), uncontrolled chemical reactions, chronic toxic gas releases, foaming, and erosion and corrosion. Heat load in excess of the design limit, uncontrolled chemical reactions, chronic toxic gas releases, foaming, and erosion and corrosion have been shown not to be safety concerns. The effect of pump operation on future GREs could not be quantified. The problem with evaluating the long-term effects of pump operation on GREs is a lack of knowledge and uncertainty. In particular, the phenomena governing gas retention, particle size distribution, and settling are not well understood, nor are the interactions among these factors understood. There is a possibility that changes in these factors could increase the size of future GREs. Bounding estimates of the potential increase in size of GREs are not possible because of a lack of engineering data. Proper management of the hazards can reduce, but not eliminate, the possibility of undesirable changes. Maintaining temperature within the historical limits can reduce the possibility of undesirable changes. A monitoring program to detect changes in the gas composition and crust thickness will help detect slowly occurring changes. Because pump operation has be shown to eliminate GREs, continued pump operation can eliminate the hazards associated with future GREs

  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. 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.

  11. Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps

    Science.gov (United States)

    Vedovato, Natascia

    2014-01-01

    A single Na+/K+-ATPase pumps three Na+ outwards and two K+ inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na+ than K+ generates outward current across the cell membrane. Less well understood is the ability of Na+/K+ pumps to generate an inward current of protons. Originally noted in pumps deprived of external K+ and Na+ ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K+ and Na+ concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na+ release from phosphorylated Na+/K+ pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na+/K+ pumps that enables proton import is not required for completion of the 3 Na+/2 K+ transport cycle. However, the back-step occurs readily during Na+/K+ transport when external K+ ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na+-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na+ and K+ ions that passes through binding site II. The inferred occurrence of Na+/K+ exchange and H+ import during the same conformational cycle of a single molecule identifies the Na+/K+ pump as a hybrid transporter. Whether Na+/K+ pump–mediated proton inflow may have any physiological or pathophysiological significance remains to be clarified. PMID

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  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. 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.

  20. 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.

  1. 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.

  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. 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.

  4. 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....

  5. 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.

  6. 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...

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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...

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. Proton radius, Darwin-Foldy term and radiative corrections

    International Nuclear Information System (INIS)

    Jentschura, U.D.

    2011-01-01

    We discuss the role of the so-called Darwin-Foldy term in the evaluation of the proton and deuteron charge radii from atomic hydrogen spectroscopy and nuclear scattering data. The question of whether this term should be included or excluded from the nuclear radius has been controversially discussed in the literature. We attempt to clarify which literature values correspond to which conventions. A detailed discussion of the conventions appears useful because a recent experiment [R. Pohl et al., Nature 466, 213 (2010)] has indicated that there is a discrepancy between the proton charge radii inferred from ordinary ('electronic') atomic hydrogen and muonic hydrogen. We also investigate the role of quantum electrodynamic radiative corrections in the determination of nuclear radii from scattering data, and propose a definition of the nuclear self energy which is compatible with the subtraction of the radiative corrections in scattering experiments. (author)

  3. 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.

  4. LONG-TERM TRENDS IN THE SOLAR WIND PROTON MEASUREMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, Heather A.; McComas, David J. [Southwest Research Institute, San Antonio, TX (United States); DeForest, Craig E. [Southwest Research Institute, Boulder, CO (United States)

    2016-11-20

    We examine the long-term time evolution (1965–2015) of the relationships between solar wind proton temperature ( T {sub p}) and speed ( V {sub p}) and between the proton density ( n {sub p}) and speed using OMNI solar wind observations taken near Earth. We find a long-term decrease in the proton temperature–speed ( T {sub p}– V {sub p}) slope that lasted from 1972 to 2010, but has been trending upward since 2010. Since the solar wind proton density–speed ( n {sub p}– V {sub p}) relationship is not linear like the T {sub p}– V {sub p} relationship, we perform power-law fits for n {sub p}– V {sub p}. The exponent (steepness in the n {sub p}– V {sub p} relationship) is correlated with the solar cycle. This exponent has a stronger correlation with current sheet tilt angle than with sunspot number because the sunspot number maxima vary considerably from cycle to cycle and the tilt angle maxima do not. To understand this finding, we examined the average n {sub p} for different speed ranges, and found that for the slow wind n {sub p} is highly correlated with the sunspot number, with a lag of approximately four years. The fast wind n {sub p} variation was less, but in phase with the cycle. This phase difference may contribute to the n {sub p}– V {sub p} exponent correlation with the solar cycle. These long-term trends are important since empirical formulas based on fits to T {sub p} and V {sub p} data are commonly used to identify interplanetary coronal mass ejections, but these formulas do not include any time dependence. Changes in the solar wind density over a solar cycle will create corresponding changes in the near-Earth space environment and the overall extent of the heliosphere.

  5. 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.

  6. 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

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

    Science.gov (United States)

    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

  8. 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

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  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. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. [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.

  9. 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.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. 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

  14. 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...

  15. 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.

  16. 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.

  17. 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).

  18. The selectivity of the Na(+)/K(+)-pump is controlled by binding site protonation and self-correcting occlusion.

    Science.gov (United States)

    Rui, Huan; Artigas, Pablo; Roux, Benoît

    2016-08-04

    The Na(+)/K(+)-pump maintains the physiological K(+) and Na(+) electrochemical gradients across the cell membrane. It operates via an 'alternating-access' mechanism, making iterative transitions between inward-facing (E1) and outward-facing (E2) conformations. Although the general features of the transport cycle are known, the detailed physicochemical factors governing the binding site selectivity remain mysterious. Free energy molecular dynamics simulations show that the ion binding sites switch their binding specificity in E1 and E2. This is accompanied by small structural arrangements and changes in protonation states of the coordinating residues. Additional computations on structural models of the intermediate states along the conformational transition pathway reveal that the free energy barrier toward the occlusion step is considerably increased when the wrong type of ion is loaded into the binding pocket, prohibiting the pump cycle from proceeding forward. This self-correcting mechanism strengthens the overall transport selectivity and protects the stoichiometry of the pump cycle.

  19. An implantable centrifugal blood pump for long term circulatory support.

    Science.gov (United States)

    Yamazaki, K; Litwak, P; Kormos, R L; Mori, T; Tagusari, O; Antaki, J F; Kameneva, M; Watach, M; Gordon, L; Umezu, M; Tomioka, J; Koyanagi, H; Griffith, B P

    1997-01-01

    A compact centrifugal blood pump was developed as an implantable left ventricular assist system. The impeller diameter is 40 mm and the pump dimensions are 55 x 64 mm. This first prototype was fabricated from titanium alloy, resulting in a pump weight of 400 g including a brushless DC motor. Weight of the second prototype pump was reduced to 280 g. The entire blood contacting surface is coated with diamond like carbon to improve blood compatibility. Flow rates of over 7 L/min against 100 mmHg pressure at 2,500 rpm with 9 W total power consumption have been measured. A newly designed mechanical seal with a recirculating purge system ("Cool-Seal") is used as a shaft seal. In this seal system, seal temperature is kept under 40 degrees C to prevent heat denaturation of blood proteins. Purge fluid also cools the pump motor coil and journal bearing. The purge fluid is continuously purified and sterilized by an ultrafiltration filter incorporated into the paracorporeal drive console. In vitro experiments with bovine blood demonstrated an acceptably low hemolysis rate (normalized index of hemolysis = 0.005 +/- 0.002 g/100 L). In vivo experiments are currently ongoing using calves. Via left thoracotomy, left ventricular apex-descending aorta bypass was performed utilizing a PTFE (Polytetrafluoroethylene) vascular graft, with the pump placed in the left thoracic cavity. In two in vivo experiments, pump flow rate was maintained at 5-8 L/min, and pump power consumption remained stable at 9-10 W. All plasma free hemoglobin levels were measured at < 15 mg/dl. The seal system has demonstrated good seal capability with negligible purge fluid consumption (< 0.5 ml/ day). Both animals remain under observation after 162 and 91 days of continuous pump function.

  20. The role of large‐scale heat pumps for short term integration of renewable energy

    DEFF Research Database (Denmark)

    Mathiesen, Brian Vad; Blarke, Morten; Hansen, Kenneth

    2011-01-01

    technologies is focusing on natural working fluid hydrocarbons, ammonia, and carbon dioxide. Large-scale heat pumps are crucial for integrating 50% wind power as anticipated to be installed in Denmark in 2020, along with other measures. Also in the longer term heat pumps can contribute to the minimization...... savings with increased wind power and may additionally lead to economic savings in the range of 1,500-1,700 MDKK in total in the period until 2020. Furthermore, the energy system efficiency may be increased due to large heat pumps replacing boiler production. Finally data sheets for large-scale ammonium......In this report the role of large-scale heat pumps in a future energy system with increased renewable energy is presented. The main concepts for large heat pumps in district heating systems are outlined along with the development for heat pump refrigerants. The development of future heat pump...

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

    Science.gov (United States)

    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.

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

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    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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

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

    Science.gov (United States)

    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. 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.

  11. 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.

  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. 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

  14. PUMPS

    Science.gov (United States)

    Thornton, J.D.

    1959-03-24

    A pump is described for conveving liquids, particure it is not advisable he apparatus. The to be submerged in the liquid to be pumped, a conduit extending from the high-velocity nozzle of the injector,and means for applying a pulsating prcesure to the surface of the liquid in the conduit, whereby the surface oscillates between positions in the conduit. During the positive half- cycle of an applied pulse liquid is forced through the high velocity nozzle or jet of the injector and operates in the manner of the well known water injector and pumps liquid from the main intake to the outlet of the injector. During the negative half-cycle of the pulse liquid flows in reverse through the jet but no reverse pumping action takes place.

  15. Mixer pump long term operations plan for Tank 241-SY-101 mitigation

    International Nuclear Information System (INIS)

    Irwin, J.J.

    1994-01-01

    This document provides the general Operations Plan for performance of the mixer pump long term operations for Tank 241-SY-101 mitigation of gas retention and periodic release in Tank 101-SY. This operations plan will utilize a 112 kW (150 hp) mixing pump to agitate/suspend the particulates in the tank

  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. 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.

  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. 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

  20. 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

  1. Protonation of key acidic residues is critical for the K⁺-selectivity of the Na/K pump.

    Science.gov (United States)

    Yu, Haibo; Ratheal, Ian M; Artigas, Pablo; Roux, Benoît

    2011-09-11

    The sodium-potassium (Na/K) pump is a P-type ATPase that generates Na(+) and K(+) concentration gradients across the cell membrane. For each hydrolyzed ATP molecule, the pump extrudes three Na(+) and imports two K(+) by alternating between outward- and inward-facing conformations that preferentially bind K(+) or Na(+), respectively. Remarkably, the selective K(+) and Na(+) binding sites share several residues, and how the pump is able to achieve the selectivity required for the functional cycle is unclear. Here, free energy-perturbation molecular dynamics (FEP/MD) simulations based on the crystal structures of the Na/K pump in a K(+)-loaded state (E2·P(i)) reveal that protonation of the high-field acidic side chains involved in the binding sites is crucial to achieving the proper K(+) selectivity. This prediction is tested with electrophysiological experiments showing that the selectivity of the E2P state for K(+) over Na(+) is affected by extracellular pH.

  2. Regulatory assembly of the vacuolar proton pump VoV1-ATPase in yeast cells by FLIM-FRET

    Science.gov (United States)

    Ernst, Stefan; Batisse, Claire; Zarrabi, Nawid; Böttcher, Bettina; Börsch, Michael

    2010-02-01

    We investigate the reversible disassembly of VOV1-ATPase in life yeast cells by time resolved confocal FRET imaging. VOV1-ATPase in the vacuolar membrane pumps protons from the cytosol into the vacuole. VOV1-ATPase is a rotary biological nanomotor driven by ATP hydrolysis. The emerging proton gradient is used for secondary transport processes as well as for pH and Ca2+ homoeostasis in the cell. The activity of the VOV1-ATPase is regulated through assembly / disassembly processes. During starvation the two parts of VOV1-ATPase start to disassemble. This process is reversed after addition of glucose. The exact mechanisms are unknown. To follow the disassembly / reassembly in vivo we tagged two subunits C and E with different fluorescent proteins. Cellular distributions of C and E were monitored using a duty cycle-optimized alternating laser excitation scheme (DCO-ALEX) for time resolved confocal FRET-FLIM measurements.

  3. 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...

  4. Tritium Sequestration in Gen IV NGNP Gas Stream via Proton Conducting Ceramic Pumps

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fanglin Frank [Univ. of South Carolina, Columbia, SC (United States); Adams, Thad M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Brinkman, Kyle [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Reifsnider, Kenneth [Univ. of South Carolina, Columbia, SC (United States)

    2011-09-30

    Several types of high-temperature proton conductors based on SrCeO3 and BaCeO3 have been systematically investigated in this project for tritium separation in NGNP applications. One obstacle for the field application is the chemical stability issues in the presence of steam and CO2 for these proton conductors. Several strategies to overcome such issues have been evaluated, including A site doping and B site co-doping method for perovskite-structured proton conductors. Novel zirconium-free proton conductors have also been developed with improved electrical conductivity and enhanced chemical stability. Novel catalytic materials for the proton-conducting separation membranes have been investigated. A tubular geometry proton-conducting membrane has been developed for the proton separation membranes. Total dose rate estimated from tritium decay (beta emission) under realistic membrane operating conditions, combined with electron irradiation experiments, indicates that proton ceramic materials possess the appropriate radiation stability for this application.

  5. Pump

    International Nuclear Information System (INIS)

    Mole, C.J.

    1983-01-01

    An electromagnetic pump for circulating liquid -metal coolant through a nuclear reactor wherein opposite walls of a pump duct serve as electrodes to transmit current radially through the liquid-metal in the ducts. A circumferential electric field is supplied to the liquid-metal by a toroidal electromagnet which has core sections interposed between the ducts. The windings of the electromagnet are composed of metal which is superconductive at low temperatures and the electromagnet is maintained at a temperature at which it is superconductive by liquid helium which is fed through the conductors which supply the excitation for the electromagnet. The walls of the ducts joining the electrodes include metal plates insulated from the electrodes backed up by insulators so that they are capable of withstanding the pressure of the liquid-metal. These composite wall structures may also be of thin metal strips of low electrical conductivity backed up by sturdy insulators. (author)

  6. 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.

  7. 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

  8. Identification of pumping influences in long-term water level fluctuations.

    Science.gov (United States)

    Harp, Dylan R; Vesselinov, Velimir V

    2011-01-01

    Identification of the pumping influences at monitoring wells caused by spatially and temporally variable water supply pumping can be a challenging, yet an important hydrogeological task. The information that can be obtained can be critical for conceptualization of the hydrogeological conditions and indications of the zone of influence of the individual pumping wells. However, the pumping influences are often intermittent and small in magnitude with variable production rates from multiple pumping wells. While these difficulties may support an inclination to abandon the existing dataset and conduct a dedicated cross-hole pumping test, that option can be challenging and expensive to coordinate and execute. This paper presents a method that utilizes a simple analytical modeling approach for analysis of a long-term water level record utilizing an inverse modeling approach. The methodology allows the identification of pumping wells influencing the water level fluctuations. Thus, the analysis provides an efficient and cost-effective alternative to designed and coordinated cross-hole pumping tests. We apply this method on a dataset from the Los Alamos National Laboratory site. Our analysis also provides (1) an evaluation of the information content of the transient water level data; (2) indications of potential structures of the aquifer heterogeneity inhibiting or promoting pressure propagation; and (3) guidance for the development of more complicated models requiring detailed specification of the aquifer heterogeneity. Copyright © 2010 The Author(s). Journal compilation © 2010 National Ground Water Association.

  9. The selectivity of the Na+/K+-pump is controlled by binding site protonation and self-correcting occlusion

    Science.gov (United States)

    Rui, Huan; Artigas, Pablo; Roux, Benoît

    2016-01-01

    The Na+/K+-pump maintains the physiological K+ and Na+ electrochemical gradients across the cell membrane. It operates via an 'alternating-access' mechanism, making iterative transitions between inward-facing (E1) and outward-facing (E2) conformations. Although the general features of the transport cycle are known, the detailed physicochemical factors governing the binding site selectivity remain mysterious. Free energy molecular dynamics simulations show that the ion binding sites switch their binding specificity in E1 and E2. This is accompanied by small structural arrangements and changes in protonation states of the coordinating residues. Additional computations on structural models of the intermediate states along the conformational transition pathway reveal that the free energy barrier toward the occlusion step is considerably increased when the wrong type of ion is loaded into the binding pocket, prohibiting the pump cycle from proceeding forward. This self-correcting mechanism strengthens the overall transport selectivity and protects the stoichiometry of the pump cycle. DOI: http://dx.doi.org/10.7554/eLife.16616.001 PMID:27490484

  10. 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.

  11. 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....

  12. FEATURES OF LONG-TERM MECHANICAL CIRCULATORY SUPPORT WITH CONTINUOUS-FLOW PUMP

    Directory of Open Access Journals (Sweden)

    G. P. Itkin

    2012-01-01

    Full Text Available In a review of the comparative analysis of methods and tools for long-term mechanical circulatory support with continuous flow and pulsatile flow implantable pumps. Particular attention is paid to the choice of the optimal modes of the operation of pumps based on the physical principles of the interaction between a the steady flow of blood to the pulsatile mechanics of the heart chambers. 

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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...

  19. 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.

  20. 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...

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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...

  9. EVAHEART: an implantable centrifugal blood pump for long-term circulatory support.

    Science.gov (United States)

    Yamazaki, Kenji; Kihara, Shinichiro; Akimoto, Takehide; Tagusari, Osamu; Kawai, Akihiko; Umezu, Mitsuo; Tomioka, Jun; Kormos, Robert L; Griffith, Bartley P; Kurosawa, Hiromi

    2002-11-01

    We developed "EVAHEART": a compact centrifugal blood pump system as an implantable left ventricular assist device for long-term circulatory support. The 55 x 64 mm pump is made from pure titanium, and weighs 370 g. The entire blood-contacting surface is covered with an anti-thrombogenic coating of diamond like carbon (DLC) or 2-methacryloyloxyethyl phosphorylcholine (MPC) to improve blood compatibility. Flows exceeding 12 L/min against 100 mmHg pressure at 2600 rpm was measured. A low-temperature mechanical seal with recirculating cooling system is used to seal the shaft. EVAHEART demonstrated an acceptably low hemolysis rate with normalized index of hemolysis of 0.005 +/- 0.002 g/100L. We evaluated the pump in long-term in-vivo experiments with seven calves. Via left thoracotomy, we conducted left ventricular apex-descending aorta bypass, placing the pump in the left thoracic cavity. Pump flow rates was maintained at 5-9 L/min, pump power consumption remained stable at 9-10 W in all cases, plasma free Hb levels were less than 15 mg/dl, and the seal system showed good seal capability throughout the experiments. The calves were sacrificed on schedule on postoperative day 200, 222, 142, 90, 151, 155, and 133. No thrombi formed on the blood contacting surface with either the DLC or MPC coating, and no major organ thromboembolisms occurred except for a few small renal infarcts. EVAHEART centrifugal blood pump demonstrated excellent performance in long-term in-vivo experiments.

  10. A plant-like proton-pump partnership in the malaria parasite

    International Nuclear Information System (INIS)

    Allen, R.J.W.; Saliba, K.J.; Zissis, S.; Kirk, K.

    2001-01-01

    Full text: The 'intraerythrocytic' form of the human malaria parasite. Plasmodium falciparum contains an acidic 'digestive vacuole' which is believed to be the main site of haemoglobin degradation, and the major site of action of many antimalarial drugs. The mechanism/s by which this organelle is acidified have not been investigated. In plant cells, the internal acidic vacuole has on its membrane two types of H + -pumps which contribute to the generation of an acidic pH: a vacuolar-type H + -ATPase (V-H + -ATPase) and a vacuolar H + -pyrophosphatase (V-H + -PPase). The presence of a V-H + -ATPase on the digestive vacuole membrane of P. falciparum has been demonstrated by immuno-electron microscopy (J. Biol. Chem. (2000) 275: 34353-34358) but its functional activity on this organelle has not been demonstrated. Two V-H + -PPase genes have been shown to be expressed in the intraerythrocytic stage of the P. falciparum parasite (Mol. Biochem. Parasitol. (2001) 114: 183-195); however, immunological methods failed to detect either on the parasite digestive vacuole. In this study we use a combination of NMR spectroscopy and fluorescence techniques to show that (i) P. falciparum contains low levels of pyrophosphate, and (ii) that both ATP and pyrophosphate are able to energise the acidification of the parasite's digestive vacuole. We propose that, like many plant cells the digestive vacuole of P. falciparum parasites has, on its membrane, a V-H + -PPase as well as a V-H + -ATPaSe, and that both pumps contribute to the pH regulation of this organelle

  11. A plant-like proton-pump partnership in the malaria parasite

    Energy Technology Data Exchange (ETDEWEB)

    Allen, R J.W.; Saliba, K J; Zissis, S; Kirk, K [Australian National University, ACT (Australia)

    2001-07-01

    Full text: The 'intraerythrocytic' form of the human malaria parasite. Plasmodium falciparum contains an acidic 'digestive vacuole' which is believed to be the main site of haemoglobin degradation, and the major site of action of many antimalarial drugs. The mechanism/s by which this organelle is acidified have not been investigated. In plant cells, the internal acidic vacuole has on its membrane two types of H{sup +}-pumps which contribute to the generation of an acidic pH: a vacuolar-type H{sup +}-ATPase (V-H{sup +}-ATPase) and a vacuolar H{sup +}-pyrophosphatase (V-H{sup +}-PPase). The presence of a V-H{sup +}-ATPase on the digestive vacuole membrane of P. falciparum has been demonstrated by immuno-electron microscopy (J. Biol. Chem. (2000) 275: 34353-34358) but its functional activity on this organelle has not been demonstrated. Two V-H{sup +}-PPase genes have been shown to be expressed in the intraerythrocytic stage of the P. falciparum parasite (Mol. Biochem. Parasitol. (2001) 114: 183-195); however, immunological methods failed to detect either on the parasite digestive vacuole. In this study we use a combination of NMR spectroscopy and fluorescence techniques to show that (i) P. falciparum contains low levels of pyrophosphate, and (ii) that both ATP and pyrophosphate are able to energise the acidification of the parasite's digestive vacuole. We propose that, like many plant cells the digestive vacuole of P. falciparum parasites has, on its membrane, a V-H{sup +}-PPase as well as a V-H{sup +}-ATPaSe, and that both pumps contribute to the pH regulation of this organelle.

  12. 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.

  13. 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.

  14. 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

    with minimal therapeutic benefits. Educating clinicians regarding SUP guidelines and the adverse effects of long-term use of acid suppression can improve the cost effectiveness of PPI therapy. Keywords: proton pump inhibitor, stress ulcer, prophylaxis, gastrointestinal bleeding, intensive care unit, critical care

  15. Nonadiabatic rate constants for proton transfer and proton-coupled electron transfer reactions in solution: Effects of quadratic term in the vibronic coupling expansion.

    Science.gov (United States)

    Soudackov, Alexander V; Hammes-Schiffer, Sharon

    2015-11-21

    Rate constant expressions for vibronically nonadiabatic proton transfer and proton-coupled electron transfer reactions are presented and analyzed. The regimes covered include electronically adiabatic and nonadiabatic reactions, as well as high-frequency and low-frequency proton donor-acceptor vibrational modes. These rate constants differ from previous rate constants derived with the cumulant expansion approach in that the logarithmic expansion of the vibronic coupling in terms of the proton donor-acceptor distance includes a quadratic as well as a linear term. The analysis illustrates that inclusion of this quadratic term in the framework of the cumulant expansion framework may significantly impact the rate constants at high temperatures for proton transfer interfaces with soft proton donor-acceptor modes that are associated with small force constants and weak hydrogen bonds. The effects of the quadratic term may also become significant in these regimes when using the vibronic coupling expansion in conjunction with a thermal averaging procedure for calculating the rate constant. In this case, however, the expansion of the coupling can be avoided entirely by calculating the couplings explicitly for the range of proton donor-acceptor distances sampled. The effects of the quadratic term for weak hydrogen-bonding systems are less significant for more physically realistic models that prevent the sampling of unphysical short proton donor-acceptor distances. Additionally, the rigorous relation between the cumulant expansion and thermal averaging approaches is clarified. In particular, the cumulant expansion rate constant includes effects from dynamical interference between the proton donor-acceptor and solvent motions and becomes equivalent to the thermally averaged rate constant when these dynamical effects are neglected. This analysis identifies the regimes in which each rate constant expression is valid and thus will be important for future applications to proton

  16. Nonadiabatic rate constants for proton transfer and proton-coupled electron transfer reactions in solution: Effects of quadratic term in the vibronic coupling expansion

    International Nuclear Information System (INIS)

    Soudackov, Alexander V.; Hammes-Schiffer, Sharon

    2015-01-01

    Rate constant expressions for vibronically nonadiabatic proton transfer and proton-coupled electron transfer reactions are presented and analyzed. The regimes covered include electronically adiabatic and nonadiabatic reactions, as well as high-frequency and low-frequency proton donor-acceptor vibrational modes. These rate constants differ from previous rate constants derived with the cumulant expansion approach in that the logarithmic expansion of the vibronic coupling in terms of the proton donor-acceptor distance includes a quadratic as well as a linear term. The analysis illustrates that inclusion of this quadratic term in the framework of the cumulant expansion framework may significantly impact the rate constants at high temperatures for proton transfer interfaces with soft proton donor-acceptor modes that are associated with small force constants and weak hydrogen bonds. The effects of the quadratic term may also become significant in these regimes when using the vibronic coupling expansion in conjunction with a thermal averaging procedure for calculating the rate constant. In this case, however, the expansion of the coupling can be avoided entirely by calculating the couplings explicitly for the range of proton donor-acceptor distances sampled. The effects of the quadratic term for weak hydrogen-bonding systems are less significant for more physically realistic models that prevent the sampling of unphysical short proton donor-acceptor distances. Additionally, the rigorous relation between the cumulant expansion and thermal averaging approaches is clarified. In particular, the cumulant expansion rate constant includes effects from dynamical interference between the proton donor-acceptor and solvent motions and becomes equivalent to the thermally averaged rate constant when these dynamical effects are neglected. This analysis identifies the regimes in which each rate constant expression is valid and thus will be important for future applications to proton

  17. Tritium Sequestration in Gen IV NGNP Gas Stream via Proton Conducting Ceramic Pumps

    International Nuclear Information System (INIS)

    Chen, Franglin Frank; Adams, Thad M.; Brinkman, Kyle; Reifsnider, Kenneth

    2011-01-01

    Several perovskite structured proton conductors based on SrCeO 3 and BaCeO 3 have been investigated in the project. The solid solutions for SrCeO 3 and BaCeO 3 were first investigated. The morphological and electrical properties of Ba 1-x Sr x Ce 0.8 Y 0.2 O 3-δ with x varying from 0 to 1 prepared by a modified Pechini method were investigated as potential high temperature proton conductors. Dense microstructures were achieved for all the samples upon sintering at 1500ees)C for 5 h. The phase structure analysis indicated that perovskite phase was formed for 0≤x≤0.2, while for x larger than 0.5, impurity phases of Sr 2 CeO 4 and Y 2 O 3 appeared. The stability tests indicated that the resistance to boiling water for Ba 1-x Sr x Ce 0.8 Y 0.2 O 3-δ was between that of BaCe 0.8 Y 0.2 O 3-δ and SrCe 0.8 Y 0.2 O 3-δ Due to the tendency of the reaction with CO 2 for both BaCe 0.8 Y 0.2 O 3-δ and SrCe 0.8 Y 0.2 O 3-δ , it was not surprising that Ba 1-x Sr x Ce 0.8 Y 0.2 O 3-δ was also not stable in CO 2 containing atmospheres. The conductivity tests indicated that Ba 1-x Sr x Ce 0.8 Y 0.2 O 3-δ possessed the electrical conductivity between BaCe 0.8 Y 0.2 O 3-δ and SrCe 0.8 Y 0.2 O 3-δ . The conductivity decreased and the activation energy increased with the increase in Sr content in Ba 1-x Sr x Ce 0.8 Y 0.2 O 3-δ .

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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...

  12. 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.

  13. 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

  14. A long-term analysis of pumped hydro storage to firm wind power

    International Nuclear Information System (INIS)

    Foley, A.M.; Leahy, P.G.; Li, K.; McKeogh, E.J.; Morrison, A.P.

    2015-01-01

    Highlights: • This is a long term generation analysis of a high wind power system. • A high CO 2 and fossil fuel price is closest to Ireland’s EU ETS 2020 target. • New pumped storage to firm wind is limited unless strong market costs exist. • Reserve for wind power show that ancillary services are relevant for balancing. - Abstract: Although pumped hydro storage is seen as a strategic key asset by grid operators, financing it is complicated in new liberalised markets. It could be argued that the optimum generation portfolio is now determined by the economic viability of generators based on a short to medium term return on investment. This has meant that capital intensive projects such as pumped hydro storage are less attractive for wholesale electricity companies because the payback periods are too long. In tandem a significant amount of wind power has entered the generation mix, which has resulted in operating and planning integration issues due to wind’s inherent uncertain, varying spatial and temporal nature. These integration issues can be overcome using fast acting gas peaking plant or energy storage. Most analysis of wind power integration using storage to date has used stochastic optimisation for power system balancing or arbitrage modelling to examine techno-economic viability. In this research a deterministic dynamic programming long term generation expansion model is employed to optimise the generation mix, total system costs and total carbon dioxide emissions, and unlike other studies calculates reserve to firm wind power. The key finding of this study is that the incentive to build capital-intensive pumped hydro storage to firm wind power is limited unless exogenous market costs come very strongly into play. Furthermore it was demonstrated that reserve increases with increasing wind power showing the importance of ancillary services in future power systems

  15. Automatic estimation of aquifer parameters using long-term water supply pumping and injection records

    Science.gov (United States)

    Luo, Ning; Illman, Walter A.

    2016-09-01

    Analyses are presented of long-term hydrographs perturbed by variable pumping/injection events in a confined aquifer at a municipal water-supply well field in the Region of Waterloo, Ontario (Canada). Such records are typically not considered for aquifer test analysis. Here, the water-level variations are fingerprinted to pumping/injection rate changes using the Theis model implemented in the WELLS code coupled with PEST. Analyses of these records yield a set of transmissivity ( T) and storativity ( S) estimates between each monitoring and production borehole. These individual estimates are found to poorly predict water-level variations at nearby monitoring boreholes not used in the calibration effort. On the other hand, the geometric means of the individual T and S estimates are similar to those obtained from previous pumping tests conducted at the same site and adequately predict water-level variations in other boreholes. The analyses reveal that long-term municipal water-level records are amenable to analyses using a simple analytical solution to estimate aquifer parameters. However, uniform parameters estimated with analytical solutions should be considered as first rough estimates. More accurate hydraulic parameters should be obtained by calibrating a three-dimensional numerical model that rigorously captures the complexities of the site with these data.

  16. 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.

  17. [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.

  18. 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.

  19. 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.

  20. 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

  1. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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

  4. 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

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

    Science.gov (United States)

    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. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Long-Term Quality of Life Outcome After Proton Beam Monotherapy for Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Coen, John J., E-mail: jcoen@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Paly, Jonathan J.; Niemierko, Andrzej; Weyman, Elizabeth [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Rodrigues, Anita [Department of Medical Oncology, Massachusetts General Hospital, Boston, MA (United States); Shipley, William U.; Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Talcott, James A. [Department of Medical Oncology, Massachusetts General Hospital, Boston, MA (United States)

    2012-02-01

    Objectives: High-dose external radiation for localized prostate cancer results in favorable clinical outcomes and low toxicity rates. Here, we report long-term quality of life (QOL) outcome for men treated with conformal protons. Methods: QOL questionnaires were sent at specified intervals to 95 men who received proton radiation. Of these, 87 men reported 3- and/or 12-month outcomes, whereas 73 also reported long-term outcomes (minimum 2 years). Symptom scores were calculated at baseline, 3 months, 12 months, and long-term follow-up. Generalized estimating equation models were constructed to assess longitudinal outcomes while accounting for correlation among repeated measures in an individual patient. Men were stratified into functional groups from their baseline questionnaires (normal, intermediate, or poor function) for each symptom domain. Long-term QOL changes were assessed overall and within functional groups using the Wilcoxon signed-rank test. Results: Statistically significant changes in all four symptom scores were observed in the longitudinal analysis. For the 73 men reporting long-term outcomes, there were significant change scores for incontinence (ID), bowel (BD) and sexual dysfunction (SD), but not obstructive/irritative voiding dysfunction (OID). When stratified by baseline functional category, only men with normal function had increased scores for ID and BD. For SD, there were significant changes in men with both normal and intermediate function, but not poor function. Conclusions: Patient reported outcomes are sensitive indicators of treatment-related morbidity. These results quantitate the long-term consequences of proton monotherapy for prostate cancer. Analysis by baseline functional category provides an individualized prediction of long-term QOL scores. High dose proton radiation was associated with small increases in bowel dysfunction and incontinence, with more pronounced changes in sexual dysfunction.

  19. 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.

  20. 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

  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. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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...

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Short- and Medium-term Atmospheric Effects of Very Large Solar Proton Events

    Science.gov (United States)

    Jackman, Charles H.; Marsh, Daniel R.; Vitt, Francis M.; Garcia, Rolando R.; Fleming, Eric L.; Labow, Gordon J.; Randall, Cora E.; Lopez-Puertas, Manuel; Funke, Bernd

    2007-01-01

    Long-term variations in ozone have been caused by both natural and humankind related processes. In particular, the humankind or anthropogenic influence on ozone from chlorofluorocarbons and halons (chlorine and bromine) has led to international regulations greatly limiting the release of these substances. These anthropogenic effects on ozone are most important in polar regions and have been significant since the 1970s. Certain natural ozone influences are also important in polar regions and are caused by the impact of solar charged particles on the atmosphere. Such natural variations have been studied in order to better quantify the human influence on polar ozone. Large-scale explosions on the Sun near solar maximum lead to emissions of charged particles (mainly protons and electrons), some of which enter the Earth's magnetosphere and rain down on the polar regions. "Solar proton events" have been used to describe these phenomena since the protons associated with these solar events sometimes create a significant atmospheric disturbance. We have used the National Center for Atmospheric Research (NCAR) Whole Atmosphere Community Climate Model (WACCM) to study the short- and medium-term (days to a few months) influences of solar proton events between 1963 and 2005 on stratospheric ozone. The four largest events in the past 45 years (August 1972; October 1989; July 2000; and October-November 2003) caused very distinctive polar changes in layers of the Earth's atmosphere known as the stratosphere (12-50 km; -7-30 miles) and mesosphere (50-90 km; 30-55 miles). The solar protons connected with these events created hydrogen- and nitrogen- containing compounds, which led to the polar ozone destruction. The hydrogen-containing compounds have very short lifetimes and lasted for only a few days (typically the duration of the solar proton event). On the other hand, the nitrogen-containing compounds lasted much longer, especially in the Winter. The nitrogen oxides were predicted

  14. The Long-term Middle Atmospheric Influence of Very Large Solar Proton Events

    Science.gov (United States)

    Jackman, Charles H.; Marsh, Daniel R.; Vitt, Francis M.; Garcia, Rolando R.; Randall, Cora E.; Fleming, Eric L.; Frith, Stacey M.

    2008-01-01

    Long-term variations in ozone have been caused by both natural and humankind related processes. The humankind or anthropogenic influence on ozone originates from the chlorofluorocarbons and halons (chlorine and bromine) and has led to international regulations greatly limiting the release of these substances. Certain natural ozone influences are also important in polar regions and are caused by the impact of solar charged particles on the atmosphere. Such natural variations have been studied in order to better quantify the human influence on polar ozone. Large-scale explosions on the Sun near solar maximum lead to emissions of charged particles (mainly protons and electrons), some of which enter the Earth's magnetosphere and rain down on the polar regions. "Solar proton events" have been used to describe these phenomena since the protons associated with these solar events sometimes create a significant atmospheric disturbance. We have used the National Center for Atmospheric Research (NCAR) Whole Atmosphere Community Climate Model (WACCM) to study the long-term (> few months) influences of solar proton events from 1963 through 2004 on stratospheric ozone and temperature. There were extremely large solar proton events in 1972, 1989,2000,2001, and 2003. These events caused very distinctive polar changes in layers of the Earth's atmosphere known as the stratosphere (12-50 km; -7-30 miles) and mesosphere (50-90 km; 30-55 miles). The solar protons connected with these events created hydrogen- and nitrogen-containing compounds, which led to the polar ozone destruction. The nitrogen-containing compounds, called odd nitrogen, lasted much longer than the hydrogen-containing compounds and led to long-lived stratospheric impacts. An extremely active period for these events occurred in the five-year period, 2000- 2004, and caused increases in odd nitrogen which lasted for several months after individual events. Associated stratospheric ozone decreases of >lo% were calculated

  15. Long-term regulation of Na,K-ATPase pump during T-cell proliferation.

    Science.gov (United States)

    Karitskaya, Inna; Aksenov, Nikolay; Vassilieva, Irina; Zenin, Valerii; Marakhova, Irina

    2010-09-01

    The aim of the study was to elucidate the mechanism responsible for the proliferation-related regulation of Na,K-ATPase pump. Our data demonstrate that in mitogen-stimulated human blood lymphocytes, enhanced ouabain-sensitive Rb(K) fluxes in the middle/late stage of G(0)/G(1)/S transit are associated with the increased number of Na,K-ATPase pumps expressed at the cell surface (as determined by the [(3)H]ouabain binding). Analysis of total RNA (reverse transcription-polymerase chain reaction) and protein (Western blotting) showed a threefold increase in the level of Na,K-ATPase alpha1-subunit and beta1-subunit mRNAs and significant increase in the Na,K-ATPase alpha1-subunit protein during the first day of mitogen-induced proliferation. The elevated K transport as well as the increased expression of Na,K-ATPase is closely associated with the IL-2-dependent stage of T-cell response. The pharmacological inhibition of IL-2-induced MEK/ERK or JAK/STAT cascades suppressed the IL-2-induced proliferation and reduced the functional and protein expressions of Na,K-ATPase. It is concluded that during the lymphocyte transition from resting stage to proliferation, (1) long-term activation of Na,K-ATPase pump is due to the enhanced expression of Na,K-ATPase protein and mRNA, and (2) the cytokine signaling via the IL-2 receptor is necessary for the cell cycle-associated upregulation of Na,K-ATPase.

  16. 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

  17. 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.

  18. Does Off-Pump Coronary Artery Bypass Grafting Negatively Impact Long-Term Survival and Freedom from Reintervention?

    Directory of Open Access Journals (Sweden)

    Shahzad G. Raja

    2013-01-01

    Full Text Available Recently published evidence has raised concerns about worse late mortality and increasing need for reintervention after off-pump coronary artery bypass grafting. We undertook this study to assess the impact of off-pump coronary artery bypass grafting on survival and freedom from reintervention at 10 years. From January 2002 to December 2002, 307 consecutive patients who had isolated multivessel off-pump coronary artery bypass grafting at our institution were compared to a control group of 397 patients that underwent multivessel on-pump coronary artery bypass grafting during the same period. In addition, univariate and risk-adjusted comparisons between the two groups were performed at 10 years. Kaplan-Meier survival was similar for the two cohorts. After adjusting for clinical covariates, off-pump coronary artery bypass grafting did not emerge as a significant independent predictor of long-term mortality (Hazard Ratio 0.91; 95% Confidence Interval 0.70–1.12, readmission to hospital for cardiac cause (Hazard Ratio 0.96; 95% Confidence Interval 0.78–1.10, or the need for reintervention (Hazard Ratio 0.93; 95% Confidence Interval 0.87–1.05. Off-pump coronary artery bypass grafting compared with on-pump coronary artery bypass grafting does not adversely impact survival or freedom from reintervention at a 10-year follow-up.

  19. Long-Term Monitoring of Mini-Split Ductless Heat Pumps in the Northeast

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, K.; Loomis, H.

    2015-06-01

    Transformations, Inc. has extensive experience building their high performance housing at a variety of Massachusetts locations, in both a production and custom home setting. The majority of their construction uses mini-split heat pumps (MSHPs) for space conditioning. This research covered the long-term performance of MSHPs in Zone 5A; it is the culmination of up to 3 years' worth of monitoring in a set of eight houses. This research examined electricity use of MSHPs, distributions of interior temperatures and humidity when using simplified (two-point) heating systems in high-performance housing, and the impact of open-door/closed-door status on temperature distributions. The use of simplified space conditioning distribution (through use of MSHPs) provides significant first cost savings, which are used to offset the increased investment in the building enclosure.

  20. [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

  1. Long-Term Outcomes After Proton Beam Therapy for Sinonasal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Russo, Andrea L.; Adams, Judith A.; Weyman, Elizabeth A.; Busse, Paul M.; Goldberg, Saveli I. [Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Varvares, Mark; Deschler, Daniel D.; Lin, Derrick T. [Head and Neck Surgical Oncology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts (United States); Delaney, Thomas F. [Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Chan, Annie W., E-mail: awchan@partners.org [Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2016-05-01

    Purpose: Squamous cell carcinoma (SCC) is the most common sinonasal cancer and is associated with one of the poor outcomes. Proton therapy allows excellent target coverage with maximal sparing of adjacent normal tissues. We evaluated the long-term outcomes in patients with sinonasal SCC treated with proton therapy. Methods and Materials: Between 1991 and 2008, 54 patients with Stage III and IV SCC of the nasal cavity and paranasal sinus received proton beam therapy at our institution to a median dose of 72.8 Gy(RBE). Sixty-nine percent underwent prior surgical resection, and 74% received elective nodal radiation. Locoregional control and survival probabilities were estimated with the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional-hazards model. Treatment toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0. Results: With a median follow-up time of 82 months in surviving patients, there were 10 local, 7 regional, and 11 distant failures. The 2-year and 5-year actuarial local control rate was 80%. The 2-year and 5-year rates of overall survival were 67% and 47%, respectively. Only smoking status was predictive for worse locoregional control, with current smokers having a 5-year rate of 23% compared with 83% for noncurrent smokers (P=.004). Karnofsky performance status ≤80 was the most significant factor predictive for worse overall survival in multivariate analysis (adjusted hazard ratio 4.5, 95% confidence interval 1.6-12.5, P=.004). There were nine grade 3 and six grade 4 toxicities, and no grade 5 toxicity. Wound adverse events constituted the most common grade 3-4 toxicity. Conclusions: Our long-term results show that proton radiation therapy is well tolerated and yields good locoregional control for SCC of the nasal cavity and paranasal sinus. Current smokers and patients with poor performance status had inferior outcomes. Prospective study is necessary to compare IMRT with proton

  2. Long-Term Outcomes After Proton Beam Therapy for Sinonasal Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Russo, Andrea L.; Adams, Judith A.; Weyman, Elizabeth A.; Busse, Paul M.; Goldberg, Saveli I.; Varvares, Mark; Deschler, Daniel D.; Lin, Derrick T.; Delaney, Thomas F.; Chan, Annie W.

    2016-01-01

    Purpose: Squamous cell carcinoma (SCC) is the most common sinonasal cancer and is associated with one of the poor outcomes. Proton therapy allows excellent target coverage with maximal sparing of adjacent normal tissues. We evaluated the long-term outcomes in patients with sinonasal SCC treated with proton therapy. Methods and Materials: Between 1991 and 2008, 54 patients with Stage III and IV SCC of the nasal cavity and paranasal sinus received proton beam therapy at our institution to a median dose of 72.8 Gy(RBE). Sixty-nine percent underwent prior surgical resection, and 74% received elective nodal radiation. Locoregional control and survival probabilities were estimated with the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional-hazards model. Treatment toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0. Results: With a median follow-up time of 82 months in surviving patients, there were 10 local, 7 regional, and 11 distant failures. The 2-year and 5-year actuarial local control rate was 80%. The 2-year and 5-year rates of overall survival were 67% and 47%, respectively. Only smoking status was predictive for worse locoregional control, with current smokers having a 5-year rate of 23% compared with 83% for noncurrent smokers (P=.004). Karnofsky performance status ≤80 was the most significant factor predictive for worse overall survival in multivariate analysis (adjusted hazard ratio 4.5, 95% confidence interval 1.6-12.5, P=.004). There were nine grade 3 and six grade 4 toxicities, and no grade 5 toxicity. Wound adverse events constituted the most common grade 3-4 toxicity. Conclusions: Our long-term results show that proton radiation therapy is well tolerated and yields good locoregional control for SCC of the nasal cavity and paranasal sinus. Current smokers and patients with poor performance status had inferior outcomes. Prospective study is necessary to compare IMRT with proton

  3. 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.

  4. Analogies between respiration and a light-driven proton pump as sources of energy for active glutamate transport in Halobacterium halobium

    Science.gov (United States)

    Belliveau, J. W.; Lanyi, J. K.

    1977-01-01

    Halobacterium halobium is known to contain sheets of bacteriorhodopsin, a pigment which upon exposure to light undergoes cyclic protonation and deprotonation, resulting in net H(+) translocation. In this paper, experiments were conducted to test H. halobium cell envelope vesicles for respiration-induced glutamate uptake. It is shown that glutamate transport in H. halobium cell envelope vesicles can occur as a result of respiration, as well as light acting on bacteriorhodopsin. Glutamate transport can be energized by the oxidation of dimethyl phenylenediamine, and the properties of the transport system are entirely analogous to those observed with illumination as the source of energy. In the case of respiration-dependent glutamate transport, the transportation is also driven by a Na(+) gradient, thereby confirming the existence of a single glutamate transport system independent of the source of energy. The analogy observed is indirect evidence that the cytochrome oxidase of H. halobium functions as a H(+) pump.

  5. 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....

  6. 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...

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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,

  17. Long-term animal experiments with an intraventricular axial flow blood pump.

    Science.gov (United States)

    Yamazaki, K; Kormos, R L; Litwak, P; Tagusari, O; Mori, T; Antaki, J F; Kameneva, M; Watach, M; Gordon, L; Mukuo, H; Umezu, M; Tomioka, J; Outa, E; Griffith, B P; Koyanagai, H

    1997-01-01

    A miniature intraventricular axial flow blood pump (IVAP) is undergoing in vivo evaluation in calves. The IVAP system consists of a miniature (phi 13.9 mm) axial flow pump that resides within the left ventricular (LV) chamber and a brushless DC motor. The pump is fabricated from titanium alloy, and the pump weight is 170 g. It produces a flow rate of over 5 L/min against 100 mmHg pressure at 9,000 rpm with an 8 W total power consumption. The maximum total efficiency exceeds 17%. A purged lip seal system is used in prototype no. 8, and a newly developed "Cool-Seal" (a low temperature mechanical seal) is used in prototype no. 9. In the Cool-Seal system, a large amount of purge flow is introduced behind the seal faces to augment convective heat transfer, keeping the seal face temperature at a low level for prevention of heat denaturation of blood proteins. The Cool-Seal system consumes < 10 cc purge fluid per day and has greatly extended seal life. The pumps were implanted in three calves (26, 30, and 168 days of support). The pump was inserted through a left thoracotomy at the fifth intercostal space. Two pursestring sutures were placed on the LV apex, and the apex was cored with a myocardial punch. The pump was inserted into the LV with the outlet cannula smoothly passing through the aortic valve without any difficulty. Only 5 min elapsed between the time of chest opening and initiation of pumping. Pump function remained stable throughout in all experiments. No cardiac arrhythmias were detected, even at treadmill exercise tests. The plasma free hemoglobin level remained in the acceptable range. Post mortem examination did not reveal any interference between the pump and the mitral apparatus. No major thromboembolism was detected in the vital organs in Cases 1 or 2, but a few small renal infarcts were detected in Case 3.

  18. 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.

    Science.gov (United States)

    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.

  19. The long-term variability of cosmic ray protons in the heliosphere: A modeling approach

    Directory of Open Access Journals (Sweden)

    M.S. Potgieter

    2013-05-01

    Full Text Available Galactic cosmic rays are charged particles created in our galaxy and beyond. They propagate through interstellar space to eventually reach the heliosphere and Earth. Their transport in the heliosphere is subjected to four modulation processes: diffusion, convection, adiabatic energy changes and particle drifts. Time-dependent changes, caused by solar activity which varies from minimum to maximum every ∼11 years, are reflected in cosmic ray observations at and near Earth and along spacecraft trajectories. Using a time-dependent compound numerical model, the time variation of cosmic ray protons in the heliosphere is studied. It is shown that the modeling approach is successful and can be used to study long-term modulation cycles.

  20. Sodium pumping: pump problems

    International Nuclear Information System (INIS)

    Guer, M.; Guiton, P.

    Information on sodium pumps for LMFBR type reactors is presented concerning ring pump design, pool reactor pump design, secondary pumps, sodium bearings, swivel joints of the oscillating annulus, and thermal shock loads

  1. Study of a plasma created by an accelerated proton beam for the characterization of a nuclear pumped laser medium

    International Nuclear Information System (INIS)

    Vialle, M.

    1985-04-01

    Processes leading to laser effect in nuclear induced plasmas can be studied with simulation experiments using charged particles beams. Such an experiment has been performed with a proton beam (2 MeV, 2 μA/cm 2 ) produced by a Van de Graaff accelerator. This beam is an excitation and ionisation source quite comparable to the laser medium source of a reactor experiment. The plasma created in a Ne target (about 100 torrs) containing N 2 impurities has been studied: - experimentally using R.F. diagnostics and spectroscopy; - theoretically by calculating the electronic distribution function in the low and medium energy region [fr

  2. Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB.

    Science.gov (United States)

    Eicher, Thomas; Seeger, Markus A; Anselmi, Claudio; Zhou, Wenchang; Brandstätter, Lorenz; Verrey, François; Diederichs, Kay; Faraldo-Gómez, José D; Pos, Klaas M

    2014-09-19

    Membrane transporters of the RND superfamily confer multidrug resistance to pathogenic bacteria, and are essential for cholesterol metabolism and embryonic development in humans. We use high-resolution X-ray crystallography and computational methods to delineate the mechanism of the homotrimeric RND-type proton/drug antiporter AcrB, the active component of the major efflux system AcrAB-TolC in Escherichia coli, and one most complex and intriguing membrane transporters known to date. Analysis of wildtype AcrB and four functionally-inactive variants reveals an unprecedented mechanism that involves two remote alternating-access conformational cycles within each protomer, namely one for protons in the transmembrane region and another for drugs in the periplasmic domain, 50 Å apart. Each of these cycles entails two distinct types of collective motions of two structural repeats, coupled by flanking α-helices that project from the membrane. Moreover, we rationalize how the cross-talk among protomers across the trimerization interface might lead to a more kinetically efficient efflux system.

  3. Short- and medium-term atmospheric constituent effects of very large solar proton events

    Directory of Open Access Journals (Sweden)

    C. H. Jackman

    2008-02-01

    Full Text Available Solar eruptions sometimes produce protons, which impact the Earth's atmosphere. These solar proton events (SPEs generally last a few days and produce high energy particles that precipitate into the Earth's atmosphere. The protons cause ionization and dissociation processes that ultimately lead to an enhancement of odd-hydrogen and odd-nitrogen in the polar cap regions (>60° geomagnetic latitude. We have used the Whole Atmosphere Community Climate Model (WACCM3 to study the atmospheric impact of SPEs over the period 1963–2005. The very largest SPEs were found to be the most important and caused atmospheric effects that lasted several months after the events. We present the short- and medium-term (days to a few months atmospheric influence of the four largest SPEs in the past 45 years (August 1972; October 1989; July 2000; and October–November 2003 as computed by WACCM3 and observed by satellite instruments. Polar mesospheric NOx (NO+NO2 increased by over 50 ppbv and mesospheric ozone decreased by over 30% during these very large SPEs. Changes in HNO3, N2O5, ClONO2, HOCl, and ClO were indirectly caused by the very large SPEs in October–November 2003, were simulated by WACCM3, and previously measured by Envisat Michelson Interferometer for Passive Atmospheric Sounding (MIPAS. WACCM3 output was also represented by sampling with the MIPAS averaging kernel for a more valid comparison. Although qualitatively similar, there are discrepancies between the model and measurement with WACCM3 predicted HNO3 and ClONO2 enhancements being smaller than measured and N2O5 enhancements being larger than measured. The HOCl enhancements were fairly similar in amounts and temporal variation in WACCM3 and MIPAS. WACCM3 simulated ClO decreases below 50 km, whereas MIPAS mainly observed increases, a very perplexing difference. Upper stratospheric

  4. Short-term memory of motor network performance via activity-dependent potentiation of Na+/K+ pump function.

    Science.gov (United States)

    Zhang, Hong-Yan; Sillar, Keith T

    2012-03-20

    Brain networks memorize previous performance to adjust their output in light of past experience. These activity-dependent modifications generally result from changes in synaptic strengths or ionic conductances, and ion pumps have only rarely been demonstrated to play a dynamic role. Locomotor behavior is produced by central pattern generator (CPG) networks and modified by sensory and descending signals to allow for changes in movement frequency, intensity, and duration, but whether or how the CPG networks recall recent activity is largely unknown. In Xenopus frog tadpoles, swim bout duration correlates linearly with interswim interval, suggesting that the locomotor network retains a short-term memory of previous output. We discovered an ultraslow, minute-long afterhyperpolarization (usAHP) in network neurons following locomotor episodes. The usAHP is mediated by an activity- and sodium spike-dependent enhancement of electrogenic Na(+)/K(+) pump function. By integrating spike frequency over time and linking the membrane potential of spinal neurons to network performance, the usAHP plays a dynamic role in short-term motor memory. Because Na(+)/K(+) pumps are ubiquitously expressed in neurons of all animals and because sodium spikes inevitably accompany network activity, the usAHP may represent a phylogenetically conserved but largely overlooked mechanism for short-term memory of neural network function. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  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. 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.

  12. 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

  13. 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.

  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. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. A magnetic fluid seal for rotary blood pumps: Long-term performance in liquid

    Science.gov (United States)

    Mitamura, Yoshinori; Takahashi, Sayaka; Amari, Shuichi; Okamoto, Eiji; Murabayashi, Shun; Nishimura, Ikuya

    A magnetic fluid (MF) seal enables mechanical contact-free rotation of the shaft and hence has excellent durability. The performance of a MF seal, however, has been reported to decrease in liquids. We have developed a MF seal that has a 'shield' mechanism and a new MF with a higher magnetization of 47.9 kA/m. The sealing performance of the MF seal installed in a rotary blood pump was studied. The seal was perfect against a pressure of 150 mmHg in a continuous flow of 4.0 L/min for 275 days and against a pressure of 175 mmHg in a continuous flow of 3.9 L/min for 217 days. We have developed a MF seal that works in liquid against pressure mostly used clinically. The magnetic fluid seal is promising as a shaft seal for rotary blood pumps.

  2. Long-term pumping test in borehole KR24 flow measurements

    Energy Technology Data Exchange (ETDEWEB)

    Rouhiainen, P.; Poellaenen, J. [PRG-Tec Oy, Espoo (Finland)

    2005-09-15

    The Difference Flow method can be used for the relatively fast determination of transmissivity and hydraulic head in fractures or fractured zones in cored boreholes. In this study, the Difference Flow method was used for hydraulic crosshole interference tests. The tests were performed in boreholes KR24 (pumped borehole) KR4, KR7, KR8, KRlO, KR14, KR22, KR22B, KR26, KR27, KR27B, KR28 and KR28B at Olkiluoto during the first and second quarters of 2004. The distance between the boreholes varies from approximately tens of meters to hundreds of meters. All the measurements were carried out in open boreholes, i.e. no packers were used. For interpretation, a normal single hole test was first performed in each borehole. Flow rates and drawdown were first measured both without pumping and with pumping the borehole under test. For practical reasons, the data set is neither complete nor similar in all tested boreholes. Connected flow to borehole KR24 was detected in all these boreholes. These flow responses were concentrated on a few zones. (orig.)

  3. A magnetic fluid seal for rotary blood pumps: effects of seal structure on long-term performance in liquid.

    Science.gov (United States)

    Mitamura, Yoshinori; Takahashi, Sayaka; Amari, Shuichi; Okamoto, Eiji; Murabayashi, Shun; Nishimura, Ikuya

    2011-03-01

    A magnetic fluid (MF) seal enables mechanical contact-free rotation of the shaft and hence has excellent durability. The performance of an MF seal, however, has been reported to decrease in liquids. We developed an MF seal that has a "shield" mechanism, and a new MF with a higher magnetization of 47.9 kA/m. The sealing performance of the MF seal installed in a rotary blood pump was studied. Three types of MF seals were used. Seal A was a conventional seal without a shield. Seal B had the same structure as that of Seal A, but the seal was installed at 1 mm below liquid level. Seal C was a seal with a shield and the MF was set at 1 mm below liquid level. Seal A failed after 6 and 11 days. Seal B showed better results (20 and 73 days). Seal C showed long-term durability (217 and 275 days). The reason for different results in different seal structures was considered to be different flow conditions near the magnetic fluid. Fluid dynamics near the MF in the pump were analyzed using computational fluid dynamics (CFD) software. We have developed an MF seal with a shield that works in liquid for >275 days. The MF seal is promising as a shaft seal for rotary blood pumps.

  4. Dry vacuum pumps

    International Nuclear Information System (INIS)

    Sibuet, R

    2008-01-01

    For decades and for ultimate pressure below 1 mbar, oil-sealed Rotary Vane Pumps have been the most popular solution for a wide range of vacuum applications. In the late 80ies, Semiconductor Industry has initiated the development of the first dry roughing pumps. Today SC applications are only using dry pumps and dry pumping packages. Since that time, pumps manufacturers have developed dry vacuum pumps technologies in order to make them attractive for other applications. The trend to replace lubricated pumps by dry pumps is now spreading over many other market segments. For the Semiconductor Industry, it has been quite easy to understand the benefits of dry pumps, in terms of Cost of Ownership, process contamination and up-time. In this paper, Technology of Dry pumps, its application in R and D/industries, merits over conventional pumps and future growth scope will be discussed

  5. 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.

  6. 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.

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. 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.

  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. 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.

  11. 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

  12. 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.

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

    Science.gov (United States)

    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.

  14. 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

  15. 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.

  16. 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.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  18. 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.

    Science.gov (United States)

    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.

  19. 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.

  20. SU-E-J-143: Short- and Near-Term Effects of Proton Therapy On Cerebral White Matter

    Energy Technology Data Exchange (ETDEWEB)

    Uh, J; Merchant, T; Ogg, R; Sabin, N; Hua, C [St. Jude Children' s Research Hospital, Memphis, TN (United States); Indelicato, D [University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

    2014-06-01

    Purpose: To assess early effects of proton therapy on the structural integrity of cerebral white matter in relation to the subsequent near-term development of such effects. Methods: Sixteen children (aged 2–19 years) with craniopharyngioma underwent proton therapy of 54 Cobalt Gray Equivalent (CGE) in a prospective therapeutic trial. Diffusion tensor imaging (DTI) was performed at baseline before proton therapy and every 3 months thereafter. Tract-based spatial statics analysis of DTI data was performed to derive the fractional anisotropy (FA) and radial diffusivity (RD) in 26 volumes of interest (VOIs). The dose distributions were spatially normalized to identify VOIs prone to high doses. The longitudinal percentage changes of the FA and RD in these VOIs at 3 and 12 months from the baseline were calculated, and their relationships were evaluated. Results: The average dose was highest to the cerebral peduncle (CP), corticospinal tract (CST) in the pons, pontine crossing tract (PCT), anterior/posterior limbs of the internal capsule (ALIC/PLIC), and genu of the corpus callosum (GCC). It ranged from 33.3 GCE (GCC) to 49.7 GCE (CP). A mild but statistically significant (P<0.05) decline of FA was observed 3 months after proton therapy in all VOIs except the PLIC and ranged from −1.7% (ALIC) to −2.8% (PCT). A significant increase of RD was found in the CP (3.5%) and ALIC (2.1%). The average longitudinal change from the baseline was reduced at 12 months for most VOIs. However, the standard deviation increased, indicating that the temporal pattern varied individually. The follow-up measurements at 3 and 12 months correlated for the CP, CST, PCT, and GCC (P < 0.04). Conclusion: DTI data suggest early (3 months) effects of proton therapy on microstructures in the white matter. The subsequent follow-up indicated individual variation of the changes, which was partly implied by the early effects.

  1. CRIEPI and SKB cooperation report. No.11. Numerical analysis for long-term pumping test at crystalline terrain

    International Nuclear Information System (INIS)

    Tanaka, Yasuharu

    2012-01-01

    A numerical analysis code for groundwater flow in rock mass, FEGM, which was developed by CRIEPI, was applied to the analysis of a long-term pumping test conducted at Olkiluoto Island in Finland. The groundwater level, the groundwater pressure and the groundwater inflow into the observation boreholes measured under the natural condition or during the pumping test could be reproduced in numerical simulations with FEGM. From this, the effectiveness of the numerical code was confirmed. And it was found that the site-scale groundwater flow is dependent on large-scale fracture zones in crystalline terrane like Olkiluoto Island. In this study, the calculated values of the groundwater inflow into the observation boreholes as well as the groundwater level and the groundwater pressure were compared to the measured ones. As a result, the reliability of the analytical model was improved. In addition, the travel times of groundwater particles from different depths at the same point to the model boundaries were compared. And the advantage of constructing waste disposal facilities at deep underground was confirmed from the viewpoint of the travel time of groundwater. (author)

  2. 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

  3. 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.

  4. 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

  5. Anaortic off-pump versus clampless off-pump using the PAS-Port device versus conventional coronary artery bypass grafting: mid-term results from a matched propensity score analysis of 5422 unselected patients.

    Science.gov (United States)

    Furukawa, Nobuyuki; Kuss, Oliver; Preindl, Konstantin; Renner, André; Aboud, Anas; Hakim-Meibodi, Kavous; Benzinger, Michael; Pühler, Thomas; Ensminger, Stephan; Fujita, Buntaro; Becker, Tobias; Gummert, Jan F; Börgermann, Jochen

    2017-10-01

    Meta-analyses from observational and randomized studies have demonstrated benefits of off-pump surgery for hard and surrogate endpoints. In some of them, increased re-revascularization was noted in the off-pump groups, which could impact their long-term survival. Therefore, we analyzed the course of all patients undergoing isolated coronary surgery regarding the major cardiac and cerebrovascular event (MACCE) criteria. A prospective register was taken from a high-volume off-pump center recording all anaortic off-pump (ANA), clampless off-pump (PAS-Port) and conventional (CONV) coronary artery bypass operations between July 2009 and June 2015. Propensity Score Matching was performed based on 28 preoperative risk variables. We identified 935 triplets (N = 2805). Compared with CONV, in-hospital mortality of both the ANA group (OR for ANA [95% CI] 0.25 [0.06; 0.83], P = 0.021), and the PAS-Port group was lower (OR for PAS-Port [95% CI] 0.50 [0.17; 1.32], P = 0.17). In the mid-term follow-up there were no significant differences between the groups regarding mortality (HR for ANA [95%-CI] 0.83 [0.55-1.26], P = 0.38; HR for PAS-Port [95%-CI] 1.06 [0.70-1.59], P = 0.79), incidence of stroke (HR for ANA 0.81 [0.43-1.53], P = 0.52; HR for PAS-Port 0.78 [0.41-1.50], P = 0.46), myocardial infarction (HR for ANA 0.53 [0.22-1.31], P = 0.17; HR for PAS-Port 0.78 [0.37-1.66], P = 0.52) or re-revascularization rate (HR for ANA 0.99 [0.67-1.44], P = 0.94; HR for PAS-Port 0.95 [0.65-1.38], P = 0.77). Both off-pump clampless techniques were associated with lower in-hospital mortality compared with conventional CABG. The mid-term course showed no difference with regard to the MACCE criteria between anaortic off-pump, clampless off-pump using PAS-Port and conventional CABG. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  6. 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

    Directory of Open Access Journals (Sweden)

    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

  7. Mechanisms of isoform-specific Na/K pump regulation by short- and long-term adrenergic activation in rat ventricular myocytes.

    Science.gov (United States)

    Yin, Jian; Guo, Hui-Cai; Yu, Ding; Wang, Hui-Ci; Li, Jun-Xia; Wang, Yong-Li

    2014-01-01

    Many stressful conditions, including cardiovascular diseases, induce long-term elevations in circulating catecholamines, thereby leading to changes of the Na/K pump and thus affecting myocardial functions. However, only short-term adrenergic regulation of the Na/K pump has been reported. The present study is the first investigation of long-term adrenergic regulation of the Na/K pump and the potential mechanism. After acutely isolated Sprague-Dawley rat myocytes were incubated with noradrenaline or isoprenaline for 24 h, Na/K pump high- (IPH) and low-affinity current (IPL), α-isoform mRNA, and α-isoform protein were examined using patch-clamp, RT-PCR, and Western blotting techniques, respectively. After the short-term incubation, isoprenaline reduced the IPL through a PKA-dependent pathway that involves α1-isoform translocation from the membrane to early endosomes, and noradrenaline increased the IPH through a PKC-dependent pathway that involves α2-isoform translocation from late endosomes to the membrane. After long-term incubation, isoprenaline increased the IPL, α1-isoform mRNA, and α1-isoform protein, and noradrenaline reduced the IPH, α2-isoform mRNA, and α1-isoform protein through a PKA-or PKC-dependent pathway, respectively. These results suggest that long-term adrenergic Na/K pump regulation is isoform-specific and negatively feeds back on the short-term response. Furthermore, long-term regulation involves transcription and translation of the respective α-isoform, whereas short-term regulation involves the translocation of the available α-isoform to the plasma membrane. © 2014 S. Karger AG, Basel.

  8. Mechanisms of Isoform-Specific Na/K Pump Regulation by Short- and Long-Term Adrenergic Activation in Rat Ventricular Myocytes

    Directory of Open Access Journals (Sweden)

    Jian Yin

    2014-05-01

    Full Text Available Background: Many stressful conditions, including cardiovascular diseases, induce long-term elevations in circulating catecholamines, thereby leading to changes of the Na/K pump and thus affecting myocardial functions. However, only short-term adrenergic regulation of the Na/K pump has been reported. The present study is the first investigation of long-term adrenergic regulation of the Na/K pump and the potential mechanism. Methods: After acutely isolated Sprague-Dawley rat myocytes were incubated with noradrenaline or isoprenaline for 24 h, Na/K pump high- (IPH and low-affinity current (IPL, α-isoform mRNA, and α-isoform protein were examined using patch-clamp, RT-PCR, and Western blotting techniques, respectively. Results: After the short-term incubation, isoprenaline reduced the IPL through a PKA-dependent pathway that involves α1-isoform translocation from the membrane to early endosomes, and noradrenaline increased the IPH through a PKC-dependent pathway that involves α2-isoform translocation from late endosomes to the membrane. After long-term incubation, isoprenaline increased the IPL, α1-isoform mRNA, and α1-isoform protein, and noradrenaline reduced the IPH, α2-isoform mRNA, and α1-isoform protein through a PKA-or PKC-dependent pathway, respectively. Conclusions: These results suggest that long-term adrenergic Na/K pump regulation is isoform-specific and negatively feeds back on the short-term response. Furthermore, long-term regulation involves transcription and translation of the respective α-isoform, whereas short-term regulation involves the translocation of the available α-isoform to the plasma membrane.

  9. Investigating Effect of Drug Use on Short-term Complications and Bleeding in Patients Undergoing Off-pump CABG (OPCAB

    Directory of Open Access Journals (Sweden)

    M Hadadzadeh

    2013-08-01

    Full Text Available Introduction: Opioid abuse is a major social and health problem in many parts of the world especially in Iran. There are not much information about effect of drugs (addiction on short-term complications and bleeding after CABG. This study aimed to assess the relationship between addiction with short-term complications and bleeding after CABG. Methods: This is a descriptive study in which 100 male patients who underwent off-pump CABG in Afshar hospital in yazd were followed during 3 months to investigate their short-term complications. preoperative and post-operative Hb, Plt, Pt, Ptt, bleeding and packed cells after operation were recorded. Then, collected data was analyzed by chi-square, fisher and exact test . Results: In this study, 30 patients were addicts and 70 male patients were non-addicts. All patients were males and similar in preoperative characteristics such as HTN, DM, HLP, CAD, LIMA usage and NYHA FC. Addicted patients were younger than non-addicts and most of them were cigarette smokers. Regarding medical and dietary recommendation after operation, addicted patients observed these recommendation significantly less than non-addicted patients. After operation, pulmonary, neurologic and infective complications were significantly more common in addicted patients. Conclusion: According the study results and other similar studies, drug use in patients with cardiovascular disease is noticeable. Moreover, regarding the postoperative outcomes in addicted patients, more studies needs to be conducted in this field.

  10. Long-term residual radioactivity in an intermediate-energy proton linac

    Science.gov (United States)

    Blaha, J.; La Torre, F. P.; Silari, M.; Vollaire, J.

    2014-07-01

    A new 160 MeV H- linear accelerator (LINAC4) is being installed at CERN to replace the present 50 MeV LINAC2 as proton injector of the PS Booster (PSB). During operation, the accelerator components will be activated by the beam itself and by the secondary radiation field. Detailed Monte Carlo simulations, for various beam energies and several decay times, were performed to predict the residual radioactivity in the main accelerator components and to estimate the residual dose rate inside the tunnel. The results of this study will facilitate future dismantling, handling and storage of the activated parts and consequently minimize the radiation dose to involved workers. The component activation was also compared with the exemption limits given in the current Swiss legislation and to the CERN design values, in order to make predictions for the future storage and disposal of radioactive waste. The airborne radioactivity induced by particles escaping the beam dump and the activation of the beam dump cooling water circuit were also quantified. The aim of this paper is to provide data of sufficiently general interest to be used for similar studies at other intermediate-energy proton accelerator facilities.

  11. Long-term residual radioactivity in an intermediate-energy proton linac

    International Nuclear Information System (INIS)

    Blaha, J.; La Torre, F.P.; Silari, M.; Vollaire, J.

    2014-01-01

    A new 160 MeV H − linear accelerator (LINAC4) is being installed at CERN to replace the present 50 MeV LINAC2 as proton injector of the PS Booster (PSB). During operation, the accelerator components will be activated by the beam itself and by the secondary radiation field. Detailed Monte Carlo simulations, for various beam energies and several decay times, were performed to predict the residual radioactivity in the main accelerator components and to estimate the residual dose rate inside the tunnel. The results of this study will facilitate future dismantling, handling and storage of the activated parts and consequently minimize the radiation dose to involved workers. The component activation was also compared with the exemption limits given in the current Swiss legislation and to the CERN design values, in order to make predictions for the future storage and disposal of radioactive waste. The airborne radioactivity induced by particles escaping the beam dump and the activation of the beam dump cooling water circuit were also quantified. The aim of this paper is to provide data of sufficiently general interest to be used for similar studies at other intermediate-energy proton accelerator facilities

  12. Mid-term results of off-pump coronary artery bypass grafting assessed by multi-slice computed tomography

    International Nuclear Information System (INIS)

    Yoshida, Seijiro; Nitta, Yoshio; Oda, Katsuhiko

    2004-01-01

    Off-pump coronary artery bypass (OPCAB) has recently increased in popularity, but the long-term results are still unknown. We evaluated the mid-term results of OPCAB surgery using multi-slice computed tomography (MSCT), which is a non-invasive postoperative evaluation method. Thirty-one consecutive patients who underwent OPCAB surgery at least 2 years prior to the study were selected. The age was 50 to 79 years (66.9±6.5) and the ratio of men to women was 26:5. Coronary angiography was performed in all patients at 2 weeks postoperatively. The follow-up was complete, and mean follow-up was 30.9 months. There were no hospital deaths and 1 non-cardiac late death. The graft patency rate in coronary angiography was left internal thoracic artery (LITA) 30/30 (100%), right internal thoracic artery (RITA) 2/2 (100%), radial artery (RA) 14/15 (93%), saphenous vein graft (SVG) 15/17 (88%). No graft became occluded on MSCT study and all patients have been angina-free during the follow-up period. We suggest that OPCAB is feasible in most patients with good patency and low mortality. MSCT is an effective follow up method for the morphological findings and noninvasive quantitative evaluation of the bypass grafts. (author)

  13. 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

  14. 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

  15. Changes in Chemical and Isotopic Composition of Groundwater During a Long Term Pumping Test in Brestovica Karst Aquifer

    Energy Technology Data Exchange (ETDEWEB)

    Mezga, K.; Urbanc, J. [Geological Survey of Slovenia, Department of Hydrogeology, Ljubljana (Slovenia)

    2013-07-15

    A pumping test of the Klarici water supply near Brestovica was performed in August 2008, in order to determine the karst groundwater resource capacity. Groundwater was pumped for a month with a total capacity of 470 L/s. During the experiment, sampling for chemical and isotopic composition of groundwater and surface water was carried out. Intensive pumping in dry meteorological conditions caused a lowering of the water table and changes in the chemical and isotopic composition of pumped water. Local meteoric waters are infiltrated into the aquifer at a lower mean altitude; therefore the {delta}{sup 18}O is enriched with the heavy oxygen isotope. The duration of pumping resulted in changes in the isotopic composition of oxygen due to a greater impact of the intergranular Soca River aquifer on the karst aquifer. On the basis of isotope composition it was possible to quantify the impact of the Soca River on the karst aquifer. (author)

  16. Decision document for performing a long-term pumping test at the S-3 Site, Oak Ridge Y-12 Plant, Oak Ridge, Tennessee

    International Nuclear Information System (INIS)

    1995-02-01

    One of the principal problems confronting the remediation of Bear Creek Valley is the cleanup of contaminated groundwater. The S-3 Site is one of the locations in the valley where groundwater is most contaminated, and contamination from the S-3 Site has also caused extensive contamination of downgradient groundwater. This groundwater plume, therefore, has a high priority in the Bear Creek Valley remedial process. Pumping and treating groundwater was identified early in the feasibility study as a likely remedial alternative for the S-3 Site groundwater plume. The hydrology and geochemistry of the plume are extremely complex. There is a high degree of uncertainty in the current understanding of how the aquifer will react physically and chemically to pumping, making evaluation of a pump-and-treat alternative impractical at the present time. Before a pump-and-treat alternative can be evaluated, its technical practicability, effectiveness, and projected cost must be determined. A long-term pumping test (LTPT) at the S-3 Site has been proposed so that the information necessary to carry out this evaluation can be collected. This document constitutes the first phase in the planning process for this test

  17. Long-term residual radioactivity in an intermediate-energy proton linac

    CERN Document Server

    Blaha, J; Silari, M; Vollaire, J

    2014-01-01

    A new 160 MeV H−H− linear accelerator (LINAC4) is being installed at CERN to replace the present 50 MeV LINAC2 as proton injector of the PS Booster (PSB). During operation, the accelerator components will be activated by the beam itself and by the secondary radiation field. Detailed Monte Carlo simulations, for various beam energies and several decay times, were performed to predict the residual radioactivity in the main accelerator components and to estimate the residual dose rate inside the tunnel. The results of this study will facilitate future dismantling, handling and storage of the activated parts and consequently minimize the radiation dose to involved workers. The component activation was also compared with the exemption limits given in the current Swiss legislation and to the CERN design values, in order to make predictions for the future storage and disposal of radioactive waste. The airborne radioactivity induced by particles escaping the beam dump and the activation of the beam dump cooling w...

  18. Detection of pump degradation

    International Nuclear Information System (INIS)

    Casada, D.A.

    1994-01-01

    There are a variety of stressors that can affect the operation of centrifugal pumps. These can generally be classified as: Mechanical; Hydraulic; Tribological; Chemical; and Other (including those associated with the pump driver). Although these general stressors are active in essentially all centrifugal pumps, the stressor level and the extent of wear and degradation can vary greatly. Parameters that affect the extent of stressor activity are manifold. In order to assure the long-term operational readiness of a pump, it is important to both understand the nature and magnitude of the specific degradation mechanisms and to monitor the performance of the pump

  19. Changes in Chemical and Isotopic Composition of Groundwater during Long-Term Pumping Test in Brestovica Karst Aquifer

    International Nuclear Information System (INIS)

    Mezga, Kim; Urbanc, Janko

    2011-01-01

    The main aim of the experimental pumping test, which was carried out in the dry summer period in August 2008 for 30 days, was to assess the groundwater resource quantity which could be pumped at the time of the highest water needs for the Slovene Coast and Karst areas. Further, we wanted to test the chemical status of groundwater to assure its suitability for further use and to assess the influence of the Soca River aquifer on this karst aquifer

  20. Hair Mercury Negatively Correlates with Calcium Pump Activity in Human Term Newborns and Their Mothers at Delivery

    OpenAIRE

    Huel, Guy; Sahuquillo, Josiane; Debotte, Ginette; Oury, Jean-François; Takser, Larissa

    2007-01-01

    Background Calcium homeostasis is a known target of several environmental toxicants including lead and mercury. Objective Our goal was to determine the relationship between Hg exposure and erythrocyte Ca pump activity in women at delivery and in their newborns. Methods We determined total Hg as well as Pb concentrations in 81 hair and blood samples obtained at delivery. Basal and calmodulin-stimulated Ca pump activity was measured in red blood cells from cord blood and maternal erythrocyte pl...

  1. 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

  2. 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.

    Science.gov (United States)

    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.

  3. Penis Pump

    Science.gov (United States)

    ... your appointment might be less involved. Choosing a penis pump Some penis pumps are available without a ... it doesn't get caught in the ring. Penis pumps for penis enlargement Many advertisements in magazines ...

  4. Relationship between opioid therapy, tissue-damaging procedures, and brain metabolites as measured by proton MRS in asphyxiated term neonates.

    Science.gov (United States)

    Angeles, Danilyn M; Ashwal, Stephen; Wycliffe, Nathaniel D; Ebner, Charlotte; Fayard, Elba; Sowers, Lawrence; Holshouser, Barbara A

    2007-05-01

    To examine the effects of opioid and tissue-damaging procedures (TDPs) [i.e. procedures performed in the neonatal intensive care unit (NICU) known to result in pain, stress, and tissue damage] on brain metabolites, we reviewed the medical records of 28 asphyxiated term neonates (eight opioid-treated, 20 non-opioid treated) who had undergone magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) within the first month of life as well as eight newborns with no clinical findings of asphyxial injury. We found that lower creatine (Cr), myoinositol (Ins), and N-acetylaspartate (NAA)/choline (Cho) (p OGM) NAA/Cr was decreased (p = 0.03) and lactate (Lac) was present in a significantly higher amount (40%; p = 0.03) in non-opioid-treated neonates compared with opioid-treated neonates. Compared with controls, untreated neonates showed larger changes in more metabolites in basal ganglia (BG), thalami (TH), and OGM with greater significance than treated neonates. Our data suggest that TDPs affect spectral metabolites and that opioids do not cause harm in asphyxiated term neonates exposed to repetitive TDPs in the first 2-4 DOL and may provide a degree of neuroprotection.

  5. Modeling and optimization of a heat-pump-assisted high temperature proton exchange membrane fuel cell micro-combined-heat-and-power system for residential applications

    DEFF Research Database (Denmark)

    Arsalis, Alexandros; Kær, Søren Knudsen; Nielsen, Mads Pagh

    2015-01-01

    In this study a micro-combined-heat-and-power (micro-CHP) system is coupled to a vapor-compression heat pump to fulfill the residential needs for heating (space heating and water heating) and electricity in detached single-family households in Denmark. Such a combination is assumed to be attractive...... for application, since both fuel cell technology and electric heat pumps are found to be two of the most efficient technologies for generation/conversion of useful energy. The micro-CHP system is fueled with natural gas and includes a fuel cell stack, a fuel processor and other auxiliary components. The micro......-CHP system assumes heat-led operation, to avoid dumping of heat and the use of complicated thermal energy storage. The overall system is grid-interconnected to allow importing and exporting of electricity as necessary. In this study emphasis is given on the operational characterization of the system...

  6. Proton-proton bremsstrahlung

    International Nuclear Information System (INIS)

    Fearing, H.W.

    1990-01-01

    We summarize some of the information about the nucleon-nucleon force which has been obtained by comparing recent calculations of proton-proton bremsstrahlung with cross section and analyzing power data from the new TRIUMF bremsstrahlung experiment. Some comments are made as to how these results can be extended to neutron-proton bremsstrahlung. (Author) 17 refs., 6 figs

  7. 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....

  8. Hypoxia-ischemic encephalopathy in full-term neonate: correlation proton MR spectroscopy with MR imaging

    International Nuclear Information System (INIS)

    Fan Guoguang; Wu Zhenhua; Chen Liying; Guo Qiyong; Ye Binbin; Mao Jian

    2003-01-01

    Introduction: To evaluate 1 H Magnetic Resonance Spectroscopy ( 1 HMRS) in the diagnosis of hypoxia-ischemic encephalopathy (HIE) of full-term neonates correlated with Magnetic Resonance Imaging (MRI). Materials and methods: Thirty-eight cases of full-term neonates diagnosed as HIE clinically were selected to perform MRI and 1 HMRS examination. The ages ranged from 7 to 17 days, with median age of 8.2 days. In which, 26 cases were followed up and/or MRI reexamined at 6 months of age or later. Eight healthy neonates, with no evidence of birth asphyxia, also underwent 1 HMRS for comparison. SE sequences were used for routine MR examination; point resolved spectroscopy sequence was required for 1 HMRS. The metabolites in the spectra includes: N-acetylaspartate (NAA), choline compounds (CHO), creatine compounds (CR), myo-inositol (MI), lactate (LAC), glutamate and glutamine (Glu-Gln). Results: The peaks of NAA were fall in two cases; the peaks of LAC, which were elevated, appeared as typical double-peaks appearance in 26 cases; the peaks of Glu-Gln, which were also elevated, appeared as zigzag appearance in nine cases. The peaks of CR were decreased in 11 cases, while those of MI were increased in seven cases. Mild type of lesions was present on MRI in 12 cases whose LAC/CR ratio lower than 0.5; mild and moderate types of lesions were present in 15 cases whose LAC/CR ratio between 0.5 and 1.5. Whereas, nine cases of severe lesions and two cases of moderate lesions were present on MRI in 11 cases whose LAC/CR ratio greater than 1.5. Twenty-six of 38 cases were followed up and/or MRI reexamined after 6 months, in which, sequelae were present in 12 cases. Among them, eight cases of sequelae in nine cases whose LAC/CR ratio greater than 1.5 were present (account for 88.89%). Conclusion: 1 HMRS plays an important role to diagnose and predict outcome of HIE

  9. Characterization of the effects of borehole configuration and interference with long term ground temperature modelling of ground source heat pumps

    International Nuclear Information System (INIS)

    Law, Ying Lam E.; Dworkin, Seth B.

    2016-01-01

    Highlights: • Long term ground temperature response is explored using finite element methods. • Simulation method is validated against experimental and analytical data. • Temperature changes at a fast rate in the first few years and slows down gradually. • ASHRAE recommended separation distances are not always sufficient. • Thermal accumulation occurs at the centre of borehole field. - Abstract: Ground source heat pumps (GSHPs) are an environmentally friendly alternative to conventional heating and cooling systems because of their high efficiency and low greenhouse gas emissions. The ground acts as a heat sink/source for the excess/required heat inside a building for cooling and heating modes, respectively. However, imbalance in heating and cooling needs can change ground temperature over the operating duration. This increase/decrease in ground temperature lowers system efficiency and causes the ground to foul—failing to accept or provide more heat. In order to ensure that GSHPs can operate to their designed conditions, thermal modelling is required to simulate the ground temperature during system operation. In addition, the borehole field layout can have a major impact on ground temperature. In this study, four buildings were studied—a hospital, fast-food restaurant, residence, and school, each with varying borehole configurations. Boreholes were modelled in a soil volume using finite-element methods and heating and cooling fluxes were applied to the borehole walls to simulate the GSHP operation. 20 years of operation were modelled for each building for 2 × 2, 4 × 4, and 2 × 8 borehole configurations. Results indicate that the borehole separation distance of 6 m, recommended by ASHRAE, is not always sufficient to prevent borehole thermal interactions. Benefits of using a 2 × 8 configuration as opposed to a 4 × 4 configuration, which can be observed because of the larger perimeter it provides for heat to dissipate to surrounding soil were

  10. Centrifugal pumps

    CERN Document Server

    Anderson, HH

    1981-01-01

    Centrifugal Pumps describes the whole range of the centrifugal pump (mixed flow and axial flow pumps are dealt with more briefly), with emphasis on the development of the boiler feed pump. Organized into 46 chapters, this book discusses the general hydrodynamic principles, performance, dimensions, type number, flow, and efficiency of centrifugal pumps. This text also explains the pumps performance; entry conditions and cavitation; speed and dimensions for a given duty; and losses. Some chapters further describe centrifugal pump mechanical design, installation, monitoring, and maintenance. The

  11. Intrathecal catheter-syringe adaptor for short-term intrathecal analgesia with an externalized pump: a case report.

    Science.gov (United States)

    Wilkes, Denise; Cook, Michael; Solanki, Daneshvari

    2010-01-01

    In most patients, cancer pain is effectively treated with conservative medical management consisting of oral and/or transdermal analgesics. Cancer patients tend to fail conservative medical management near the end of their life expectancy, thus requiring alternative routes of analgesia such as intravenous, epidural, or intrathecal. The intrathecal route provides the most effective analgesia due to the close proximity of the opioid receptors in the spinal cord. Though there are many techniques that exist for intrathecal drug delivery, complications can limit effectiveness such as infection, bleeding, cerebrospinal fluid (CSF) leaks, post-dural puncture headaches (PDPH), pump and/or catheter malfunctions, or limitations of technical expertise. Therefore, an important goal in palliative cancer pain therapy is to use equipment that is going to have the fewest number of complications and will be the most familiar to the health care providers. We describe the combination of the Medtronic Indura 1P catheter, which has the least catheter-related complications and can be used with any external drug infusion pump. These are regular infusion pumps that the health care workers are familiar with so they can provide excellent and efficient service to the patient. In an operating room, the intrathecal catheter was placed using sterile technique under fluoroscopic guidance. The epidural space was identified with loss of resistance technique. Then the introducer needle (supplied in the Indura 1P catheter kit) was advanced until free-flowing CSF was obtained. The spinal catheter was advanced into the intrathecal space through the introducer needle to lumbar 2-3 level. The catheter was tunneled subcutaneously 10 cm lateral to the catheter exit site. A syringe filling device was inserted into the catheter opening and was secured with silk suture. A luer lock syringe was attached to the syringe filling device and CSF was aspirated. The syringe filling device was capped and later

  12. Short- and long-term quantitation reproducibility of brain metabolites in the medial wall using proton echo planar spectroscopic imaging.

    Science.gov (United States)

    Tsai, Shang-Yueh; Lin, Yi-Ru; Wang, Woan-Chyi; Niddam, David M

    2012-11-15

    Proton echo planar spectroscopic imaging (PEPSI) is a fast magnetic resonance spectroscopic imaging (MRSI) technique that allows mapping spatial metabolite distributions in the brain. Although the medial wall of the cortex is involved in a wide range of pathological conditions, previous MRSI studies have not focused on this region. To decide the magnitude of metabolic changes to be considered significant in this region, the reproducibility of the method needs to be established. The study aims were to establish the short- and long-term reproducibility of metabolites in the right medial wall and to compare regional differences using a constant short-echo time (TE30) and TE averaging (TEavg) optimized to yield glutamatergic information. 2D sagittal PEPSI was implemented at 3T using a 32 channel head coil. Acquisitions were repeated immediately and after approximately 2 weeks to assess the coefficients of variation (COV). COVs were obtained from eight regions-of-interest (ROIs) of varying size and location. TE30 resulted in better spectral quality and similar or lower quantitation uncertainty for all metabolites except glutamate (Glu). When Glu and glutamine (Gln) were quantified together (Glx) reduced quantitation uncertainty and increased reproducibility was observed for TE30. TEavg resulted in lowered quantitation uncertainty for Glu but in less reliable quantification of several other metabolites. TEavg did not result in a systematically improved short- or long-term reproducibility for Glu. The ROI volume was a major factor influencing reproducibility. For both short- and long-term repetitions, the Glu COVs obtained with TEavg were 5-8% for the large ROIs, 12-17% for the medium sized ROIs and 16-26% for the smaller cingulate ROIs. COVs obtained with TE30 for the less specific Glx were 3-5%, 8-10% and 10-15%. COVs for N-acetyl aspartate, creatine and choline using TE30 with long-term repetition were between 2-10%. Our results show that the cost of more specific

  13. Relative biological effectiveness of 160 MeV protons. II. Biological data and their interpretation in terms of microdosimetry

    International Nuclear Information System (INIS)

    Hall, E.J.; Kellerer, A.M.; Rossi, H.H.; Lam, Y.M.P.

    1978-01-01

    The radiobiological effectiveness of 160 MeV protons was measured relative to 60 Co γ rays using Chinese hamster cells cultured in vitro. Separate experiments were performed with cells irradiated in suspension, or attached to plastic tissue culture flasks. Proton irradiations were performed in the incident plateau of the depth dose profile and with the Bragg peak spread out to cover 10 cm. In all cases the relative biological effectiveness (RBE) for protons relative to gamma rays was 1.2 for doses in excess of about 200 rad. The attached cell experiments indicate an increasing RBE at low doses, which is consistent with the microdosimetric measurements

  14. Power consumption analysis of pump station control systems based on fuzzy controllers with discrete terms in iThink software

    Science.gov (United States)

    Muravyova, E. A.; Bondarev, A. V.; Sharipov, M. I.; Galiaskarova, G. R.; Kubryak, A. I.

    2018-03-01

    In this article, power consumption of pumping station control systems is discussed. To study the issue, two simulation models of oil level control in the iThink software have been developed, using a frequency converter only and using a frequency converter and a fuzzy controller. A simulation of the oil-level control was carried out in a graphic form, and plots of pumps power consumption were obtained. Based on the initial and obtained data, the efficiency of the considered control systems has been compared, and also the power consumption of the systems was shown graphically using a frequency converter only and using a frequency converter and a fuzzy controller. The models analysis has shown that it is more economical and safe to use a control circuit with a frequency converter and a fuzzy controller.

  15. 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.

  16. Solar Activity from 2006 to 2014 and Short-term Forecasts of Solar Proton Events Using the ESPERTA Model

    Energy Technology Data Exchange (ETDEWEB)

    Alberti, T.; Lepreti, F. [Dipartimento di Fisica, Università della Calabria, Ponte P. Bucci, Cubo 31C, 87036, Rende (CS) (Italy); Laurenza, M.; Storini, M.; Consolini, G. [INAF-IAPS, Via del Fosso del Cavaliere 100, I-00133, Roma (Italy); Cliver, E. W., E-mail: tommaso.alberti@unical.it, E-mail: monica.laurenza@iaps.inaf.it [National Solar Observatory, Boulder, CO (United States)

    2017-03-20

    To evaluate the solar energetic proton (SEP) forecast model of Laurenza et al., here termed ESPERTA, we computed the input parameters (soft X-ray (SXR) fluence and ∼1 MHz radio fluence) for all ≥M2 SXR flares from 2006 to 2014. This database is outside the 1995–2005 interval on which ESPERTA was developed. To assess the difference in the general level of activity between these two intervals, we compared the occurrence frequencies of SXR flares and SEP events for the first six years of cycles 23 (1996 September–2002 September) and 24 (2008 December–2014 December). We found a reduction of SXR flares and SEP events of 40% and 46%, respectively, in the latter period. Moreover, the numbers of ≥M2 flares with high values of SXR and ∼1 MHz fluences (>0.1 J m{sup −2} and >6 × 10{sup 5} sfu × minute, respectively) are both reduced by ∼30%. A somewhat larger percentage decrease of these two parameters (∼40% versus ∼30%) is obtained for the 2006–2014 interval in comparison with 1995–2005. Despite these differences, ESPERTA performance was comparable for the two intervals. For the 2006–2014 interval, ESPERTA had a probability of detection (POD) of 59% (19/32) and a false alarm rate (FAR) of 30% (8/27), versus a POD = 63% (47/75) and an FAR = 42% (34/81) for the original 1995–2005 data set. In addition, for the 2006–2014 interval the median (average) warning time was estimated to be ∼2 hr (∼7 hr), versus ∼6 hr (∼9 hr), for the 1995–2005 data set.

  17. Spot Scanning-Based Proton Therapy for Intracranial Meningioma: Long-Term Results From the Paul Scherrer Institute

    International Nuclear Information System (INIS)

    Weber, Damien C.; Schneider, Ralf; Goitein, Gudrun; Koch, Tamara; Ares, Carmen; Geismar, Jan H.; Schertler, Andreas; Bolsi, Alessandra; Hug, Eugen B.

    2012-01-01

    Background: To assess the long-term clinical results of spot scanning proton therapy (PT) in the treatment of intracranial meningiomas. Patients and Methods: Thirty-nine patients with meningioma (histologically proven 34/39) were treated with PT between July 1997 and January 2010. Thirty-two (82.1%) patients were treated as primary treatment (exclusive PT, n = 8; postoperative PT, n = 24). Mean age was 48.3 ± 17.9 years and 32 (82.1%) patients had skull base lesions. For patients undergoing surgery, 24 patients had a diagnosis of World Health Organization (WHO) Grade I and 10 of a WHO Grade II/III meningioma, respectively. The female-to-male ratio was 3.3. The median administered dose was 56.0 Gy (relative biologic effectiveness [RBE]) (range, 52.2–66.6) at 1.8–2.0 Gy (RBE) per fraction. Gross tumor volume (GTV) ranged from 0.76 to 546.5 cm 3 (median, 21.5). Late toxicity was assessed according to Common Terminology Criteria for Adverse Events version 3.0. Mean follow-up time was 62.0 months and all patients were followed for >6 months. Results: Six patients presented with tumor recurrence and 6 patients died during follow-up, of which 4 of tumor progression. Five-year actuarial local control and overall survival rates were 84.8% and 81.8%, respectively, for the entire cohort and 100% for benign histology. Cumulative 5-year Grade ≥3 late toxicity-free survival was 84.5%. On univariate analysis, LC was negatively influenced by WHO grade (p = 0.001), GTV (p = 0.013), and male gender (p = 0.058). Conclusions: PT is a safe and effective treatment for patients with untreated, recurrent, or incompletely resected intracranial meningiomas. WHO grade and tumor volume was an adverse prognostic factor for local control.

  18. Experimental study of two-phase flow in a proton exchange membrane fuel cell in short-term microgravity condition

    International Nuclear Information System (INIS)

    Guo, Hang; Liu, Xuan; Zhao, Jian Fu; Ye, Fang; Ma, Chong Fang

    2014-01-01

    Highlights: • Two-phase flow in PEMFC cathode channels is observed in different gravity environments. • The PEMFC shows different operating behavior in normal and microgravity conditions. • Water tends can be removed in microgravity conditions at high water production regime. • Liquid aggregation occurs in microgravity conditions at low water production regime. • Effect of gravity on performance and two-phase flow at two operating regimes is studied. - Abstract: Water management is important for improving the performance and stability of proton exchange membrane fuel cells (PEMFCs) for space applications. An in situ visual observation was conducted on the gas–liquid two-phase flow in the cathode channels of a PEMFC in short-term microgravity condition. The microgravity environment was supplied by a drop tower. A single serpentine flow channel with a depth of 2 mm and a width of 2 mm was applied as the cathode flow field. A membrane electrode assembly comprising of a Nafion 112 membrane sandwiched between gas diffusion layers was used. The anode and cathode were loaded with 1 mg cm −2 platinum. The PEMFC shows a distinct operating behavior in microgravity because of the effect of gravity on the two-phase flow. At a high water production regime, cell performance is enhanced by 4.6% and the accumulated liquid water in the flow channel tends can be removed in microgravity conditions to alleviate flooding. At a low water production regime, cell performance deteriorates by 6.6% and liquid aggregation occurs in the flow channel because of the coalescence of dispersed water droplets in microgravity conditions, thus squeezing the flow channel. The operating behavior of PEMFC in microgravity conditions is different from that in normal gravity conditions. Further studies are needed on PEMFC operating characteristics and liquid management for space applications

  19. Spot Scanning-Based Proton Therapy for Intracranial Meningioma: Long-Term Results From the Paul Scherrer Institute

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Damien C., E-mail: damien.weber@unige.ch [Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Schneider, Ralf; Goitein, Gudrun; Koch, Tamara; Ares, Carmen; Geismar, Jan H.; Schertler, Andreas; Bolsi, Alessandra; Hug, Eugen B. [Center for Proton Therapy, Paul Scherrer Institute, Viligen (Switzerland)

    2012-07-01

    Background: To assess the long-term clinical results of spot scanning proton therapy (PT) in the treatment of intracranial meningiomas. Patients and Methods: Thirty-nine patients with meningioma (histologically proven 34/39) were treated with PT between July 1997 and January 2010. Thirty-two (82.1%) patients were treated as primary treatment (exclusive PT, n = 8; postoperative PT, n = 24). Mean age was 48.3 {+-} 17.9 years and 32 (82.1%) patients had skull base lesions. For patients undergoing surgery, 24 patients had a diagnosis of World Health Organization (WHO) Grade I and 10 of a WHO Grade II/III meningioma, respectively. The female-to-male ratio was 3.3. The median administered dose was 56.0 Gy (relative biologic effectiveness [RBE]) (range, 52.2-66.6) at 1.8-2.0 Gy (RBE) per fraction. Gross tumor volume (GTV) ranged from 0.76 to 546.5 cm{sup 3} (median, 21.5). Late toxicity was assessed according to Common Terminology Criteria for Adverse Events version 3.0. Mean follow-up time was 62.0 months and all patients were followed for >6 months. Results: Six patients presented with tumor recurrence and 6 patients died during follow-up, of which 4 of tumor progression. Five-year actuarial local control and overall survival rates were 84.8% and 81.8%, respectively, for the entire cohort and 100% for benign histology. Cumulative 5-year Grade {>=}3 late toxicity-free survival was 84.5%. On univariate analysis, LC was negatively influenced by WHO grade (p = 0.001), GTV (p = 0.013), and male gender (p = 0.058). Conclusions: PT is a safe and effective treatment for patients with untreated, recurrent, or incompletely resected intracranial meningiomas. WHO grade and tumor volume was an adverse prognostic factor for local control.

  20. Reduced volume and increased training intensity elevate muscle Na+/K+ pump {alpha}2-subunit expression as well as short- and long-term work capacity in humans

    DEFF Research Database (Denmark)

    Bangsbo, Jens; Gunnarsson, Thomas Petursson; Wendell, Jesper

    2009-01-01

    was unaltered, but the 3-K (3,000 m) time was reduced (Pexpression and performance remained unaltered in CON. The present data suggest that both short- and long-term......% reduction in the amount of training but including speed endurance training consisting of 6-12 30-s sprint runs 3-4 times a week (SET, n=12) or a control group (CON, n=5), which continued the endurance training (about 55 km(.)wk(-1)). For SET the expression of the muscle Na(+)/K(+) pump alpha2-subunit was 68...

  1. Genetic Polymorphisms in Endothelin-1 as Predictors for Long-Term Survival and the Cardiac Index in Patients Undergoing On-Pump Cardiac Surgery.

    Directory of Open Access Journals (Sweden)

    Ashham Mansur

    Full Text Available Genetic variants within the endothelin-1 gene (EDN1 have been associated with several cardiovascular diseases and may act as genetic prognostic markers. Here, we explored the overall relevance of EDN1 polymorphisms for long-term survival in patients undergoing on-pump cardiac surgery. A prospectively collected cohort of 455 Caucasian patients who underwent cardiac surgery with cardiopulmonary bypass was followed up for 5 years. The obtained genotypes and inferred haplotypes were analyzed for their associations with the five-year mortality rate (primary endpoint. The EDN1 T-1370G and K198N genotype distributions did not deviate from Hardy-Weinberg equilibrium and the major allele frequencies were 83% and 77%, respectively. The cardiovascular risk factors were equally distributed in terms of the different genotypes and haplotypes associated with the two polymorphisms. The five-year mortality rate did not differ among the different EDN1 T-1370G and K198N genotypes and haplotypes. Haplotype analysis revealed that carriers of the G-T (compound EDN1 T-1370G G/K198N T haplotype had a higher cardiac index than did non-carriers (p = 0.0008; however, this difference did not reach significance after adjusting for multiple testing. The results indicate that common variations in EDN1 do not act as prognostic markers for long-term survival in patients undergoing on-pump cardiac surgery.

  2. Detection of pump degradation

    International Nuclear Information System (INIS)

    Casada, D.

    1995-01-01

    There are a variety of stressors that can affect the operation of centrifugal pumps. Although these general stressors are active in essentially all centrifugal pumps, the stressor level and the extent of wear and degradation can vary greatly. Parameters that affect the extent of stressor activity are manifold. In order to assure the long-term operational readiness of a pump, it is important to both understand the nature and magnitude of the specific degradation mechanisms and to monitor the performance of the pump. The most commonly applied method of monitoring the condition of not only pumps, but rotating machinery in general, is vibration analysis. Periodic or continuous special vibration analysis is a cornerstone of most pump monitoring programs. In the nuclear industry, non-spectral vibration monitoring of safety-related pumps is performed in accordance with the ASME code. Pump head and flow rate are also monitored, per code requirements. Although vibration analysis has dominated the condition monitoring field for many years, there are other measures that have been historically used to help understand pump condition; advances in historically applied technologies and developing technologies offer improved monitoring capabilities. The capabilities of several technologies (including vibration analysis, dynamic pressure analysis, and motor power analysis) to detect the presence and magnitude of both stressors and resultant degradation are discussed

  3. Champagne Heat Pump

    Science.gov (United States)

    Jones, Jack A.

    2004-01-01

    The term champagne heat pump denotes a developmental heat pump that exploits a cycle of absorption and desorption of carbon dioxide in an alcohol or other organic liquid. Whereas most heat pumps in common use in the United States are energized by mechanical compression, the champagne heat pump is energized by heating. The concept of heat pumps based on other absorption cycles energized by heat has been understood for years, but some of these heat pumps are outlawed in many areas because of the potential hazards posed by leakage of working fluids. For example, in the case of the water/ammonia cycle, there are potential hazards of toxicity and flammability. The organic-liquid/carbon dioxide absorption/desorption cycle of the champagne heat pump is similar to the water/ammonia cycle, but carbon dioxide is nontoxic and environmentally benign, and one can choose an alcohol or other organic liquid that is also relatively nontoxic and environmentally benign. Two candidate nonalcohol organic liquids are isobutyl acetate and amyl acetate. Although alcohols and many other organic liquids are flammable, they present little or no flammability hazard in the champagne heat pump because only the nonflammable carbon dioxide component of the refrigerant mixture is circulated to the evaporator and condenser heat exchangers, which are the only components of the heat pump in direct contact with air in habitable spaces.

  4. Long-term outcomes after proton therapy, with concurrent chemotherapy, for stage II–III inoperable non-small cell lung cancer

    International Nuclear Information System (INIS)

    Nguyen, Quynh-Nhu; Ly, Ngoc Bui; Komaki, Ritsuko; Levy, Lawrence B.; Gomez, Daniel R.; Chang, Joe Y.; Allen, Pamela K.; Mehran, Reza J.; Lu, Charles; Gillin, Michael; Liao, Zhongxing; Cox, James D.

    2015-01-01

    Purpose: We report long-term disease control, survival, and toxicity for patients with locally advanced non-small cell lung cancer prospectively treated with concurrent proton therapy and chemotherapy on a nonrandomized case-only observational study. Methods: All patients received passive-scatter proton therapy, planned with 4D-CT–based simulation; all received proton therapy concurrent with weekly chemotherapy. Endpoints were local and distant control, disease-free survival (DFS), and overall survival (OS). Results: The 134 patients (21 stage II, 113 stage III; median age 69 years) had a median gross tumor volume (GTV) of 70 cm 3 (range, 5–753 cm 3 ); 77 patients (57%) received 74 Gy(RBE), and 57 (42%) received 60–72 Gy(RBE) (range, 60–74.1 Gy(RBE)). At a median follow-up time of 4.7 years, median OS times were 40.4 months (stage II) and 30.4 months (stage III). Five-year DFS rates were 17.3% (stage II) and 18.0% (stage III). OS, DFS, and local and distant control rates at 5 years did not differ by disease stage. Age and GTV were related to OS and DFS. Toxicity was tolerable, with 1 grade 4 esophagitis and 16 grade 3 events (2 pneumonitis, 6 esophagitis, 8 dermatitis). Conclusion: This report of outcomes after proton therapy for 134 patients indicated that this regimen produced excellent OS with tolerable toxicity

  5. Heat pumps

    CERN Document Server

    Macmichael, DBA

    1988-01-01

    A fully revised and extended account of the design, manufacture and use of heat pumps in both industrial and domestic applications. Topics covered include a detailed description of the various heat pump cycles, the components of a heat pump system - drive, compressor, heat exchangers etc., and the more practical considerations to be taken into account in their selection.

  6. 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

  7. 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.

  8. Heat pumps

    CERN Document Server

    Brodowicz, Kazimierz; Wyszynski, M L; Wyszynski

    2013-01-01

    Heat pumps and related technology are in widespread use in industrial processes and installations. This book presents a unified, comprehensive and systematic treatment of the design and operation of both compression and sorption heat pumps. Heat pump thermodynamics, the choice of working fluid and the characteristics of low temperature heat sources and their application to heat pumps are covered in detail.Economic aspects are discussed and the extensive use of the exergy concept in evaluating performance of heat pumps is a unique feature of the book. The thermodynamic and chemical properties o

  9. Influence of the dynamic Stark effect on long-term frequency stability of a self-oscillating magnetometer with laser-pumped alkali atoms

    Science.gov (United States)

    Baranov, A. A.; Ermak, S. V.; Kulachenkov, N. K.; Petrenko, M. V.; Sagitov, E. A.; Semenov, V. V.

    2017-11-01

    This paper presents the results of investigation Stark shift effect influence on the long-term stability of a dual scheme of quantum magnetometers. Such scheme allows suppressing Stark shift components when a certain pumping light polarization is applied. As a result, long-term stability of a quantum sensor increases. However, when low-frequency (LF) and microwave fields are attached to a single vapor cell a coherence circulation in hyperfine structure of alkali atoms takes place. Physical origin of this effect is associated with the so called “dressed” atom theory, when atom is “dressed” by LF field. It yields in multiphoton absorption and resonance frequency shift. First estimates for this shift based on density matrix evolution formalism are provided in the paper.

  10. Detection of pump degradation

    International Nuclear Information System (INIS)

    Casada, D.

    1994-01-01

    There are a variety of stressors that can affect the operation of centrifugal pumps. Although these general stressors are active in essentially all centrifugal pumps, the stressor level and the extent of wear and degradation can vary greatly. Parameters that affect the extent of stressor activity are manifold. In order to assure the long-term operational readiness of a pump, it is important to both understand the nature and magnitude of the specific degradation mechanisms and to monitor the performance of the pump. The most commonly applied method of monitoring the condition of not only pumps, but rotating machinery in general, is vibration analysis. Periodic or continuous spectral vibration analysis is a cornerstone of most pump monitoring programs. In the nuclear industry, non-spectral vibration monitoring of safety-related pumps is performed in accordance with the ASME code. Although vibration analysis has dominated the condition monitoring field for many years, there are other measures that have been historically used to help understand pump condition: advances in historically applied technologies and developing technologies offer improved monitoring capabilities. The capabilities of several technologies (including vibration analysis, dynamic pressure analysis, and motor power analysis) to detect the presence and magnitude of both stressors and resultant degradation are discussed

  11. Groundwater sampling at Olkiluoto, Eurajoki from the borehole OL-KR6 during a long-term pumping test in 2006

    International Nuclear Information System (INIS)

    Hirvonen, H.; Hatanpaeae, E.; Ahokas, H.

    2007-05-01

    A long-term pumping test at borehole OL-KR6 at Olkiluoto was initiated in 2001. Since then, flow and in situ EC measurements as well as groundwater sampling from specific sampling sections have been performed yearly. The aim of this study was to obtain information on the potential connections via fractures both to the sea and to deep saline groundwater during long-term pumping of the open borehole. In 2006, four groundwater samples were collected from four different sampling depths (98.5-100.5 m, 125-130 m, 135-137 m and 422-425 m). The groundwater samples were taken in stages using PAVE equipment. The water types found in the groundwater samples from OL-KR6 were Na-Ca-Cl (for samples from depths of 98.5-100.5 m and 125-130 m) and Na-Cl (for samples from depths of 135-137 m and 422-425 m). The sample from depth 422-425 m was saline (TDS> 10000 mg/l), while other waters were brackish (1000 mg < TDS <10000 mg/l). This study presents the sampling methods and analysis results of groundwater samples from deep borehole OL-KR6, and draws a comparison between the results of the in situ EC measurements and the EC results measured during groundwater sampling. This report also contains a short comparison of the results obtained from the long-term pumping test conducted between 2001-2006. In situ EC results and EC results measured in laboratory are in quite good agreement. At sampling depth, 422-425 m, EC increased between 2004-2006. At a depth of 423 m, much variation in situ EC-values indicates that routes of groundwater may change during long-term pumping due to the limited storages of different aquifers or the heterogeneity of the content of groundwater in different locations in the bedrock. The minor systematic difference between in situ and sampling EC at a depth of 136 m was probably due to the different flow fields during flow logging and water sampling. The dominant gas in the groundwater samples was nitrogen. Carbon dioxide was the second dominant gas, except for the

  12. 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

  13. Effect of milrinone on short term outcome of patients with myocardial dysfunction undergoing off-pump coronary artery bypass graft: a randomized clinical trial.

    Directory of Open Access Journals (Sweden)

    Mehdi Hadadzadeh

    2013-10-01

    Full Text Available Myocardial dysfunction is a major complication in cardiac surgery that needs inotropic support. This study evaluates the effect of milrinone on patients with low ventricular ejection fraction undergoing off- pump coronary artery bypass graft (OPCAB. The present study is designed to evaluate the effect of milrinone on myocardial dysfunction. Eighty patients with low ventricular ejection fraction (<35%, candidate for elective OPCAB, were enrolled in this study. They were randomly assigned to two groups. One group received milrinone (50 μg/kg intravenously and another group received a saline as placebo followed by 24 hours infusion of each agent (0.5 μg/kg/min. Short outcome of patients such as hemodynamic parameters and left ventricular ejection fraction were variables evaluated. Serum levels of creatine phosphokinase, the MB isoenzyme of creatine kinase, occurrence of arrhythmias and mean duration of mechanical ventilation were significantly lower in milrinone group (P<0.05. The mean post operative left ventricular ejection fraction was significantly higher in milrinone group (P=0.031. There were no statistical significant differences between the two groups in terms of intra-aortic balloon pump, inotropic support requirement, myocardial ischemia, myocardial infarction, duration of inotropic support, duration of intensive care unit stay, mortality and morbidity rate. Administration of milrinone in patients undergoing OPCAB with low ventricular ejection fraction is useful and effective.

  14. Effect of milrinone on short term outcome of patients with myocardial dysfunction undergoing off-pump coronary artery bypass graft: a randomized clinical trial.

    Science.gov (United States)

    Hadadzadeh, Mehdi; Hosseini, Seyed Habib; Mostafavi Pour Manshadi, Seyed Mohammad Yousof; Naderi, Nafiseh; Emami Meybodi, Mahmood

    2013-01-01

    Myocardial dysfunction is a major complication in cardiac surgery that needs inotropic support. This study evaluates the effect of milrinone on patients with low ventricular ejection fraction undergoing off- pump coronary artery bypass graft (OPCAB). The present study is designed to evaluate the effect of milrinone on myocardial dysfunction. Eighty patients with low ventricular ejection fraction (milrinone (50 μg/kg) intravenously and another group received a saline as placebo followed by 24 hours infusion of each agent (0.5 μg/kg/min). Short outcome of patients such as hemodynamic parameters and left ventricular ejection fraction were variables evaluated. Serum levels of creatine phosphokinase, the MB isoenzyme of creatine kinase, occurrence of arrhythmias and mean duration of mechanical ventilation were significantly lower in milrinone group (P<0.05). The mean post operative left ventricular ejection fraction was significantly higher in milrinone group (P=0.031). There were no statistical significant differences between the two groups in terms of intra-aortic balloon pump, inotropic support requirement, myocardial ischemia, myocardial infarction, duration of inotropic support, duration of intensive care unit stay, mortality and morbidity rate. Administration of milrinone in patients undergoing OPCAB with low ventricular ejection fraction is useful and effective.

  15. Centrifugal pumps

    CERN Document Server

    Gülich, Johann Friedrich

    2014-01-01

    This book gives an unparalleled, up-to-date, in-depth treatment of all kinds of flow phenomena encountered in centrifugal pumps including the complex interactions of fluid flow with vibrations and wear of materials. The scope includes all aspects of hydraulic design, 3D-flow phenomena and partload operation, cavitation, numerical flow calculations, hydraulic forces, pressure pulsations, noise, pump vibrations (notably bearing housing vibration diagnostics and remedies), pipe vibrations, pump characteristics and pump operation, design of intake structures, the effects of highly viscous flows, pumping of gas-liquid mixtures, hydraulic transport of solids, fatigue damage to impellers or diffusers, material selection under the aspects of fatigue, corrosion, erosion-corrosion or hydro-abrasive wear, pump selection, and hydraulic quality criteria. As a novelty, the 3rd ed. brings a fully analytical design method for radial impellers, which eliminates the arbitrary choices inherent to former design procedures. The d...

  16. Long Term Osmotic Mini Pump Treatment with Alpha-MSH Improves Myocardial Function in Zucker Diabetic Fatty Rats

    Directory of Open Access Journals (Sweden)

    Miklos Szokol

    2017-10-01

    Full Text Available The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH, in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF rats. Serum parameters, blood pressure, and weight gain were monitored along with oral glucose tolerance (OGTT. Echocardiography was conducted and, following sacrifice, the effects of treatment on ischemia/reperfusion cardiac injury were assessed using the isolated working heart method. Nicotinamide adenine dinucleotide phosphate (NADPH oxidase activity was measured to evaluate levels of oxidative stress, and force measurements were performed on isolated cardiomyocytes to determine calcium sensitivity, active tension and myofilament co-operation. Vascular status was also evaluated on isolated arterioles using a contractile force measurement setup. The echocardiographic parameters ejection fraction (EF, fractional shortening (FS, isovolumetric relaxation time (IVRT, mitral annular plane systolic excursion (MAPSE, and Tei-index were significantly better in the MSH-treated group compared to ZDF controls. Isolated working heart aortic and coronary flow was increased in treated rats, and higher Hill coefficient indicated better myofilament co-operation in the MSH-treated group. We conclude that MSH improves global heart functions in ZDF rats, but these effects are not related to the vascular status.

  17. Pumping life

    DEFF Research Database (Denmark)

    Sitsel, Oleg; Dach, Ingrid; Hoffmann, Robert Daniel

    2012-01-01

    The name PUMPKIN may suggest a research centre focused on American Halloween traditions or the investigation of the growth of vegetables – however this would be misleading. Researchers at PUMPKIN, short for Centre for Membrane Pumps in Cells and Disease, are in fact interested in a large family o......’. Here we illustrate that the pumping of ions means nothing less than the pumping of life....

  18. Proton transfer events in GFP.

    Science.gov (United States)

    Di Donato, Mariangela; van Wilderen, Luuk J G W; Van Stokkum, Ivo H M; Stuart, Thomas Cohen; Kennis, John T M; Hellingwerf, Klaas J; van Grondelle, Rienk; Groot, Marie Louise

    2011-09-28

    Proton transfer is one of the most important elementary processes in biology. Green fluorescent protein (GFP) serves as an important model system to elucidate the mechanistic details of this reaction, because in GFP proton transfer can be induced by light absorption. Illumination initiates proton transfer through a 'proton-wire', formed by the chromophore (the proton donor), water molecule W22, Ser205 and Glu222 (the acceptor), on a picosecond time scale. To obtain a more refined view of this process, we have used a combined approach of time resolved mid-infrared spectroscopy and visible pump-dump-probe spectroscopy to resolve with atomic resolution how and how fast protons move through this wire. Our results indicate that absorption of light by GFP induces in 3 ps (10 ps in D(2)O) a shift of the equilibrium positions of all protons in the H-bonded network, leading to a partial protonation of Glu222 and to a so-called low barrier hydrogen bond (LBHB) for the chromophore's proton, giving rise to dual emission at 475 and 508 nm. This state is followed by a repositioning of the protons on the wire in 10 ps (80 ps in D(2)O), ultimately forming the fully deprotonated chromophore and protonated Glu222.

  19. Test of a cryogenic helium pump

    International Nuclear Information System (INIS)

    Lue, J.W.; Miller, J.R.; Walstrom, P.L.; Herz, W.

    1981-01-01

    The design of a cryogenic helium pump for circulating liquid helium in a magnet and the design of a test loop for measuring the pump performance in terms of mass flow vs pump head at various pump speeds are described. A commercial cryogenic helium pump was tested successfully. Despite flaws in the demountable connections, the piston pump itself has performed satisfactorily. A helium pump of this type is suitable for the use of flowing supercritical helium through Internally Cooled Superconductor (ICS) magnets. It has pumped supercritical helium up to 7.5 atm with a pump head up to 2.8 atm. The maximum mass flow rate obtained was about 16 g/s. Performance of the pump was degraded at lower pumping speeds

  20. Combined proton and photon irradiation for craniopharyngioma: Long-term results of the early cohort of patients treated at Harvard Cyclotron Laboratory and Massachusetts General Hospital

    International Nuclear Information System (INIS)

    Fitzek, Markus M.; Linggood, Rita M.; Adams, Judy; Munzenrider, John E.

    2006-01-01

    Purpose: We report the results of the early cohort of patients treated for craniopharyngioma with combined proton-photon irradiation at the Massachusetts General Hospital and the Harvard Cyclotron Laboratory. Methods and Materials: Between 1981 and 1988, 15 patients with craniopharyngioma were treated in part or entirely with fractionated 160 MeV proton beam therapy. The group consisted of 5 children (median age, 15.9 years) and 10 adults (median age, 36.2 years). Median dose prescribed to the tumor was 56.9 cobalt Gray equivalent (CGE; 1 proton Gray = 1.1 CGE). The median proton component was 26.9 CGE. Patients were treated after documented recurrence after initial surgery (n = 6) or after subtotal resection or biopsy (n = 9). None had had prior radiation therapy. Results: Median observation period of surviving patients (n = 11) was 13.1 years from radiotherapy. One patient was lost to follow-up with tumor control after 5.2 years. Actuarial 10-year survival rate was 72%. Four patients have died 5-9.1 years after treatment, two from local failure. Actuarial 5- and 10-year local control rates were 93% and 85%, respectively. The functional status of the living adult patients is unaltered from their preradiotherapy status; all of them continued leading normal or near normal working lives. None of the patients treated as a child had experienced recurrence of tumor. One child shows learning difficulties and slight retardation, comparable to his preradiotherapy status. The others have professional achievements within the normal range. Conclusion: Results in terms of survival and local control are comparable with other contemporary series. Although no formal neuropsychological testing was performed, the surrogate measures of lifestyle and professional accomplishments appear to be satisfactory

  1. 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.

  2. 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.

  3. Energizing porters by proton-motive force.

    Science.gov (United States)

    Nelson, N

    1994-11-01

    It is generally accepted that the chemistry of water was the most crucial determinant in shaping life on earth. Among the more important chemical features of water is its dissociation into protons and hydroxyl ions. The presence of relatively high proton concentrations in the ambient solution resulted in the evolution of proton pumps during the dawn of life on earth. These proton pumps maintained neutral pH inside the cells and generated electrochemical gradients of protons (proton-motive force) across their membranes. The existence of proton-motive force enabled the evolution of porters driven by it that are most probably among the more primitive porters in the world. The directionality of the substrate transport by the porters could be to both sides of the membranes because they can serve as proton symporters or antiporters. One of the most important subjects of this meeting is the mechanism by which proton-motive and other ion-motive forces drive the transport processes through porters. Is there a common mechanism of action for all proton-driven porters? Is there some common partial reaction by which we can identify the way that porters are energized by proton-motive force? Is there a common coupling between proton movement and uptake or secretion of certain molecules? Even a partial answer to one of these questions would advance our knowledge... or confusion. As my mentor Efraim Racker used to say: 'If you are not totally confused you do not understand the issue'.

  4. Quasi-four-particle first-order Faddeev-Watson-Lovelace terms in proton-helium scattering

    Science.gov (United States)

    Safarzade, Zohre; Akbarabadi, Farideh Shojaei; Fathi, Reza; Brunger, Michael J.; Bolorizadeh, Mohammad A.

    2017-06-01

    The Faddeev-Watson-Lovelace equations, which are typically used for solving three-particle scattering problems, are based on the assumption of target having one active electron while the other electrons remain passive during the collision process. So, in the case of protons scattering from helium or helium-like targets, in which there are two bound-state electrons, the passive electron has a static role in the collision channel to be studied. In this work, we intend to assign a dynamic role to all the target electrons, as they are physically active in the collision. By including an active role for the second electron in proton-helium-like collisions, a new form of the Faddeev-Watson-Lovelace integral equations is needed, in which there is no disconnected kernel. We consider the operators and the wave functions associated with the electrons to obey the Pauli exclusion principle, as the electrons are indistinguishable. In addition, a quasi-three-particle collision is assumed in the initial channel, where the electronic cloud is represented as a single identity in the collision.

  5. Polarized proton target-IV. Operations manual

    International Nuclear Information System (INIS)

    Hill, D.; Fletcher, O.; Moretti, A.; Onesto, F.

    1976-01-01

    Standard operating procedures are presented for the vacuum, cryogenic, and electronic systems of a polarized proton target. The systems are comprised of (1) a target cryostat; (2) a 4 He pumping system; (3) a 3 He pumping system; (4) a microwave system; (5) a magnet and power supply; (6) a computerized polarization monitor; and (7) miscellaneous auxiliary equipment

  6. Electrostatic coupling of ion pumps.

    Science.gov (United States)

    Nieto-Frausto, J; Lüger, P; Apell, H J

    1992-01-01

    In this paper the electrostatic interactions between membrane-embedded ion-pumps and their consequences for the kinetics of pump-mediated transport processes have been examined. We show that the time course of an intrinsically monomolecular transport reaction can become distinctly nonexponential, if the reaction is associated with charge translocation and takes place in an aggregate of pump molecules. First we consider the electrostatic coupling of a single dimer of ion-pumps embedded in the membrane. Then we apply the treatment to the kinetic analysis of light-driven proton transport by bacteriorhodopsin which forms two-dimensional hexagonal lattices. Finally, for the case of nonordered molecules, we also consider a model in which the pumps are randomly distributed over the nodes of a lattice. Here the average distance is equal to that deduced experimentally and the elemental size of the lattice is the effective diameter of one single pump. This latter model is applied to an aggregate of membrane-embedded Na, K- and Ca-pumps. In all these cases the electrostatic potential considered is the exact solution calculated from the method of electrical images for a plane membrane of finite thickness immersed in an infinite aqueous solution environment. The distributions of charges (ions or charged binding sites) are considered homogeneous or discrete in the membrane and/or in the external solution. In the case of discrete distributions we compare the results from a mean field approximation and a stochastic simulation.

  7. Liquid metals pumping

    International Nuclear Information System (INIS)

    Le Frere, J.P.

    1984-01-01

    Pumps used to pump liquid metals depend on the liquid metal and on the type of application concerned. One deals more particularly with electromagnetic pumps, the main pumps used with mechanical pumps. To pump sodium in the nuclear field, these two types of pumps are used; the pumps of different circuits of Super Phenix are presented and described [fr

  8. A Short-term ESPERTA-based Forecast Tool for Moderate-to-extreme Solar Proton Events

    Science.gov (United States)

    Laurenza, M.; Alberti, T.; Cliver, E. W.

    2018-04-01

    The ESPERTA (Empirical model for Solar Proton Event Real Time Alert) forecast tool has a Probability of Detection (POD) of 63% for all >10 MeV events with proton peak intensity ≥10 pfu (i.e., ≥S1 events, S1 referring to minor storms on the NOAA Solar Radiation Storms scale), from 1995 to 2014 with a false alarm rate (FAR) of 38% and a median (minimum) warning time (WT) of ∼4.8 (0.4) hr. The NOAA space weather scale includes four additional categories: moderate (S2), strong (S3), severe (S4), and extreme (S5). As S1 events have only minor impacts on HF radio propagation in the polar regions, the effective threshold for significant space radiation effects appears to be the S2 level (100 pfu), above which both biological and space operation impacts are observed along with increased effects on HF propagation in the polar regions. We modified the ESPERTA model to predict ≥S2 events and obtained a POD of 75% (41/55) and an FAR of 24% (13/54) for the 1995–2014 interval with a median (minimum) WT of ∼1.7 (0.2) hr based on predictions made at the time of the S1 threshold crossing. The improved performance of ESPERTA for ≥S2 events is a reflection of the big flare syndrome, which postulates that the measures of the various manifestations of eruptive solar flares increase as one considers increasingly larger events.

  9. Electromagnetic pump

    International Nuclear Information System (INIS)

    Ito, Koji; Suetake, Norio; Aizawa, Toshie; Nakasaki, Masayoshi

    1998-01-01

    The present invention provides an electromagnetic pump suitable to a recycling pump for liquid sodium as coolants of an FBR type reactor. Namely, a stator module of the electromagnetic pump of the present invention comprises a plurality of outer laminate iron core units and outer stator modules stacked alternately in the axial direction. With such a constitution, even a long electromagnetic pump having a large number of outer stator coils can be manufactured without damaging electric insulation of the outer stator coils. In addition, the inner circumferential surface of the outer laminate iron cores is urged and brought into contact with the outer circumferential surface of the outer duct by an elastic material. With such a constitution, Joule loss heat generated in the outer stator coils and internal heat generated in the outer laminate iron cores can be released to an electroconductive fluid flowing the inner circumference of the outer duct by way of the outer duct. (I.S.)

  10. Electrokinetic pump

    Science.gov (United States)

    Patel, Kamlesh D.

    2007-11-20

    A method for altering the surface properties of a particle bed. In application, the method pertains particularly to an electrokinetic pump configuration where nanoparticles are bonded to the surface of the stationary phase to alter the surface properties of the stationary phase including the surface area and/or the zeta potential and thus improve the efficiency and operating range of these pumps. By functionalizing the nanoparticles to change the zeta potential the electrokinetic pump is rendered capable of operating with working fluids having pH values that can range from 2-10 generally and acidic working fluids in particular. For applications in which the pump is intended to handle highly acidic solutions latex nanoparticles that are quaternary amine functionalized can be used.

  11. 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...

  12. 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

  13. 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

  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. 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.

  16. Proton dynamics in cancer.

    Science.gov (United States)

    Huber, Veronica; De Milito, Angelo; Harguindey, Salvador; Reshkin, Stephan J; Wahl, Miriam L; Rauch, Cyril; Chiesi, Antonio; Pouysségur, Jacques; Gatenby, Robert A; Rivoltini, Licia; Fais, Stefano

    2010-06-15

    Cancer remains a leading cause of death in the world today. Despite decades of research to identify novel therapeutic approaches, durable regressions of metastatic disease are still scanty and survival benefits often negligible. While the current strategy is mostly converging on target-therapies aimed at selectively affecting altered molecular pathways in tumor cells, evidences are in parallel pointing to cell metabolism as a potential Achilles' heel of cancer, to be disrupted for achieving therapeutic benefit. Critical differences in the metabolism of tumor versus normal cells, which include abnormal glycolysis, high lactic acid production, protons accumulation and reversed intra-extracellular pH gradients, make tumor site a hostile microenvironment where only cancer cells can proliferate and survive. Inhibiting these pathways by blocking proton pumps and transporters may deprive cancer cells of a key mechanism of detoxification and thus represent a novel strategy for a pleiotropic and multifaceted suppression of cancer cell growth.Research groups scattered all over the world have recently started to investigate various aspects of proton dynamics in cancer cells with quite encouraging preliminary results. The intent of unifying investigators involved in this research line led to the formation of the "International Society for Proton Dynamics in Cancer" (ISPDC) in January 2010. This is the manifesto of the newly formed society where both basic and clinical investigators are called to foster translational research and stimulate interdisciplinary collaboration for the development of more specific and less toxic therapeutic strategies based on proton dynamics in tumor cell biology.

  17. Proton dynamics in cancer

    Directory of Open Access Journals (Sweden)

    Pouysségur Jacques

    2010-06-01

    Full Text Available Abstract Cancer remains a leading cause of death in the world today. Despite decades of research to identify novel therapeutic approaches, durable regressions of metastatic disease are still scanty and survival benefits often negligible. While the current strategy is mostly converging on target-therapies aimed at selectively affecting altered molecular pathways in tumor cells, evidences are in parallel pointing to cell metabolism as a potential Achilles' heel of cancer, to be disrupted for achieving therapeutic benefit. Critical differences in the metabolism of tumor versus normal cells, which include abnormal glycolysis, high lactic acid production, protons accumulation and reversed intra-extracellular pH gradients, make tumor site a hostile microenvironment where only cancer cells can proliferate and survive. Inhibiting these pathways by blocking proton pumps and transporters may deprive cancer cells of a key mechanism of detoxification and thus represent a novel strategy for a pleiotropic and multifaceted suppression of cancer cell growth. Research groups scattered all over the world have recently started to investigate various aspects of proton dynamics in cancer cells with quite encouraging preliminary results. The intent of unifying investigators involved in this research line led to the formation of the "International Society for Proton Dynamics in Cancer" (ISPDC in January 2010. This is the manifesto of the newly formed society where both basic and clinical investigators are called to foster translational research and stimulate interdisciplinary collaboration for the development of more specific and less toxic therapeutic strategies based on proton dynamics in tumor cell biology.

  18. Pumps and pump facilities. 2. ed.

    International Nuclear Information System (INIS)

    Bohl, W.; Bauerfeind, H.; Gutmann, G.; Leuschner, G.; Matthias, H.B.; Mengele, R.; Neumaier, R.; Vetter, G.; Wagner, W.

    1981-01-01

    This book deals with the common fundamental aspects of liquid pumps and gives an exemplary choice of the most important kinds of pumps. The scientific matter is dealt with by means of practical mathematical examples among other ways of presenting the matter. Survey of contents: Division on main operational data of pumps - pipe characteristics - pump characteristics - suction behaviour of the pumps - projecting and operation of rotary pumps - boiler feed pumps - reactor feed pumps - oscillating positive-displacement pumps - eccentric spiral pumps. (orig./GL) [de

  19. Cerebellar Volume and Proton Magnetic Resonance Spectroscopy at Term, and Neurodevelopment at 2 Years of Age in Preterm Infants

    Science.gov (United States)

    van Kooij, Britt J. M.; Benders, Manon J. N. L.; Anbeek, Petronella; van Haastert, Ingrid C.; de Vries, Linda S.; Groenendaal, Floris

    2012-01-01

    Aim: To assess the relation between cerebellar volume and spectroscopy at term equivalent age, and neurodevelopment at 24 months corrected age in preterm infants. Methods: Magnetic resonance imaging of the brain was performed around term equivalent age in 112 preterm infants (mean gestational age 28wks 3d [SD 1wk 5d]; birthweight 1129g [SD 324g]).…

  20. SU-E-J-125: Classification of CBCT Noises in Terms of Their Contribution to Proton Range Uncertainty

    International Nuclear Information System (INIS)

    Brousmiche, S; Orban de Xivry, J; Macq, B; Seco, J

    2014-01-01

    Purpose: This study assesses the potential use of CBCT images in adaptive protontherapy by estimating the contribution of the main sources of noise and calibration errors to the proton range uncertainty. Methods: Measurements intended to highlight each particular source have been achieved by adapting either the testbench configuration, e.g. use of filtration, fan-beam collimation, beam stop arrays, phantoms and detector reset light, or the sequence of correction algorithms including water precorrection. Additional Monte-Carlo simulations have been performed to complement these measurements, especially for the beam hardening and the scatter cases. Simulations of proton beams penetration through the resulting images have then been carried out to quantify the range change due to these effects. The particular case of a brain irradiation is considered mainly because of the multiple effects that the skull bones have on the internal soft tissues. Results: On top of the range error sources is the undercorrection of scatter. Its influence has been analyzed from a comparison of fan-beam and full axial FOV acquisitions. In this case, large range errors of about 12 mm can be reached if the assumption is made that the scatter has only a constant contribution over the projection images. Even the detector lag, which a priori induces a much smaller effect, has been shown to contribute for up to 2 mm to the overall error if its correction only aims at reducing the skin artefact. This last result can partially be understood by the larger interface between tissues and bones inside the skull. Conclusion: This study has set the basis of a more systematical analysis of the effect CBCT noise on range uncertainties based on a combination of measurements, simulations and theoretical results. With our method, even more subtle effects such as the cone-beam artifact or the detector lag can be assessed. SBR and JOR are financed by iMagX, a public-private partnership between the region Wallone

  1. High conductive, long-term durable, anhydrous proton conductive solid-state electrolyte based on a metal-organic framework impregnated with binary ionic liquids: Synthesis, characteristic and effect of anion

    Science.gov (United States)

    Chen, Hui; Han, Shu-Yan; Liu, Rui-Heng; Chen, Teng-Fei; Bi, Kai-Lun; Liang, Jian-Bo; Deng, Yu-Heng; Wan, Chong-Qing

    2018-02-01

    Incorporating ionic liquids (abbreviated as ILs) into porous metal-organic framework (MOF) to obtain ILs@MOF nanocomposites is documented as a feasible method to achieve new type of anhydrous proton conductor with high performance. We newly synthesized a series of ILs with different acid counter anions (R-SO3-) and their ILs@MOF hybrid materials, i.e. SA-EIMS@MIL-101, MSA-EIMS@MIL-101 and PTSA-EIMS@MIL-101 (SA = sulfate acid, MSA = methanesulfonate acid, PTSA = p-toluenesulfonate acid, EIMS = 1-(1-ethyl-3-imidazolium)propane-3-sulfonate). Such hybrid materials displayed as anhydrous proton conduction with long-term durability even heated at 150 °C open to air. σ value of SA-EIMS@MIL-101 is up to 1.89 × 10-3 S cm-1, being in the range of the most conductive MOF-based materials. MOF support exhibited favorable proton transport and long-term retention for ILs. Anion volumes of R-SO3- displayed significant effects on the proton conductivity of such hybrid ILs@MOF materials. The smaller the van der Waals volume of R-SO3- is, the higher the conductivity of ILs@MOF is. This work suggests that the combination of a variety of the incorporated ILs and a MOF framework would afford high proton transport and gives an idea to explore the safe, anhydrous, solid-state electrolyte for high temperature proton exchange membrane fuel cell.

  2. Mid-term follow-up outcomes of 2-staged hybrid coronary revascularization compared with off-pump coronary artery bypass for patients with multivessel coronary artery disease.

    Science.gov (United States)

    Wu, Song; Ling, Yunpeng; Fu, Yuanhao; Zhang, Lufeng; Yang, Hang; Guo, Lijun; Gao, Wei; Wan, Feng

    2017-06-01

    Two-staged hybrid coronary revascularization (HCR) is a novel procedure in selected patients with multivessel coronary artery disease. However, few studies are available on the mid-term or long-term outcomes of this 2-staged procedure as compared to off-pump coronary artery bypass (OPCAB). To compare in-hospital and mid-term follow-up outcomes of 2-staged HCR with OPCAB in patients with multivessel coronary artery disease. The present retrospective study analyzed the data from 73 patients who underwent the 2-staged HCR (HCR group) during 2012-2014 at the heart center. Three hundred and eighty-three patients who underwent conventional OPCAB by the same surgeon were selected for the comparative analysis performed on in-hospital and mid-term follow-up outcomes between the two groups. No significant difference was observed in the preoperative outcome between the two groups. The HCR group had a shorter operation duration (152.9 ±43.8 vs. 262.6 ±51.8 min, p < 0.05), less bleeding (558.6 ±441.3 vs. 1035.5 ±613.3 ml, p < 0.05), shorter mechanical ventilation (9.4 ±7.4 vs. 19.0 ±18.3 h, p < 0.05), and less blood transfusion (12 (16.4%) vs. 200 (52.2%), p < 0.05). The mean follow-up duration was 25.0 ±9.6 months in the HCR group and 22.8 ±10.6 months in the OPCAB group. The incidence of major adverse cardiac or cerebrovascular events (MACCE) was similar in both groups (4 (5.5%) vs. 10 (2.8%), p = 0.408). The estimated 3-year survival was similar in both groups (log-rank χ 2 = 1.041, p = 0.308). The 2-staged HCR is a safe and effective surgical procedure and may offer similar mid-term follow-up outcomes to OPCAB.

  3. Proton therapy

    International Nuclear Information System (INIS)

    Smith, Alfred R

    2006-01-01

    Proton therapy has become a subject of considerable interest in the radiation oncology community and it is expected that there will be a substantial growth in proton treatment facilities during the next decade. I was asked to write a historical review of proton therapy based on my personal experiences, which have all occurred in the United States, so therefore I have a somewhat parochial point of view. Space requirements did not permit me to mention all of the existing proton therapy facilities or the names of all of those who have contributed to proton therapy. (review)

  4. Long-term Cosmetic Outcomes and Toxicities of Proton Beam Therapy Compared With Photon-Based 3-Dimensional Conformal Accelerated Partial-Breast Irradiation: A Phase 1 Trial

    International Nuclear Information System (INIS)

    Galland-Girodet, Sigolène; Pashtan, Itai; MacDonald, Shannon M.; Ancukiewicz, Marek; Hirsch, Ariel E.; Kachnic, Lisa A.; Specht, Michelle; Gadd, Michele; Smith, Barbara L.; Powell, Simon N.; Recht, Abram; Taghian, Alphonse G.

    2014-01-01

    Purpose: To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. Methods and Materials: From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. Results: At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBT patients, compared with 94% for photon patients (P=.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% (P=.0013); pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62% and 18% (P=.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively (P=.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) (P=.22). Conclusions: Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity

  5. Long-term Cosmetic Outcomes and Toxicities of Proton Beam Therapy Compared With Photon-Based 3-Dimensional Conformal Accelerated Partial-Breast Irradiation: A Phase 1 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Galland-Girodet, Sigolène; Pashtan, Itai; MacDonald, Shannon M.; Ancukiewicz, Marek [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Hirsch, Ariel E.; Kachnic, Lisa A. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts (United States); Specht, Michelle; Gadd, Michele; Smith, Barbara L. [Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Powell, Simon N. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Recht, Abram [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (United States); Taghian, Alphonse G., E-mail: ataghian@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2014-11-01

    Purpose: To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. Methods and Materials: From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. Results: At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBT patients, compared with 94% for photon patients (P=.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% (P=.0013); pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62% and 18% (P=.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively (P=.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) (P=.22). Conclusions: Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity.

  6. -pumping pyrophosphatase in pepper plants

    KAUST Repository

    Vigani, Gianpiero; Rolli, Eleonora; Marasco, Ramona; Dell'Orto, Marta; Michoud, Gregoire; Soussi, Asma; Raddadi, Noura; Borin, Sara; Sorlini, Claudia; Zocchi, Graziano; Daffonchio, Daniele

    2018-01-01

    It has been previously shown that the transgenic overexpression of the plant root vacuolar proton pumps H+ -ATPase (V-ATPase) and H+ -PPase (V-PPase) confer tolerance to drought. Since plant-root endophytic bacteria can also promote drought tolerance, we hypothesize that such promotion can be associated to the enhancement of the host vacuolar proton pumps expression and activity. To test this hypothesis, we selected two endophytic bacteria endowed with an array of in vitro plant growth promoting traits. Their genome sequences confirmed the presence of traits previously shown to confer drought resistance to plants, such as the synthesis of nitric oxide and of organic volatile organic compounds. We used the two strains on pepper (Capsicuum annuum L.) because of its high sensitivity to drought. Under drought conditions, both strains stimulated a larger root system and enhanced the leaves' photosynthetic activity. By testing the expression and activity of the vacuolar proton pumps, H+ -ATPase (V-ATPase) and H+ -PPase (V-PPase), we found that bacterial colonization enhanced V-PPase only. We conclude that the enhanced expression and activity of V-PPase can be favoured by the colonization of drought-tolerance-inducing bacterial endophytes. This article is protected by copyright. All rights reserved.

  7. -pumping pyrophosphatase in pepper plants

    KAUST Repository

    Vigani, Gianpiero

    2018-05-22

    It has been previously shown that the transgenic overexpression of the plant root vacuolar proton pumps H+ -ATPase (V-ATPase) and H+ -PPase (V-PPase) confer tolerance to drought. Since plant-root endophytic bacteria can also promote drought tolerance, we hypothesize that such promotion can be associated to the enhancement of the host vacuolar proton pumps expression and activity. To test this hypothesis, we selected two endophytic bacteria endowed with an array of in vitro plant growth promoting traits. Their genome sequences confirmed the presence of traits previously shown to confer drought resistance to plants, such as the synthesis of nitric oxide and of organic volatile organic compounds. We used the two strains on pepper (Capsicuum annuum L.) because of its high sensitivity to drought. Under drought conditions, both strains stimulated a larger root system and enhanced the leaves\\' photosynthetic activity. By testing the expression and activity of the vacuolar proton pumps, H+ -ATPase (V-ATPase) and H+ -PPase (V-PPase), we found that bacterial colonization enhanced V-PPase only. We conclude that the enhanced expression and activity of V-PPase can be favoured by the colonization of drought-tolerance-inducing bacterial endophytes. This article is protected by copyright. All rights reserved.

  8. Long-term morphine delivery via slow release morphine pellets or osmotic pumps: Plasma concentration, analgesia, and naloxone-precipitated withdrawal.

    Science.gov (United States)

    McLane, Virginia D; Bergquist, Ivy; Cormier, James; Barlow, Deborah J; Houseknecht, Karen L; Bilsky, Edward J; Cao, Ling

    2017-09-15

    Slow-release morphine sulfate pellets and osmotic pumps are common routes of chronic morphine delivery in mouse models, but direct comparisons of these drug delivery systems are lacking. In this study, we assessed the efficacy of slow-release pellets versus osmotic pumps in delivering morphine to adult mice. Male C57BL/6NCr mice (8weeksold) were implanted subcutaneously with slow-release pellets (25mg morphine sulfate) or osmotic pumps (64mg/mL, 1.0μL/h). Plasma morphine concentrations were quantified via LC-MS/MS, analgesic efficacy was determined by tail flick assay, and dependence was assessed with naloxone-precipitated withdrawal behaviors (jumping) and physiological effects (excretion, weight loss). Morphine pellets delivered significantly higher plasma drug concentrations compared to osmotic pumps, which were limited by the solubility of the morphine sulfate and pump volume/flow rate. Within 96h post-implantation, plasma morphine concentrations were indistinguishable in pellet vs. pump-treated samples. While osmotic pump did not have an antinociceptive effect in the tail flick assay, pumps and pellets induced comparable dependence symptoms (naloxone-precipitated jumping behavior) from 24-72h post-implantation. In this study, we compared slow-release morphine pellets to osmotic minipumps for morphine delivery in mice. We found that osmotic pumps and subcutaneous morphine sulfate pellets yielded significantly different pharmacokinetics over a 7-day period, and as a result significantly different antinociceptive efficacy. Nonetheless, both delivery methods induced dependence as measured by naloxone-precipitated withdrawal. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Maternal response to two electric breast pumps

    Science.gov (United States)

    Mechanical characteristics of breast pumps have been shown to influence milk extraction and hormone release in laboratory settings. However, few studies evaluate impact of differences in pump design on long-term breastfeeding success. This study evaluated the impact of a novel pump design on milk ex...

  10. Fluidic pumps

    International Nuclear Information System (INIS)

    Priestman, G.H.

    1990-01-01

    A fluidic pump has primary and secondary vessels connected by a pipe, a displacement vessel having liquid to be delivered through a pipe via a rectifier provided with a feed tank. A drive unit delivers pressure fluid to a line to raise liquid and compress trapped gas or liquid in the space, including the pipe between the liquids in the two vessels and thus drive liquid out of the displacement vessel. The driving gas is therefore separated by the barrier liquid and the trapped gas or liquid from the liquid to be pumped which liquid could be e.g. radioactive. (author)

  11. Pumped storage

    International Nuclear Information System (INIS)

    Strauss, P.L.

    1991-01-01

    The privately financed 1,000 MW Rocky Point Pumped Storage Project located in central Colorado, USA, will be one of the world's highest head, 2,350 feet reversible pump/turbine projects. The project will offer an economical supply of peaking power and spinning reserve power to Colorado and other southwestern states. This paper describes how the project will be made compatible with the environmental conditions in the project area and the type of terrestrial mitigation measures that are being proposed for those situations where the project impacts the environment, either temporarily or permanently

  12. The prognostic value of proton magnetic resonance spectroscopy in term newborns treated with therapeutic hypothermia following asphyxia

    NARCIS (Netherlands)

    Sijens, Paul E.; Wischniowsky, Katharina; ter Horst, Hendrik J.

    2017-01-01

    Objective: The purpose of this study was to correlate brain metabolism assessed shortly after therapeutic hyperthermia by H-1 magnetic resonance spectroscopy (MRS), with neurodevelopmental outcome. Methods: At the age of 6.0 +/- 1.8 days, brain metabolites of 35 term asphyxiated newborns, treated

  13. 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

  14. Potential long-term effects of MDMA on the basal ganglia-thalamocortical circuit: a proton MR spectroscopy and diffusion-tensor imaging study.

    Science.gov (United States)

    Liu, Hua-Shan; Chou, Ming-Chung; Chung, Hsiao-Wen; Cho, Nai-Yu; Chiang, Shih-Wei; Wang, Chao-Ying; Kao, Hung-Wen; Huang, Guo-Shu; Chen, Cheng-Yu

    2011-08-01

    To investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA, commonly known as "ecstasy") on the alterations of brain metabolites and anatomic tissue integrity related to the function of the basal ganglia-thalamocortical circuit by using proton magnetic resonance (MR) spectroscopy and diffusion-tensor MR imaging. This study was approved by a local institutional review board, and written informed consent was obtained from all subjects. Thirty-one long-term (>1 year) MDMA users and 33 healthy subjects were enrolled. Proton MR spectroscopy from the middle frontal cortex and bilateral basal ganglia and whole-brain diffusion-tensor MR imaging were performed with a 3.0-T system. Absolute concentrations of metabolites were computed, and diffusion-tensor data were registered to the International Consortium for Brain Mapping template to facilitate voxel-based group comparison. The mean myo-inositol level in the basal ganglia of MDMA users (left: 4.55 mmol/L ± 2.01 [standard deviation], right: 4.48 mmol/L ± 1.33) was significantly higher than that in control subjects (left: 3.25 mmol/L ± 1.30, right: 3.31 mmol/L ± 1.19) (P 50 voxels). Increased myo-inositol and Cho concentrations in the basal ganglia of MDMA users are suggestive of glial response to degenerating serotonergic functions. The abnormal metabolic changes in the basal ganglia may consequently affect the inhibitory effect of the basal ganglia to the thalamus, as suggested by the increased FA in the thalamus and abnormal changes in water diffusion in the corresponding basal ganglia-thalamocortical circuit. © RSNA, 2011.

  15. Cardiopulmonary bypass and intra-aortic balloon pump use is associated with higher short and long term mortality after transcatheter aortic valve replacement: a PARTNER trial substudy.

    Science.gov (United States)

    Shreenivas, Satya S; Lilly, Scott M; Szeto, Wilson Y; Desai, Nimesh; Anwaruddin, Saif; Bavaria, Joseph E; Hudock, Kristin M; Thourani, Vinod H; Makkar, Raj; Pichard, Augusto; Webb, John; Dewey, Todd; Kapadia, Samir; Suri, Rakesh M; Xu, Ke; Leon, Martin B; Herrmann, Howard C

    2015-08-01

    Transcatheter aortic valve replacement (TAVR) with the balloon-expandable Sapien transcatheter heart valve improves survival compared to standard therapy in patients with severe aortic stenosis (AS) and is noninferior to surgical aortic valve replacement (AVR) in patients at high operative risk. Nonetheless, a significant proportion of patients may require pre-emptive or emergent support with cardiopulmonary bypass (CPB) and/or intra-aortic balloon pump (IABP) during TAVR due to pre-existing comorbid conditions or as a result of procedural complications. We hypothesized that patients who required CPB or IABP would have increased periprocedural complications and reduced long-term survival. In addition, we sought to determine whether preprocedural variables could predict the need for CPB and IABP. The study population included 2,525 patients in the PARTNER Trial (Cohort A and B) and the continuing access registry (CAR). Patients that received CPB or IABP were compared to patients that did not receive either, and then further divided into those that received support pre-TAVR and those that were placed on support emergently. One-hundred sixty-three patients (6.5%) were placed on CPB and/or IABP. The use of CPB or IABP was associated with higher 1 year mortality (49.1% vs. 21.6%, P non-CPB/IABP cases (53.3% and 40.3% vs. 21.6%, P < 0.001). These findings indicate that CPB and IABP use in TAVR portends a poor prognosis and its utilization, particularly in the setting of pre-emptive use, needs reconsideration. © 2015 Wiley Periodicals, Inc.

  16. Implications of the "observer effect" on modelling a long-term pumping test with hydraulically conductive boreholes in a discrete fracture network system.

    Science.gov (United States)

    Holton, D.; Frampton, A.; Cvetkovic, V.

    2006-12-01

    The Onkalo underground research facility for rock characterisation for nuclear waste disposal is located at Olkiluoto island, just off the Finnish coast in the Baltic Sea. Prior to the start of the excavation of the Onkalo facility, an extensive amount of hydraulic data has been collected during various pumping experiments from a large number of boreholes placed throughout an area of approximately 10 km2, reaching depths of 1000 meters below sea level. In particular, the hydraulic borehole data includes classical measurements of pressure, but also new measurements of flow rate and flow direction in boreholes (so called flow-logging). These measurements indicate large variations in heterogeneity and are a clear reflection of the discrete nature of the system. Here we present results from an ongoing project which aims to explore and asses the implications of these new flow-logging measurements to site descriptive modelling and modelling at performance assessment scales. The main challange of the first phase of this project is to obtain a greater understanding of a strongly heterogenious and anisotropic groundwater system in which open boreholes are located; that is, a system in which the observation boreholes themselves create new hydraulic conductive features of the groundwater system. The results presented are from recent hydraulic flow modelling simulations with a combined continuous porous media and discrete fracture network approach using a commercial finite-element software. An advantage of this approach is we may adapt a continuum mesh on the regional scale, were only a few conductive features are known, together with a local scale discrete fracture network approach, where detailed site-investigation has revealed a large amount of conductive features. Current findings indicate the system is sensitive to certain combinations of hydraulic features, and we quantify the significance of including these variations in terms of their implications for reduction of

  17. Ultrafast proton shuttling in Psammocora cyan fluorescent protein.

    Science.gov (United States)

    Kennis, John T M; van Stokkum, Ivo H M; Peterson, Dayna S; Pandit, Anjali; Wachter, Rebekka M

    2013-09-26

    Cyan, green, yellow, and red fluorescent proteins (FPs) homologous to green fluorescent protein (GFP) are used extensively as model systems to study fundamental processes in photobiology, such as the capture of light energy by protein-embedded chromophores, color tuning by the protein matrix, energy conversion by Förster resonance energy transfer (FRET), and excited-state proton transfer (ESPT) reactions. Recently, a novel cyan fluorescent protein (CFP) termed psamFP488 was isolated from the genus Psammocora of reef building corals. Within the cyan color class, psamFP488 is unusual because it exhibits a significantly extended Stokes shift. Here, we applied ultrafast transient absorption and pump-dump-probe spectroscopy to investigate the mechanistic basis of psamFP488 fluorescence, complemented with fluorescence quantum yield and dynamic light scattering measurements. Transient absorption spectroscopy indicated that, upon excitation at 410 nm, the stimulated cyan emission rises in 170 fs. With pump-dump-probe spectroscopy, we observe a very short-lived (110 fs) ground-state intermediate that we assign to the deprotonated, anionic chromophore. In addition, a minor fraction (14%) decays with 3.5 ps to the ground state. Structural analysis of homologous proteins indicates that Glu-167 is likely positioned in sufficiently close vicinity to the chromophore to act as a proton acceptor. Our findings support a model where unusually fast ESPT from the neutral chromophore to Glu-167 with a time constant of 170 fs and resulting emission from the anionic chromophore forms the basis of the large psamFP488 Stokes shift. When dumped to the ground state, the proton on neutral Glu is very rapidly shuttled back to the anionic chromophore in 110 fs. Proton shuttling in excited and ground states is a factor of 20-4000 faster than in GFP, which probably results from a favorable hydrogen-bonding geometry between the chromophore phenolic oxygen and the glutamate acceptor, possibly

  18. Structure and operation of bacterial tripartite pumps.

    Science.gov (United States)

    Hinchliffe, Philip; Symmons, Martyn F; Hughes, Colin; Koronakis, Vassilis

    2013-01-01

    In bacteria such as Pseudomonas aeruginosa and Escherichia coli, tripartite membrane machineries, or pumps, determine the efflux of small noxious molecules, such as detergents, heavy metals, and antibiotics, and the export of large proteins including toxins. They are therefore influential in bacterial survival, particularly during infections caused by multidrug-resistant pathogens. In these tripartite pumps an inner membrane transporter, typically an ATPase or proton antiporter, binds and translocates export or efflux substrates. In cooperation with a periplasmic adaptor protein it recruits and opens a TolC family cell exit duct, which is anchored in the outer membrane and projects across the periplasmic space between inner and outer membranes. Assembled tripartite pumps thus span the entire bacterial cell envelope. We review the atomic structures of each of the three pump components and discuss how these have allowed high-resolution views of tripartite pump assembly, operation, and possible inhibition.

  19. Solar Pump

    Science.gov (United States)

    Pique, Charles

    1987-01-01

    Proposed pump moves liquid by action of bubbles formed by heat of sun. Tube of liquid having boiling point of 100 to 200 degrees F placed at focal axis of cylindrical reflector. Concentrated sunlight boils liquid at focus, and bubbles of vapor rise in tube, carrying liquid along with them. Pressure difference in hot tube sufficient to produce flow in large loop. Used with conventional flat solar heating panel in completely solar-powered heat-storage system.

  20. Long-term pumping test to study the impact of an open-loop geothermal system on seawater intrusion in a coastal aquifer: the case study of Bari (Southern Italy)

    Science.gov (United States)

    Clementina Caputo, Maria; Masciale, Rita; Masciopinto, Costantino; De Carlo, Lorenzo

    2016-04-01

    The high cost and scarcity of fossil fuels have promoted the increased use of natural heat for a number of direct applications. Just as for fossil fuels, the exploitation of geothermal energy should consider its environmental impact and sustainability. Particular attention deserves the so-called open loop geothermal groundwater heat pump (GWHP) system, which uses groundwater as geothermal fluid. From an economic point of view, the implementation of this kind of geothermal system is particularly attractive in coastal areas, which have generally shallow aquifers. Anyway the potential problem of seawater intrusion has led to laws that restrict the use of groundwater. The scarcity of freshwater could be a major impediment for the utilization of geothermal resources. In this study a new methodology has been proposed. It was based on an experimental approach to characterize a coastal area in order to exploit the low-enthalpy geothermal resource. The coastal karst and fractured aquifer near Bari, in Southern Italy, was selected for this purpose. For the purpose of investigating the influence of an open-loop GWHP system on the seawater intrusion, a long-term pumping test was performed. The test simulated the effects of a prolonged withdrawal on the chemical-physical groundwater characteristics of the studied aquifer portion. The duration of the test was programmed in 16 days, and it was performed with a constant pumping flowrate of 50 m3/h. The extracted water was outflowed into an adjacent artificial channel, by means of a piping system. Water depth, temperature and electrical conductivity of the pumped water were monitored for 37 days, including also some days before and after the pumping duration. The monitored parameters, collected in the pumping and in five observation wells placed 160 m down-gradient with respect to the groundwater flow direction, have been used to estimate different scenarios of the impact of the GWHP system on the seawater intrusion by mean of a

  1. A Preliminary Urinary Metabolomics Study of Sprague-Dawley Rats after Short-term Ketamine Administration by Proton Nuclear Magnetic Resonance Spectroscopy

    Directory of Open Access Journals (Sweden)

    Xiang Lu

    2016-01-01

    Full Text Available Drug abuse has become a global problem. The mass spectrometry-based metabolic consequences of ketamine administration in anesthesia and therapy have been well studied, but to the best of our knowledge, metabolomic studies of ketamine abuse based on nuclear magnetic resonance (NMR spectroscopy are still lacking. In this study, twenty Sprague–Dawley rats were randomly assigned into two groups: a control group (n = 10 and a ketamine group (n = 10. The animals in the ketamine group received intraperitoneal injections of ketamine twice daily at 12-h intervals at progressively increasing doses over a period of 9 days, while the control group received an equal volume of saline. The urine samples were collected for 24 h at days 0, 1, 3, 5, 7, and 9 for the metabolomics study. The metabolic changes in urine after short-term ketamine administration were analyzed by proton NMR coupled with multivariate statistical analysis. The results indicated that short-term ketamine exposure led to significant alterations of the metabolites in the urine of the rats. Specifically, 1,3,7-trimethyluric acid, 1,3-dimethyluric acid, acetoacetic acid, acetylglycine, creatine, sarcosine, dimethylglycine, glycine, and theobromine were significantly increased in the urine. Significant changes were also found in metabolites related to antioxidant and energy metabolism, including acetoacetic acid, succinate, 1,3,7-trimethyluric acid, 1,3-dimethyluric acid, creatine, and taurine. Our findings indicated that short-term ketamine administration leads to disorder of energy metabolism and oxidative stress. In addition, the modified metabolites identified could serve as the new biological markers and potential biological indices reflecting the underlying mechanism of ketamine abuse.

  2. Exchangers man the pumps

    Science.gov (United States)

    Barkla, Bronwyn J; Hirschi, Kendal D

    2008-01-01

    Tonoplast-localised proton-coupled Ca2+ transporters encoded by cation/H+ exchanger (CAX) genes play a critical role in sequestering Ca2+ into the vacuole. These transporters may function in coordination with Ca2+ release channels, to shape stimulus-induced cytosolic Ca2+ elevations. Recent analysis of Arabidopsis CAX knockout mutants, particularly cax1 and cax3, identified a variety of phenotypes including sensitivity to abiotic stresses, which indicated that these transporters might play a role in mediating the plant's stress response. A common feature of these mutants was the perturbation of H+-ATPase activity at both the tonoplast and the plasma membrane, suggesting a tight interplay between the Ca2+/H+ exchangers and H+ pumps. We speculate that indirect regulation of proton flux by the exchangers may be as important as the direct regulation of Ca2+ flux. These results suggest cautious interpretation of mutant Ca2+/H+ exchanger phenotypes that may be due to either perturbed Ca2+ or H+ transport. PMID:19841670

  3. Brain changes in long-term zen meditators using proton magnetic resonance spectroscopy and diffusion tensor imaging: a controlled study.

    Directory of Open Access Journals (Sweden)

    Nicolás Fayed

    Full Text Available INTRODUCTION: This work aimed to determine whether (1H magnetic resonance imaging (MRI, magnetic resonance spectroscopy (MRS, diffusion-weighted imaging (DWI and diffusion tensor imaging (DTI are correlated with years of meditation and psychological variables in long-term Zen meditators compared to healthy non-meditator controls. MATERIALS AND METHODS: Design. Controlled, cross-sectional study. Sample. Meditators were recruited from a Zen Buddhist monastery. The control group was recruited from hospital staff. Meditators were administered questionnaires on anxiety, depression, cognitive impairment and mindfulness. (1H-MRS (1.5 T of the brain was carried out by exploring four areas: both thalami, both hippocampi, the posterior superior parietal lobule (PSPL and posterior cingulate gyrus. Predefined areas of the brain were measured for diffusivity (ADC and fractional anisotropy (FA by MR-DTI. RESULTS: Myo-inositol (mI was increased in the posterior cingulate gyrus and Glutamate (Glu, N-acetyl-aspartate (NAA and N-acetyl-aspartate/Creatine (NAA/Cr was reduced in the left thalamus in meditators. We found a significant positive correlation between mI in the posterior cingulate and years of meditation (r = 0.518; p = .019. We also found significant negative correlations between Glu (r = -0.452; p = .045, NAA (r = -0.617; p = .003 and NAA/Cr (r = -0.448; P = .047 in the left thalamus and years of meditation. Meditators showed a lower Apparent Diffusion Coefficient (ADC in the left posterior parietal white matter than did controls, and the ADC was negatively correlated with years of meditation (r = -0.4850, p = .0066. CONCLUSIONS: The results are consistent with the view that mI, Glu and NAA are the most important altered metabolites. This study provides evidence of subtle abnormalities in neuronal function in regions of the white matter in meditators.

  4. Pumping behavior of sputter ion pumps

    International Nuclear Information System (INIS)

    Chou, T.S.; McCafferty, D.

    The ultrahigh vacuum requirements of ISABELLE is obtained by distributed pumping stations. Each pumping station consists of 1000 l/s titanium sublimation pump for active gases (N 2 , H 2 , O 2 , CO, etc.), and a 20 l/s sputter ion pump for inert gases (methane, noble gases like He, etc.). The combination of the alarming production rate of methane from titanium sublimation pumps (TSP) and the decreasing pumping speed of sputter ion pumps (SIP) in the ultrahigh vacuum region (UHV) leads us to investigate this problem. In this paper, we first describe the essential physics and chemistry of the SIP in a very clean condition, followed by a discussion of our measuring techniques. Finally measured methane, argon and helium pumping speeds are presented for three different ion pumps in the range of 10 -6 to 10 -11 Torr. The virtues of the best pump are also discussed

  5. Brain Changes in Long-Term Zen Meditators Using Proton Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: A Controlled Study

    Science.gov (United States)

    Fayed, Nicolás; Lopez del Hoyo, Yolanda; Andres, Eva; Serrano-Blanco, Antoni; Bellón, Juan; Aguilar, Keyla; Cebolla, Ausias; Garcia-Campayo, Javier

    2013-01-01

    Introduction This work aimed to determine whether 1H magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) are correlated with years of meditation and psychological variables in long-term Zen meditators compared to healthy non-meditator controls. Materials and Methods Design. Controlled, cross-sectional study. Sample. Meditators were recruited from a Zen Buddhist monastery. The control group was recruited from hospital staff. Meditators were administered questionnaires on anxiety, depression, cognitive impairment and mindfulness. 1H-MRS (1.5 T) of the brain was carried out by exploring four areas: both thalami, both hippocampi, the posterior superior parietal lobule (PSPL) and posterior cingulate gyrus. Predefined areas of the brain were measured for diffusivity (ADC) and fractional anisotropy (FA) by MR-DTI. Results Myo-inositol (mI) was increased in the posterior cingulate gyrus and Glutamate (Glu), N-acetyl-aspartate (NAA) and N-acetyl-aspartate/Creatine (NAA/Cr) was reduced in the left thalamus in meditators. We found a significant positive correlation between mI in the posterior cingulate and years of meditation (r = 0.518; p = .019). We also found significant negative correlations between Glu (r = −0.452; p = .045), NAA (r = −0.617; p = .003) and NAA/Cr (r = −0.448; P = .047) in the left thalamus and years of meditation. Meditators showed a lower Apparent Diffusion Coefficient (ADC) in the left posterior parietal white matter than did controls, and the ADC was negatively correlated with years of meditation (r = −0.4850, p = .0066). Conclusions The results are consistent with the view that mI, Glu and NAA are the most important altered metabolites. This study provides evidence of subtle abnormalities in neuronal function in regions of the white matter in meditators. PMID:23536796

  6. The long-term effect of erythropoiesis stimulating agents given to preterm infants. A proton magnetic resonance spectroscopy study on neurometabolites in early childhood

    International Nuclear Information System (INIS)

    Gasparovic, Charles; Caprihan, Arvind; Yeo, Ronald A.; Phillips, John; Lowe, Jean R.; Ohls, Robin K.; Campbell, Richard

    2018-01-01

    Erythropoiesis stimulating agents (ESAs) are neuroprotective in cell and animal models of preterm birth. Prematurity has been shown to alter neurometabolite levels in children in studies using proton magnetic resonance spectroscopy (1H-MRS). We hypothesized that ESA treatment in premature infants would tend to normalize neurometabolites by 4-6 years of age. Children in a longitudinal study of neurodevelopment underwent MRI and 1H-MRS at approximately 4 years and 6 years of age. Prematurely born children (500-1,250 g birth weight) received ESAs (erythropoietin or darbepoetin) or placebo during their neonatal hospitalization, and these groups were compared to healthy term controls. 1H-MRS spectra were obtained from the anterior cingulate (gray matter) and frontal lobe white matter, assessing combined N-acetylaspartate and N-acetylaspartylglutamate (tNAA), myo-inositol, choline compounds (Cho), combined creatine and phosphocreatine, and combined glutamate and glutamine. No significant (P≤0.5) group differences were observed for any metabolite level. Significant age-related increases in white-matter tNAA and Cho were observed, as well as a trend for increased gray-matter tNAA. Neither prematurity nor neonatal ESA treatment was associated with differences in brain metabolite levels in the children of this study at a significance level of 0.05. These findings suggest that earlier differences that might have existed had normalized by 4-6 years of age or were too small to be statistically significant in the current sample. (orig.)

  7. Long-term cerebral metabolite changes on proton magnetic resonance spectroscopy in patients cured of acute lymphoblastic leukemia with previous intrathecal methotrexate and cranial irradiation prophylaxis

    International Nuclear Information System (INIS)

    Chan Yuleung; Roebuck, Derek J.; Yuen Manpan; Yeung Kawai; Lau Kamying; Li Chikong; Chik Kiwai

    2001-01-01

    Purpose: To evaluate the long-term brain metabolite changes on 1 H-MRS in acute lymphoblastic leukemia (ALL) patients who had intrathecal methotrexate (ITMTX) and cranial irradiation (CRT) for central nervous system (CNS) prophylaxis against CNS relapse. Methods and Materials: Thirty-seven ALL patients (12 females, 25 males) with history of ITMTX and CRT for CNS prophylaxis were studied. Age ranges at the time of diagnosis and at magnetic resonance examination were 0.8-13 years and 12-27 years, respectively. The interval since diagnosis was 5.6-19 years. T2-weighted and gradient-recalled echo (GRE) magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ( 1 H-MRS) were performed to assess brain injury. Results: On MRI, 3 leukoencephalopathy (LEP) and 1 infarct were detected. Twenty-two patients had evidence of hemosiderin. On 1 H-MRS no statistically significant difference in choline (Cho)/creatine (Cr) and N-acetylaspartate (NAA)/Cr was associated with LEP. A lower Cho/Cr (p=0.006) and NAA/Cr (p=0.078) was observed in brains with hemosiderin. Linear-regression analysis showed no statistically significant relationship between NAA/Cr or Cho/Cr with age at diagnosis, but there was a statistically significant decreasing trend of NAA/Cr and Cho/Cr with the interval since diagnosis. Conclusion: Long-term brain injury in ALL survivors after CNS prophylaxis with ITMTX and CRT was reflected by decreasing NAA/Cr and Cho/Cr with the interval since diagnosis. The lower Cho/Cr associated with hemosiderin but not LEP suggested a different pathophysiology for these brain lesions

  8. [Why proton therapy? And how?

    Science.gov (United States)

    Thariat, Juliette; Habrand, Jean Louis; Lesueur, Paul; Chaikh, Abdulhamid; Kammerer, Emmanuel; Lecomte, Delphine; Batalla, Alain; Balosso, Jacques; Tessonnier, Thomas

    2018-03-01

    Proton therapy is a radiotherapy, based on the use of protons, charged subatomic particles that stop at a given depth depending on their initial energy (pristine Bragg peak), avoiding any output beam, unlike the photons used in most of the other modalities of radiotherapy. Proton therapy has been used for 60 years, but has only become ubiquitous in the last decade because of recent major advances in particle accelerator technology. This article reviews the history of clinical implementation of protons, the nature of the technological advances that now allows its expansion at a lower cost. It also addresses the technical and physical specificities of proton therapy and the clinical situations for which proton therapy may be relevant but requires evidence. Different proton therapy techniques are possible. These are explained in terms of their clinical potential by explaining the current terminology (such as cyclotrons, synchrotrons or synchrocyclotrons, using superconducting magnets, fixed line or arm rotary with passive diffusion delivery or active by scanning) in basic words. The requirements associated with proton therapy are increased due to the precision of the depth dose deposit. The learning curve of proton therapy requires that clinical indications be prioritized according to their associated uncertainties (such as range uncertainties and movement in lung tumors). Many clinical indications potentially fall under proton therapy ultimately. Clinical strategies are explained in a paralleled manuscript. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  9. The proton radius puzzle

    Science.gov (United States)

    Bonesini, Maurizio

    2017-12-01

    The FAMU (Fisica degli Atomi Muonici) experiment has the goal to measure precisely the proton Zemach radius, thus contributing to the solution of the so-called proton radius "puzzle". To this aim, it makes use of a high-intensity pulsed muon beam at RIKEN-RAL impinging on a cryogenic hydrogen target with an high-Z gas admixture and a tunable mid-IR high power laser, to measure the hyperfine (HFS) splitting of the 1S state of the muonic hydrogen. From the value of the exciting laser frequency, the energy of the HFS transition may be derived with high precision ( 10-5) and thus, via QED calculations, the Zemach radius of the proton. The experimental apparatus includes a precise fiber-SiPMT beam hodoscope and a crown of eight LaBr3 crystals and a few HPGe detectors for detection of the emitted characteristic X-rays. Preliminary runs to optimize the gas target filling and its operating conditions have been taken in 2014 and 2015-2016. The final run, with the pump laser to drive the HFS transition, is expected in 2018.

  10. Pump characteristics and applications

    CERN Document Server

    Volk, Michael

    2013-01-01

    Providing a wealth of information on pumps and pump systems, Pump Characteristics and Applications, Third Edition details how pump equipment is selected, sized, operated, maintained, and repaired. The book identifies the key components of pumps and pump accessories, introduces the basics of pump and system hydraulics as well as more advanced hydraulic topics, and details various pump types, as well as special materials on seals, motors, variable frequency drives, and other pump-related subjects. It uses example problems throughout the text, reinforcing the practical application of the formulae

  11. Geothermal heat pump

    International Nuclear Information System (INIS)

    Bruno, R.; Tinti, F.

    2009-01-01

    In recent years, for several types of buildings and users, the choice of conditioning by heat pump and low enthalpy geothermal reservoir has been increasing in the Italian market. In fact, such systems are efficient in terms of energy and consumption, they can perform, even at the same time, both functions, heating and cooling and they are environmentally friendly, because they do not produce local emissions. This article will introduce the technology and will focus on critical points of a geothermal field design, from actual practice, to future perspectives for the geo exchanger improvement. Finally, the article presents a best practice case in Bologna district, with an economic analysis showing the convenience of a geothermal heat pump. Conclusions of the real benefits of these plants can be drawn: compared to a non-negligible initial cost, the investment has a pay-back period almost always acceptable, usually less than 10 years. [it

  12. Internal pump

    International Nuclear Information System (INIS)

    Kushima, Jun; Hayashi, Youjiro; Ueda, Masayuki.

    1997-01-01

    The present invention relates to an internal pump. A water hole allowing communication between internal and external circumferences of a stretch tube is provided at the portion of the stretch tube corresponding to a position where an end face of a nozzle portion of a motor case and an end face of a diffuser are joined with each other so that hot filtered water inside a pressure container which has entered from where the end face of the nozzle portion of the motor case and the end face of the diffuser are joined with each other is combined with the purged water so that it can be sent back to the pressure container again. (author) figs

  13. A short-term rating method for heat pump heating systems; phase 5: test of the fault diagnosis systems; Kurztestmethode fuer Waermepumpenanlagen; Phase 5: Test der Fehlerdiagnosesysteme

    Energy Technology Data Exchange (ETDEWEB)

    Zogg, D.; Esfandiar, S.

    2001-07-01

    This final report for the Swiss Federal Office of Energy (SFOE) describes the testing phase of a project that developed systems for the operational monitoring and optimisation of heat pump installations along with a diagnosis system for faults. The heat pump is considered as a sub-system. The report describes two monitoring systems and a simulation model that are used to monitor the state of the heat pump both during commissioning as well as during operation. The aim is also to detect faults as early as possible during the whole of the operational life of the installation. A state-orientated approach is propagated as being cheaper than fixed service intervals or repairing after breakdown and standstill. The development of the two monitoring systems called 'HeatWatch' and 'FuzzyWatch' is described. The effort needed for the parametrisation and training of these systems is discussed. The testing of the systems on two test beds using real-life measured values for a single-family home and further simulation data is described and the results listed. The authors state that the monitoring systems can also be used for refrigeration and air-conditioning systems.

  14. Breastfeeding FAQs: Pumping

    Science.gov (United States)

    ... of pump is best? You can buy or rent a breast pump from lactation consultants, hospitals, retail ... place to do it. Many companies offer their employees pumping and nursing areas. If yours doesn't, ...

  15. Unraveling the Mechanism of a Reversible Photoactivated Molecular Proton Crane

    NARCIS (Netherlands)

    van der Loop, T.H.; Ruesink, F.; Amirjalayer, S.; Sanders, H. J.; Buma, W.J.; Woutersen, S.

    2014-01-01

    Structural dynamics of the photoactivated mol. proton crane 7-​hydroxy-​8-​(morpholinomethyl)​quinoline has been studied using femtosecond UV-​pump IR-​probe spectroscopy. Upon electronic excitation, a proton is transferred from the hydroxy to the amine group located on the rotatable morpholino side

  16. The Toolbox of Proton Spin Physics in Historical Perspective

    International Nuclear Information System (INIS)

    Haeberli, Willy

    2008-01-01

    This paper was part of the general-interest session on lecture day, and is thus addressed to a general audience. A 50-year historic overview of the development of the tools of proton spin physics is presented: nuclear scattering, ion sources for polarized protons and deuterons based on atomic beam and optical pumping methods, and polarized gas targets

  17. Rotary piston blood pumps: past developments and future potential of a unique pump type.

    Science.gov (United States)

    Wappenschmidt, Johannes; Autschbach, Rüdiger; Steinseifer, Ulrich; Schmitz-Rode, Thomas; Margreiter, Raimund; Klima, Günter; Goetzenich, Andreas

    2016-08-01

    The design of implantable blood pumps is either based on displacement pumps with membranes or rotary pumps. Both pump types have limitations to meet the clinical requirements. Rotary piston blood pumps have the potential to overcome these limitations and to merge the benefits. Compared to membrane pumps, they are smaller and with no need for wear-affected membranes and valves. Compared to rotary pumps, the blood flow is pulsatile instead of a non-physiological continuous flow. Furthermore, the risk of flow-induced blood damage and platelet activation may be reduced due to low shear stress to the blood. The past developments of rotary piston blood pumps are summarized and the main problem for long-term application is identified: insufficient seals. A new approach with seal-less drives is proposed and current research on a simplified rotary piston design is presented. Expert commentary: The development of blood pumps focuses mainly on the improvement of rotary pumps. However, medical complications indicate that inherent limitations of this pump type remain and restrict the next substantial step forward in the therapy of heart failure patients. Thus, research on different pump types is reasonable. If the development of reliable drives and bearings succeeds, rotary piston blood pumps become a promising alternative.

  18. LMFBR with booster pump in pumping loop

    International Nuclear Information System (INIS)

    Rubinstein, H.J.

    1975-01-01

    A loop coolant circulation system is described for a liquid metal fast breeder reactor (LMFBR) utilizing a low head, high specific speed booster pump in the hot leg of the coolant loop with the main pump located in the cold leg of the loop, thereby providing the advantages of operating the main pump in the hot leg with the reliability of cold leg pump operation

  19. Liquid metal pump

    Science.gov (United States)

    Pennell, William E.

    1982-01-01

    The liquid metal pump comprises floating seal rings and attachment of the pump diffuser to the pump bowl for isolating structural deflections from the pump shaft bearings. The seal rings also eliminate precision machining on large assemblies by eliminating the need for a close tolerance fit between the mounting surfaces of the pump and the seals. The liquid metal pump also comprises a shaft support structure that is isolated from the pump housing for better preservation of alignment of shaft bearings. The shaft support structure also allows for complete removal of pump internals for inspection and repair.

  20. Liquid metal pump

    International Nuclear Information System (INIS)

    Pennell, W.E.

    1982-01-01

    The liquid metal pump comprises floating seal rings and attachment of the pump diffuser to the pump bowl for isolating structural deflections from the pump shaft bearings. The seal rings also eliminate precision machining on large assemblies by eliminating the need for a close tolerance fit between the mounting surfaces of the pump and the seals. The liquid metal pump also comprises a shaft support structure that is isolated from the pump housing for better preservation of alignment of shaft bearings. The shaft support structure also allows for complete removal of pump internals for inspection and repair

  1. Heat pump technology

    CERN Document Server

    Von Cube, Hans Ludwig; Goodall, E G A

    2013-01-01

    Heat Pump Technology discusses the history, underlying concepts, usage, and advancements in the use of heat pumps. The book covers topics such as the applications and types of heat pumps; thermodynamic principles involved in heat pumps such as internal energy, enthalpy, and exergy; and natural heat sources and energy storage. Also discussed are topics such as the importance of the heat pump in the energy industry; heat pump designs and systems; the development of heat pumps over time; and examples of practical everyday uses of heat pumps. The text is recommended for those who would like to kno

  2. User friendliness, efficiency & spray quality of stirrup pumps versus hand compression pumps for indoor residual spraying.

    Science.gov (United States)

    Kumar, Vijay; Kesari, Shreekant; Chowdhury, Rajib; Kumar, Sanjiv; Sinha, Gunjan; Hussain, Saddam; Huda, M Mamun; Kroeger, Axel; Das, Pradeep

    2013-01-01

    Indoor residual spraying (IRS) is a proven tool to reduce visceral leishmaniasis vectors in endemic villages. In India IRS is being done with stirrup pumps, whereas Nepal, Bangladesh, and other countries use compression pumps. The present study was conducted with the objectives to compare the efficiency, cost and user friendliness of stirrup and compression pumps. The study was carried out in Gorigawan village of the Vaishali district in north Bihar and included a total population of 3259 inhabitants in 605 households. Spraying with 50 per cent DDT was done by two teams with 6 persons per team under the supervision of investigators over 5 days with each type of pump (10 days in total using 2 stirrup pumps and 3 compression pumps) by the same sprayers in an alternate way. The spraying technique was observed using an observation check list, the number of houses and room surfaces sprayed was recorded and an interview with sprayers on their satisfaction with the two types of pumps was conducted. On average, 65 houses were covered per day with the compression pump and 56 houses were covered with the stirrup pump. The surface area sprayed per squad per day was higher for the compression pump (4636 m²) than for the stirrup pump (4102 m²). Observation showed that it was easy to maintain the spray swath with the compression pump but very difficult with the stirrup pump. The wastage of insecticide suspension was negligible for the compression pump but high for the stirrup pump. The compression pump was found to be more user friendly due to its lower weight, easier to operate, lower operation cost, higher safety and better efficiency in terms of discharge rate and higher area coverage than the stirrup pump.

  3. Optical silencing of body wall muscles induces pumping inhibition in Caenorhabditis elegans

    OpenAIRE

    Takahashi, Megumi; Takagi, Shin

    2017-01-01

    Feeding, a vital behavior in animals, is modulated depending on internal and external factors. In the nematode Caenorhabditis elegans, the feeding organ called the pharynx ingests food by pumping driven by the pharyngeal muscles. Here we report that optical silencing of the body wall muscles, which drive the locomotory movement of worms, affects pumping. In worms expressing the Arch proton pump or the ACR2 anion channel in the body wall muscle cells, the pumping rate decreases after activatio...

  4. Proton therapy in Australia

    International Nuclear Information System (INIS)

    Jackson, M.

    2000-01-01

    Full text: Proton therapy has been in use since 1954 and over 25,000 patients have been treated worldwide. Until recently most patients were treated at physics research facilities but with the development of more compact and reliable accelerators it is now possible to realistically plan for proton therapy in an Australian hospital. The Australian National Proton Project has been formed to look at the feasibility of a facility which would be primarily for patient treatment but would also be suitable for research and commercial applications. A detailed report will be produced by the end of the year. The initial clinical experience was mainly with small tumours and other lesions close to critical organs. Large numbers of eye tumours have also been treated. Protons have a well-defined role in these situations and are now being used in the treatment of more common cancers. With the development of hospital-based facilities, over 2,500 patients with prostate cancer have been treated using a simple technique which gives results at least as good as radical surgery, external beam radiotherapy or brachytherapy. Importantly, the incidence of severe complications is very low. There are encouraging results in many disease sites including lung, liver, soft tissue sarcomas and oesophagus. As proton therapy becomes more widely available, randomised trials comparing it with conventional radiotherapy or Intensity Modulated Radiation Therapy (IMRT) will be possible. In most situations the use of protons will enable a higher dose to be given safely but in situations where local control rates are already satisfactory, protons are expected to produce less complications than conventional treatment. The initial costs of a proton facility are high but the recurrent costs are similar to other forms of high technology radiotherapy. . Simple treatment techniques with only a few fields are usually possible and proton therapy avoids the high integral doses associated with IMRT. This reduction in

  5. Short-term optimization of the new Avce pumping plant and three existing hydro power plants on the Soca river in Slovenia

    International Nuclear Information System (INIS)

    Bregar, Zvonko

    2007-01-01

    In the following years a new pumping plant Avce is going to join the existing cascade of three small-regulating-basin hydro power plants (HPPs) on the Soca river in Slovenia. The pumping plant operation will have to be synchronous to the operation of existing plants and vice versa since all four plants depend upon the same inflow and since they all belong to the same generation company that buys and sells electricity to a day-ahead electricity market. The Soca river has torrent alpine characteristics so there are doubts about the operation of the system in frequent dry seasons. As shown in this article, such questions can be effectively solved by first presenting the hydro system of four HPPs under study as a directed graph and then as a mixed integer linear program (MILP): a set of equations and inequations modeling technical issues of HPPs and a target function (the day-ahead market price) modeling the electricity market. A small and simple MILP model called Flores has been used for this study. The MILP approach requires only to specify the problem since the solution is found by using available commercial computer solvers. It can be applied on-line and it can be augmented to include also the transmission constraints, ancillary services, etc. (author)

  6. Short-term optimization of the new Avce pumping plant and three existing hydro power plants on the Soca river in Slovenia

    Energy Technology Data Exchange (ETDEWEB)

    Bregar, Zvonko [Milan Vidmar Electric Power Research Institute, Hajdrihova 2, SI-1000 Ljubljana (Slovenia)

    2007-08-15

    In the following years a new pumping plant Avce is going to join the existing cascade of three small-regulating-basin hydro power plants (HPPs) on the Soca river in Slovenia. The pumping plant operation will have to be synchronous to the operation of existing plants and vice versa since all four plants depend upon the same inflow and since they all belong to the same generation company that buys and sells electricity to a day-ahead electricity market. The Soca river has torrent alpine characteristics so there are doubts about the operation of the system in frequent dry seasons. As shown in this article, such questions can be effectively solved by first presenting the hydro system of four HPPs under study as a directed graph and then as a mixed integer linear program (MILP): a set of equations and inequations modeling technical issues of HPPs and a target function (the day-ahead market price) modeling the electricity market. A small and simple MILP model called Flores has been used for this study. The MILP approach requires only to specify the problem since the solution is found by using available commercial computer solvers. It can be applied on-line and it can be augmented to include also the transmission constraints, ancillary services, etc. (author)

  7. Polarized proton collider at RHIC

    International Nuclear Information System (INIS)

    Alekseev, I.; Allgower, C.; Bai, M.; Batygin, Y.; Bozano, L.; Brown, K.; Bunce, G.; Cameron, P.; Courant, E.; Erin, S.; Escallier, J.; Fischer, W.; Gupta, R.; Hatanaka, K.; Huang, H.; Imai, K.; Ishihara, M.; Jain, A.; Lehrach, A.; Kanavets, V.; Katayama, T.; Kawaguchi, T.; Kelly, E.; Kurita, K.; Lee, S.Y.; Luccio, A.; MacKay, W.W.; Mahler, G.; Makdisi, Y.; Mariam, F.; McGahern, W.; Morgan, G.; Muratore, J.; Okamura, M.; Peggs, S.; Pilat, F.; Ptitsin, V.; Ratner, L.; Roser, T.; Saito, N.; Satoh, H.; Shatunov, Y.; Spinka, H.; Syphers, M.; Tepikian, S.; Tominaka, T.; Tsoupas, N.; Underwood, D.; Vasiliev, A.; Wanderer, P.; Willen, E.; Wu, H.; Yokosawa, A.; Zelenski, A.N.

    2003-01-01

    In addition to heavy ion collisions (RHIC Design Manual, Brookhaven National Laboratory), RHIC will also collide intense beams of polarized protons (I. Alekseev, et al., Design Manual Polarized Proton Collider at RHIC, Brookhaven National Laboratory, 1998, reaching transverse energies where the protons scatter as beams of polarized quarks and gluons. The study of high energy polarized protons beams has been a long term part of the program at BNL with the development of polarized beams in the Booster and AGS rings for fixed target experiments. We have extended this capability to the RHIC machine. In this paper we describe the design and methods for achieving collisions of both longitudinal and transverse polarized protons in RHIC at energies up to √s=500 GeV

  8. Proton decay theory

    International Nuclear Information System (INIS)

    Marciano, W.J.

    1983-01-01

    Topics include minimal SU(5) predictions, gauge boson mediated proton decay, uncertainties in tau/sub p/, Higgs scalar effects, proton decay via Higgs scalars, supersymmetric SU(5), dimension 5 operators and proton decay, and Higgs scalars and proton decay

  9. Solar Pumping : The Basics

    OpenAIRE

    World Bank Group

    2018-01-01

    Solar photovoltaic water pumping (SWP) uses energy from solar photovoltaic (PV) panels to power an electric water pump. The entire process, from sunlight to stored energy, is elegant and simple. Over last seven years, the technology and price of solar pumping have evolved dramatically and hence the opportunities it presents. Solar pumping is most competitive in regions with high solar inso...

  10. Multiple pump housing

    Science.gov (United States)

    Donoho, II, Michael R.; Elliott; Christopher M.

    2010-03-23

    A fluid delivery system includes a first pump having a first drive assembly, a second pump having a second drive assembly, and a pump housing. At least a portion of each of the first and second pumps are located in the housing.

  11. Proton therapy

    International Nuclear Information System (INIS)

    Jongen, Y.

    1995-01-01

    Ideal radiotherapy deposits a large amount of energy in the tumour volume, and none in the surrounding healthy tissues. Proton therapy comes closer to this goal because of a greater concentration of dose, well defined proton ranges and points of energy release which are precisely known - the Bragg peak1. In the past, the development of clinical proton therapy has been hampered by complexity, size, and cost. To be clinically effective, energies of several hundred MeV are required; these were previously unavailable for hospital installations, and pioneering institutions had to work with complex, inadequate equipment originally intended for nuclear physics research. Recently a number of specialist organizations and commercial companies have been working on dedicated systems for proton therapy. One, IBA of Belgium, has equipment for inhouse hospital operation which encompasses a complete therapy centre, delivered as a turnkey package and incorporating a compact, automated, higher energy cyclotron with isocentric gantries. Their system will be installed at Massachusetts General Hospital, Boston. The proton therapy system comprises: - a 235 MeV isochronous cyclotron to deliver beams of up to 1.5 microamps, but with a hardware limitation to restrict the maximum possible dose; - variable energy beam (235 to 70 MeV ) with energy spread and emittance verification; - a beam transport and switching system to connect the exit of the energy selection system to the entrances of a number of gantries and fixed beamlines. Along the beam transport system, the beam characteristics are monitored with non-interceptive multiwire ionization chambers for automatic tuning; - gantries fitted with nozzles and beamline elements for beam control; both beam scattering and beam wobbling techniques are available for shaping the beam;

  12. Centrifugal pump handbook

    CERN Document Server

    Pumps, Sulzer

    2010-01-01

    This long-awaited new edition is the complete reference for engineers and designers working on pump design and development or using centrifugal pumps in the field. This authoritative guide has been developed with access to the technical expertise of the leading centrifugal pump developer, Sulzer Pumps. In addition to providing the most comprehensive centrifugal pump theory and design reference with detailed material on cavitation, erosion, selection of materials, rotor vibration behavior and forces acting on pumps, the handbook also covers key pumping applications topics and operational

  13. Sequential Vein Bypass Grafting is Not Associated with an Increase of Either In-hospital or Mid-term Adverse Events in Off-pump Coronary Artery Bypass Grafting

    Directory of Open Access Journals (Sweden)

    Fucheng Xiao

    2015-01-01

    Full Text Available Background: The impact of sequential vein bypass grafting on clinical outcomes is less known in off-pump coronary artery bypass grafting (CABG. We aimed to evaluate the effects of sequential vein bypass grafting on clinical outcomes in off-pump CABG. Methods: From October 2009 to September 2013 at the Fuwai Hospital, 127 patients with at least one sequential venous graft were matched with 127 patients of individual venous grafts only, using propensity score matching method to obtain risk-adjusted outcome comparison. In-hospital measurement was composite outcome of in-hospital death, myocardial infarction (MI, stroke, requirement for intra-aortic ballon pump (IABP assistance and prolonged ventilation. Major adverse cardiac events (MACEs: Death, MI or repeat revascularization and angina recurrence were considered as mid-term endpoints. Results: No significant difference was observed among the groups in baseline characteristics. Intraoperative mean blood flow per vein graft was 40.4 ml in individual venous grafts groups versus 59.5 ml in sequential venous grafts groups (P < 0.001. There were no differences between individual and sequential venous grafts groups with regard to composite outcome of in-hospital mortality, MI, stroke, IABP assistance and prolonged ventilation (11.0% vs. 14.2%, P = 0.45. Individual in-hospital measurement also did not differ significantly between the two groups. At about four years follow-up, the survival estimates free from M