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Sample records for term proton pump

  1. Proton pump inhibitors

    Science.gov (United States)

    Proton pump inhibitors (PPIs) are medicines that work by reducing the amount of stomach acid made by ... Proton pump inhibitors are used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This ...

  2. Meta-analysis : comparing the efficacy of proton pump inhibitors in short-term use

    NARCIS (Netherlands)

    Klok, RM; Postma, MJ; Van Hout, BA; Brouwers, JRBJ

    2003-01-01

    Background: Proton pump inhibitors have a prominent role in the management of acid-related diseases. Controlling expenses on proton pump inhibitors would yield great economic benefits for Dutch health care. Aim: To investigate whether clinical differences in proton pump inhibitors exist. Methods: We

  3. A Case of Severe Iron Deficiency Anemia Associated with Long-Term Proton Pump Inhibitor Use

    Directory of Open Access Journals (Sweden)

    David N. Dado, DO

    2017-01-01

    Full Text Available The use of proton pump inhibitors (PPIs in the treatment of gastrointestinal diseases has evolved over recent years. Initially intended for short-term use, PPIs are increasingly being used, often inappropriately, as long-term maintenance medications. The mechanism of action of PPIs is suppression of gastric basal and stimulated acid secretion by inhibiting the parietal cell H+/K+ ATP pump with a resultant increase in gastric pH and hypo- or achlorhydria. Although short-term use is related to few adverse effects, long-term use is associated with numerous complications. We present the case of a 58-year-old man with severe iron deficiency anemia due to malabsorption suspected to be caused by long-term PPI use. An extensive medical work up failed to reveal any definitive source of bleeding. An iron malabsorption test confirmed that iron was not being absorbed from the gastrointestinal tract. The Naranjo Adverse Drug Reaction Probability Scale and the Horn and Hansten Drug Interaction Probability Scale are suggestive of an association between long-term PPI use and the observed iron deficiency anemia. However, the patient’s death and lack of an autopsy prevented confirmatory follow-up data from being obtained to connect long-term PPI use as the culprit. Although there are currently no recommendations regarding screening for iron deficiency and/or anemia in patients on long-term PPI therapy, physicians should be aware of this potential side effect and consider monitoring in high-risk patients.

  4. Review article: long-term use of proton pump inhibitors in GORD--help or hindrance?

    NARCIS (Netherlands)

    Tytgat, G. N.

    2001-01-01

    Many patients with gastro-oesophageal reflux disease (GORD) experience chronic relapses and require maintenance therapy for symptomatic relief. This article reviews possible mechanisms for chronic relapse in GORD, and discusses the risks and benefits of proton pump inhibitors as maintenance therapy

  5. 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

  6. 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...

  7. Plant proton pumps

    DEFF Research Database (Denmark)

    Gaxiola, Roberto A.; Palmgren, Michael Gjedde; Schumacher, Karin

    2007-01-01

    to their constantly changing environments and at the same time maintain optimal metabolic conditions, the expression, activity and interplay of the pumps generating these H+ gradients have to be tightly regulated. In this review, we will highlight results on the regulation, localization and physiological roles...... of these H+- pumps, namely the plasma membrane H+-ATPase, the vacuolar H+-ATPase and the vacuolar H+-PPase. 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved....

  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. Proton pump inhibitors and gastroenteritis

    NARCIS (Netherlands)

    R.J. Hassing (Robert); A. Verbon (Annelies); H. de Visser (Herman); A. Hofman (Albert); B.H.Ch. Stricker (Bruno)

    2016-01-01

    textabstractAn 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

  10. Proton Pump Inhibitors and Gastritis

    OpenAIRE

    Suzuki, Masayuki; Suzuki, Hidekazu; Hibi, Toshifumi

    2008-01-01

    Proton pump inhibitors (PPIs) are novel compounds that strongly inhibit the H+/K+-ATPase in the gastric parietal cells to cause profound suppression of acid secretion. Acid-generating ATPase, also known as vacuolar-type ATPase, is located in the lysozomes of leukocytes and osteoclasts and its activity is also reportedly influenced by treatment with PPIs. This concept is supported by the results of studies using autoradiography in which 3H-Lansoprazole uptake sites were clearly detected in the...

  11. 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

  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. [Interaction between clopidogrel and proton pump inhibitors

    NARCIS (Netherlands)

    Harmsze, A.M.; Boer, A. de; Boot, H.; Deneer, V.H.; Heringa, M.; Mol, P.G.; Schalekamp, T.; Verduijn, M.M.; Verheugt, F.W.A.; Comte, M. le

    2011-01-01

    The drug interaction between proton pump inhibitors and clopidogrel has been the subject of much study in recent years. Contradictory results regarding the effect of proton pump inhibitors on platelet reactivity and on clinical outcome in clopidogrel-treated patients have been reported in

  14. Protons and how they are transported by proton pumps.

    Science.gov (United States)

    Buch-Pedersen, M J; Pedersen, B P; Veierskov, B; Nissen, P; Palmgren, M G

    2009-01-01

    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 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.

  15. Proton pump inhibitors and gastroenteritis.

    Science.gov (United States)

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

    2016-10-01

    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.

  16. Strategies for discontinuation of proton pump inhibitors

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  17. Long-term use of antibiotics and proton pump inhibitors predict development of infections in patients with cirrhosis.

    Science.gov (United States)

    O'Leary, Jacqueline G; Reddy, K Rajender; Wong, Florence; Kamath, Patrick S; Patton, Heather M; Biggins, Scott W; Fallon, Michael B; Garcia-Tsao, Guadalupe; Subramanian, Ram M; Malik, Raza; Thacker, Leroy R; Bajaj, Jasmohan S

    2015-04-01

    Bacterial infections, particularly repeated infections, are significant causes of morbidity and mortality among patients with cirrhosis. We investigated and characterized risk factors for repeat infections in these patients. In a prospective study, we collected data from 188 patients hospitalized with cirrhosis and infections and enrolled in the North American Consortium for the Study of End-Stage Liver Disease (12 centers). Patients were followed up for 6 months after hospital discharge and data were analyzed on type of infections and factors associated with subsequent infections. Six months after hospital discharge, 14% of subjects had received liver transplants, 27% died, and 59% were alive without liver transplantation. After discharge, 45% had subsequent infections, but only 26% of the subsequent infections occurred at the same site. Compared with patients not re-infected, patients with repeat infections were older and a higher proportion used proton pump inhibitors (PPIs) (P = .006), rifaximin (P index infection resolution. Those at highest risk include previously infected older patients receiving PPIs and/or SBP prophylaxis, although these associations do not prove that these factors cause the infections. New strategies are needed to prevent infections in patients with cirrhosis. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Long-term Use of Antibiotics and Proton-Pump Inhibitors Predict Development of Infections in Patients with Cirrhosis

    Science.gov (United States)

    O'Leary, Jacqueline G.; Reddy, K. Rajender; Wong, Florence; Kamath, Patrick S.; Patton, Heather M.; Biggins, Scott W.; Fallon, Michael B.; Garcia-Tsao, Guadalupe; Subramanian, Ram M.; Malik, Raza; Thacker, Leroy R.; Bajaj, Jasmohan S.

    2014-01-01

    Background & Aims Bacterial infections, particularly repeated infections, are significant causes of morbidity and mortality among patients with cirrhosis. We investigated and characterized risk factors for repeat infections in these patients. Methods In prospective study, we collected data from 188 patients hospitalized with cirrhosis and infections and enrolled in the North American Consortium for the Study of End-Stage Liver Disease (12 centers). Patients were followed for 6 months after hospital discharge and data were analyzed on type of infections and factors associated with subsequent infections. Results Six months after hospital discharge, 14% of subjects had received liver transplants, 27% died, and 59% were alive without liver transplantation. Following discharge, 45% had subsequent infections, but only 26% of the subsequent infections occurred at the same site. Compared to patients not re-infected, patients with repeat infections were older and a higher proportion used proton-pump inhibitors (PPIs, P=.006), rifaximin (P<.001), or prophylactic therapy for spontaneous bacterial peritonitis (SBP, P<.001). Logistic regression showed that SBP prophylaxis (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.56–7.63), PPI use (OR, 2.94; 95% CI, 1.39-6.20), SBP at hospital admission (OR, 0.37; 95% CI, 0.15–0.91), and age (OR, 1.06; 95% CI, 1.02-1.11) were independent predictors of subsequent infections. Conclusion Patients hospitalized with cirrhosis and infections are at high risk for subsequent infections, mostly at different sites, within 6 months of index infection resolution. Those at highest risk include previously infected older patients receiving PPIs and/or SBP prophylaxis, although these associations do not prove that these factors cause the infections. New strategies are needed to prevent infections in patients with cirrhosis. PMID:25130937

  19. Use of antacids, alginates and proton pump inhibitors

    DEFF Research Database (Denmark)

    Lødrup, Anders; Reimer, Christine; Bytzer, Peter

    2014-01-01

    OBJECTIVE: Both over-the-counter medicine, such as antacids or alginates, and proton pump inhibitors (PPI) are used for treating acid-related disorders. We sought to describe what characterizes users of these different medicines, including long-term PPI users within the general population. METHOD...

  20. 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

  1. [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.

  2. 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.

  3. Proton Pump Inhibitor Use and the Antifracture Efficacy of Alendronate

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Eiken, Pia Agnete; Eastell, Richard

    2011-01-01

    BACKGROUND: Proton pump inhibitors (PPIs) are widely used in elderly patients and are frequently coadministered in users of oral bisphosphonates. Biologically, PPIs could affect the absorption of calcium, vitamin B(12), and bisphosphonates and could affect the osteoclast proton pump, thus...

  4. Proton pump inhibitors and symptomatic hypomagnesemic hypoparathyroidism.

    Science.gov (United States)

    Fatuzzo, P; Portale, G; Scollo, V; Zanoli, L; Granata, Antonio

    2017-04-01

    Hypomagnesemia is a common but often overlooked problem in hospitalized patients. Unrecognized hypomagnesemia can cause serious complications. The association of hypokalemia and hypocalcemia is strongly evocative of a magnesium deficiency. Research into the causes of hypomagnesemia is imperative, as it will definitely change the approach, treatment and prognosis. We report the case of a 65-year-old man with chronic hypocalcemia and hypokalemia associated with cerebellar syndrome, a solitary seizure and cerebellar hyperintensities on magnetic resonance imaging. After the detection and treatment of hypomagnesemia with oral supplements of magnesium and the replacement of pantoprazole with ranitidine, we observed immediate relief of the symptoms. In conclusion, in clinical practice, magnesium depletion should be investigated in elderly patients with hypocalcemia treated with proton pump inhibitors for many years, in particular in the presence of neurological disorders.

  5. The safety of proton pump inhibitors in pregnancy

    DEFF Research Database (Denmark)

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

    1999-01-01

    on The Pharmaco-Epidemiological Prescription Database of North Jutland and the Danish Hospital Discharge Registry. RESULTS: Three babies with malformations were found among 38 women exposed to proton pump inhibitors from 30 days before conception to the end of the first trimester. No cases of stillbirth were...... 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....

  6. 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.

  7. 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.

  8. Proton pump inhibitors affect the gut microbiome.

    Science.gov (United States)

    Imhann, Floris; Bonder, Marc Jan; Vich Vila, Arnau; Fu, Jingyuan; Mujagic, Zlatan; Vork, Lisa; Tigchelaar, Ettje F; 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

    2016-05-01

    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 promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome. The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis. 211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon's diversity and with changes in 20% of the bacterial taxa (false discovery rate microbiome of PPI-users, including the genus Rothia (p=9.8×10(-38)). In PPI users we observed a significant increase in bacteria: genera Enterococcus, Streptococcus, Staphylococcus and the potentially pathogenic species Escherichia coli. The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs. 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/

  9. Exploring the proton pump and exit pathway for pumped protons in cytochrome ba3 from Thermus thermophilus.

    Science.gov (United States)

    Chang, Hsin-Yang; Choi, Sylvia K; Vakkasoglu, Ahmet Selim; Chen, Ying; Hemp, James; Fee, James A; Gennis, Robert B

    2012-04-03

    The heme-copper oxygen reductases are redox-driven proton pumps. In the current work, the effects of mutations in a proposed exit pathway for pumped protons are examined in the ba(3)-type oxygen reductase from Thermus thermophilus, leading from the propionates of heme a(3) to the interface between subunits I and II. Recent studies have proposed important roles for His376 and Asp372, both of which are hydrogen-bonded to propionate-A of heme a(3), and for Glu126(II) (subunit II), which is hydrogen-bonded to His376. Based on the current results, His376, Glu126(II), and Asp372 are not essential for either oxidase activity or proton pumping. In addition, Tyr133, which is hydrogen-bonded to propionate-D of heme a(3), was also shown not to be essential for function. However, two mutations of the residues hydrogen-bonded to propionate-A, Asp372Ile and His376Asn, retain high electron transfer activity and normal spectral features but, in different preparations, either do not pump protons or exhibit substantially diminished proton pumping. It is concluded that either propionate-A of heme a(3) or possibly the cluster of groups centered about the conserved water molecule that hydrogen-bonds to both propionates-A and -D of heme a(3) is a good candidate to be the proton loading site.

  10. A case of gastric polyposis in antral area of stomach following prolonged proton-pump therapy

    Directory of Open Access Journals (Sweden)

    Alqutub, Adel Nazmi

    2010-01-01

    Full Text Available We describe the clinical scenario of a young male with history of non ulcer dyspepsia who had endoscopic evidence of gastric polyposis in antral area. The polyps disappeared four months after proton pump inhibitors were stopped. Proton pump inhibitors have been linked to gastric fundal polyposis and not antral gland polyposis. This is the first report originating from an Asian country describing antral gland polyposis (AGPs in a patient on long-term PPI therapy with no evidence of Helicobacter pylori. A case report with brief review is presented.

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

    LENUS (Irish Health Repository)

    Cahir, Caitriona

    2012-01-01

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

  12. 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 ...

  13. 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

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

    African Journals Online (AJOL)

    Purpose: To evaluate the current prescription pattern and appropriateness of proton pump inhibitors (PPIs) in two of the largest tertiary hospitals in Jordan, and also to determine their utilization rate among the admitted patients. Methods: A retrospective cross-sectional study was conducted over 10 months ...

  15. Use of proton-pump inhibitors among adults

    DEFF Research Database (Denmark)

    Pottegård, Anton; Broe, Anne; Hallas, Jesper

    2016-01-01

    BACKGROUND: The use of proton-pump inhibitors (PPIs) has increased over the last decade. The objective of this study was to provide detailed utilization data on PPI use over time, with special emphasis on duration of PPI use and concomitant use of ulcerogenic drugs. METHODS: Using the nationwide...

  16. 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

    -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...... the functional unit of ATP-coupled proton transport across the plasma membrane, and the structure is locked in a functional state not previously observed in P-type ATPases. The transmembrane domain reveals a large cavity, which is likely to be filled with water, located near the middle of the membrane plane...

  17. 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...

  18. 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 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...... 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...

  19. 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

  20. 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

  1. [Mechanisms of proton pumping in bacteriorhodopsin]. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Ebrey, T.G.

    1995-12-31

    This report consists of two parts namely a brief statement of the progress made during the past four years of the project and more extensive discussion of the current state of understanding of molecular mechanisms controlling the proton pump (bacteriorhodopsin). Detailed descriptions are provided of how the protein undergoes conformational changes on absorbing a photon. Studies are described where the protein structure has been manipulated and the biochemical properties are assessed.

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

    NARCIS (Netherlands)

    Hess, M.W.; Baaij, J.H.F. de; Gommers, L.M.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2015-01-01

    BACKGROUND: 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

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

    Directory of Open Access Journals (Sweden)

    Cahir Caitriona

    2012-11-01

    Full Text Available Abstract Background 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. Methods Retrospective population-based cohort study in the Republic of Ireland using the Health Services Executive (HSE Primary Care Reimbursement Services (PCRS pharmacy claims database. The HSE-PCRS scheme is means tested and provides free health care including medications to approximately 30% of the Irish population. Prescription items are WHO ATC coded and details of every drug dispensed and claimants’ demographic data are available. Potential cost savings (net ingredient cost were estimated according to UK NICE clinical guidelines for all HSE-PCRS claimants on PPI therapy for ≥3 consecutive months starting in 2007 with a one year follow up (n=167,747. Five scenarios were evaluated; (i change to PPI initiation (cheapest brand; and after 3 months (ii therapeutic switching (cheaper brand/generic equivalent; (iii dose reduction (maintenance therapy; (iv therapeutic switching and dose reduction and (v therapeutic substitution (H2 antagonist. Results Total net ingredient cost was €88,153,174 for claimants on PPI therapy during 2007. The estimated costing savings for each of the five scenarios in a one year period were: (i €36,943,348 (42% reduction; (ii €29,568,475 (34%; (iii €21,289,322 (24%; (iv €40,505,013 (46%; (v €34,991,569 (40%. Conclusion There are opportunities for substantial cost savings in relation to PPI prescribing if implementation of clinical guidelines in terms of generic substitution and step-down therapy is implemented on a national basis.

  4. 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...

  5. Effects of proton pump inhibitors on pediatric inflammatory esophagogastric polyps.

    Science.gov (United States)

    Choi, Kyong Eun; Kim, Mi Jin; Lee, Ji Hyuk; Lee, Jong Seung; Lee, Jee Hyun; Choe, Yon Ho

    2012-01-01

    The aim of this study was to investigate the effects of proton pump inhibitors on symptomatic inflammatory esophagogastric polyps (IEPs) in a pediatric cohort and to determine the optimal duration of treatment. The 11 patients with IEPs were managed with lansoprazole. Follow-up endoscopies were performed at 2 and 6 months after the start of medication. Medication was discontinued when the clinical symptoms completely resolved and the polyp size was reduced by more than 50% compared to the initial size. The initial polyp size was 13.7 ± 3.3 mm. After 2 months of medication, the polyp size was reduced to 8.0 ± 5.8 mm. At 6 months, the polyp size was 4.7 ± 2.2 mm. The mean duration of medication was 4.8 ± 2.1 months. The duration of medication and the change in the polyp size appeared to have a linear correlation (p polyp size, the optimal duration of treatment was more than 7 months for complete resolution of the polyps. Proton pump inhibitor was effective for the treatment of IEPs. About 5 months of lansoprazole was adequate to treat IEPs in children. The optimal duration for complete resolution of the polyp might be more than 7 months. Copyright © 2012 S. Karger AG, Basel.

  6. 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.

  7. Use of Proton Pump Inhibitors and Risks of Fundic Gland Polyps and Gastric Cancer : Systematic Review and Meta-analysis

    NARCIS (Netherlands)

    Tran-Duy, An; Spaetgens, Bart; Hoes, Arno W|info:eu-repo/dai/nl/101111762; de Wit, Niek J|info:eu-repo/dai/nl/100525393; Stehouwer, Coen D A

    2016-01-01

    BACKGROUND & AIMS: There have been increasing numbers of case reports and observational studies of adverse events in patients receiving long-term therapy with proton pump inhibitors (PPIs). The effects of PPI therapy on risks of fundic gland polyps (FGPs) and gastric cancer have received

  8. Acute interstitial nephritis due to proton pump inhibitors

    Directory of Open Access Journals (Sweden)

    K Sampathkumar

    2013-01-01

    Full Text Available Proton pump inhibitors (PPI are commonly prescribed for dyspepsia and acid peptic disease. Acute interstitial nephritis (AIN is an uncommon though important side-effect of these classes of drugs. We describe four cases: three females and one male. PPIs implicated were pantoprazole in two, omeprazole and esomeprazole in one each. AIN developed after an average period of 4 weeks of drug therapy. The symptoms were vomiting, loin pain, and oliguria. Minimal proteinuria with pyuria were seen and the mean serum creatinine was 4.95 ± 4 mg/dl. Two patients required hemodialysis. Renal biopsy showed interstitial mononuclear, plasma cell and eosinophilic infiltrates in all cases. PPI was stopped and steroids were started in all. Renal recovery was total in two and partial in two. A high index of suspicion is required to diagnose PPI induced AIN. Renal biopsy for confirmation followed up by prompt steroid therapy results in renal functional improvement.

  9. 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.

  10. 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...... Danish health registries. Case-patients (n=721) were defined as patients ≥45 years notified with listeriosis, July 1994 to December 2012. We selected 34,800 control-subjects by risk-set sampling. Controls were individually matched for age, sex, municipality and time. Person data on use of PPI and other...... conditional logistic regression, matched odds ratios (ORs) adjusted for CMI and confounders were estimated. RESULTS: The adjusted OR with current use of PPIs for development of listeriosis was 2.81 (95% confidence interval [CI], 2.14-3.69). PPI usage up to 90 days before the index date remained statistically...

  11. 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.

  12. Correlation between proton pump inhibitors and risk of pyogenic liver abscess.

    Science.gov (United States)

    Lin, Hsien-Feng; Liao, Kuan-Fu; Chang, Ching-Mei; Lin, Cheng-Li; Lai, Shih-Wei

    2017-08-01

    Little is known about the relationship between proton pump inhibitors use and pyogenic liver abscess. The objective of this study was to evaluate the correlation between proton pump inhibitors use and pyogenic liver abscess in Taiwan. This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. Subjects aged 20 to 84 who experienced their first episode of pyogenic liver abscess were enrolled as the case group (n = 1372). Randomly selected subjects aged 20 to 84 without pyogenic liver abscess were enrolled as the control group (n = 1372). Current use, early use, and late use of proton pump inhibitors was defined as subjects whose last one tablet for proton pump inhibitors was noted ≤30 days, between 31 to 90 days and ≥91 days before the date of admission for pyogenic liver abscess. Subjects who never received a prescription for proton pump inhibitors were defined as nonusers of proton pump inhibitors. A multivariable unconditional logistic regression model was used to measure the odds ratio and 95% confidence interval to evaluate the correlation between proton pump inhibitors use and pyogenic liver abscess. After adjusting for confounders, the adjusted odds ratio of pyogenic liver abscess was 7.59 for subjects with current use of proton pump inhibitors (95% confidence interval 5.05, 11.4), when compared with nonusers. Current use of proton pump inhibitors is associated with a greater risk of pyogenic liver abscess.

  13. 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.

  14. 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.

  15. Proton pump inhibitors and risk for Clostridium difficile associated diarrhea.

    Science.gov (United States)

    Biswal, Sasmita

    2014-01-01

    Increased incidence of Clostridium difficile infection (CDI) among in-patients is associated with significant increased mortality, morbidity, and stay in the hospitals. This has occurred despite heightened awareness of the risks of broad-spectrum antibiotics, overall reduction in antibiotic use and increased focus on hospital hygiene. So though the main risk factor for CDI is use of broad-spectrum antibiotics, the use of proton pump inhibitors (PPIs) as a novel potential contributor has been implicated, because of their ability to substantially reduce gastric acid secretion which is an important host defense mechanism in suppressing the ingested C. difficile or its spores. Antibiotic disruption of the normal intestinal flora and reduced gastric acidity have been suggested as the risk factors for C. difficile-associated diarrhea (CDAD). Based on such assumptions the use of PPIs may be associated with an increased risk of CDAD. While a definite association between PPI use and CDAD has not yet been confirmed, the possibility and such an association however cannot be ruled out at present. Thus among the identified risk factors, the use of PPI is important, previously unrecognized and modifiable risk factors whose use should be carefully evaluated among hospital in-patients receiving antibiotics, especially in those with a diagnosis of C. difficile diarrhea.

  16. 1-Arylsulfonyl-2-(Pyridylmethylsulfinyl Benzimidazoles as New Proton Pump Inhibitor Prodrugs

    Directory of Open Access Journals (Sweden)

    Young-moon Cho

    2009-12-01

    Full Text Available 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.

  17. 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.

  18. 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.

  19. Comparison of proton pump inhibitor and histamine-2 receptor antagonist in the prevention of recurrent peptic ulcers/erosions in long-term low-dose aspirin users: a retrospective cohort study.

    Science.gov (United States)

    Chen, Wen-Chi; Li, Yun-Da; Chiang, Po-Hung; Tsay, Feng-Woei; Chan, Hoi-Hung; Tsai, Wei-Lun; Tsai, Tzung-Jiun; Wang, E-Ming; Cheng, Jin-Shiung; Lai, Kwok-Hung

    2014-01-01

    Proton pump inhibitor and histamine-2 receptor antagonist can prevent aspirin-related ulcers/erosions but few studies compare the efficacy of these two agents. Aims. We evaluated the efficacy of omeprazole and famotidine in preventing recurrent ulcers/erosions in low-dose aspirin users. The 24-week clinical outcomes of the patients using low-dose aspirin for cardiovascular protection with a history of ulcers/erosions and cotherapy of omeprazole or famotidine were retrospectively reviewed. The incidence of gastrointestinal symptoms, recurrent ulcers/erosions, erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was analyzed. A total of 104 patients (famotidine group, 49 patients; omeprazole group, 55 patients) were evaluated. Famotidine group had more gastrointestinal symptoms episodes than omeprazole group (46.9% versus 23.6%, P=0.01). Fifteen famotidine group patients and 5 omeprazole group patients had recurrent ulcers/erosions (30.6% versus 9.1%, P=0.005). Lanza scale was significantly lower in omeprazole group than in famotidine group (1.2±0.7 versus 1.7±1.1, P=0.008). Only 1 famotidine group patient had ulcer bleeding. The incidences of erosive esophagitis and thromboembolic events were comparable between both groups. Omeprazole was superior to famotidine with less gastrointestinal symptoms and recurrent ulcers/erosions in patients using 24-week low-dose aspirin. The risk of erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was similar between both groups.

  20. Allosteric interactions and proton conducting pathways in proton pumping aa(3) oxidases: heme a as a key coupling element.

    Science.gov (United States)

    Capitanio, Nazzareno; Palese, Luigi Leonardo; Capitanio, Giuseppe; Martino, Pietro Luca; Richter, Oliver-Matthias H; Ludwig, Bernd; Papa, Sergio

    2012-04-01

    In this paper allosteric interactions in protonmotive heme aa(3) terminal oxidases of the respiratory chain are dealt with. The different lines of evidence supporting the key role of H(+)/e(-) coupling (redox Bohr effect) at the low spin heme a in the proton pump of the bovine oxidase are summarized. Results are presented showing that the I-R54M mutation in P. denitrificans aa(3) oxidase, which decreases by more than 200mV the E(m) of heme a, inhibits proton pumping. Mutational amino acid replacement in proton channels, at the negative (N) side of membrane-inserted prokaryotic aa(3) oxidases, as well as Zn(2+) binding at this site in the bovine oxidase, uncouples proton pumping. This effect appears to result from alteration of the structural/functional device, closer to the positive, opposite (P) surface, which separates pumped protons from those consumed in the reduction of O(2) to 2 H(2)O. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. 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/

  2. Influence of Proton Pump Inhibitor Use in Gastrointestinal Polyps

    Directory of Open Access Journals (Sweden)

    Wen-Hung Hsu

    2010-02-01

    Full Text Available Proton pump inhibitors (PPIs are the most potent anti-acid agents and are extensively used worldwide. PPI-induced hypergastrinemia is one of the very few side effects associated with these drugs. However, because hypergastrinemia is related to the occurrence of colonic adenomatous polyps, the purpose of this study was to analyze the relationship between the occurrence of gastrointestinal polyps and hypergastrinemia induced by PPIs. This study included 259 patients who underwent colonoscopy and esophagogastroduodenoscopy between January and August 2007. Chart records, including medication history and fasting plasma gastrin level, were reviewed and analyzed. Any subtle polypoid lesions in the stomach and colon were sampled by biopsy for histological examination. Helicobacter pylori infection status was examined by a rapid urea test during esophagogastroduodenoscopy. All patients underwent endoscopy examinations. A total of 122 patients were receiving PPI treatment for either peptic ulcer disease or reflux esophagitis and were included as the study group. The remaining 137 patients were not treated with PPIs and served as the non-PPI group. The mean fasting gastrin level in PPI users versus non-PPI users was 121.8 ng/L versus 56.8 ng/L, respectively (p < 0.001. Although the prevalence of gastric gland polyps was higher in the PPI group (65.6% vs. 37.2%, p < 0.001, there was no difference in the prevalence of colonic adenomatous polyps observed (22.13% vs. 22.62%, p = 0.928. In conclusion, the prevalence of gastric polyps, particularly fundic gland polyps, was higher among PPI users. However, the prevalence of colonic polyps was not affected by PPI use, regardless of past history of colonic adenomatous polyps.

  3. General pharmacology of IY-81149, a new proton pump inhibitor.

    Science.gov (United States)

    Kim, E J; Lee, R K; Lee, S M; Kim, D Y

    2001-01-01

    IY-81149 (2-[(4-methoxy-3-methyl)-2-pyridinyl]methylsulfinyl -5-(1H-pyrrol-1-yl)-1H-benzimidazole, CAS 172152-36-2) is a new proton pump inhibitor and expected to be an antiulcer drug. Its general pharmacological effects were studied in this paper. The doses given were vehicle control, 0.3, 1, 3, 100, 300 and 1000 mg/kg and were administered orally. The animals used in this study were mouse, rat, guinea pig and beagle dog. IY-81149 decreased spontaneous locomotor activity at 1000 mg/kg and showed a weak effect in motor performance at 300 and 1000 mg/kg. IY-81149 prolonged the hexobarbital-induced sleeping time dose dependently at 100, 300 and 1000 mg/kg. Oral administration of IY-81149 caused a dose-dependent hypothermic effect up to 300 mg/kg and showed analgesic effect at 1000 mg/kg. IY-81149 produced an antisecretory effect in pylorus ligated rats. The total gastric volume and acidity were significantly decreased at doses ranging from 1 to 3 mg/kg. However, IY-81149 had no effects on general behavior, did not show anticonvulsant activity, and did not affect blood pressure and heart rate, LVP (left ventricular peak systolic pressure), LVEDP (left ventricular end diastolic pressure), LVDP (left ventricular developing pressure), DP (double product), HR (heart rate), CFR (coronary flow rate), smooth muscle contraction, respiration, intestinal transport and renal function. These findings demonstrate that IY-81149 possesses weak central nervous system action and inhibitory effects on microsomal enzymes and gastric secretion after single administration. The results suggest that IY-81149 does not exert any notable pharmacological effects on the cardiovascular system, autonomic nerve system or smooth muscle function at all doses tested.

  4. 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.

  5. Proton-pumping mechanism of cytochrome c oxidase: A kinetic master-equation approach

    Science.gov (United States)

    Kim, Young C.; Hummer, Gerhard

    2011-01-01

    Cytochrome c oxidase (CcO) is an efficient energy transducer that reduces oxygen to water and converts the released chemical energy into an electrochemical membrane potential. As a true proton pump, CcO translocates protons across the membrane against this potential. Based on a wealth of experiments and calculations, an increasingly detailed picture of the reaction intermediates in the redox cycle has emerged. However, the fundamental mechanism of proton pumping coupled to redox chemistry remains largely unresolved. Here we examine and extend a kinetic master-equation approach to gain insight into redox-coupled proton pumping in CcO. Basic principles of the CcO proton pump emerge from an analysis of the simplest kinetic models that retain essential elements of the experimentally determined structure, energetics, and kinetics, and that satisfy fundamental physical principles. The master-equation models allow us to address the question of how pumping can be achieved in a system in which all reaction steps are reversible. Whereas proton pumping does not require the direct modulation of microscopic reaction barriers, such kinetic gating greatly increases the pumping efficiency. Further efficiency gains can be achieved by partially decoupling the proton uptake pathway from the ative-site region. Such a mechanism is consistent with the proposed Glu valve, in which the side chain of a key glutamic acid shuttles between the D channel and the active-site region. We also show that the models predict only small proton leaks even in the absence of turnover. The design principles identified here for CcO provide a blueprint for novel biology-inspired fuel cells, and the master-equation formulation should prove useful also for other molecular machines. PMID:21946020

  6. 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...... 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...

  7. Comparison of Proton Pump Inhibitor and Histamine-2 Receptor Antagonist in the Prevention of Recurrent Peptic Ulcers/Erosions in Long-Term Low-Dose Aspirin Users: A Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Wen-Chi Chen

    2014-01-01

    Full Text Available Background. Proton pump inhibitor and histamine-2 receptor antagonist can prevent aspirin-related ulcers/erosions but few studies compare the efficacy of these two agents. Aims. We evaluated the efficacy of omeprazole and famotidine in preventing recurrent ulcers/erosions in low-dose aspirin users. Methods. The 24-week clinical outcomes of the patients using low-dose aspirin for cardiovascular protection with a history of ulcers/erosions and cotherapy of omeprazole or famotidine were retrospectively reviewed. The incidence of gastrointestinal symptoms, recurrent ulcers/erosions, erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was analyzed. Results. A total of 104 patients (famotidine group, 49 patients; omeprazole group, 55 patients were evaluated. Famotidine group had more gastrointestinal symptoms episodes than omeprazole group (46.9% versus 23.6%, P=0.01. Fifteen famotidine group patients and 5 omeprazole group patients had recurrent ulcers/erosions (30.6% versus 9.1%, P=0.005. Lanza scale was significantly lower in omeprazole group than in famotidine group (1.2±0.7 versus 1.7±1.1, P=0.008. Only 1 famotidine group patient had ulcer bleeding. The incidences of erosive esophagitis and thromboembolic events were comparable between both groups. Conclusions. Omeprazole was superior to famotidine with less gastrointestinal symptoms and recurrent ulcers/erosions in patients using 24-week low-dose aspirin. The risk of erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was similar between both groups.

  8. ENDOSCOPIC AND HISTOPATHOLOGIC GASTRIC CHANGES IN CHRONIC USERS OF PROTON-PUMP INHIBITORS

    Directory of Open Access Journals (Sweden)

    Sílvia Maria Perrone CAMILO

    2015-03-01

    Full Text Available Background Proton-pump inhibitors have been used for at least two decades. They are among the most commonly sold drugs in the world. However, some controversy remains about the indications for their use and the consequences of their prolonged use. Objectives To evaluate and compare the endoscopic and histopathologic gastric changes in chronic users of proton-pump inhibitors to changes in non-users. Methods A prospective study performed at a tertiary Public Hospital involving 105 patients undergoing upper-gastrointestinal endoscopy. Subjects included 81 proton-pump inhibitor users and 24 non-users (control group. Biopsies of the antral-type mucosa, the antral-fundic transition, and the fundus were evaluated by the Sydney System. The presence of erosion or ulceration, lymphatic follicles, reactive gastropathy, and polypoid or epithelial hyperplasia was also determined. Serum levels of gastrin were measured. Results We found two polyps, one in each group, both of which were negative for Helicobacter pylori. There were two cases of parietal cell hyperplasia in users of proton-pump inhibitors. Gastrin was elevated in 28 users of proton-pump inhibitors and in four members of the control group. We did not find statistically significant differences in the endoscopic or histopathologic findings between the two groups. Conclusions Chronic use of proton-pump inhibitors for the duration examined was not associated with significant gastric changes. An interesting finding was that the 4 chronic users of proton-pump inhibitors who had serum gastrin levels above 500 pg/mL also had positive serology for Chagas disease.

  9. 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.

  10. Use of proton pump inhibitors and risk of fragility hip fracture in a Mediterranean region.

    Science.gov (United States)

    Reyes, Carlen; Formiga, Francesc; Coderch, Marta; Hoyo, Jordi; Ferriz, Gemma; Casanovas, Jordi; Monteserín, Rosa; Brotons, Carlos; Rojas, Marta; Moral, Irene

    2013-02-01

    To determine whether there is an increased risk of hip fracture associated with the use of proton pump inhibitors in a Mediterranean area after adjusting for other potential risk factors. Retrospective multicenter case-control study carried out in 6 primary health care centers in Catalonia, Spain. Cases were patients aged 50years and over with a fragility hip fracture registered between January 2007 and December 2010, matched with 2 controls by sex and age. use of proton pump inhibitors (type, dosage) in the 5years previous to the hip fracture, socio-demographic data, body mass index, alcohol and tobacco consumption as well as health conditions and drugs associated with an increase risk of fragility hip fracture. 358 cases were matched with 698 controls. The mean age was 82years old in both groups. Women represented 77.1% in the case group and 76.9% in the control group. Crude association between proton pump inhibitors and hip fracture was 1.44 (95% CI, 1.09-1.89) and adjusted OR was 1.24 (95% CI, 0.93-1.65). No association was found with the continuous or discontinuous use of proton pump inhibitors, OR 1.17 (95% CI, 0.77-1.79), and OR of 1.16 (95% CI, 0.85-1.60) respectively. No association was found when restricting the analysis by sex, OR of 1.19 (95% CI, 0.27-5.14) or by age, younger or older than 80years, OR of 0.72 (95% CI, 0.24-2.15). The use of proton pump inhibitors was not associated with an increased risk of hip fracture after adjusting for other risk factors in a Mediterranean area. This result suggests the existence of protective environmental factors linked to this southern area of Europe that eventually could compensate for the potential harm produced by proton pump inhibitors. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. 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.

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

    Science.gov (United States)

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

    2012-10-01

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

  13. 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

  14. 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 te...

  15. EFFECT OF PANTOPRAZOL A PROTON PUMP INHIBITOR ON SMALL INTESTINAL PANETH CELLS

    Directory of Open Access Journals (Sweden)

    Orhan ÖZATİK

    2012-08-01

    Full Text Available In previous studies of proton pump inhibitors may have effects on systems other than the stomach has not been investigated sufficiently. Especially in patients treated in intensive care conditions and the resulting use of the mucosal immune system may be very important complication of a defect or failure might be the result does not have any work was done. Therefore, in our study, the mucosal immune system, which is one of the components of the cells on primarily paneth, proton pump inhibitors was to investigate the possible effects. For this purpose, 42 Wistar Albino rats, separatedinto six different groups. In addition, each H2 receptor blocker and proton pump inhibitor groups, with antibiotics given; the existence of bacteria in the environment and between paneth cells releaseantimicrobial agent relationship has been planned to be exposed. As a result of the histological examination with light microscope, pantoprazol to be effective on the small bowel paneth cells andthus a component of the mucosal immune system, antibiotic peptides that block degranulation was found. This effect, the close enteroendocrine cells, mast cells and leukocytes of lamina propria ofileum also directly or indirectly affect.Our findings generally common knowledge, pantoprazol outside gastric parietal cell proton pump containing cells was also thought to influence. In conclusion our study results show that paneth cellsecretion activities in both groups were not needed are corroborative with the fact that mucosal immunity potential can only be induced by microbial environment.

  16. Clinical effects of proton pump inhibitors: Focus on pharmacogenetics, kinetics and dynamics

    NARCIS (Netherlands)

    N.G.M. Hunfeld (Nicole)

    2010-01-01

    textabstractThis thesis describes the clinical effects of proton pump inhibitors, with focus on pharmacogenetics, kinetics and dynamics. The aims were to investigate the occurence of Rebound Acid Hypersecretion and to investigate the speed of onset, the duration of effect and the difference in

  17. Proton pump inhibitors do not increase the risk of acute rejection

    NARCIS (Netherlands)

    Boekel, G.A.J van; Kerkhofs, C.H.; Logt, F. van de; Hilbrands, L.B.

    2014-01-01

    Background: Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid (MPA). Proton pump inhibitors impair exposure to MPA due to incomplete conversion from MMF. Lower exposure to MPA could result in an increased risk of acute rejection. We investigated whether MMF-treated renal transplant

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

    DEFF Research Database (Denmark)

    Wod, Mette; Hallas, Jesper; Andersen, Kjeld

    2018-01-01

    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 ...

  19. [Immediate type reactions to proton pump inhibitors using pantoprazole and omeprazole as examples].

    Science.gov (United States)

    Dohr, J; Hunzelmann, N; Brown, A

    2018-02-01

    Proton pump inhibitors (PPIs) belong to the most frequently taken drugs worldwide. Hypersensitivity to these medications is rare, but can lead to severe immediate type reactions. Especially cross-reactivity between the different PPIs can occur. In this case series, we describe 4 patients with immediate type reactions to pantoprazole and/or omeprazole.

  20. 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

  1. 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.

  2. 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.

  3. Proton Pump Inhibitors and Risk of Drug Interactions

    Directory of Open Access Journals (Sweden)

    S.M. Tkach

    2015-04-01

    Full Text Available In the article, the current data regarding drug interactions of proton pomp inhibitors (PPI with other preparations are discussed. It is concluded that the risk of adverse drug interactions is enhanced by the use of PPIs and drugs primarily metabolized by cytochrome isoenzyme CYP2C19. If the simultaneous application of IPP with many other drugs, including clopidogrel, is necessary, the preference should be given to pantoprazole.

  4. Proton pump-driven cutaneous chloride uptake in anuran amphibia

    DEFF Research Database (Denmark)

    Jensen, Lars Jørn; Willumsen, Niels J.; Amstrup, Jan

    2003-01-01

    is saturating, voltage independent, and sensitive to DIDS and carbonic-anhydrase inhibitors. Depending on anuran species and probably on acid/base balance of the animal, apical exit of protons is coupled to an exchange of Cl(-) with base (HCO(3)(-)) either in the apical membrane (gamma-type of MR cell....... Several studies have indicated that the transport modes of MR cells are regulated via ion- and acid/base balance of the animal, but the signalling mechanisms have not been investigated. Estimates of energy consumption by the H(+)-ATPase and the Na(+)/K(+)-ATPase indicate that the gamma-cell accomplishes...... estimated by pH-stat titration and mathematical modelling of pH-profiles in the unstirred layer on the external side of the epithelium. H(+) secretion is voltage-dependent, sensitive to carbonic-anhydrase inhibitors, and rheogenic with a charge/ion-flux ratio of unity. Cl(-) uptake from freshwater...

  5. Short term pumped storage scheduling using two proposed techniques

    OpenAIRE

    M.M. Salama, M.M. Elgazar, S.M. Abdelmaksoud, H.A. Henry

    2014-01-01

    In this paper, a genetic algorithm and constriction factor based particle swarm optimization technique are proposed for solving the short term pumped storage hydro thermal scheduling problem. The performance efficiency of the proposed techniques is demonstrated on hydrothermal test system comprising of five thermal units and one pumped storage power plant. A wide rang of thermal and hydraulic constraints are taken into consideration such as real power balance constraint, minimum and maximum l...

  6. 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.

  7. Effect of Proton Pump Inhibitors in Bronchiectatic Patients with Gastroesophageal Reflux Disease.

    Science.gov (United States)

    Ahn, Byungkyu; Lee, Dong Ho; Lee, Chang Min; Hwang, Jae Jin; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung

    2016-07-25

    Bronchiectasis is aggravated by gastroesophageal reflux disease (GERD) owing to micro aspiration. Some researchers note the effect of antireflux surgery in bronchiectasis with GERD. However, few have investigated the effects of medical antireflux therapy. We investigated the effect of proton pump inhibitors (PPIs) in bronchiectasis with GERD. From March 2003 to May 2015, the clinical records of patients who had bronchiectasis with GERD were reviewed. Patients underwent an initial pulmonary function test (PFT) and chest computed tomography when diagnosed with bronchiectasis. One group with typical GERD symptoms was treated with PPIs, while the other group was not. Both groups underwent PFTs within six months after completing PPI therapy. Population characteristics and associations were compared between the groups. Two hundred and fifty-seven patients (124 male, 133 female; mean age 67.6±10.0 years) were included. There were no significant differences between the groups in terms of forced vital capacity (FVC; p=0.239), forced expiratory volume in one second (FEV1; p=0.555), or FEV1/FVC (p=0.374) after PPI therapy. However, there were significant improvements in FVC (p=0.002) and FEV1 (p=0.006) in patients with high BMI in the PPI treatment group. PPIs have no effect on the pulmonary function in patients with bronchiectasis and GERD. However, PPIs were noted to produce improvements in lung function in patients with bronchiectasis and high BMI.

  8. 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...

  9. High-dose versus low-dose intravenous proton pump inhibitor treatment for bleeding peptic ulcers.

    Science.gov (United States)

    Leontiadis, Grigorios I; Howden, Colin W; Barkun, Alan N

    2012-12-01

    Peptic ulcer bleeding is a common medical emergency associated with significant mortality and healthcare costs. All recent guidelines agree on the beneficial role of proton pump inhibitor treatment, but there is still controversy regarding the optimal dose and route of administration of proton pump inhibitors. The evaluated article reports on a large, single-center randomized controlled trial that compared the clinical efficacy of a low-dose twice-daily intravenous bolus regimen with a high-dose continuous intravenous infusion regimen in 875 patients with acute bleeding from peptic ulcers. The high-dose regimen was associated with significant reductions in rebleeding, blood transfusion requirements and length of hospital stay. There was no demonstrable difference in mortality or the need for endoscopic hemostatic treatment or surgery. We discuss the strengths and limitations of the evaluated article, as well as the implications for clinical practice.

  10. Acido-basic properties of proton pump inhibitors in aqueous solutions.

    Science.gov (United States)

    Kristl, Albin

    2009-01-01

    The pharmacological characteristics of proton pump inhibitors are related to their protolytic behavior estimated by their pK(a) values. Lansoprazole is a potent anti-acid drug from this group. Because of its poor stability a rapid spectrophotometric method was developed for the determination of its pK(a) values. Three pK(a) values were obtained: an acidic pK(a1) = 8.84 and two basic, pK(a2) = 4.15 and pK(a3) = 1.33. These pK(a) values were discussed from the point of lansoprazole structure and instability with the aim of locating basic and acidic moieties in the molecule of proton pump inhibitors. They were also compared with experimentally determined pK(a) values from the literature and with some pK(a) values calculated by different programs.

  11. Decrease in Switches to 'Unsafe' Proton Pump Inhibitors After Communications About Interactions with Clopidogrel.

    Science.gov (United States)

    Kruik-Kollöffel, Willemien J; van der Palen, Job; van Herk-Sukel, Myrthe P P; Kruik, H Joost; Movig, Kris L L

    2017-08-01

    In 2009 and 2010 medicines regulatory agencies published official safety statements regarding the concomitant use of proton pump inhibitors and clopidogrel. We wanted to investigate a change in prescription behaviour in prevalent gastroprotective drug users (2008-2011). Data on drug use were retrieved from the Out-patient Pharmacy Database of the PHARMO Database Network. We used interrupted time series analyses (ITS) to estimate the impact of each safety statement on the number of gastroprotective drug switches around the start of clopidogrel and during clopidogrel use. After the first statement (June 2009), significantly fewer patients switched from another proton pump inhibitor to (es)omeprazole (-14.9%; 95% CI -22.6 to -7.3) at the moment they started clopidogrel compared to the period prior to this statement. After the adjusted statement in February 2010, the switch percentage to (es)omeprazole decreased further (-4.5%; 95% CI -8.1 to -0.9). We observed a temporary increase in switches from proton pump inhibitors to histamine 2-receptor antagonists after the first statement; the decrease in the reverse switch was statistically significant (-23.0%; 95% CI -43.1 to -2.9). With ITS, we were able to demonstrate a decrease in switches from other proton pump inhibitors to (es)omeprazole and an increase of the reverse switch to almost 100%. We observed a partial and temporary switch to histamine 2-receptor antagonists. This effect of safety statements was shown for gastroprotective drug switches around the start of clopidogrel treatment.

  12. 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

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

    OpenAIRE

    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 techniqu...

  14. 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.

  15. 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.

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

    Science.gov (United States)

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

    2018-02-01

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

  17. The influence of changes in hospital drug formulary on the prescription of proton pump inhibitors

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    Raquel Vázquez-Mourelle

    2017-01-01

    Full Text Available Objective: To analyze the impact of introducing omeprazole in the drug formulary of the Hospital de Barbanza on prescriptions made in hospital and out-of-hospital (Outpatient Units and Primary Care for all Proton Pump Inhibitors (PPIs. Material and methods: A 36-month retrospective descriptive study in a level I hospital. The basic units of work are Dose-Population- Day in the outpatient setting, and the Defined Daily Dose/stays-day for hospitalized patients; the proportion of DDDs for omeprazole vs. the rest of PPIs is used as measure of efficiency. For statistical analysis, we built a segmented regression model. Results: In the outpatient units, there are statistically significant changes for pantoprazole and rabeprazole. The first drug, which was stable before the intervention, suffered an immediate decrease; rabeprazole, which was increasing before the intervention, presented a subsequent downward trend. In Primary Care, a statistically significant change was confirmed for pantoprazole, with a long-term decreasing trend. In hospitalization, statistically significant changes were observed for pantoprazole and omeprazole; the first one with an immediate decrease and a long-term tendency to decrease, while omeprazole experienced an immediate increase and long-term growth. The evolution of the omeprazole percentage vs. all PPIs showed increases in all three scenarios. Conclusions: A shift to a more efficient prescription of PPIs was observed in all healthcare settings following the introduction of omeprazole in the hospital drug formulary. The inclusion of efficient drugs, or the removal of those inefficient, can be a potentially useful tool in order to improve prescription profiles.

  18. 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

  19. 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

    2015-01-01

    AIM: To investigate the influence of proton pump inhibitors (PPIs) exposure on the diagnosis of Helicobacter pylori (H. pylori) gastritis and intestinal metaplasia. METHODS: 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. RESULTS: 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 pylori was less likely. Chronic use of PPIs may mask H. pylori infections promoting the diagnosis of non-H. pylori gastritis and leads to a significant drop in H. pylori densities and to an increased risk of intestinal metaplasia. CONCLUSION: 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. PMID:25914469

  20. 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.

  1. 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

  2. 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

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

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    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.

  4. Design of Photoactive Ruthenium Complexes to Study Electron Transfer and Proton Pumping in Cytochrome Oxidase

    Science.gov (United States)

    Durham, Bill; Millett, Francis

    2011-01-01

    This review describes the development and application of photoactive ruthenium complexes to study electron transfer and proton pumping reactions in cytochrome c oxidase (CcO). CcO uses four electrons from Cc to reduce O2 to two waters, and pumps four protons across the membrane. The electron transfer reactions in cytochrome oxidase are very rapid, and cannot be resolved by stopped-flow mixing techniques. Methods have been developed to covalently attach a photoactive tris(bipyridine)ruthenium group [Ru(II)] to Cc to form Ru-39-Cc. Photoexcitation of Ru(II) to the excited state Ru(II*), a strong reductant, leads to rapid electron transfer to the ferric heme group in Cc, followed by electron transfer to CuA in CcO with a rate constant of 60,000 s−1. Ruthenium kinetics and mutagenesis studies have been used to define the domain for the interaction between Cc and CcO. New ruthenium dimers have also been developed to rapidly inject electrons into CuA of CcO with yields as high as 60%, allowing measurement of the kinetics of electron transfer and proton release at each step in the oxygen reduction mechanism. PMID:21939635

  5. Pantoprazole, a proton pump inhibitor, increases orthodontic tooth movement in rats

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    Mohsen Shirazi

    2014-06-01

    Full Text Available Objective(s:Pantoprazole, is a proton pump inhibitor (PPI prescribed for the treatment of upper gastrointestinal disorders, which in high doses has been suggested to decrease calcium absorption leading to hypocalcaemia and therefore osteoporosis. The aim of this study was to assess whether pantoprazol, could alter the rate of orthodontic tooth movement (OTM in rats. Materials and Methods: A time course study was established using 72 rats which were divided into six groups of 12 samples each (four: vehicle; eight: pantoprazole + vehicle. Pantoprazole at a dose of 200 mg/kg suspended in carboxymethyl cellulose (0.25 percent was administered by a gastric tube. The upper incisors and first molars were ligated by a 5 mm nickel-titanium closed-coil spring to deliver an initial force of 60 g. Animals were euthanized two weeks after orthodontic treatment followed by assessment of tooth movement and histomorphometric evaluation of the detached maxillae. Lateral skull radiographs were obtained once a week, starting from the first day to the 6th week of the study. OTM and bone density data were analyzed using independent sample t-test and repeated measures ANOVA. Results: No significant changes in OTM measurements and optical density were observed in vehicle-receiving animals during the study (P=0.994. OTM was significantly increased after six weeks pantoprazole therapy which continued until the 7th week of the experiment (P=0.007. Optical density significantly increased in the pantoprazole-treated rats after six weeks. Conclusion: Long term PPI therapy at high doses could lead to osteoporosis and enhanced OTM.

  6. The appropriate use of proton pump inhibitors (PPIs): Need for a reappraisal.

    Science.gov (United States)

    Savarino, Vincenzo; Dulbecco, Pietro; de Bortoli, Nicola; Ottonello, Andrea; Savarino, Edoardo

    2017-01-01

    The advent of powerful acid-suppressive drugs, such as proton pump inhibitors (PPIs), has revolutionized the management of acid-related diseases and has minimized the role of surgery. The major and universally recognized indications for their use are represented by treatment of gastro-esophageal reflux disease, eradication of Helicobacter pylori infection in combination with antibiotics, therapy of H. pylori-negative peptic ulcers, healing and prophylaxis of non-steroidal anti-inflammatory drug-associated gastric ulcers and control of several acid hypersecretory conditions. However, in the last decade, we have witnessed an almost continuous growth of their use and this phenomenon cannot be only explained by the simple substitution of the previous H2-receptor antagonists, but also by an inappropriate prescription of these drugs. This endless increase of PPI utilization has created an important problem for many regulatory authorities in terms of increased costs and greater potential risk of adverse events. The main reasons for this overuse of PPIs are the prevention of gastro-duodenal ulcers in low-risk patients or the stress ulcer prophylaxis in non-intensive care units, steroid therapy alone, anticoagulant treatment without risk factors for gastro-duodenal injury, the overtreatment of functional dyspepsia and a wrong diagnosis of acid-related disorder. The cost for this inappropriate use of PPIs has become alarming and requires to be controlled. We believe that gastroenterologists together with the scientific societies and the regulatory authorities should plan educational initiatives to guide both primary care physicians and specialists to the correct use of PPIs in their daily clinical practice, according to the worldwide published guidelines. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  7. Is there a relationship between hypomagnesemia and proton-pump inhibitors in patients on chronic hemodialysis?

    Science.gov (United States)

    Mikolasevic, I; Milic, S; Stimac, D; Zaputovic, L; Lukenda Zanko, V; Gulin, T; Jakopcic, I; Klaric, D; Gulin, M; Orlic, L

    2016-05-01

    We investigated the association among long-term proton-pump inhibitors (PPIs) use with serum magnesium (Mg) levels in chronic hemodialysis (HD) patients, as well as possible association among PPI use and increased risk of cardiovascular (CVD) morbidity in HD patients. Of 418 HD patients that were screened for inclusion, 136 were excluded due to incomplete medical data, duration of renal replacement therapy (RRT) for less than 12months, use of Mg-based-phosphate binders or other Mg-based medications or either to presence of chronic increased GI losses. Among 282 patients included in the study, 170 patients were on PPIs. Serum Mg levels were significantly lower among PPI users vs. non-users (0.94±0.2 vs. 1.03±0.2mmol/L; p<0.0001). The median duration of PPI use was 27±9.6months (range from 12 to 108) and it was not significantly associated with Mg levels (r=0.116; p=0.167). Additionally, residual renal function didn't show a significant correlation with Mg concentration (r=-0.102; p=NS) in both groups of patients. The use of PPIs was an independent and strong predictor of low Mg concentrations even in multivariate analysis (OR 3.05; 95% CI 1.2498-7.4594, p=0.01). On the other hand, the daily dose of PPIs was not associated with low Mg levels. PPI users had a higher rate of adverse CVD events during the 1 year of follow-up in comparison to non-PPI users but that difference wasn't statistically significant (17.6% vs. 10.7%; p=0.110). We have found a significant association between PPI use and lower serum Mg levels in chronic HD patients. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  8. Proton Pump Inhibitor-Responsive Oesophageal Eosinophilia: An Entity Challenging Current Diagnostic Criteria for Eosinophilic Oesophagitis

    Science.gov (United States)

    Molina-Infante, Javier; Bredenoord, Albert J.; Cheng, Edaire; Dellon, Evan S.; Furuta, Glenn T.; Gupta, Sandeep K.; Hirano, Ikuo; Katzka, David A.; Moawad, Fouad J.; Rothenberg, Marc E.; Schoepfer, Alain; Spechler, Stuart; Wen, Ting; Straumann, Alex; Lucendo, Alfredo J.

    2016-01-01

    Consensus diagnostic recommendations to distinguish gastro-oesophageal reflux disease (GORD) from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPI) unexpectedly uncovered an entity called “PPI-responsive oesophageal eosinophilia” (PPI-REE). PPI-REE refers to patients with clinical and histologic features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that PPI-REE and EoE patients at baseline are clinically, endoscopically and histologically indistinguishable, and have significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in PPI-REE patients, similar to the effects of topical steroids in EoE patients. Additionally, recent series have reported that EoE patients responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunologic mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic, and therapeutic features cannot be reliably distinguished. For patients with symptoms and histologic features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment, before diet and topical steroids. The reasons why some EoE patients respond to PPI, while others do not, remain to be elucidated. PMID:26685124

  9. [Analysis of the use of proton pump inhibitors in primary health care].

    Science.gov (United States)

    Hernández-Arroyo, M J; Díaz-Madero, A; Enríquez-Gutiérrez, E; Teijeiro-Bermejo, M C; Sáez-Rodríguez, E; Gutiérrez-Martín, M R

    2017-11-15

    The increase in the consumption of anti-ulcer drugs is accompanied by a high rate of incorrect use. The objectives of this study were to analyse the adequacy of repeat prescriptions of proton pump inhibitors (PPIs) in a Medical Centre, and to evaluate the efficacy of an improvement intervention. A cross-sectional, descriptive and observational study of prevalence was conducted on patients in a medical centre under treatment with PPIs for at least 3consecutive months (November 2016-January 2017). An analysis was performed that included the indication, dosage and time of treatment with PPIs, drug interactions, and possible risks that could be related with their use. An intervention was carried out to optimise rational and efficient prescribing of these medicines. A total of 703 patients were included in the study, which is 5.4% of the total adult patients that are assigned to the centre. Adequacy criteria were not met by 436 (62.0%). Of these, 52.5% were women, 70.0% were over 65 years old, and had been on treatment for a mean of 2.7 ± 1.9 years. Interactions were observed in 48.1%, and 29.0% had some risk factors. After the intervention, the inadequate prescribing was corrected in 112 (25.7%) patients, which was a reduction of 46.1% (P<.001). There is a high prevalence of prescription and inadequacy of PPIs in the long term. This suggests that it is necessary to improve training of professionals to strengthen rational use and to reduce risks. The launch of an intervention programme has led to the revision and optimisation of treatments. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  10. TOPPITS: Trial Of Proton Pump Inhibitors in Throat Symptoms. Study protocol for a randomised controlled trial.

    Science.gov (United States)

    Watson, Gillian; O'Hara, James; Carding, Paul; Lecouturier, Jan; Stocken, Deborah; Fouweather, Tony; Wilson, Janet

    2016-04-01

    Persistent throat symptoms and Extra Oesophageal Reflux (EOR) are among the commonest reasons for attendance at a secondary care throat or voice clinic. There is a growing trend to treat throat symptom patients with proton pump inhibitors (PPIs) to suppress stomach acid, but most controlled studies fail to demonstrate a significant benefit of PPI over placebo. In addition, patient views on PPI use vary widely. A UK multi-centre, randomised, controlled trial for adults with persistent throat symptoms to compare the effectiveness of treatment with the proton pump inhibitor (PPI) lansoprazole versus placebo. The trial includes a six-month internal pilot, during which three sites will recruit 30 participants in total, to assess the practicality of the trial and assess the study procedures and willingness of the patient population to participate. If the pilot is successful, three additional sites will be opened to recruitment, and a further 302 participants recruited across the six main trial sites. Further trial sites may be opened, as necessary. The main trial will continue for a further 18 months. Participants will be followed up for 12 months from randomisation, throughout which both primary and secondary outcome data will be collected. The primary outcome is change in Reflux Symptom Index (RSI) score, the 'area standard' for this type of assessment, after 16 weeks (four months) of treatment. Secondary outcomes are RSI changes at 12 months after randomisation, Quality of Life assessment at four and 12 months, laryngeal mucosal changes, assessments of compliance and side effects, and patient-reported satisfaction. TOPPITS is designed to evaluate the relative effectiveness of treatment with a proton pump inhibitor versus placebo in patients with persistent throat symptoms. This will provide valuable information to clinicians and GPs regarding the treatment and management of care for these patients, on changes in symptoms, and in Quality of Life, over time. ISRCTN

  11. Proton Pump Inhibitor use in Hospitalized Patients: Is Overutilization Becoming a Problem?

    Directory of Open Access Journals (Sweden)

    Cheryl Durand

    2012-01-01

    Full Text Available Proton pump inhibitors (PPIs are among the most common classes of medications prescribed. Though they were previously thought of as safe, recent literature has shown risks associated with their use including increased risk for Clostridium difficile infection, pneumonia, and fractures. Due to these risks, it is important to determine if PPIs are being used appropriately. This review evaluates seven studies in hospitalized patients. Additionally, this review evaluates literature pertaining to recently discovered adverse reactions; all studies found PPIs are being overutilized. Findings highlight the importance of evaluating appropriate therapy with these agents and recommending discontinuation if a proper indication does not exist.

  12. Proton Pump Inhibitors in the Management of Tachypnoea following Panproctocolectomy: A Case of High Output Ileostomy

    Directory of Open Access Journals (Sweden)

    Neville Azzopardi

    2011-04-01

    Full Text Available High output ileostomies are important complications of stoma formation following bowel surgery. Adequate management of such stomas might prevent severe morbidity and mortality when this potentially fatal complication develops. In this case report, we describe a female patient with a recent ileostomy formation following panproctocolectomy for ulcerative colitis who presented with progressively increasing shortness of breath. The patient was found to have a hypochloraemic metabolic acidosis on arterial blood gases. She rapidly improved with adequate sodium and fluid replacement and with the use of a course of proton pump inhibitors. This case highlights the importance of recognising high output ileostomies early and important management issues in their regard.

  13. Lactobacillus paracasei F19 versus placebo for the prevention of proton pump inhibitor-induced bowel symptoms: a randomized clinical trial.

    Science.gov (United States)

    Compare, Debora; Rocco, Alba; Sgamato, Costantino; Coccoli, Pietro; Campo, Salvatore Maria Antonio; Nazionale, Immacolata; Larussa, Tiziana; Luzza, Francesco; Chiodini, Paolo; Nardone, Gerardo

    2015-04-01

    Proton pump inhibitors may foster intestinal dysbiosis and related bowel symptoms. To evaluate the effect of Lactobacillus paracasei F19 on bowel symptom onset in patients on long-term proton pump inhibitors. In this randomized, double-blind, placebo-controlled study, patients with typical gastroesophageal reflux disease symptoms receiving pantoprazole 40 mg/d for six months were randomly assigned to receive: (A) Lactobacillus paracasei F19 bid for three days/week for six months; (B) placebo bid for three days/week for six months; (C) Lactobacillus paracasei F19 bid for three days/week for three months and placebo bid for three days/week for the following three months; (D) placebo bid for three days/week for three months and Lactobacillus paracasei F19 bid for three days/week for the following three months. Bloating, flatulence, abdominal pain and bowel habit were assessed monthly. 100/312 patients were enrolled. In the parallel groups, the treatment-by-time interaction affected bloating (p = 0.015), while Lactobacillus paracasei F19 treatment alone affected flatulence (p = 0.011). Moreover, the treatment-by-time interaction significantly affected the mean score of bloating (p = 0.01) and flatulence (p Lactobacillus paracasei F19 supplementation prevents bowel symptom onset in patients on long-term proton pump inhibitors. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  14. Effects of membrane curvature and pH on proton pumping activity of single cytochrome bo3enzymes.

    Science.gov (United States)

    Li, Mengqiu; Khan, Sanobar; Rong, Honglin; Tuma, Roman; Hatzakis, Nikos S; Jeuken, Lars J C

    2017-09-01

    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 bo 3 , 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 bo 3 was found to decrease with increased curvature of the membrane. Furthermore, proton uptake at the N-side (proton entrance) was insensitive to pH between pH6.4-8.4, while proton release at the P-side had an optimum pH of ~7.4, suggesting that the pH optimum is related to proton release from the proton exit site. Our previous single-enzyme experiments identified rare, long-lived conformation states of cytochrome bo 3 where protons leak back under turn-over conditions. Here, we analyzed and found that ~23% of cytochrome bo 3 proteoliposomes show ΔpH half-lives below 50s after stopping turnover, while only ~5% of the proteoliposomes containing a non-pumping mutant, E286C cytochrome bo 3 exhibit such fast decays. These single-enzyme results confirm our model in which HCO exhibit heterogeneous pumping rates and can adopt rare leak states in which protons are able to rapidly flow back. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Mermelstein J

    2018-03-01

    Full Text Available Joseph Mermelstein,1 Alanna Chait Mermelstein,2 Maxwell M Chait3 1Gasteroenterology and Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA Abstract: 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. Keywords: PPI failure, resistant GERD, acid-related diseases, gastroesophageal reflux disease, acid reflux, proton pump inhibitors

  17. Prescribing patterns and economic costs of proton pump inhibitors in Colombia.

    Science.gov (United States)

    Machado-Alba, Jorge; Fernández, Alejandra; Castrillón, Juan Daniel; Campo, Carlos Felipe; Echeverri, Luis Felipe; Gaviria, Andrés; Londoño, Manuel José; Ochoa, Sergio Andrés; Ruíz, Joaquín Octavio

    2013-01-01

    To determine the prescribing patterns for proton pump inhibitors and to estimate the economic cost of their use in a group of patients affiliated with the Colombian Health System. This is a descriptive observational study. Data for analysis consisted of prescriptions dispensed between October 1st, 2010 and October 31st, 2010 and were collected from a systematic database of 4.2 million members. Socio-demographic variables were considered along with the defined daily dose,comedication, convenience of the indication for proton pump inhibitor use and costs. In this study, 113,560 prescriptions were dispensed in 89 cities, mostly to women (57.6%) with a mean age of 54.4 ± 18.7 years; the drugs were omeprazole (n= 111.294; 97.81%),esomeprazole (n= 1.378; 1.2%), lansoprazole (n= 524; 0.4%), pantoprazole and rabeprazole. The indication for 87.349 of the formulas (76.9%) was justified and statistically associated with the use of NSAIDs, antithrombotics, corticosteroids, anti-ulcer, antibiotics and prokinetics. No justification was found for 26.211 (23.1%) of the prescriptions, which were associated with antidiabetics, antihypertensives, hypolipidemics and others (p Colombia.

  18. 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.

  19. 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.

  20. 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.

  1. Long-term results of proton beam irradiated uveal melanomas

    International Nuclear Information System (INIS)

    Gragoudas, E.S.; Seddon, J.M.; Egan, K.

    1987-01-01

    The first 128 consecutive patients with uveal melanomas treated with proton beam irradiation were studied in order to evaluate survival and visual acuity status of patients with relatively long-term follow-up. The median follow-up was 5.4 years, and no patient was lost to follow-up. All tumors showed regression. The most recent visual acuity was 20/40 or better in 35% and 20/100 or better in 58%. Eight eyes were enucleated because of complications. Metastasis developed in 26 patients (20.5%) from 3 months to 7 years after treatment. Results indicate that proton irradiation is quite successful for achieving local control of uveal melanomas. A large proportion of the treated eyes maintained useful vision. Five-year follow-up data indicate that proton irradiation has no deleterious effect on the likelihood of the development of metastasis

  2. 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.

  3. Clostridium difficile Infection and Proton Pump Inhibitor Use in Hospitalized Pediatric Cystic Fibrosis Patients

    Directory of Open Access Journals (Sweden)

    John F. Pohl

    2011-01-01

    Full Text Available Children with cystic fibrosis (CF often take proton pump inhibitors (PPIs, which helps improve efficacy of fat absorption with pancreatic enzyme replacement therapy. However, PPI use is known to be associated with Clostridium difficile-(C. diff- associated diarrhea (CDAD. We retrospectively evaluated the incidence of C. diff infection from all pediatric hospital admissions over a 5-year period at a single tertiary children's hospital. We found significantly more C. diff-positive stool tests in hospitalized patients with CF compared to patients with no diagnosis of CF. However, use of a PPI was not associated with an increased risk of CDAD in hospitalized CF patients. In summary, C. diff infection is more common in hospitalized pediatric CF patients although PPI use may not be a risk factor for CDAD development in this patient population.

  4. Immediate and Delayed Hypersensitivity Reactions to Proton Pump Inhibitors: Evaluation and Management.

    Science.gov (United States)

    Otani, Iris M; Banerji, Aleena

    2016-03-01

    PPIs are among the most commonly administered medications in the USA and are generally well tolerated. Immediate and delayed immune-mediated hypersensitivity reactions are rare but increasingly recognized adverse effects of proton pump inhibitors (PPIs). Immediate hypersensitivity reactions can occur due to IgE-mediated hypersensitivity to PPIs and can be evaluated by immediate hypersensitivity skin testing and oral provocation challenge testing. A desensitization protocol can be used when PPI use cannot be avoided in an allergic patient. Delayed hypersensitivity reactions to PPIs have also been reported. Occupational exposures causing cutaneous reactions to PPIs are the most commonly reported delayed hypersensitivity reaction, followed by drug-induced subacute cutaneous lupus erythematosus. This review presents a summary of the clinical presentation, diagnostic evaluation, and management of immune-mediated hypersensitivity reactions to PPIs.

  5. Use of proton pump inhibitors and the risk of community-acquired pneumonia

    DEFF Research Database (Denmark)

    Gulmez, Sinem Ezgi; Holm, Anette; Frederiksen, Henrik

    2007-01-01

    BACKGROUND: Recently, the use of proton pump inhibitors (PPIs) has been associated with an increased risk of pneumonia. We aimed to confirm this association and to identify the risk factors. METHODS: We conducted a population-based case-control study using data from the County of Funen, Denmark....... Cases (n=7642) were defined as all patients with a first-discharge diagnosis of community-acquired pneumonia from a hospital during 2000 through 2004. We also selected 34 176 control subjects, who were frequency matched to the cases by age and sex. Data on the use of PPIs and other drugs......, on microbiological samples, on x-ray examination findings, and on comorbid conditions were extracted from local registries. Confounders were controlled by logistic regression. RESULTS: The adjusted odds ratio (OR) associating current use of PPIs with community-acquired pneumonia was 1.5 (95% confidence interval [CI...

  6. 'Lemonade Legs': Why do Some Patients Get Profound Hypomagnesaemia on Proton-Pump Inhibitors?

    Science.gov (United States)

    Atkinson, Nathan S. S.; Reynolds, D. John M.

    2015-01-01

    Proton pump inhibitors (PPIs) are widely used though an association with hypomagnesaemia and hypocalcaemia has only been described since 2006. Patients typically present after years of stable dosing with musculoskeletal, neurological or cardiac arrhythmic symptoms, but it is likely that many cases are under-recognised. Magnesium levels resolve rapidly on discontinuation of PPI therapy and hypomagnesaemia recurs rapidly on rechallenge with any agent in the class. The cellular mechanisms of magnesium homeostasis are increasingly being understood, including both passive paracellular absorption through claudins and active transcellular transporters, including the transient receptor potential channels (TRPM6) identified in the intestine and nephron. PPIs may alter luminal pH by modulating pancreatic secretions, affecting non-gastric H+K+ATPase secretion, altering transporter transcription or channel function. A small reduction in intestinal absorption appears pivotal in causing cumulative deficiency. Risk factors have been associated to help identify patients at risk of this effect but clinical vigilance remains necessary for diagnosis. PMID:26130997

  7. 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

  8. 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.

  9. 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...... before and after PPI initiation. Sensitivity analyses revealed no differences among individual PPIs. CONCLUSIONS: We found no evidence of a clinically meaningful drug-drug interaction between PPIs and warfarin in a Northern European patient population of unselected patients from an everyday outpatient...... 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...

  10. [Proton Pump Inhibitor and High-dose Methotrexate: Two Cases Reports].

    Science.gov (United States)

    Evrard, Julien; Farnier, Elodie; Carcel, Corine; Lachenal, Florence; Vial, Thierry; Pont, Emmanuelle

    2015-01-01

    Methotrexate (MTX) is a cytotoxic agent prescribed at high dose in treatment of malignancy. Association of MTX to proton pump inhibitor (PPI) is not recommended if doses are more than 20 mg per weeks and only to take into account for smaller doses. Review relate some cases of delayed elimination of methotrexate in patients taking PPI, which increase risk of toxic event. However, currently there is no status quo on interaction between PPI and MTX according to available data. We report two clinical cases illustrating one more time a toxic event to MTX in presence of PPI. In absence of risk/benefit ratio set correctly, an assessment of appropriateness of PPI prescription before MTX therapy can limit an iatrogenic risk. © 2015 Société Française de Pharmacologie et de Thérapeutique.

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

    Directory of Open Access Journals (Sweden)

    Nobata Kouichi

    2007-08-01

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

  12. Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a systematic review

    NARCIS (Netherlands)

    Jaspers Focks, J.; Brouwer, M.A.; Oijen, M.G.H. van; Lanas, A.; Bhatt, D.L.; Verheugt, F.W.A.

    2013-01-01

    BACKGROUND: Clopidogrel as an adjunct to aspirin has improved outcomes after acute coronary syndromes, but laboratory studies suggest a reduced antiplatelet effect when proton pump inhibitors (PPIs) are co-administered. Despite corroborating data from retrospective studies, new clinical data fuel

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

    Directory of Open Access Journals (Sweden)

    Nabil Sultan

    2008-01-01

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

  14. Noncompliance with guidelines on proton pump inhibitor prescription as gastroprotection in hospitalized surgical patients who are prescribed NSAIDs

    NARCIS (Netherlands)

    P.M.L.A. van den Bemt (Patricia); N. Chaaouit (Naoual); E.M.M. van Lieshout (Esther); M.H.J. Verhofstad (Michiel)

    2016-01-01

    textabstractBackground and aims As NSAIDs can cause serious upper gastrointestinal harm, guidelines have been established for the prescribing of proton pump inhibitors (PPIs) in high-risk patients using NSAIDs. Studies examining guideline compliance in surgical patients are scarce. Therefore, a

  15. Teaching the Fundamentals of Biological Research with Primary Literature: Learning from the Discovery of the Gastric Proton Pump

    Science.gov (United States)

    Zhu, Lixin

    2011-01-01

    For the purpose of teaching collegians the fundamentals of biological research, literature explaining the discovery of the gastric proton pump was presented in a 50-min lecture. The presentation included detailed information pertaining to the discovery process. This study was chosen because it demonstrates the importance of having a broad range of…

  16. Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation

    DEFF Research Database (Denmark)

    Schmidt, M; Johansen, M B; Robertson, D J

    2012-01-01

    Aliment Pharmacol Ther 2012; 35: 165-174 SUMMARY: Background  Cytochrome P450 inhibition by proton pump inhibitors (PPIs) may attenuate the effectiveness of clopidogrel. Aim  To examine whether PPI use modifies the association between clopidogrel use and major adverse cardiovascular events (MACE...

  17. 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.

  18. Proton pump inhibitors exert anti-allergic effects by reducing TCTP secretion.

    Directory of Open Access Journals (Sweden)

    Sunghee Choi

    Full Text Available BACKGROUND: Extracellular translationally controlled tumor protein (TCTP is known to play a role in human allergic responses. TCTP has been identified outside of macrophages, in activated mononuclear cells, and in biological fluids from allergic patients. Even TCTP devoid of signal sequences, is secreted to extracellular environment by an yet undefined mechanism. This study is aimed at understanding the mechanism of TCTP release and its regulation. A secondary goal is to see if inhibitors of TCTP release can serve as potential anti-allergic asthmatic drugs. METHODOLOGY/PRINCIPAL FINDINGS: Using Western blotting assay in HEK293 and U937 cells, we found that TCTP secretion is reduced by omeprazole and pantoprazole, both of which are proton pump inhibitors. We then transfected HEK293 cells with proton pump expression vectors to search for the effects of exogeneously overexpressed H(+/K(+-ATPase on the TCTP secretion. Based on these in vitro data we checked the in vivo effects of pantoprazole in a murine model of ovalbumin-induced allergy. Omeprazole and pantoprazole reduced TCTP secretion from HEK293 and U937 cells in a concentration-dependent fashion and the secretion of TCTP from HEK293 cells increased when they over-expressed H(+/K(+-ATPase. In a murine model of ovalbumin-induced allergy, pretreatment with pantoprazole reduced infiltration of inflammatory cells, increased goblet cells, and increased TCTP secretion induced by OVA challenge. CONCLUSION: Since Omeprazole and pantoprazole decrease the secretion of TCTP which is associated with the development of allergic reaction, they may have the potential to serve as anti-allergic (asthmatic drugs.

  19. Lack of proton pump inhibitor trial prior to commencing therapy for eosinophilic esophagitis is common in the community.

    Science.gov (United States)

    Whitson, M J; Lynch, K L; Yang, Y-X; Metz, D C; Falk, G W

    2017-12-22

    Eosinophilic esophagitis is characterized by eosinophil inflammation restricted to the esophagus and the resulting symptoms of esophageal dysfunction. Critical to the diagnosis of eosinophilic esophagitis is a trial of proton pump inhibitor therapy to exclude alternative causes of esophageal eosinophilia such as proton pump inhibitor-responsive esophageal eosinophilia. While consensus guidelines recommend a proton pump inhibitor trial prior to diagnosis, little is known about its implementation in clinical practice. The primary aim of this study is to assess the frequency of proton pump inhibitor trial prior to the diagnosis of eosinophilic esophagitis in community practice. The secondary aim is to assess the frequency of other treatments for eosinophilic esophagitis, including topical steroids and/or dietary therapy, in patients who did not undergo a proton pump inhibitor trial prior to diagnosis or who had an alternative diagnosis to eosinophilic esophagitis upon completed workup. We conducted a single-center, case series of patients referred to the Hospital of the University of Pennsylvania for eosinophilic esophagitis management between 2010 and 2015. This case series consisted of 125 patients who were referred from community practitioners with a presumptive diagnosis of eosinophilic esophagitis. Upon review, 90 out of 125 (72%) patients had not had a proton pump inhibitor trial or esophageal pH testing prior to the diagnosis of eosinophilic esophagitis being made. Of these patients, 77.8% (70/90) had already received either topical steroid or dietary therapy for presumed eosinophilic esophagitis. Of the 125 patients initially diagnosed with eosinophilic esophagitis, 32 (25.6%) were found to have an alternative diagnosis, and 79.2% of this subset of patients (25/32) had previously received topical steroid or dietary therapy. This study demonstrates that a substantial number of patients with presumed eosinophilic esophagitis have not had a proton pump inhibitor

  20. Up in Smoke: Uncovering a Lack of Evidence for Proton Pump Inhibitors as a Source of Tetrahydrocannibol Immunoassay False Positives.

    Science.gov (United States)

    Powers, Jennifer L; Rasmussen, Natalie N; Hurst, Dow; Strathmann, Frederick G

    2017-11-08

    It is recommended that positives in immunoassay drug screens be followed up with more specific confirmatory testing. The drug package insert for pantoprazole mentions reports of false-positive urine screening tests for tetrahydrocannabinol in patients receiving proton pump inhibitors, but no method details or data are given, referenced, or found in literature searches. Thus, we investigated this using our laboratory's assay. A spiked sample and samples from 32 patients taking a proton pump inhibitor were analyzed using the EMIT II Plus Cannabinoid assay with a 20 ng/mL cutoff. Additionally, we examined urine samples from 50 patients with false-positive or low-positive screens for evidence of a proton pump inhibitor. To determine whether O-desmethyl pantoprazole sulfate, the major metabolite, shares any structural or electrostatic similarity to suggest a basis for cross-reactivity in the immunoassay, we used computational techniques for analyses. Molecular electrostatic potential energy (MEP) maps were calculated for the global minimum conformers, and the maximum common substructure Tanimoto similarity was calculated for the modeled compounds. Neither the spiked sample nor the patient samples were found to screen positive. None of the false-positive or low-positive screens were found to contain a proton pump inhibitor. Computational studies showed very little similarity in shape or electrostatics between the two molecules. We find no supporting evidence of pantoprazole as the cause of false positives in the EMIT II Plus Cannabinoid assay and caution the use of proton pump inhibitors as an explanation for tetrahydrocannabinol immunoassay false positives. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  1. 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.

  2. 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.

  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...... pumping rates remained constant. Titration of ATP down to ~1% of apparent Km for ATPase activity exclusively affected the distributions of the durations the pump spends in active and inactive states. The dramatic consequence of our findings is that ATP reduction decreased ATP/H+ stoichiometry of the pump....... 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. Biophysical comparison of ATP-driven proton pumping mechanisms suggests a kinetic advantage for the rotary process depending on coupling ratio

    OpenAIRE

    Anandakrishnan, Ramu; Zuckerman, Daniel M.

    2017-01-01

    ATP-driven proton pumps, which are critical to the operation of a cell, maintain cytosolic and organellar pH levels within a narrow functional range. These pumps employ two very different mechanisms: an elaborate rotary mechanism used by V-ATPase H+ pumps, and a simpler alternating access mechanism used by P-ATPase H+ pumps. Why are two different mechanisms used to perform the same function? Systematic analysis, without parameter fitting, of kinetic models of the rotary, alternating access an...

  5. Cyanobacterial light-driven proton pump, gloeobacter rhodopsin: complementarity between rhodopsin-based energy production and photosynthesis.

    Directory of Open Access Journals (Sweden)

    Ah Reum Choi

    Full Text Available A homologue of type I rhodopsin was found in the unicellular Gloeobacter violaceus PCC7421, which is believed to be primitive because of the lack of thylakoids and peculiar morphology of phycobilisomes. The Gloeobacter rhodopsin (GR gene encodes a polypeptide of 298 amino acids. This gene is localized alone in the genome unlike cyanobacterium Anabaena opsin, which is clustered together with 14 kDa transducer gene. Amino acid sequence comparison of GR with other type I rhodopsin shows several conserved residues important for retinal binding and H+ pumping. In this study, the gene was expressed in Escherichia coli and bound all-trans retinal to form a pigment (λmax  = 544 nm at pH 7. The pKa of proton acceptor (Asp121 for the Schiff base, is approximately 5.9, so GR can translocate H+ under physiological conditions (pH 7.4. In order to prove the functional activity in the cell, pumping activity was measured in the sphaeroplast membranes of E. coli and one of Gloeobacter whole cell. The efficient proton pumping and rapid photocycle of GR strongly suggests that Gloeobacter rhodopsin functions as a proton pumping in its natural environment, probably compensating the shortage of energy generated by chlorophyll-based photosynthesis without thylakoids.

  6. 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

  7. Controlled trial of ligation plus vasoconstrictor versus proton pump inhibitor in the control of acute esophageal variceal bleeding.

    Science.gov (United States)

    Lo, Gin-Ho; Perng, Daw-Shyong; Chang, Chi-Yang; Tai, Chi-Ming; Wang, Huay-Min; Lin, Hui-Chen

    2013-04-01

    Endoscopic therapy combined with vasoconstrictor was generally recommended to treat acute variceal bleeding. However, up to 30% of patients may still encounter treatment failure. This trial was to evaluate the efficacy of combination with endoscopic variceal ligation (EVL) and proton pump inhibitor (PPI) infusion in patients with acute variceal bleeding. Cirrhotic patients presenting with acute esophageal variceal bleeding were rescued by emergency EVL. Soon after arresting of bleeding varices, eligible subjects were randomized to two groups. Vasoconstrictor group received either somatostatin or terlipressin infusion. PPI group received either omeprazole or pantoprazole. End points were initial hemostasis, very early rebleeding rate, and adverse events. Sixty patients were enrolled in vasoconstrictor group and 58 patients in PPI group. Both groups were comparable in baseline data. Initial hemostasis was achieved in 98% in vasoconstrictor group and 100% in PPI group (P = 1.0). Very early rebleeding within 48-120 h occurred in one patient (2%) in vasoconstrictor group and one patient (2%) in the PPI group (P = 1.0). Treatment failure was 4% in vasoconstrictor group and 2% in PPI group (P = 0.95). Adverse events occurred in 33 patients (55%) in vasoconstrictor group and three patients (6%) in PPI group (P EVL, adjuvant therapy with PPI infusion was similar to combination with vasoconstrictor infusion in terms of initial hemostasis, very early rebleeding rate, and associated with fewer adverse events. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  8. Effect of esomeprazole, a proton pump inhibitor on the pharmacokinetics of sonidegib in healthy volunteers.

    Science.gov (United States)

    Zhou, Jocelyn; Quinlan, Michelle; Glenn, Kelli; Boss, Hildegard; Picard, Franck; Castro, Henry; Sellami, Dalila

    2016-10-01

    This study aimed to evaluate the impact of esomeprazole on the pharmacokinetics of sonidegib. This Phase I study evaluated the impact of the proton pump inhibitor (PPI) esomeprazole on the oral absorption and pharmacokinetics (PKs) of a single dose of sonidegib under fasted conditions. A total of 42 healthy subjects were enrolled to receive either sonidegib alone (200 mg single dose) or sonidegib in combination with esomeprazole (40 mg pre-treatment 5 days and combination were given on day 6). Primary PK parameters assessed in the study were area under the concentration-time curve (AUC) from 0-14 days and 0-7 days and maximum observed plasma concentration (Cmax ). The plasma exposure (AUC0-14d, AUC0-7d and Cmax ) of a single 200 mg oral dose of sonidegib was decreased by 32-38% when sonidegib was co-administered with esomeprazole compared with sonidegib alone, with no apparent change in elimination slope and tmax . Baseline gastric pH was similar between the two arms. These results suggest a modest reduction in the extent of sonidegib absorption by esomeprazole. There was no obvious metabolic drug-drug interaction between the two agents. Both sonidegib and esomeprazole were well tolerated in the study population. © 2016 The British Pharmacological Society.

  9. 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.

  10. Influence of different proton pump inhibitors on the pharmacokinetics of voriconazole.

    Science.gov (United States)

    Qi, Fang; Zhu, Liqin; Li, Na; Ge, Tingyue; Xu, Gaoqi; Liao, Shasha

    2017-04-01

    This study aimed to determine the influence of proton pump inhibitors (PPIs) on the pharmacokinetics of voriconazole and to characterise potential drug-drug interactions (DDIs) between voriconazole and various PPIs (omeprazole, esomeprazole, lansoprazole and rabeprazole). Using adjusted physicochemical data and the pharmacokinetic (PK) parameters of voriconazole and PPIs, physiologically based pharmacokinetic (PBPK) models were built and were verified in healthy subjects using GastroPlus TM to predict the plasma concentration-time profiles of voriconazole and PPIs. These models were then used to assess potential DDIs for voriconazole when administered with PPIs. The results indicated the PBPK model-simulated plasma concentration-time profiles of both voriconazole and PPIs were consistent with the observed profiles. In addition, the DDI simulations suggested that the PK values of voriconazole increased to various degrees when combined with several PPIs. The area under the plasma concentration-time curve for the time of the simulation (AUC 0- t ) of voriconazole was increased by 39%, 18%, 12% and 1% when co-administered with omeprazole, esomeprazole, lansoprazole and rabeprazole, respectively. Omeprazole was the most potent CYP2C19 inhibitor tested, whereas rabeprazole had no influence on voriconazole (omeprazole > esomeprazole > lansoprazole > rabeprazole). However, in consideration of the therapeutic concentration range, dosage adjustment of voriconazole is unnecessary regardless of which PPI was co-administered. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  11. In Vitro Study of the Variable Effects of Proton Pump Inhibitors on Voriconazole

    Science.gov (United States)

    Niece, Krista L.; Boyd, Natalie K.

    2015-01-01

    Voriconazole is a broad-spectrum antifungal agent used for the treatment of severe fungal infections. Maintaining therapeutic concentrations of 1 to 5.5 μg/ml is currently recommended to maximize the exposure-response relationship of voriconazole. However, this is challenging, given the highly variable pharmacokinetics of the drug, which includes metabolism by cytochrome P450 (CYP450) isotypes CYP2C19, CYP3A4, and CYP2C9, through which common metabolic pathways for many medications take place and which are also expressed in different isoforms with various metabolic efficacies. Proton pump inhibitors (PPIs) are also metabolized through these enzymes, making them competitive inhibitors of voriconazole metabolism, and coadministration with voriconazole has been reported to increase total voriconazole exposure. We examined the effects of five PPIs (rabeprazole, pantoprazole, lansoprazole, omeprazole, and esomeprazole) on voriconazole concentrations using four sets of human liver microsomes (HLMs) of different CYP450 phenotypes. Overall, the use of voriconazole in combination with any PPI led to a significantly higher voriconazole yield compared to that achieved with voriconazole alone in both pooled HLMs (77% versus 59%; P voriconazole yield from that at the baseline after PPI exposure in pooled microsomes ranged from 22% with pantoprazole to 51% with esomeprazole. Future studies are warranted to confirm whether and how the deliberate coadministration of voriconazole and PPIs can be used to boost voriconazole levels in patients with difficult-to-treat fungal infections. PMID:26124167

  12. 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

  13. Effect of proton pump inhibitors on in vitro activity of tigecycline against several common clinical pathogens.

    Directory of Open Access Journals (Sweden)

    Wentao Ni

    Full Text Available In this study, we evaluated the effect of proton pump inhibitors (PPIs on in vitro antimicrobial activity of tigecycline against several species of clinical pathogens. Clinical non-duplicate isolates of Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis and three species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumonia and Enterobacter cloacae were collected from a tertiary hospital and their MICs of tigecycline alone and in combination with PPIs (omeprazole, lansoprazole and pantoprazole were determined. With one randomly selected isolate of each bacterial species, an in vitro time-kill study was performed for the confirmation of the effect of PPIs on tigecycline activity. The MIC changes after PPIs addition correlated with the PPIs concentrations in the test media. Compared with tigecycline alone, the addition of 5 mg/L PPIs could increase the MICs of tigecycline by 0 to 2-fold and the addition of 50 mg/L PPIs could increase the MICs of tigecycline by 4 to >128-fold. The time-kill study confirmed that the addition of PPIs could affect the in vitro activity of tigecycline. Even at low concentration (5 mg/L of omeprazole and pantoprazole, antagonistic effect could be observed in E. cloacae and E. faecalis strains. We conclude that In vitro activity of tigecycline can be influenced by the presence of PPIs in a concentration-dependent manner.

  14. 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

  15. 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.

  16. 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.

  17. Prescribing patterns of proton pump inhibitors in older hospitalized patients in a Scottish health board.

    Science.gov (United States)

    Jarchow-Macdonald, Anna Amrit; Mangoni, Arduino A

    2013-10-01

    Proton-pump inhibitors (PPI) are extensively prescribed worldwide. However, little information is available on PPI prescribing patterns, associated clinical and demographic factors, and potential drug-drug interactions in frail older patients. Data on clinical and demographic characteristics, and full medication exposure were collected in a consecutive series of 361 older patients (age 84 ± 7 years) admitted to two acute geriatric admission units (Aberdeen, National Health Service Grampian) between 1 February 2010 and 30 June 2010. A set of predetermined criteria was used to assess appropriateness of PPI prescribing. PPI were prescribed in 148 patients (41.0%). Inappropriate overprescribing was observed in 127 patients (35.2% of the study population, 85.8% of patients prescribed PPI). PPI were inappropriately not prescribed in 20 patients (48.8% of patients with an indication for PPI treatment). Regression analysis showed that the total number of non-PPI prescribed drugs (OR 1.08; 95%CI 1.01-1.15) and a higher Charlson Comorbidity Index (OR 1.08; 95%CI 1.001-1.16) were independently associated with inappropriate PPI overprescribing. Potential drug-drug interactions were found in 75 patients (22.8% of the study population), mainly in patients with PPI overprescribing. Inappropriate PPI prescribing is common in frail older hospitalized patients, and might increase the risk of drug-drug interactions. Polypharmacy and comorbidity were independently associated with inappropriate PPI prescribing in this group. © 2013 Japan Geriatrics Society.

  18. Proton-pump inhibitor use is associated with lower urinary magnesium excretion.

    Science.gov (United States)

    William, Jeffrey H; Nelson, Rachel; Hayman, Najwah; Mukamal, Kenneth J; Danziger, John

    2014-12-01

    Although multiple recent studies have confirmed an association between chronic proton-pump inhibitor (PPI) use and hypomagnesaemia, the physiologic explanation for this association remains uncertain. To address this, we investigated the association of PPI use with urinary magnesium excretion. We measured 24-hour urine magnesium excretion in collections performed for nephrolithiasis evaluation in 278 consecutive ambulatory patients and determined PPI use from contemporaneous medical records. There were 50 (18%) PPI users at the time of urine collection. The mean daily urinary magnesium was 84.6 ± 42.8 mg in PPI users, compared with 101.2 ± 41.1 mg in non-PPI users (P = 0.01). In adjusted analyses, PPI use was associated with 10.54 ± 5.30 mg/day lower daily urinary magnesium excretion (P = 0.05). Diuretic use did not significantly modify the effect of PPI on urinary magnesium. As a control, PPI use was not associated with other urinary indicators of nutritional intake. Our findings suggest that PPI use is associated with lower 24-hour urine magnesium excretion. Whether this reflects decreased intestinal uptake due to PPI exposure, or residual confounding due to decreased magnesium intake, requires further study. © 2014 Asian Pacific Society of Nephrology.

  19. 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.

  20. Investigation of proton pump inhibitors binding with bovine serum albumin and their relationship to molecular structure

    International Nuclear Information System (INIS)

    Zhang Yuping; Shi Shuyun; Peng Mijun

    2012-01-01

    The interactions of three proton pump inhibitors (PPIs), omeprazole, pantoprazole and ilaprazole with bovine serum albumin (BSA) have been investigated by fluorescence, synchronous fluorescence, ultraviolet–visible (UV–vis) and circular dichroism (CD). Various binding parameters have been calculated at various temperatures. The results indicated that omeprazole, pantoprazole and ilaprazole had a strong ability to quench the intrinsic fluorescence of BSA with static quenching mechanism, and the binding affinities were significantly affected by different substituents and polarities as the order ilaprazole>pantoprazole>omeprazole. The site marker competitive experiments indicated that the binding of omeprazole, pantoprazole and ilaprazole to BSA primarily took place in subdomain IIA. The results of thermodynamic parameters ΔG, ΔH and ΔS indicated that electrostatic interaction played a major role for PPIs–BSA association. The distance r between PPIs and BSA was evaluated according to the theory of Förster's energy transfer. The quantitative analysis of synchronous fluorescence and CD spectra showed the change in secondary structure of the BSA upon interaction with PPIs by a reduction of α-helix. All the above results many have relevant insight into the PPIs' availability and distribution. - Highlights: ► The interactions of three PPIs with BSA have been investigated. ► The fluorescence quenching mechanism is static quenching. ► Binding affinities were greatly affected by the substituents and polarities. ► The binding of three PPIs to BSA primarily took place in subdomain IIA.

  1. Proton pump inhibitors overuse: only inappropriate prescriptions or further iatrogenic damage?

    Directory of Open Access Journals (Sweden)

    Mario Visconti

    2015-09-01

    Full Text Available Proton pump inhibitors (PPIs are the most potent drugs for reducing gastric acid secretion; so, since their release in the late 1980s, they have been recommended as the first therapeutic choice for many gastroesophageal diseases, risk reduction in or healing of non-steroidal anti-inflammatory drugs-associated ulcer disease and stress ulcer prophylaxis in intensive care unit patients. Thus PPIs account for a significant proportion of pharmaceutical health-care expenditure. Much of this high expenditure results from overuse of PPIs in account of inappropriate indications or prolongation of therapies for excessive time compared to real need. PPIs overutilization occurs in all medical care settings: in the majority of hospitalized patients with low risks for gastrointestinal bleeding, in patients healed at discharge from hospital, in outpatients in ambulatory practice. However potential adverse effects associated with PPIs therapy have been described, including enteric (especially by Clostridium difficile in elderly patients and pneumonia infections, nutritional deficiencies, rebound acid hypersecretion, acute interstitial nephritis, gastric neoplasms, bone fractures. Caution is required for some coprescription, particularly with clopidogrel.

  2. 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.

  3. Proton Pump Inhibitors and Kidney Disease - GI Upset for the Nephrologist?

    Science.gov (United States)

    Toth-Manikowski, Stephanie; Grams, Morgan E

    2017-05-01

    Widely regarded as safe and effective, proton pump inhibitors (PPIs) are among the most commonly used medications in the world today. However, a spate of observational studies suggest an association between PPI use and adverse events, including infection, bone fracture, and dementia. This review details evidence linking the use of PPI therapy to the development of kidney disease, including early case reports of acute interstitial nephritis and subsequent large observational studies of acute kidney injury (AKI), chronic kidney disease (CKD), and end-stage renal disease (ESRD). The majority of studies showed higher risk of kidney outcomes among persons prescribed PPI medications, with effect sizes that were slightly higher for AKI (∼2-3-fold) compared to CKD and ESRD (1.2-1.8-fold). Although observational pharmaco-epidemiology studies are limited by the possibility of residual confounding and confounding by indication, many of the described studies conducted rigorous sensitivity analyses aimed at minimizing these biases, including new-user design, comparison to similar agents (e.g., histamine 2 receptor antagonists), and evaluation for a dose-response, with robust results. Given the widespread use of PPIs, even a small effect on kidney outcomes could result in large public health burden. Timely cessation of PPI therapy when there is no clear indication for use might reduce the population burden of kidney disease.

  4. 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

  5. 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

    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...... 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...... of biomass consumption as base load in the energy system. Large heat pumps may also contribute to developing future smart energy systems as they can create flexibility between the electricity and heating/cooling sectors. A case study of Denmark in 2020 indicates that large heat pumps can increase fuel...

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

    NARCIS (Netherlands)

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

    2014-01-01

    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

  7. 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.

  8. 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.

  9. The frequency of CYP2C19 genetic polymorphisms in Russian patients with peptic ulcers treated with proton pump inhibitors.

    Science.gov (United States)

    Sychev, D A; Denisenko, N P; Sizova, Z M; Grachev, A V; Velikolug, K A

    2015-01-01

    Proton pump inhibitors, which are widely used as acid-inhibitory agents for the treatment of peptic ulcers, are mainly metabolized by 2C19 isoenzyme of cytochrome P450 (CYP2C19). CYP2C19 has genetic polymorphisms, associated with extensive, poor, intermediate or ultra-rapid metabolism of proton pump inhibitors. Genetic polymorphisms of CYP2C19 could be of clinical concern in the treatment of peptic ulcers with proton pump inhibitors. To investigate the frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles and genotypes in Russian patients with peptic ulcers. We retrospectively reviewed the cases of 971 patients of Caucasian origin with Russian nationality from Moscow region with endoscopically and histologically proven ulcers, 428 males (44%) and 543 females (56%). The mean age was 44.6±11.9 years (range: 15-88 years). DNA was extracted from ethylenediaminetetraacetic acid whole blood samples (10 mL). The polymorphisms CYP2C19 681G.A (CYP2C19*2, rs4244285), CYP2C19 636 G.A (CYP2C19*3, rs4986893) and CYP2C19 -806 C.T (CYP2C19*17, rs12248560) were evaluated using real-time polymerase chain reaction. Regarding CYP2C19 genotype, 317 patients (32.65%) out of 971 were CYP2C19*1/*1 carriers classified as extensive metabolizers. Three hundred and eighty-six (39.75%) with CYP2C19*1/*17 or CYP2C19*17/*17 genotype were ultra-rapid metabolizers. Two hundred and fifty-one people (25.85%) were intermediate metabolizers with CYP2C19*1/*2, CYP2C19*2/*17, CYP2C19*1/*3, CYP2C19*3/*17 genotypes. Seventeen patients (1.75%) with CYP2C19*2/*2, CYP2C19*3/*3, CYP2C19*2/*3 genotypes were poor metabolizers. The allele frequencies were the following: CYP2C19*2 - 0.140, CYP2C19*3 - 0.006, CYP2C19*17 - 0.274. There is a high frequency of CYP2C19 genotypes associated with modified response to proton pump inhibitors in Russian patients with peptic ulcers. Genotyping for CYP2C19 polymorphisms is suggested to be a useful tool for personalized dosing of proton pump inhibitors.

  10. Single enantiomer versus racemate: chiral distinction in the proton pump inhibitors omeprazole and esomeprazole.

    Science.gov (United States)

    Marom, Hili; Pogodin, Sergey; Agranat, Israel

    2014-04-01

    Chiral distinction in the proton pump inhibitor drugs omeprazole and in its chiral-switch esomeprazole magnesium was studied employing the Density Functional Theory (DFT) method. At B3LYP/6-311G(d,p), the 6-methoxy∙∙∙6-methoxy and 5-methoxy∙∙∙5-methoxy homochiral and heterochiral dimers were calculated. The chiral distinction free energies (ΔΔG(298,(RS-SS))) between the cyclic C2-(S,S)- and Ci-(R,S)-dimers with two intermolecular hydrogen bonds are 3.8, 1.9 (with BSSE counterpoise correction), and -6.9 (with D3 dispersion and BSSE counterpoise corrections) kJ/mol. Adding water as an implicit solvent (polarized continuum model [PCM] model) resulted in a chiral distinction energy of -3.3 kJ/mol, indicating a reversal of the order of the relative stabilities of C2-(S,S)- and Ci-(R,S)-dimers. The chiral distinction free energies between the corresponding (less stable) C1-dimers with one intermolecular hydrogen bond are -9.3, -5.8 (with BSSE CC), 17.6 (D3 + BSSE CC), and -3.2 (H2O) kJ/mol. The results highlight the contention that omeprazole is not just a superposition of its enantiomer constituents. They are consistent with the pharmacological evidence of enantiomer-enantiomer interactions in omeprazole versus esomeprazole and the differences between the drugs omeprazole and esomeprazole magnesium and support the lodged application for regulatory supplementary protection certificate (SPC) exclusivity for the esomeprazole-related combination drug Vimovo. Copyright © 2014 Wiley Periodicals, Inc.

  11. Association between use of proton pump inhibitors and occurrence of colon diverticulitis.

    Science.gov (United States)

    Ho, Bo-Lung; Hu, Hsiao-Yun; Chang, Shen-Shong

    2016-01-01

    Some recent studies have described the adverse effects of proton pump inhibitors (PPIs). PPI use and colonic diverticulitis are both associated with bacterial enteric infection and translocation. The aim of this study was to assess the association between PPI use and colonic diverticulitis. We conducted a population-based nested case-control study in part by use of data retrospectively collected from the National Health Insurance Research Database. Diverticulitis patients were identified using inpatient discharge records with International Classification of Diseases, Ninth Revision, Clinical Modification codes (562.11 and 562.13), and were recruited as the study cohort. The controls were matched to the study patients by age, sex, nonsteroidal anti-inflammatory drugs use, laxative use, and index date. The cumulative defined daily dose (DDD) was estimated as the sum of the dispensed DDD of any PPI. The adjusted odds ratio and 95% confidence interval (CI) were estimated using multiple logistic regression. We enrolled 690 patients with acute diverticulitis, along with 2760 patients who comprised the control group. The adjusted odds ratios for the study cohort compared with PPI nonusers, after adjusting for possible confounders (including sex, age, comorbidities, and medication), were 1.29 (95% CI = 0.70-2.36) and 1.02 (95% CI = 0.59-1.76) for the group with cumulative PPI use ≥42 and ≥55 DDDs over an exposure period of 90 and 180 days, respectively, prior to the claimed date of hospitalization for colonic diverticulitis. The study showed that use of PPIs did not increase the risk of colon diverticulitis. Copyright © 2015. Published by Elsevier Taiwan LLC.

  12. In-hospital gastric protection with proton pump inhibitors: adverse effects beyond (overutilization?

    Directory of Open Access Journals (Sweden)

    Paolo Montanari

    2013-04-01

    Full Text Available Background: Proton pump inhibitors (PPIs have provided important benefits in the management of gastroesophageal reflux disease (GERD, peptic ulcer disease and in the prevention of non steroidal antiinflammatory drugs and aspirin-related ulcer complications. PPIs are also the most commonly used medications for stress ulcer prophylaxis, despite little evidence to support their use in non-intensive care unit. Discussion: Considering the widespread use of PPIs, these agents’ overall safety profile is unquestionable. However, there is growing evidence that PPIs use may be associated with an increased risk of enteric infections, pneumonia, hip fractures, vitamin B12 deficiency. Overall, until now, none of these adverse effects have discouraged the PPIs treatment. Recently attention has been placed on a more important potential adverse effect of PPIs, their interaction with clopidogrel to which they are associated for the prophylaxis of gastrointestinal bleeding. Preliminary results of laboratory tests suggest that omeprazole reduces clopidogrel’s antiplatelet effect. The interaction seems to involve the competitive inhibition of the CYP2C19 isoenzyme. The effect appears to be clinically important, as some retrospective studies have shown an increase in adverse cardiovascular outcomes when PPIs and clopidogrel are used concomitantly. Some studies indicate that pantoprazole and esomeprazole are not associated with impaired response to clopidogrel. However, the available data for PPIs other than omeprazole do not allow definitive conclusions to be drawn about whether is a class effect. Conclusions: Specifically designed and randomized clinical studies are needed to define the interaction between PPIs and clopidogrel. Moreover, alternative treatment strategies with histamine- 2 receptor antagonists that are not dependent on cytochrome p450 2C19 should be tested in future studies.

  13. Proton pump inhibitors inhibit metformin uptake by organic cation transporters (OCTs.

    Directory of Open Access Journals (Sweden)

    Anne T Nies

    Full Text Available Metformin, an oral insulin-sensitizing drug, is actively transported into cells by organic cation transporters (OCT 1, 2, and 3 (encoded by SLC22A1, SLC22A2, or SLC22A3, which are tissue specifically expressed at significant levels in various organs such as liver, muscle, and kidney. Because metformin does not undergo hepatic metabolism, drug-drug interaction by inhibition of OCT transporters may be important. So far, comprehensive data on the interaction of proton pump inhibitors (PPIs with OCTs are missing although PPIs are frequently used in metformin-treated patients. Using in silico modeling and computational analyses, we derived pharmacophore models indicating that PPIs (i.e. omeprazole, pantoprazole, lansoprazole, rabeprazole, and tenatoprazole are potent OCT inhibitors. We then established stably transfected cell lines expressing the human uptake transporters OCT1, OCT2, or OCT3 and tested whether these PPIs inhibit OCT-mediated metformin uptake in vitro. All tested PPIs significantly inhibited metformin uptake by OCT1, OCT2, and OCT3 in a concentration-dependent manner. Half-maximal inhibitory concentration values (IC(50 were in the low micromolar range (3-36 µM and thereby in the range of IC(50 values of other potent OCT drug inhibitors. Finally, we tested whether the PPIs are also transported by OCTs, but did not identify PPIs as OCT substrates. In conclusion, PPIs are potent inhibitors of the OCT-mediated metformin transport in vitro. Further studies are needed to elucidate the clinical relevance of this drug-drug interaction with potential consequences on metformin disposition and/or efficacy.

  14. The use of proton pump inhibitors is positively associated with osteoporosis in postmenopausal women in Germany.

    Science.gov (United States)

    Jacob, L; Hadji, P; Kostev, K

    2016-10-01

    To analyze the association between the use of proton pump inhibitors (PPIs) and osteoporosis in German postmenopausal women. This study included 3092 women with osteoporosis and 3092 women without osteoporosis. Cases and controls were matched on the basis of age, health insurance, index year, and physician. The main outcome of the study was the risk of osteoporosis dependent on predefined risk factors. Gastrointestinal disorders potentially associated with osteoporosis were determined. The presence of PPIs including the duration of therapy was also assessed. Multivariate logistic regression models were fitted with osteoporosis as a dependent variable. The mean age was 72.3 years; 5.6% of both osteoporosis patients and controls had private health insurance coverage. Gastrointestinal disorders occurred significantly more frequently in osteoporosis patients than in controls. The use of PPI drugs was also significantly more common in osteoporosis patients than in matched controls. Osteoporosis development was found to be associated with disorders of the esophagus (odds ratio (OR) 1.19, p = 0.013) and gastritis/duodenitis (OR 1.14; p = 0.045). Interestingly, the use of PPIs also led to an increase in the risk of developing osteoporosis (OR 1.62; p osteoporosis increased with the duration of PPI therapy from 1.58 for 1 year of therapy or less to 1.72 for at least 5 years of treatment. The use of PPIs was a risk factor for osteoporosis and this risk increased with therapy duration in German women. Esophagus disorders and gastritis/duodenitis also increased the risk of developing this chronic condition.

  15. 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.

  16. Proton pump inhibitors in prevention of low-dose aspirin-associated upper gastrointestinal injuries.

    Science.gov (United States)

    Mo, Chen; Sun, Gang; Lu, Ming-Liang; Zhang, Li; Wang, Yan-Zhi; Sun, Xi; Yang, Yun-Sheng

    2015-05-07

    To determine the preventive effect and safety of proton pump inhibitors (PPIs) in low-dose aspirin (LDA)-associated gastrointestinal (GI) ulcers and bleeding. We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register from inception to December 2013, and checked conference abstracts of randomized controlled trials (RCTs) on the effect of PPIs in reducing adverse GI events (hemorrhage, ulcer, perforation, or obstruction) in patients taking LDA. The preventive effects of PPIs were compared with the control group [taking placebo, a cytoprotective agent, or an H2 receptor antagonist (H2RA)] in LDA-associated upper GI injuries. The meta-analysis was performed using RevMan 5.1 software. We evaluated 8780 participants in 10 RCTs. The meta-analysis showed that PPIs decreased the risk of LDA-associated upper GI ulcers (OR = 0.16; 95%CI: 0.12-0.23) and bleeding (OR = 0.27; 95%CI: 0.16-0.43) compared with control. For patients treated with dual anti-platelet therapy of LDA and clopidogrel, PPIs were able to prevent the LDA-associated GI bleeding (OR = 0.36; 95%CI: 0.15-0.87) without increasing the risk of major adverse cardiovascular events (MACE) (OR = 1.00; 95%CI: 0.76-1.31). PPIs were superior to H2RA in prevention of LDA-associated GI ulcers (OR = 0.12; 95%CI: 0.02-0.65) and bleeding (OR = 0.32; 95%CI: 0.13-0.79). PPIs are effective in preventing LDA-associated upper GI ulcers and bleeding. Concomitant use of PPI, LDA and clopidogrel did not increase the risk of MACE.

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

    Directory of Open Access Journals (Sweden)

    Andrei Vasile OLTEANU

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    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

  19. Proton pump inhibitors increase the incidence of bone fractures in hepatitis C patients.

    Science.gov (United States)

    Mello, Michael; Weideman, Rick A; Little, Bertis B; Weideman, Mark W; Cryer, Byron; Brown, Geri R

    2012-09-01

    While proton pump inhibitors (PPI) may increase the risk of bone fractures, the incidence of new bone fractures in a chronic hepatitis C virus (HCV) infected cohort, with or without PPI exposure, has not been explored. A retrospective cohort study of the incidence of bone fractures over 10 years in 9,437 HCV antibody positive patients in the Dallas VA Hepatitis C Registry was performed. The study endpoint was the incidence of verified new bone fractures per patient-years (pt-yrs) in PPI users compared to non-PPI users. PPI use was defined as those taking a PPI for ≥360 days. Pt-yrs of exposure for PPI users began on the first PPI prescription date, and pt-yrs of exposure for non-PPI users began with first date of any non-PPI prescription. For both HCV groups, the final date of patients' study duration was defined by end of PPI exposure, bone fracture occurrence, death or end of study evaluation period. Exclusion criteria included use of bone health modifying medications ≥30 days. Statistical differences in fracture incidence between groups were determined by multivariate regression analysis. Among the total study population analyzed (n = 2,573), 109 bone fractures occurred. Unadjusted bone fracture incidences were 13.99/1,000 pt-yrs vs. 5.86/1,000 pt-yrs in PPI and non-PPI users, respectively. The adjusted hazard ratio for new bone fractures was 3.87 (95 % CI 2.46-6.08) (p 1 year increased the risk of new bone fractures by more than threefold.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Effect of proton pump inhibitors on gastric pH in patients exposed to severe stress.

    Science.gov (United States)

    Lenz, Kurt; Buder, Robert; Firlinger, Fritz; Lohr, Gerald; Voglmayr, Martin

    2015-01-01

    The incidence of upper gastrointestinal bleeding from stress ulcers has decreased within the last 30 years. Improvements in intensive care medicine including advanced equipment for artificial ventilation, better sedoanalgesic therapies, and the use of stress ulcer prophylaxis are credited for the decline. To determine the effectiveness of proton pump inhibitors (PPIs) on gastric pH in patients exposed to a defined severe stress situation during a specified time period. Prospective open study in a tertiary community hospital. A high dose (80 mg bolus followed by 8 mg/h) of either pantoprazol or omeprazol was infused in 17 patients with opiate dependence who were undergoing ultra-rapid opiate withdrawal by barbiturate anesthesia. Gastric pH. Gastric pH did not change significantly in the majority of patients (mean pH 1.2 ± 0.9 immediately before, 1.5 ± 1.6 at 60 min after, and 1.3 ± 1.5 at 120 min after PPI infusion began). Gastric pH increased temporarily in two of the nine patients receiving omeprazol. In two of the eight patients, pantoprazol led to a late but sustained increase in gastric pH (pH 3.9 and 6.0 at 120 min post infusion). High doses of PPIs are ineffective in elevating gastric pH in patients exposed to severe stress such as ultra-rapid opiate detoxification. Therefore, adequate sedoanalgesia might be the main factor responsible for preventing stress-related bleeding in critically ill patients.

  3. 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.

  4. Potential Mechanisms of Hematological Adverse Drug Reactions in Patients Receiving Clozapine in Combination With Proton Pump Inhibitors.

    Science.gov (United States)

    Wiciński, Michał; Węclewicz, Mateusz M; Miętkiewicz, Mateusz; Malinowski, Bartosz; Grześk, Elżbieta; Klonowska, Joanna

    2017-03-01

    Clozapine is a second-generation antipsychotic which has proven efficacy in treating the symptoms of schizophrenia. Although clozapine therapy is associated with a number of adverse drug reactions, it is frequently used. One of the most common adverse drug reactions is gastroesophageal reflux disease which is an indication for treatment with proton pump inhibitors (PPIs). Coadministration of clozapine and PPIs increases the risk of hematological adverse drug reactions, including neutropenia and agranulocytosis. The mechanism in idiosyncratic agranulocytosis is not dose related and involves either a direct toxic or an immune-allergic effect. It is suspected that the clozapine metabolites nitrenium ion and N-desmethylclozapine may cause apoptosis or impair growth of granulocytes. Formation of N-desmethylclozapine is correlated with activity of the cytochrome P450 enzymes 1A2 and 3A4 (CYP1A2 and CYP3A4). Nitrenium ion is produced by the flavin-containing monooxygenase system of leukocytes. A drug interaction between clozapine and a PPI is a consequence of the induction of common metabolic pathways either by the PPI or clozapine. Findings to date suggest that indirect induction of flavin-containing monooxygenase by omeprazole through the aryl hydrocarbon receptor increases the expression of the enzyme mRNA and in the long term may cause the increase in activity. Moreover, induction of CYP1A2, especially by omeprazole and lansoprazole, may increase the serum concentration of N-desmethylclozapine, which can accumulate in lymphocytes and may achieve toxic levels. Another hypothesis that may explain hematological adverse drug reactions is competitive inhibition of CYP2C19, which may contribute to increased serum concentrations of toxic metabolites.

  5. 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.

  6. Off-pump versus on-pump coronary revascularization: meta-analysis of mid- and long-term outcomes.

    Science.gov (United States)

    Chaudhry, Umar A R; Harling, Leanne; Rao, Christopher; Ashrafian, Hutan; Ibrahim, Michael; Kokotsakis, John; Casula, Roberto; Athanasiou, Thanos

    2014-08-01

    Early outcomes for off-pump coronary artery bypass grafting (OPCAB) have been extensively compared with on-pump coronary revascularization (ONCAB); however, the long-term effects of OPCAB continue to be debated. This study aims to compare the mid-term (>1year; ≤5 years) and long-term (>5 years) survival and major adverse cardiovascular and cerebrovascular events of OPCAB versus ONCAB. A systematic search identified 32 studies meeting our inclusion criteria. These were analyzed using random effects modeling, with subgroup evaluation according to study type. Primary outcomes were mid- and long-term survival over a follow-up period greater than 1 year. Secondary outcomes were mid- and long-term events including repeat revascularization, myocardial infarction, angina, heart failure, and cerebrovascular accidents. Off-pump coronary artery bypass grafting confers similar overall mid-term survival when compared with ONCAB (hazard ratio, 1.06; 95% confidence interval, 0.95 to 1.19; p=0.31). On-pump coronary artery bypass grafting was associated with a significant trend towards a long-term survival advantage (hazard ratio, 1.06; 95% confidence interval, 1.00 to 1.13; p=0.05); however, this was no longer present when subgroup analysis of only randomized controlled trials, registry-based studies, and propensity-matched studies was performed. There was an increase in angina recurrence among two studies after OPCAB, but no difference was seen in 11 other studies reporting data as odds ratio. No significant differences were observed in other secondary outcomes. This analysis demonstrates comparable mid-term mortality and mid- to long-term morbidity between OPCAB and ONCAB. On-pump coronary artery bypass grafting may be associated with improved long-term survival when all study types are analyzed; however, analysis of only randomized controlled trials and propensity-matched studies demonstrates comparable long-term mortality between OPCAB and ONCAB. Copyright © 2014 The

  7. Off-Pump Conversion: In-hospital Mortality and Long-Term Survival.

    Science.gov (United States)

    Pullan, Mark; Oo, Aung; Poullis, Michael

    2017-06-01

    Background  There is an ongoing debate on the benefits and risks of off-pump coronary artery bypass grafting (CABG) surgery. The fate of patients who start with their procedure being an off-pump one and then have to undergo conversion to an on-pump procedure is debated with regard to in-hospital mortality and unknown with regard to long-term survival. We investigated the in-hospital mortality and long-term survival of patients who underwent conversion from off- to on-pump surgery. Methods  We performed a multivariate and propensity analysis on in-hospital mortality and long-term survival of postisolated CABG patients in a single institution having 15,704 patients of which 5,353 who underwent off-pump CABG were analyzed. Results  In-hospital mortality was 2.15% for the study cohort, and 73 (1.4%) off-pump cases were converted. Univariate analysis demonstrated that patients undergoing conversion had a significantly increased in-hospital mortality ( p  pump by a team of surgeons and anesthetists who are dedicated off-pump specialists does not have an impact on in-hospital mortality or long-term survival. Georg Thieme Verlag KG Stuttgart · New York.

  8. 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

  9. The frequency of CYP2C19 genetic polymorphisms in Russian patients with peptic ulcers treated with proton pump inhibitors

    Directory of Open Access Journals (Sweden)

    Sychev DA

    2015-05-01

    Full Text Available DA Sychev,1,2 NP Denisenko,1,2 ZM Sizova,2 AV Grachev,3 KA Velikolug4 1Russian Medical Academy of Post-Graduate Education, 2I.M. Sechenov First Moscow State Medical University, 3SM-Clinic, 4Out-patient department Number 51 branch 3, Moscow, Russia Introduction: Proton pump inhibitors, which are widely used as acid-inhibitory agents for the treatment of peptic ulcers, are mainly metabolized by 2C19 isoenzyme of cytochrome P450 (CYP2C19. CYP2C19 has genetic polymorphisms, associated with extensive, poor, intermediate or ultra-rapid metabolism of proton pump inhibitors. Genetic polymorphisms of CYP2C19 could be of clinical concern in the treatment of peptic ulcers with proton pump inhibitors. Aim: To investigate the frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles and genotypes in Russian patients with peptic ulcers. Methods: We retrospectively reviewed the cases of 971 patients of Caucasian origin with Russian nationality from Moscow region with endoscopically and histologically proven ulcers, 428 males (44% and 543 females (56%. The mean age was 44.6±11.9 years (range: 15–88 years. DNA was extracted from ethylenediaminetetraacetic acid whole blood samples (10 mL. The polymorphisms CYP2C19 681G>A (CYP2C19*2, rs4244285, CYP2C19 636 G>A (CYP2C19*3, rs4986893 and CYP2C19 -806 C>T (CYP2C19*17, rs12248560 were evaluated using real-time polymerase chain reaction. Results: Regarding CYP2C19 genotype, 317 patients (32.65% out of 971 were CYP2C19*1/*1 carriers classified as extensive metabolizers. Three hundred and eighty-six (39.75% with CYP2C19*1/*17 or CYP2C19*17/*17 genotype were ultra-rapid metabolizers. Two hundred and fifty-one people (25.85% were intermediate metabolizers with CYP2C19*1/*2, CYP2C19*2/*17, CYP2C19*1/*3, CYP2C19*3/*17 genotypes. Seventeen patients (1.75% with CYP2C19*2/*2, CYP2C19*3/*3, CYP2C19*2/*3 genotypes were poor metabolizers. The allele frequencies were the following: CYP2C19*2 – 0.140, CYP2C19*3 – 0.006, CYP

  10. Pleiotropic effect of the proton pump inhibitor esomeprazole leading to suppression of lung inflammation and fibrosis.

    Science.gov (United States)

    Ghebremariam, Yohannes T; Cooke, John P; Gerhart, William; Griego, Carol; Brower, Jeremy B; Doyle-Eisele, Melanie; Moeller, Benjamin C; Zhou, Qingtao; Ho, Lawrence; de Andrade, Joao; Raghu, Ganesh; Peterson, Leif; Rivera, Andreana; Rosen, Glenn D

    2015-08-01

    The beneficial outcome associated with the use of proton pump inhibitors (PPIs) in idiopathic pulmonary fibrosis (IPF) has been reported in retrospective studies. To date, no prospective study has been conducted to confirm these outcomes. In addition, the potential mechanism by which PPIs improve measures of lung function and/or transplant-free survival in IPF has not been elucidated. Here, we used biochemical, cell biological and preclinical studies to evaluate regulation of markers associated with inflammation and fibrosis. In our in vitro studies, we exposed primary lung fibroblasts, epithelial and endothelial cells to ionizing radiation or bleomycin; stimuli typically used to induce inflammation and fibrosis. In addition, we cultured lung fibroblasts from IPF patients and studied the effect of esomeprazole on collagen release. Our preclinical study tested efficacy of esomeprazole in a rat model of bleomycin-induced lung injury. Furthermore, we performed retrospective analysis of interstitial lung disease (ILD) databases to examine the effect of PPIs on transplant-free survival. The cell culture studies revealed that esomeprazole controls inflammation by suppressing the expression of pro-inflammatory molecules including vascular cell adhesion molecule-1, inducible nitric oxide synthase, tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1β and IL-6). The antioxidant effect is associated with strong induction of the stress-inducible cytoprotective protein heme oxygenase-1 (HO1) and the antifibrotic effect is associated with potent inhibition of fibroblast proliferation as well as downregulation of profibrotic proteins including receptors for transforming growth factor β (TGFβ), fibronectin and matrix metalloproteinases (MMPs). Furthermore, esomeprazole showed robust effect in mitigating the inflammatory and fibrotic responses in a murine model of acute lung injury. Finally, retrospective analysis of two ILD databases was performed to assess the effect

  11. Inappropriate Use of Proton Pump Inhibitors in Elderly Patients Discharged from Acute Care Hospitals.

    Science.gov (United States)

    Schepisi, R; Fusco, S; Sganga, F; Falcone, B; Vetrano, D L; Abbatecola, A; Corica, F; Maggio, M; Ruggiero, C; Fabbietti, P; Corsonello, A; Onder, G; Lattanzio, F

    2016-01-01

    Proton-pump inhibitors (PPI) are extensively prescribed in older patients. However, little information is available on factors associated to PPI prescribing patterns among older patients discharged from hospital. To evaluate the appropriateness and clinical correlates of PPI prescription at discharge in a population of 1081 older patients discharged from acute care Italian hospitals. We used data from the CRiteria to Assess Appropriate Medication Use among Elderly Complex Patients (CRIME) study, a multicenter observational study. The appropriateness of PPI prescriptions was defined according to the Italian Medicines Agency (AIFA) rules. Correlates of overprescribing (i.e prescribing without recognized AIFA indications) and underprescribing (i.e. not prescribing despite the presence of recognized AIFA indications) were investigated by logistic regression analysis. Overprescribing was observed in 30% of patients receiving PPIs at discharge. Underprescribing was observed in 11% of patients not receiving PPIs at discharge. Overprescribing of PPIs at discharge was negatively associated with age (OR=0.88, 95%CI=0.85-0.91), depression (OR=0.58, 95%CI=0.35-0.96), use of aspirin (OR=0.03, 95%CI=0.02-0.06) and systemic corticosteroids (OR=0.02, 95%CI=0.01-0.04). The negative association with number of medications (OR=0.95, 95%CI=0.88-1.03) and overall comorbidities (OR=0.92, 95%CI=0.83-1.02) was nearly significant. Conversely, older age (OR=1.09, 95%CI=1.04-1.14), use of aspirin (OR=24.0, 95%CI=11.5-49.8) and systemic corticosteroids (OR=19.3, 95%CI=11.5-49.8) and overall comorbidities (OR=1.22, 95%CI=1.04-1.42) were independent correlates of underprescribing. Overprescribing of PPIs is more frequent in younger patients with lower burden of depression, whilst underprescribing is characterized by older age and greater burden of comorbidity and polypharmacy. Hospitalization should be considered as a clue to identify inappropriate use of PPIs and improve appropriateness of

  12. 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.

  13. Performance evaluation and parametric optimization of a proton exchange membrane fuel cell/heat-driven heat pump hybrid system

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, X.; Chen, J. [Department of Physics, Xiamen University, Xiamen 361005 (China)

    2012-06-15

    With the help of the current models of proton exchange membrane (PEM) fuel cells and three-heat-source heat pumps, a generic model of a PEM fuel cell/heat-driven heat pump hybrid system is established, so that the waste heat produced in the PEM fuel cell may be availably utilized. Based on the theory of electrochemistry and non-equilibrium thermodynamics, expressions for the efficiency and power output of the PEM fuel cell, the coefficient of performance and rate of pumping heat of the heat-driven heat pump, and the equivalent efficiency and power output of the hybrid system are derived. The curves of the equivalent efficiency and power output of the hybrid system varying with the electric current density and the equivalent power output versus efficiency curves are represented through numerical calculation. The general performance characteristics of the hybrid system are analyzed. The optimally operating regions of some important parameters of the hybrid system are determined. The influence of some main irreversible losses on the performance of the hybrid system is discussed in detail. The advantages of the hybrid system are revealed. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  14. Gastric Hyperplastic Polyps Associated with Proton Pump Inhibitor Use in a Case without a History of Helicobacter pylori Infection.

    Science.gov (United States)

    Miyamoto, Shuichi; Kato, Mototsugu; Matsuda, Kana; Abiko, Satoshi; Tsuda, Momoko; Mizushima, Takeshi; Yamamoto, Keiko; Ono, Shoko; Kudo, Takahiko; Shimizu, Yuichi; Hatanaka, Kanako C; Tsunematsu, Izumi; Sakamoto, Naoya

    2017-01-01

    A 56-year-old man with gastroesophageal reflux disease (GERD) was referred to our hospital. Esophagogastroduodenoscopy (EGD) revealed no evidence of any polypoid lesions in the stomach, and the patient had no history of Helicobacter pylori infection. He received omeprazole (20 mg) once daily for the GERD. EGD was performed at 1 year after the start of omeprazole administration, and this time, gastric hyperplastic polyps (GHPs) were detected. The GHPs increased in size as the omeprazole treatment continued, but they markedly decreased in size following omeprazole discontinuation. Thus, the administration of proton pump inhibitors may be a risk factor for the development of GHP independent of H. pylori infection.

  15. 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.

  16. 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.

  17. Are proton pump inhibitors the first choice for acute treatment of gastric ulcers? A meta analysis of randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Ward Alexandra

    2002-07-01

    Full Text Available Abstract Background Gastric ulcers are a frequent problem in the United States. Proton pump inhibitors have been shown to increase healing rates and improve clinical symptoms. The objective of this study is to compare gastric ulcer healing rates for patients treated with a proton pump inhibitor (PPI (omeprazole, rabeprazole, pantoprazole, or lansoprazole, an histamine 2- receptor antagonist (ranitidine or placebo. Methods A literature search was conducted to identify randomized, controlled clinical trials that included a PPI in at least one treatment arm and assessed the gastric ulcer healing rates endoscopically. The healing rates were estimated for each treatment at specific time points, and Rate Ratios (RR and 95% confidence intervals (CI were estimated for each trial. Results Sixteen trials met the inclusion criteria: four compared a PPI versus placebo, nine compared a PPI versus ranitidine (no trials of rabeprazole versus ranitidine met the inclusion criteria, and three compared a newer PPI (lansoprazole, pantoprazole or rabeprazole versus omeprazole. In relation to ranitidine, the pooled RR of PPIs (lansoprazole, omeprazole and pantoprazole was 1.33 (95% CI 1.24 to 1.42 at four weeks. In each trial, greater improvement in the studied clinical symptoms was found with the newer PPIs (rabeprazole, pantoprazole and lansoprazole when compared to omeprazole. Conclusion In this study treatment with PPIs resulted in higher healing rates than ranitidine or placebo. This evidence suggests that the first choice for gastric ulcer treatment for the greater relief of symptoms is one of the newer PPIs.

  18. Thin-Layer Chemical Modulations by a Combined Selective Proton Pump and pH Probe for Direct Alkalinity Detection.

    Science.gov (United States)

    Afshar, Majid Ghahraman; Crespo, Gastón A; Bakker, Eric

    2015-07-06

    We report a general concept based on a selective electrochemical ion pump used for creating concentration perturbations in thin layer samples (∼40 μL). As a first example, hydrogen ions are released from a selective polymeric membrane (proton pump) and the resulting pH is assessed potentiometrically with a second membrane placed directly opposite. By applying a constant potential modulation for 30 s, an induced proton concentration of up to 350 mM may be realized. This concept may become an attractive tool for in situ titrations without the need for sampling, because the thin layer eventually re-equilibrates with the contacting bulk sample. Acid-base titrations of NaOH and Na2 CO3 are demonstrated. The determination of total alkalinity in a river water sample is carried out, giving levels (23.1 mM) comparable to that obtained by standard methods (23.6 mM). The concept may be easily extended to other ions (cations, anions, polyions) and may become attractive for environmental and clinical applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. 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)

  20. The consequences of a deuterium exchange test on proposed mechanisms for the purple membrane proton pump

    International Nuclear Information System (INIS)

    Lin, M.; Seltzer, S.

    1979-01-01

    Among the mechanisms proposed to account for aspects of the light-driven pumping cycle, three require carbon-hydrogen bond ruptures and reformations within the retinal moiety. This report describes a test of these proposals whereby the hydrogens of the apoprotein were exchanged in D 2 O and the reconstituted and active pigment was subjected to light-driven pumping in D 2 O. Retinal from these samples was found to have no deuterium incorporated. (Auth.)

  1. 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

  2. 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. 

  3. Activity of tonoplast proton pumps and Na+/H+ exchange in potato cell cultures is modulated by salt.

    Science.gov (United States)

    Queirós, Filipa; Fontes, Natacha; Silva, Paulo; Almeida, Domingos; Maeshima, Masayoshi; Gerós, Hernâni; Fidalgo, Fernanda

    2009-01-01

    The efficient exclusion of excess Na from the cytoplasm and vacuolar Na(+) accumulation are the main mechanisms for the adaptation of plants to salt stress. This is typically carried out by transmembrane transport proteins that exclude Na(+) from the cytosol in exchange for H(+), a secondary transport process which is energy-dependent and driven by the proton-motive force generated by plasma-membrane and tonoplast proton pumps. Tonoplast enriched-vesicles from control and 150 mM NaCl-tolerant calli lines were used as a model system to study the activity of V-H(+)-PPase and V-H(+)-ATPase and the involvement of Na(+) compartmentalization into the vacuole as a mechanism of salt tolerance in Solanum tuberosum. Both ATP- and pyrophosphate (PP(i))-dependent H(+)-transport were higher in tonoplast vesicles from the salt-tolerant line than in vesicles from control cells. Western blotting of tonoplast proteins confirmed that changes in V-H(+)-PPase activity are correlated with increased protein amount. Conversely, immunodetection of the A-subunit of V-H(+)-ATPase revealed that a mechanism of post-translational regulation is probably involved. Na(+)-dependent dissipation of a pre-established pH gradient was used to measure Na(+)/H(+) exchange in tonoplast vesicles. The initial rates of proton efflux followed Michaelis-Menten kinetics and the V(max) of proton dissipation was 2-fold higher in NaCl-tolerant calli when compared to the control. H(+)-coupled exchange was specific for Na(+) and Li(+) and not for K(+). The increase of both the pH gradient across the tonoplast and the Na(+)/H(+) antiport activity in response to salt strongly suggests that Na(+) sequestration into the vacuole contributes to salt tolerance in potato.

  4. Biophysical comparison of ATP-driven proton pumping mechanisms suggests a kinetic advantage for the rotary process depending on coupling ratio.

    Science.gov (United States)

    Anandakrishnan, Ramu; Zuckerman, Daniel M

    2017-01-01

    ATP-driven proton pumps, which are critical to the operation of a cell, maintain cytosolic and organellar pH levels within a narrow functional range. These pumps employ two very different mechanisms: an elaborate rotary mechanism used by V-ATPase H+ pumps, and a simpler alternating access mechanism used by P-ATPase H+ pumps. Why are two different mechanisms used to perform the same function? Systematic analysis, without parameter fitting, of kinetic models of the rotary, alternating access and other possible mechanisms suggest that, when the ratio of protons transported per ATP hydrolyzed exceeds one, the one-at-a-time proton transport by the rotary mechanism is faster than other possible mechanisms across a wide range of driving conditions. When the ratio is one, there is no intrinsic difference in the free energy landscape between mechanisms, and therefore all mechanisms can exhibit the same kinetic performance. To our knowledge all known rotary pumps have an H+:ATP ratio greater than one, and all known alternating access ATP-driven proton pumps have a ratio of one. Our analysis suggests a possible explanation for this apparent relationship between coupling ratio and mechanism. When the conditions under which the pump must operate permit a coupling ratio greater than one, the rotary mechanism may have been selected for its kinetic advantage. On the other hand, when conditions require a coupling ratio of one or less, the alternating access mechanism may have been selected for other possible advantages resulting from its structural and functional simplicity.

  5. Pharmacoeconomic analysis of proton pump inhibitor therapy and interventions to control Helicobacter pylori infection

    NARCIS (Netherlands)

    Klok, Rogier Martijn

    2006-01-01

    In dit proefschrift worden de farmacoeconomische aspecten van problemen in het bovenste deel van het gastrointestinale tract besproken. De uitwisselbaarheid van proton pomp remmers (PPRs) wordt besproken net als switch patronen na het aflopen van het patent van omeprazol, de eerste PPR op de

  6. Impact of concomitant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome

    NARCIS (Netherlands)

    Yan, Yan; Wang, Xiao; Fan, Jing-Yao; Nie, Shao-Ping; Raposeiras-Roubín, Sergio; Abu-Assi, Emad; Henriques, Jose P. Simao; D'Ascenzo, Fabrizio; Saucedo, Jorge; González-Juanatey, José R.; Wilton, Stephen B.; Kikkert, Wouter J.; Nuñez-Gil, Iván; Ariza-Sole, Albert; Song, Xian-Tao; Alexopoulos, Dimitrios; Liebetrau, Christoph; Kawaji, Tetsuma; Moretti, Claudio; Huczek, Zenon; Fujii, Toshiharu; Correia, Luis C.; Kawashiri, Masa-Aki; Kedev, Sasko

    2016-01-01

    Background There is great debate on the possible adverse interaction between proton pump inhibitors (PPIs) and clopidogrel. In addition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomitant administration of PPIs and

  7. 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, Cecilie; 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...

  8. A systematic comparison of triple therapies for treatment of Helicobacter pylori infection with proton pump inhibitor/ ranitidine bismuth citrate plus clarithromycin and either amoxicillin or a nitroimidazole.

    NARCIS (Netherlands)

    Janssen, M.J.R.; Oijen, A.H.A.M. van; Verbeek, A.L.M.; Jansen, J.B.M.J.; Boer, W.A. de

    2001-01-01

    BACKGROUND: Triple therapies with proton pump inhibitor/ranitidine bismuth citrate (RBC), clarithromycin (C) and either amoxicillin (A) or a nitroimidazole (I) are widely accepted as treatment for Helicobacter pylori infection. However, it is not clear which of these antibiotic combinations should

  9. The effect of oral administration of ursodeoxycholic acid and high-dose proton pump inhibitors on the histology of Barrett's esophagus

    NARCIS (Netherlands)

    Bozikas, A.; Marsman, W. A.; Rosmolen, W. D.; van Baal, J. W. P. M.; Kulik, W.; ten Kate, F. J. W.; Krishnadath, K. K.; Bergman, J. J. G. H. M.

    2008-01-01

    Bile acids may play a role in the pathogenesis of Barrett's esophagus (BE). Bile composition can be influenced by oral administration of ursodeoxycholic acid (UDCA). We prospectively investigated the effect of proton pump inhibitors (PPI) supplemented with UDCA in vivo in patients with BE. Patients

  10. 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.

  11. Are higher doses of proton pump inhibitors better in acute peptic bleeding?

    Directory of Open Access Journals (Sweden)

    Alejandro Villalón

    2016-06-01

    Full Text Available Si bien existe consenso acerca de la utilidad de los inhibidores de la bomba de protones en la hemorragia digestiva péptica aguda, persiste la controversia sobre cuál es la dosis óptima. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos seis revisiones sistemáticas que en conjunto incluyen 27 estudios aleatorizados evaluando esta pregunta. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que las dosis altas de inhibidores de la bomba de protones probablemente resultan en poca o nula diferencia en el riesgo de resangrado y mortalidad. El balance riesgo/beneficio y costo/beneficio son probablemente desfavorables a la utilización de dosis altas.

  12. Oral versus intravenous proton pump inhibitors in preventing re-bleeding for patients with peptic ulcer bleeding after successful endoscopic therapy

    Directory of Open Access Journals (Sweden)

    Yen Hsu-Heng

    2012-06-01

    Full Text Available Abstract Background High dose intravenous proton pump inhibitor after endoscopic therapy for peptic ulcer bleeding has been recommended as adjuvant therapy. Whether oral proton pump inhibitor can replace intravenous proton pump inhibitor in this setting is unknown. This study aims to compare the clinical efficacy of oral and intravenous proton pump inhibitor after endoscopic therapy. Methods Patients with high-risk bleeding peptic ulcers after successful endoscopic therapy were randomly assigned as oral lansoprazole or intravenous esomeprazole group. Primary outcome of the study was re-bleeding rate within 14 days. Secondary outcome included hospital stay, volume of blood transfusion, surgical intervention and mortality within 1 month. Results From April 2010 to Feb 2011, 100 patients were enrolled in this study. The re-bleeding rates were 4% (2/50 in the intravenous group and 4% (2/50 in the oral group. There was no difference between the two groups with regards to the hospital stay, volume of blood transfusion, surgery or mortality rate. The mean duration of hospital stay was 1.8 days in the oral lansoprazole group and 3.9 days in the intravenous esomeprazole group (p > 0.01. Conclusion Patients receiving oral proton pump inhibitor have a shorter hospital stay. There is no evidence of a difference in clinical outcomes between oral and intravenous PPI treatment. However, the study was not powered to prove equivalence or non-inferiority. Future studies are still needed. Trial registration NCT01123031

  13. 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.

  14. Baseline haemoglobin A1c influences retinal function after long-term insulin pump therapy

    DEFF Research Database (Denmark)

    Klefter, Oliver N; Holfort, Stig K; Larsen, Michael

    2016-01-01

    PURPOSE: The purpose of the study was to characterize the long-term effect of insulin pump therapy (CSII) on electroretinography and dark adaptometry and to examine the influence of baseline glycaemic control on retinal function in patients with type 1 diabetes mellitus. METHODS: This prospective...

  15. Comparison of Mid-Term Graft Patency between On-Pump and Off-Pump Coronary Artery Bypass Grafting.

    Science.gov (United States)

    Seki, Tatsuya; Yoshida, Toshihito

    2017-06-20

    Multiple studies have compared on-pump coronary artery bypass (ONCAB) grafting with off-pump coronary artery bypass (OPCAB) grafting, but the optimal surgical strategy has yet to be established. Furthermore, there is limited evidence regarding mid-term graft patency rates. Between April 2001 and March 2014, 365 consecutive patients underwent isolated coronary artery bypass grafting (CABG; male: 75%; mean age: 69 ± 10 years). After propensity-score-matched analysis, we assessed the results of 67 patients in each group (ONCAB: group A, OPCAB: group B). The mean follow-up period of graft patency and survival rate was 35 ± 37 months and 54 ± 47 months, respectively. There were no significant differences in baseline characteristics between the two groups. There was a trend for an increased number of distal anastomoses in group B as compared to group A (group A vs. group B: 3.8 ± 1.1 vs. 4.1 ± 1.6, P = 0.17). The total graft patency rate was tend to be lower in group A, but not statistically significant (group A: 156 months, 45.2%; group B: 96 months, 72.6%; P = 0.21). There was no difference for survival and major-adverse-cardiac-and-cerebrovascular-events (MACCE) free rate (P = 0.42 and 0.76, respectively). Propensity-score-matched analysis revealed no difference in mid-term survival rate, MACCE free rate, graft patency rates, and number of distal anastomoses between ONCAB and OPCAB groups.

  16. 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

  17. Therapy with proton-pump inhibitors for gastroesophageal reflux disease does not reduce the risk for severe exacerbations in COPD.

    Science.gov (United States)

    Baumeler, Luzia; Papakonstantinou, Eleni; Milenkovic, Branislava; Lacoma, Alicia; Louis, Renaud; Aerts, Joachim G; Welte, Tobias; Kostikas, Konstantinos; Blasi, Francesco; Boersma, Wim; Torres, Antoni; Rohde, Gernot G U; Boeck, Lucas; Rakic, Janko; Scherr, Andreas; Tamm, Michael; Stolz, Daiana

    2016-07-01

    Gastroesophageal reflux disease (GERD) symptoms are associated with a higher risk of chronic obstructive pulmonary disease (COPD) exacerbation. We hypothesize that treatment with proton pump inhibitors reduces the risk of exacerbation in patients with stable COPD. A total of 638 patients with stable COPD for ≥6 weeks, ≥10 pack-years of smoking and Global Initiative for Chronic Obstructive Lung Disease II-IV seeking care in tertiary hospitals in eight European countries in the Predicting Outcome using Systemic Markers in Severe Exacerbations-COPD cohort was prospectively evaluated by us. Comorbidities including associated medical treatment were assessed at baseline, at exacerbation and at biannual visits. Median observation time was 24 months. The primary study outcomes were exacerbation and/or death. A total of 85 (13.3%) of COPD patients were on anti-GERD therapy. These patients had higher annual and higher severe exacerbation rates (P = 0.009 and P = 0.002), decreased quality of life (SF-36: activity score P = 0.004, St. George's Respiratory Questionnaire: physical functioning P = 0.013 and social functioning P = 0.007), higher body mass airflow obstruction, dyspnea and exercise capacity index (P = 0.033) and Modified Medical Research Council scores (P = 0.002), shorter 6-min walking distance (P = 0.0004) and a higher adjusted Charlson score (P GERD therapy was associated with a shorter time to severe exacerbation (HR 2.05 95% CI 1.37-3.08). Using three multivariable Cox-regression models, this association was independent of the following: (i) adjusted Charlson score and FEV1% predicted (HR 1.91 95% CI 1.26-2.90); (ii) adjusted Charlson score, body mass, airflow obstruction, dyspnea and exercise capacity index and Modified Medical Research Council (HR 1.62 95% CI 1.04-2.54); and (iii) adjusted Charlson score, FEV1% predicted and nine classes of medication for comorbidities (HR 1.63 95% CI 1.04-2.53). These findings

  18. 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

  19. 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

  20. Enhancement of hemocompatibility of the MERA monopivot centrifugal pump: toward medium-term use.

    Science.gov (United States)

    Yamane, Takashi; Kosaka, Ryo; Nishida, Masahiro; Maruyama, Osamu; Yamamoto, Yoshihiro; Kuwana, Katsuyuki; Kawamura, Hiroshi; Shiraishi, Yasuyuki; Yambe, Tomoyuki; Sankai, Yoshiyuki; Tsutsui, Tatsuo

    2013-02-01

    The MERA monopivot centrifugal pump has been developed for use in open-heart surgery, circulatory support, and bridge-to-decision for up to 4 weeks. The pump has a closed-type, 50-mm diameter impeller with four straight paths. The impeller is supported by a monopivot bearing and is driven by a radial-flux magnet-coupling motor. Because flow visualization experiments have clarified sufficient pivot wash and stagnation at the sharp corner of the pivot support was suggested, sharp corners were removed in the design stage. The index of hemolysis of the pump operating at more than 200 mm Hg was found to be lower than that of a commercial pump. Four-week animal tests were then conducted two times; improvement of thrombus formation was seen in the female pivot through modification of female pivot geometry. Overall antithrombogenicity was also recorded. Finally, to assure mid-term use, an additional 4-week durability test revealed that the rate of the axial pivot wear was as small as 1.1 µm/day. The present in vitro and in vivo studies revealed that the MERA monopivot centrifugal pump has sufficient hemocompatibility and durability for up to 4 weeks. © 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  1. 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 .

  2. 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

  3. Long-Term Outcomes of On- Versus Off-Pump Coronary Artery Bypass Grafting.

    Science.gov (United States)

    Smart, Neil A; Dieberg, Gudrun; King, Nicola

    2018-03-06

    When comparing effects of on- versus off-pump coronary artery bypass grafting (CABG), it is important to assess the long-term clinical outcomes. However, most research conducted thus far has concentrated on short-term outcomes and ignored the long-term clinical outcomes, especially the 5-year outcomes of the largest randomized controlled trials. The aim of this systematic review and meta-analysis was to investigate the long-term clinical outcomes of on- versus off-pump CABG. To identify potential studies systematic searches were carried out using various databases. The search strategy included the key concepts of cardiopulmonary bypass AND off-pump AND long term OR 5-year outcomes. This was followed by a meta-analysis investigating mortality, incidence of myocardial infarction, incidence of angina, need for revascularization, and incidence of stroke. Six studies totaling 8,145 participants were analyzed. In the on-pump group mortality was 12.3%, compared with 13.9% in the off-pump group. The odds ratio (OR) for this comparison was 1.16 (95% confidence interval [CI]: 1.02 to 1.32; p = 0.03; 13.9% vs. 12.3%). In contrast, there were no differences in the incidence of myocardial infarction (OR: 1.06: 95% CI: 0.91 to 1.25; p = 0.45; 8.4% vs. 7.9%), incidence of angina (OR: 1.09; 95% CI: 0.75 to 1.57; p = 0.65; 2.3% vs. 2.1%), need for revascularization (OR: 1.15; 95% CI: 0.95 to 1.40; p = 0.16; 5.9% vs. 5.1%), and the incidence of stroke (OR: 0.78; 95% CI: 0.56 to 1.10; p = 0.16; 2.2% vs. 2.8%). Statistically, on-pump CABG appeared to offer superior long-term survival, although the clinical significance of this may be more uncertain. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. 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.

  5. 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.

  6. In vitro Approaches to Support Bioequivalence and Substitutability of Generic Proton Pump Inhibitors via Nasogastric Tube Administration.

    Science.gov (United States)

    Ren, Ping; Cui, Minglei; Anand, Om; Xia, Li; Zhao, Zhuojun J; Sun, Dajun; Sharp, Trueman; Conner, Dale P; Peters, John; Jiang, Wenlei; Stier, Ethan; Jiang, Xiaojian

    2017-11-01

    Administration of proton pump inhibitors (PPIs) through nasogastric tubes may present risks. If the PPI drug products are not prepared properly, clogging or obstruction of nasogastric tubes can pose a safety concern. In addition, the integrity of the enteric coating of the drug product may be damaged resulting in reduced bioavailability of the active moiety. From the perspective of administration of generic PPIs when compared to the reference drug product, differences in formulation can potentially result in a greater relative risk for the generic drug product. As part of the assessment of bioequivalence, the Office of Generic Drugs (OGD) has developed a suite of in vitro testing to compare the delivery of the generic and reference products via nasogastric tubes. These in vitro tests assess essential attributes associated with the likelihood of clogging and maintenance of the enteric coating. These in vitro tests include studies evaluating sedimentation, granule size distribution, drug recovery, and acid resistance. One of the challenges is that while the administration of PPIs through nasogastric tubes is common in clinical practice, this issue is not uniformly addressed in the FDA approved label of the reference drug products. This paper discusses the design and rationale for in vitro testing of PPI formulations with respect to bioequivalence via nasogastric tube administration and in addition, it summarizes commonly occurring deficiencies in the in vitro nasogastric tube testing of 14 recent Abbreviated New Drug Applications (ANDA) submitted for five generic PPI drug products.

  7. Proton pump inhibitor therapy did not increase the prevalence of small-bowel injury: A propensity-matched analysis.

    Directory of Open Access Journals (Sweden)

    Atsuo Yamada

    Full Text Available Previous studies have reported that the suppression of acid secretion by using proton pump inhibitors (PPIs results in dysbiosis of the small-bowel microbiota, leading to exacerbated small-bowel injuries, including erosions and ulcers. This study was designed to assess the association between PPI therapy and small-bowel lesions after adjustment for the differences in baseline characteristics between users and non-users of PPIs.We retrospectively studied patients suspected to be suffering from small-bowel diseases, who underwent capsule endoscopy between 2010 and 2013. We used propensity matching to adjust for the differences in baseline characteristics between users and non-users of PPIs. The outcomes included the prevalence of small-bowel lesions: erosion, ulcer, angioectasia, varices, and tumor.We selected 327 patient pairs for analysis after propensity matching, and found no significant differences in the prevalence of small-bowel injuries, including erosions and ulcers, between users and non-users of PPIs. Two subgroup analyses of the effect of the type of PPI and the effect of PPI therapy in users and non-users of nonsteroidal anti-inflammatory drugs indicated no significant differences in the prevalence of small-bowel injuries in these two groups.PPI therapy did not increase the prevalence of small-bowel injury, regardless of the type of PPI used and the use of nonsteroidal anti-inflammatory drugs.

  8. 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.

  9. Regional differences in Clostridium difficile infections in relation to fluoroquinolone and proton pump inhibitor use, Finland, 2008-2011.

    Science.gov (United States)

    Kanerva, Mari; Ollgren, Jukka; Voipio, Tinna; Mentula, Silja; Lyytikäinen, Outi

    2015-08-01

    Several antimicrobial agents and proton pump inhibitors (PPIs) have been identified as risk factors for Clostridium difficile infections (CDIs). Nationwide laboratory-based surveillance of CDIs in Finland since 2008 has shown variation in regional CDI rates. We evaluated whether regional differences in CDI rates were associated with antibacterial and PPI use. Data on mean annual incidence rates of CDIs during 2008-2011 in 21 healthcare districts (HDs) were obtained from the National Infectious Disease Register, consumption (median annual use) of antimicrobials and PPIs from the Finnish Medical Agency, availability of molecular diagnostics by a laboratory survey and data on ribotypes from the national reference laboratory. The association over the 4 years was measured by incidence rate ratio (IRR) and we performed both bivariate and multivariate analyses. During 2008-2011, PPI use increased 27% but fluoroquinolone use was stable. The level of fluoroquinolone use was strongly associated with the mean annual CDI incidence rate in different HDs over the 4-year period, but PPI use had less effect. The molecular diagnostics methodology and PCR ribotype 027 were not independently associated with CDI rate. The final multivariable model only included fluoroquinolone and PPI use; IRR for fluoroquinolones was 2.20 (95% confidence interval (CI), 1.32-3.67; p = 0.003). Fluoroquinolone use may play a role in regional differences in CDI rates. Although the use has not recently increased, regionally targeted antimicrobial stewardship campaigns promoting appropriate use of fluoroquinolones should still be encouraged since they may decrease the incidence of CDIs.

  10. 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.

  11. Clopidogrel and proton pump inhibitor (PPI interaction: separate intake and a non-omeprazole PPI the solution?

    Directory of Open Access Journals (Sweden)

    Kenngott S

    2010-05-01

    Full Text Available Abstract Background Dual therapy with aspirin and clopidogrel increases the risk of gastrointestinal bleeding. Therefore, co-therapy with a proton pump inhibitor (PPI is recommended by most guidelines. However, there are warnings against combining PPIs with clopidogrel because of their interactions with cytochrome P450 isoenzyme 2C19 (CYP2C19. Methods The effects of the combined or separate intake of 20 mg of omeprazole and 75 mg of clopidogrel on the clopidogrel-induced inhibition of platelet aggregation were measured in four healthy subjects whose CYP2C19 exon sequences were determined. The effects of co-therapy with 10 mg of rabeprazole were also examined. Results Two subjects showed the wild-type CYP2C19 sequence. The concurrent intake of omeprazole had no effect on clopidogrel-induced platelet inhibition in these subjects. Two subjects were heterozygous for the *2 allele, with predicted reduced CYP2C19 activity. One of them was a clopidogrel non-responder. In the second heterozygous subject, omeprazole co-therapy reduced the clopidogrel anti-platelet effect when taken simultaneously or separately. However, the simultaneous intake of rabeprazole did not reduce the clopidogrel effect. Conclusion The clopidogrel-PPI interaction does not seem to be a PPI class effect. Rabeprazole did not affect the clopidogrel effect in a subject with a clear omeprazole-clopidogrel interaction. The separate intake of PPI and clopidogrel may not be sufficient to prevent their interaction.

  12. Intragastric acidification increases the sensitivity of 14C-urea breath test in patients taking a proton pump inhibitor

    International Nuclear Information System (INIS)

    Ma Yongjian

    2002-01-01

    Objective: To investigate if intragastric acidification at the ingestion of 14 C-urea can decrease the likelihood of false-negative (FN) results of urea breath test (UBT) in patients taking a proton pump inhibitor (PPI). Methods: Twenty-three patients with positive 14 C-UBT (UBT-1) results underwent an acid suppression treatment with omeprazole 40 mg/d for 14 d. On day 13, patients underwent second standard UBT (YBT-2). On day 14, patients underwent a modified UBT (UBT-3), which included consuming 200 mL of 0.1 mol/L citric acid solution 30 min before and at the administration of 14 C-urea. Mean 14 CO 2 expiration and the number of FN results were compared for the three UBTs. Results: Omeprazole caused a significant decrease in mean 14 CO 2 excretion between UBT-1[(5.57 +- 3.90) Bq/mmol] and UBT-2[(1.98 +- 1.42) Bq/mmol, t=5.867, P=0.000]. Omeprazole caused 10(43.5%) FN UBT-2 results. Mean 14 CO 2 expiration in UBT-3 [(4.93 +- 3.77) Bq/mmol] was greater than that in UBT-2 (t=-4.538, P=0.000). UBT-3 caused only 2 FN results (8.7%, x 2 =6.66, P 14 C-urea increases 14 Co 2 expiration and decreases FN 14 C-UBT results in patients taking PPI

  13. Cytotoxic effects of the proton pump inhibitor omeprazole on the non-target marine microalga Tetraselmis suecica.

    Science.gov (United States)

    Seoane, Marta; Esperanza, Marta; Cid, Ángeles

    2017-10-01

    Omeprazole (OMP) is one of the most commonly used drugs for the treatment of gastro-intestinal disorders. Although it is daily consumed in high quantities and commonly detected in waters worldwide, relatively little is known about its ecotoxicity. The aim of this study was to evaluate the potential acute toxicity of increasing concentrations of OMP on the marine microalga Tetraselmis suecica analysing several cytotoxicity biomarkers by flow cytometry after 24h of exposure. Results showed that OMP caused a decrease in growth and autofluorescence, an increase in cellular volume and intracellular complexity, hyperpolarization of cytoplasmic and mitochondrial membranes and intracellular acidification. In addition, large amounts of reactive oxygen species (ROS) were generated which resulted in a decrease in the percentage of the viable population. However, the viable population showed an increase in their metabolic activity as an early response to overcome the stress. In conclusion, OMP may affect proton pumps in non-target organisms such as microalgae; it disturbed pH homeostasis and provoked an early accumulation of ROS that resulted in a rapid cell death in cells exposed to the highest concentration assayed. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Effects of IY-81149, a newly developed proton pump inhibitor, on gastric acid secretion in vitro and in vivo.

    Science.gov (United States)

    Kwon, D; Chae, J B; Park, C W; Kim, Y S; Lee, S M; Kim, E J; Huh, I H; Kim, D Y; Cho, K D

    2001-01-01

    The inhibitory effects of IY-81149 (2-[[(4-methoxy-3-methyl)-2- pyridinyl]methyl-sulfinyl]-5-(1H-pyrol-1-yl)-1H-benzimidazole, CAS 172152-36-2), a newly developed proton pump inhibitor (PPI) on gastric acid secretion were investigated in vitro and in vivo. In rabbit parietal cell preparation, IY-81149 irreversibly inhibited H+/K(+)-ATPase in dose-dependent manner with an IC50 of pump inhibitory activity of 6.0 x 10(-6) mol/l and that of omeprazole (CAS 73590-58-6) was 1 x 10(-4) mol/l at pH 7.4. On cumulation of 14C-aminopyrine in histamine stimulated parietal cells, the IC50 of IY-81149 was 9.0 x 10(-9) mol/l and that of omeprazole was 1.9 x 10(-8) mol/l. The inhibition rates of IY-81149 and omeprazole at a concentration of 1 x 10(-9) mol/l in human parietal cells were 137% and 64%, respectively. In pylorus-ligated rats, IY-81149 showed a 2-3 times stronger inhibitory activity than omeprazole against gastric acid secretion. The ED50 of IY-81149 and omeprazole administered intraduodenally was 1.6 mg/kg and 3.8 mg/kg. In the case of oral administration, the ED50 of IY-81149 and omeprazole was 1.94 mg/kg and 5.64 mg/kg, respectively. But after 24 h administration, the anti-secretory activity of IY-81149 was lower than that of omeprazole at all doses tested. In anesthetized rats, IY-81149 dose-dependently increased gastric pH which was lowered by histamine infusion. In the case of i.v. injection, the ED50 of IY-81149 and omeprazole was 1.2 and 1.4 mg/kg and in the case of i.d. administration, the ED50 of IY-81149 and omeprazole was 3.9 and 4.1 mg/kg, respectively. IY-81149 also significantly inhibited pentagastrin-stimulated gastric secretion. Its ED50 was 2.1 mg/kg and that of omeprazole was 3.5 mg/kg with i.d. administration. In the case of i.v. injection, IY-81149 was equipotent to omeprazole. IY-81149 also inhibited gastric acid secretion strongly in fistular rats. The ED50 of IY-81149 administered intraduodenally was 0.43 mg/kg and that of omeprazole was 0.68 mg

  15. Role of vacuolar membrane proton pumps in the acidification of protein storage vacuoles following germination.

    Science.gov (United States)

    Wilson, Karl A; Chavda, Burzin J; Pierre-Louis, Gandhy; Quinn, Adam; Tan-Wilson, Anna

    2016-07-01

    During soybean (Glycine max (L.) Merrill) seed development, protease C1, the proteolytic enzyme that initiates breakdown of the storage globulins β-conglycinin and glycinin at acidic pH, is present in the protein storage vacuoles (PSVs), the same subcellular compartments in seed cotyledons where its protein substrates accumulate. Actual proteolysis begins to be evident 24 h after seed imbibition, when the PSVs become acidic, as indicated by acridine orange accumulation visualized by confocal microscopy. Imidodiphosphate (IDP), a non-hydrolyzable substrate analog of proton-translocating pyrophosphatases, strongly inhibited acidification of the PSVs in the cotyledons. Consistent with this finding, IDP treatment inhibited mobilization of β-conglycinin and glycinin, the inhibition being greater at 3 days compared to 6 days after seed imbibition. The embryonic axis does not appear to play a role in the initial PSV acidification in the cotyledon, as axis detachment did not prevent acridine orange accumulation three days after imbibition. SDS-PAGE and immunoblot analyses of cotyledon protein extracts were consistent with limited digestion of the 7S and 11S globulins by protease C1 starting at the same time and proceeding at the same rate in detached cotyledons compared to cotyledons of intact seedlings. Embryonic axis removal did slow down further breakdown of the storage globulins by reactions known to be catalyzed by protease C2, a cysteine protease that normally appears later in seedling growth to continue the storage protein breakdown initiated by protease C1. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  16. Regulation of the plasma membrane proton pump (H+-ATPase) by phosphorylation

    Science.gov (United States)

    Haruta, Miyoshi; Gray, William M.; Sussman, Michael R.

    2015-01-01

    In plants and fungi, energetics at the plasma membrane is provided by a large protonmotive force (PMF) generated by the family of P-type ATPases specialized for proton transport (commonly called PM H+-ATPases or, in Arabidopsis, AHAs for Arabidopsis H+-ATPases). Studies have demonstrated that this 100-kDa protein is essential for plant growth and development. Posttranslational modifications of the H+-ATPase play critical roles in its regulation. Phosphorylation of several Thr and Ser residues within the carboxy terminal regulatory domain composed of ~ 100 amino acids change in response to environmental stimuli, endogenous hormones, and nutrient conditions. Recently developed mass spectrometric technologies provide a means to carefully quantify these changes in H+-ATPase phosphorylation at the different sites. These chemical modifications can then be genetically tested in planta by complementing the loss-of-function aha mutants with phosphomimetic mutations. Interestingly, recent data suggest that phosphatase-mediated changes in PM H+-ATPase phosphorylation are important in mediating auxin-regulated growth. Thus, as with another hormone (abscisic acid), dephosphorylation by phosphatases, rather than kinase mediated phosphorylation, may be an important focal point for regulation during plant signal transduction. Although interactions with other proteins have also been implicated in ATPase regulation, the very hydrophobic nature and high concentration of this polytopic protein presents special challenges in evaluating the biological significance of these interactions. Only by combining biochemical and genetic experiments can we attempt to meet these challenges to understand the essential molecular details by which this protein functions in planta. PMID:26476298

  17. Regulation of the plasma membrane proton pump (H(+)-ATPase) by phosphorylation.

    Science.gov (United States)

    Haruta, Miyoshi; Gray, William M; Sussman, Michael R

    2015-12-01

    In plants and fungi, energetics at the plasma membrane is provided by a large protonmotive force (PMF) generated by the family of P-type ATPases specialized for proton transport (commonly called PM H(+)-ATPases or, in Arabidopsis, AHAs for Arabidopsis H(+)-ATPases). Studies have demonstrated that this 100-kDa protein is essential for plant growth and development. Posttranslational modifications of the H(+)-ATPase play crucial roles in its regulation. Phosphorylation of several Thr and Ser residues within the carboxy terminal regulatory domain composed of ∼100 amino acids change in response to environmental stimuli, endogenous hormones, and nutrient conditions. Recently developed mass spectrometric technologies provide a means to carefully quantify these changes in H(+)-ATPase phosphorylation at the different sites. These chemical modifications can then be genetically tested in planta by complementing the loss-of-function aha mutants with phosphomimetic mutations. Interestingly, recent data suggest that phosphatase-mediated changes in PM H(+)-ATPase phosphorylation are important in mediating auxin-regulated growth. Thus, as with another hormone (abscisic acid), dephosphorylation by phosphatases, rather than kinase mediated phosphorylation, may be an important focal point for regulation during plant signal transduction. Although interactions with other proteins have also been implicated in ATPase regulation, the very hydrophobic nature and high concentration of this polytopic protein presents special challenges in evaluating the biological significance of these interactions. Only by combining biochemical and genetic experiments can we attempt to meet these challenges to understand the essential molecular details by which this protein functions in planta. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. 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

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Cristóbal de-la-Coba

    2016-04-01

    Full Text Available Introduction: 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. Objective: 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. Material and methods: 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. Results: 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. Conclusions: PPIs are safe drugs whose benefits outweigh their potential side effects both short-term and long-term, provided their indication, dosage, and

  1. Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis.

    Science.gov (United States)

    Alhazzani, Waleed; Alenezi, Farhan; Jaeschke, Roman Z; Moayyedi, Paul; Cook, Deborah J

    2013-03-01

    Critically ill patients may develop bleeding caused by stress ulceration. Acid suppression is commonly prescribed for patients at risk of stress ulcer bleeding. Whether proton pump inhibitors are more effective than histamine 2 receptor antagonists is unclear. To determine the efficacy and safety of proton pump inhibitors vs. histamine 2 receptor antagonists for the prevention of upper gastrointestinal bleeding in the ICU. We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, ACPJC, CINHAL, online trials registries (clinicaltrials.gov, ISRCTN Register, WHO ICTRP), conference proceedings databases, and reference lists of relevant articles. Randomized controlled parallel group trials comparing proton pump inhibitors to histamine 2 receptor antagonists for the prevention of upper gastrointestinal bleeding in critically ill patients, published before March 2012. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were clinically important upper gastrointestinal bleeding and overt upper gastrointestinal bleeding; secondary outcomes were nosocomial pneumonia, ICU mortality, ICU length of stay, and Clostridium difficile infection. Trial authors were contacted for additional or clarifying information. Fourteen trials enrolling a total of 1,720 patients were included. Proton pump inhibitors were more effective than histamine 2 receptor antagonists at reducing clinically important upper gastrointestinal bleeding (relative risk 0.36; 95% confidence interval 0.19-0.68; p = 0.002; I = 0%) and overt upper gastrointestinal bleeding (relative risk 0.35; 95% confidence interval 0.21-0.59; p inhibitors and histamine 2 receptor antagonists in the risk of nosocomial pneumonia (relative risk 1.06; 95% confidence interval 0.73-1.52; p = 0.76; I = 0%), ICU mortality (relative risk 1.01; 95% confidence interval 0.83-1.24; p = 0.91; I = 0%), or ICU length of stay (mean difference -0.54 days; 95

  2. 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

  3. Short term optimization of electric power plants production including pumped storage and nuclear modulation

    International Nuclear Information System (INIS)

    Fourez, M.; Jussiant, C.; Roubens, M.; Trecat, J.

    1987-01-01

    Short term optimization, including start-up costs, pumped storage, constraints on shut-off time and run-time is a classical problem solved by dynamic programming. However when minimum base production is covered only by nuclear plants and is greater then minimum load demand, some sort of optimal modulation of these plants must be taken into account. The program developed deals with this constraint in a quasi-optimal way, and allows also energy exchanges based on short term contracts. The effectiveness of the proposed algorithm has been verified at the Belgian utility where this program was developed

  4. Is the era of intravenous proton pump inhibitors coming to an end in patients with bleeding peptic ulcers? Meta-analysis of the published literature.

    Science.gov (United States)

    Jian, Zhixiang; Li, Hui; Race, Nicholas S; Ma, Tingting; Jin, Haosheng; Yin, Zi

    2016-09-01

    Oral and intravenous proton pump inhibitors (PPIs) are equipotent in raising gastric pH. However, it is not known whether oral PPIs can replace intravenous PPIs in patients with bleeding peptic ulcers. We conducted a systematic review and meta-analysis of randomized controlled trials to compare oral and intravenous PPIs among patients with peptic ulcer bleeding. A search of all major databases and relevant journals from inception to April 2015, without a restriction on languages, was performed. A total of 859 patients from seven randomized controlled trials were included in the meta-analysis. Similar pooled outcome measures were demonstrated between the two groups in terms of oral PPIs vs. intravenous PPIs in the rate of recurrent bleeding within the 30-day follow-up period [risk ratio = 0.90; 95% confidence interval (CI): 0.58, 1.39; P = 0.62; I(2)  = 0%). In terms of the rate of mortality, both oral and intravenous PPIs showed similar outcomes, and the pooled risk ratio was 0.88 (95% CI: 0.29, 2.71; P = 0.82; I(2)  = 0%). Likewise, no significant difference was detected in the need for blood transfusion and length of hospital stay; the pooled mean differences were -0.14 (95% CI: -0.39, 0.12; P = 0.29; I(2)  = 32%) and -0.60 (95% CI: -1.42, 0.23; P = 0.16; I(2)  = 79%), respectively. Our results suggest that oral PPIs are a feasible, safe alternative to intravenous PPIs in patients with bleeding peptic ulcers, and may be able to replace intravenous PPIs as the treatment of choice in these patients. © 2016 The British Pharmacological Society.

  5. 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.

  6. 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.

  7. 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

  8. Inadequate prescription of chronic consumption of proton pump inhibitors in a hospital in Mexico: Cross-sectional study

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    Jaime Alberto Sánchez-Cuén

    2013-03-01

    Full Text Available Introduction: PPIs have been an enormous therapeutic advance in acid-related diseases. However, it has been detected an abuse in its consumption. The aim of this study was to determine the frequency of inadequate prescription of chronic use of PPIs in outpatients in a speciality hospital. Material and methods: we performed a cross-sectional descriptive study review. The study population were patients, chronic users of proton pump inhibitors (PPIs, attending outpatient consult in a hospital of government workers. We defined as chronic user of PPIs that patient that takes medication daily for over a year and inappropriate prescription, that one that has not been approved by the clinical guidelines. A simple random sampling was utilized. The following parameters were investigated: diagnosis and prescription of PPIs, time of use, at which level of care PPIs were prescribed (primary care or specialist, self-medication, with or without endoscopy. For the statistical analysis, we used Student's t-test and Chi-square, 95% confidence intervals and significance 0.05 %. Results: we reviewed 153 patients, 40 (26.1 % men and 113 (73.9 % women, mean age 58 ± 11.4 years. The prescription of chronic treatment with PPIs was adequate in 64.7 % of patients and inadequate in 35.3 %. The most common appropriate prescription (31.3 % of chronic use of PPIs was due to gastroesophageal reflux disease. The most common inadequate prescription was absence of diagnosis (22.2 %, polypharmacy without nonsteroidal antiinflammatory drugs (16.6 % and chronic gastritis (16.6 %. History of endoscopy were not statistically significant. Conclusions: the frequency of inappropriate prescriptions of chronic use of PPIs was high, around 35.3 %, similar to those reported in hospitals in developed countries.

  9. Prevalence and predictors of non-evidence based proton pump inhibitor use among elderly nursing home residents in the US.

    Science.gov (United States)

    Rane, Pratik P; Guha, Sushovan; Chatterjee, Satabdi; Aparasu, Rajender R

    Proton pump inhibitors (PPIs) can lead to several adverse effects among the elderly, particularly when used inappropriately or in contrast to evidence suggested protocols. The aim of this study was to examine the prevalence and predictors of non-evidence based PPI use in elderly nursing home residents. A cross-sectional study was conducted using data from the 2004 National Nursing Home Survey (NNHS). The study sample included nursing home residents 65 years and older. Descriptive statistics were used to examine the prevalence of non-evidence based PPI use. Multivariable logistic regression was used to evaluate the patient and facility-level factors associated with non-evidence based PPI use among the elderly nursing home residents. A total of 355,600 elderly nursing home residents received at least one PPI for an overall prevalence of 26.99%. Among those elderly receiving PPIs, 48.59% of the use was not evidence based. Multivariable logistic regression revealed that residents with osteoporosis (Odds Ratio (OR): 0.55, 95% CI: 0.45-0.68), SSRI users (OR: 0.81, 95% CI: 0.68-0.97) and those residing in micropolitan area (OR: 0.79, 95% CI: 0.63-0.98) were negatively associated with prescription of PPIs without an indication. Patients with chronic cough (OR: 2.10, 95% CI: 1.12-3.96) and Medicare insurance (OR: 1.23, 95% CI: 1.01-1.50) were positively associated with prescription of PPIs without an indication. The current study found that almost half of the elderly nursing home residents used PPIs for non-evidence based indications. Given the safety concerns and high non-evidence based use of PPIs in nursing homes, there is an urgent need to optimize PPI use in the elderly. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    1995-01-01

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

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

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    Armstrong D

    2016-12-01

    Full Text Available 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

  12. Effectiveness of ranitidine bismuth citrate and proton pump inhibitor based triple therapies of Helicobacter pylori in Turkey

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    Mustafa Iscan

    2011-09-01

    Full Text Available Background : Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, MALT lymphoma, and adenocarcinoma of the stomach. The reported prevalence of H. pylori in the adult population in Turkey is 67.6%–81.3%. A national meta-analysis showed that the average H. pylori eradication rate with proton pump inhibitor-based triple regimens in Turkey had decreased from 84% in 1997 to 55.3% in 2004, suggesting a need to evaluate alternative regimens. Materials and methods : The study was a prospective, single-center trial with a parallel group design. After the selection procedure, consecutive out-patients were assigned to one of six study groups using random sampling numbers. All patients received amoxicillin 1,000 mg b.i.d. and clarithromycin 500 mg b.i.d. along with ranitidine bismuth citrate 400 mg b.i.d., or omeprazole 20 mg b.i.d., or lansoprazole 30 mg b.i.d., or rabeprazole 20 mg b.i.d., or pantoprazole 40 mg b.i.d., or esomeprazole 40 mg b.i.d. for 14 days. 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 treat and per protocol analyses. The other four groups (omeprazole, lansoprazole, pantoprazole, and esomeprazole groups showed statistically significant lower eradication rates both at intention to treat (between 57.6 and 66.7% and per protocol (between 60.3 and 72.1% analyses when compared with ranitidine bismuth citrate and rabeprazole groups (p<.05. Conclusion : Ranitidine bismuth citrate and/or rabeprazole based triple therapies must be preferred for the first-line treatment of H. pylori infection.

  13. 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.

  14. Effect of low-dose proton pump inhibitor on preventing upper gastrointestinal bleeding in chronic kidney disease patients receiving aspirin.

    Science.gov (United States)

    Lim, Hyun; Kim, Jong Hyeok; Baik, Gwang Ho; Park, Ji Won; Kang, Ho Suk; Moon, Sung Hoon; Park, Choong Kee

    2015-03-01

    Upper gastrointestinal bleeding (UGIB) leads to significant morbidity and mortality in chronic kidney disease (CKD) patients. This study determined the efficacy of using a low-dose proton pump inhibitor (PPI) to reduce the risk of non-variceal UGIB in CKD patients receiving aspirin. We retrospectively reviewed the medical records of 500 CKD patients who received aspirin between January 2008 and March 2013. Cumulative incidence analysis using the Kaplan-Meier method was performed to analyze the rate of non-variceal UGIB and association with the administration of low-dose PPI. Of the 500 patients, 191 received low-dose PPI. Over the follow-up period, which lasted 1067 person-years, three patients in the low-dose PPI group (8.9 per 1000 person-years) and 19 patients in the non-PPI group (25.9 per 1000 person-years) developed non-variceal UGIB, respectively (P = 0.113). Low-dose PPI use did not decrease the risk of UGIB in CKD patients, including patients who did not receive dialysis (P = 0.127). However, according to the subgroup analysis of 230 patients who received dialysis, the low-dose PPI group (14.4 per 1000 person-years) demonstrated significantly reduced incidence and risk of non-variceal UGIB in comparison with the non-PPI group (53.8 per 1000 person-years) (P = 0.032). Prophylactic low-dose PPI can reduce the risk of non-variceal UGIB in dialysis patients receiving aspirin. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  15. 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.

  16. Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis

    Science.gov (United States)

    Filion, Kristian B; Chateau, Dan; Targownik, Laura E; Gershon, Andrea; Durand, Madeleine; Tamim, Hala; Teare, Gary F; Ravani, Pietro; Ernst, Pierre; Dormuth, Colin R

    2014-01-01

    Objective Previous observational studies suggest that the use of proton pump inhibitors (PPIs) may increase the risk of hospitalisation for community-acquired pneumonia (HCAP). However, the potential presence of confounding and protopathic biases limits the conclusions that can be drawn from these studies. Our objective was, therefore, to examine the risk of HCAP with PPIs prescribed prophylactically in new users of non-steroidal anti-inflammatory drugs (NSAIDs). Design We formed eight restricted cohorts of new users of NSAIDs, aged ≥40 years, using a common protocol in eight databases (Alberta, Saskatchewan, Manitoba, Ontario, Quebec, Nova Scotia, US MarketScan and the UK's General Practice Research Database (GPRD)). This specific patient population was studied to minimise bias due to unmeasured confounders. High-dimensional propensity scores were used to estimate site-specific adjusted ORs (aORs) for HCAP at 6 months in PPI patients compared with unexposed patients. Fixed-effects meta-analytic models were used to estimate overall effects across databases. Results Of the 4 238 504 new users of NSAIDs, 2.3% also started a PPI. The cumulative 6-month incidence of HCAP was 0.17% among patients prescribed PPIs and 0.12% in unexposed patients. After adjustment, PPIs were not associated with an increased risk of HCAP (aOR=1.05; 95% CI 0.89 to 1.25). Histamine-2 receptor antagonists yielded similar results (aOR=0.95, 95% CI  0.75 to 1.21). Conclusions Our study does not support the proposition of a pharmacological effect of gastric acid suppressors on the risk of HCAP. PMID:23856153

  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. Muscular Adverse Drug Reactions Associated with Proton Pump Inhibitors: A Disproportionality Analysis Using the Italian National Network of Pharmacovigilance Database.

    Science.gov (United States)

    Capogrosso Sansone, Alice; Convertino, Irma; Galiulo, Maria Teresa; Salvadori, Stefano; Pieroni, Stefania; Knezevic, Tamara; Mantarro, Stefania; Marino, Alessandra; Hauben, Manfred; Blandizzi, Corrado; Tuccori, Marco

    2017-10-01

    Proton pump inhibitors (PPIs) have been implicated in the occurrence of moderate to severe myopathies in several case reports. This study was performed to assess the reporting risk of muscular adverse drug reactions (ADRs) associated with PPIs in the Italian National Network of Pharmacovigilance database. A disproportionality analysis (case/non-case) was performed using spontaneous reports collected in the database between July 1983 and May 2016. Reporting odds ratio (ROR) and 95% confidence intervals (CIs) were calculated as a measure of disproportionality. In a secondary and tertiary analysis, we explored the association of PPIs with muscular ADRs after taking into account the masking effect of statins. Moreover, the possibility of an interaction between PPIs and statins, leading to the occurrence of muscular ADRs, was also tested. The study was carried out on 274,108 reports. The ROR of muscular ADRs for PPIs, adjusted for age and gender, was 1.484 (95% CI 1.204-1.829; p < 0.001), whereas the ROR for rhabdomyolysis was 0.621 (95% CI 0.258-1.499). Similar results were obtained in the secondary analysis. The tertiary analysis, where PPIs were considered regardless of whether their role was suspected or concomitant, showed a potential disproportionate reporting for the combination PPIs-rhabdomyolysis (ROR 1.667, 95% CI 1.173-2.369; p < 0.01). The PPIs-statins combination was not associated with an enhanced ROR of muscular ADRs/rhabdomyolysis compared with statins alone. This explorative study suggests that the class of PPIs could be involved in reports of muscular ADRs, rather than any other ADR, more frequently than any non-statin drug. Our results must be corroborated by further studies.

  19. 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.

  20. 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.

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

    International Nuclear Information System (INIS)

    Coen, John J.; Paly, Jonathan J.; Niemierko, Andrzej; Weyman, Elizabeth; Rodrigues, Anita; Shipley, William U.; Zietman, Anthony L.; Talcott, James A.

    2012-01-01

    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.

  2. Breast pump use amongst mothers of healthy term infants in Melbourne, Australia: A prospective cohort study.

    Science.gov (United States)

    Johns, Helene M; Amir, Lisa H; McLachlan, Helen L; Forster, Della A

    2016-02-01

    this paper describes the use of breast pumps amongst a group of mothers of healthy term infants in Melbourne, Australia, between birth and six months post partum. a prospective cohort study; data were collected using structured questionnaires. 1003 postpartum women who had given birth to healthy infants at term were recruited from three Melbourne maternity hospitals between July 2009 and April 2011. Data were collected by face-to-face interview at recruitment and by telephone interview three and six months later. at recruitment (24 to 48 hours post partum), 60% (605/1003) of women already had a breast pump. At two weeks post partum expressing was common; 62% (290/466) of women had expressed by this time, with 40% (186/466) doing so several times a day. By six months post partum 83% (754/911) of the women had a breast pump and 40% (288/715) were expressing, although most just occasionally. The most common reasons for any expressing in the first six months were 'to be able to go out and leave the baby' (35%; 268/772); milk supply 'not enough'(27%; 207/772); and having 'too much' milk (19%; 147/772). The increasing popularity of expressing breast milk to feed infants is not driven by women returning to the workforce, as only 10% of women (80/772) expressed because they had returned to paid employment. health professionals should be aware that in some settings breast pump use is common in the first six months, and this is not always related to maternal workforce participation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Proton-pump inhibitors

    African Journals Online (AJOL)

    definition of what constitutes an adequate trial of PPIs. Six weeks of a daily PPI at a standard dose ... treatment of choice for gastro-oesophageal reflux disease and peptic ulcer disease. PPIs are considered safe and .... chronic PPI use and vitamin B12 deficiency.33 Thus, it is prudent to check vitamin B12 levels, especially ...

  4. 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

  5. Efficacy of vonoprazan for 24-week maintenance therapy of patients with healed reflux esophagitis refractory to proton pump inhibitors.

    Science.gov (United States)

    Mizuno, Hideki; Yamada, Kazutoshi; Minouchi, Keiji; Kamiyamamoto, Shinji; Hinoue, Yoshinobu

    2018-02-01

    The aim of the present study was to evaluate the efficacy of a potassium-competitive acid blocker (P-CAB), vonoprazan, for the maintenance therapy of healed reflux esophagitis (RE). A total of 60 patients were enrolled in this open-label, single-center, prospective study. All patients were diagnosed with RE with a frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) total score ≥8 following treatment with standard proton pump inhibitors (PPIs) for a minimum of 8 weeks. Standard PPI treatment was switched to vonoprazan 20 mg once daily for 4 weeks. A total of 52 patients, who had no endoscopic evidence of erosive esophagitis following vonoprazan treatment, received maintenance therapy with vonoprazan 10 mg once daily for 24 weeks. Symptoms were evaluated using the FSSG and Gastrointestinal Symptom Rating Scale (GSRS). Upper gastrointestinal endoscopies were performed following 24 weeks of maintenance therapy. The primary endpoint was to determine the proportion of patients who exhibited maintenance of healed RE refractory to PPIs following 24 weeks of maintenance therapy with vonoprazan 10 mg once daily. Secondary endpoints included evaluation of the proportion of patients with symptomatic non-relapse at 24 weeks. Maintenance therapy with vonoprazan 10 mg once daily prevented relapse of esophageal mucosal breaks in 37/43 (86.0%) patients at 24 weeks. However, the number of patients with symptomatic relapse was 1 (1.9%) and 4 (7.7%) at 4 and 8 weeks, respectively. A total of 4 patients were withdrawn due to loss to follow-up. At the end of the 24-week maintenance period, the symptomatic non-relapse rate for acid reflux-associated and dysmotility symptom FSSG scores were 86.5 and 80.8%, respectively. Furthermore, the symptomatic non-relapse rate for reflux, abdominal pain, indigestion, diarrhea, and constipation GSRS scores at 24 weeks were 86.5, 80.8, 75.0, 71.2 and 76.9%, respectively. No serious adverse events were reported during the study

  6. [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 (Ppractices evaluation improved the relevance of the prescriptions

  7. Effects of the Proton Pump Inhibitors Omeprazole and Pantoprazole on the Cytochrome P450-Mediated Metabolism of Venlafaxine.

    Science.gov (United States)

    Kuzin, Maxim; Schoretsanitis, Georgios; Haen, Ekkehard; Stegmann, Benedikt; Hiemke, Christoph; Gründer, Gerhard; Paulzen, Michael

    2017-09-02

    BACKGROUND AND OBJECTIVE: An increasing trend in prescribing proton pump inhibitors (PPIs) inevitably increases the risk of unwanted drug-drug interactions (DDIs). The aim of this study was to uncover pharmacokinetic interactions between two PPIs-omeprazole and pantoprazole-and venlafaxine. A therapeutic drug monitoring database contained plasma concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine. We considered three groups: a group of patients who received venlafaxine without confounding medications (non-PPI group, n = 906); a group of patients who were comedicated with omeprazole (n = 40); and a group of patients comedicated with pantoprazole (n = 40). Plasma concentrations of venlafaxine, O-desmethylvenlafaxine and active moiety (venlafaxine + O-desmethylvenlafaxine), as well as dose-adjusted plasma concentrations, were compared using non-parametrical tests. Daily doses of venlafaxine did not differ between groups (p = 0.949). The Mann-Whitney U test showed significantly higher plasma concentrations of active moiety, as well as venlafaxine and O-desmethylvenlafaxine, in both PPI groups [p = 0.023, p = 0.011, p = 0.026, +29% active moiety, +27% venlafaxine, +36% O-desmethylvenlafaxine (pantoprazole); p = 0.003, p = 0.039 and p < 0.001, +36% active moiety, +27% venlafaxine, +55% O-desmethylvenlafaxine (omeprazole)]. Significantly higher concentration-by-dose (C/D) values for venlafaxine and active moiety were detected in the pantoprazole group (p = 0.013, p = 0.006, respectively), while in the omeprazole group, C/D ratios for all three parameters-venlafaxine, O-desmethylvenlafaxine and active moiety-were significantly higher (p = 0.021, p < 0.001 and p < 0.001, respectively). Significantly higher plasma concentrations for all parameters (venlafaxine, O-desmethylvenlafaxine, active moiety) suggest clinically relevant inhibitory effects of both PPIs, most likely on the cytochrome P450 (CYP) 2C19-mediated

  8. Proton pump inhibitor use and fracture risk - effect modification by histamine H1 receptor blockade. Observational case-control study using National Prescription Data

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Vestergaard, Peter

    2013-01-01

    It remains unknown why proton pump inhibitor (PPI) use may be associated with risk of osteoporotic fractures; evidence of direct effects on calcium absorption or on the osteoclast in humans is weak or absent. However, the ensuing increased gastrin levels may cause histamine production through...... hypertrophy of gastric enterochromaffin like cells, which could lead to bone loss. We speculated that H1 receptor antagonists (H1RA) used for allergies would then reduce the effect of PPI on bone. We therefore conducted a register-based case-control study comprising 124,655 patients with hospital treated...

  9. 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

  10. 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

    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...... that the pH optimum is related to proton release from the proton exit site. Our previous single-enzyme experiments identified rare, long-lived conformation states of cytochrome bo3 where protons leak back under turn-over conditions. Here, we analyzed and found that ~ 23% of cytochrome bo3 proteoliposomes......-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...

  11. 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.

  12. 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

  13. Rifabutin-based high-dose proton-pump inhibitor and amoxicillin triple regimen as the rescue treatment for Helicobacter pylori.

    Science.gov (United States)

    Lim, Hyun Chul; Lee, Yong Jae; An, Byoungrak; Lee, Seung Woo; Lee, Yong Chan; Moon, Byung Soo

    2014-12-01

    Rifabutin has been known to be effective in multidrug-resistant Helicobacter pylori-harboring patients undergoing treatment failure for H. pylori infection. To evaluate the efficacy of 7-day treatment regimen consisting rifabutin daily but increasing the dose of amoxicillin and lansoprazole in patients who have failed first and second eradication and to assess the side effect profiles in South Korea. From December 2007 to May 2013, 59 H. pylori-infected patients with two previous eradication failures were enrolled for this study prospectively. The eligible patients were randomly assigned to either group A or B. Group A received lansoprazole 30 mg bid, amoxicillin 1.0 g tid and rifabutin 150 mg bid during 7 days, whereas group B received lansoprazole 60 mg bid, amoxicillin 1.0 g tid and rifabutin 150 mg bid during 7 days. In group A, H. pylori eradication was achieved in 25 (78.1%) of the 32 patients in the ITT analysis and in 25 (80.6%) of the 31 patients in the PP analysis. In group B, H. pylori eradication was achieved in 26 (96.3%) of the 27 patients in the ITT analysis and in 27 (100%) of the 26 patients in the PP analysis. There was statistically significant difference between the two groups in terms of the eradication rates in PP analysis (p = .047), whereas a marginally statistical significance was found in terms of the eradication rates in ITT analysis (p = .051). Reported side effects were mild, and treatment was well tolerated. No major changes in physical examination or in standard laboratory parameters were observed after treatment. Rifabutin-based high-dose proton-pump inhibitor (PPI)-combined therapy as empirical rescue treatment is more effective than standard dose PPI-combined rifabutin-based therapy, safe and best tolerable in third-line therapy in the Korean population. The key to successful rescue therapy with rifabutin-amoxicillin-PPI regimen may be to increase doses of PPI. © 2014 The Authors. Helicobacter Published by John Wiley & Sons Ltd.

  14. 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.

  15. 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.

  16. Impact of clinical pharmacists' recommendations on a proton pump inhibitor taper protocol in an ambulatory care practice.

    Science.gov (United States)

    Bundeff, Andrew W; Zaiken, Kathy

    2013-05-01

    Previous studies have demonstrated an association between chronic proton pump inhibitor (PPI) utilization and adverse events such as fractures, infections, hypomagnesemia, and vitamin B12 deficiency. Because patients taking PPIs for an extended period of time are more susceptible to these adverse events, an approach to tapering patients off PPIs is clinically warranted. To evaluate the impact of clinical pharmacists' recommendations to clinicians to decrease PPI use in patients when chronic therapy is not indicated. Clinical pharmacists electronically sent PPI taper recommendations for qualifying patients to primary care providers the day before each patient's appointment. Using insurance claims data, an average pills per month (PPM) count was calculated for the 5-month period prior to initiating the PPI taper as well as for the 5-month period after the date of taper initiation. The PPM count was calculated by dividing the total number of pills a patient received by the total number of days in that period, multiplied by 30. The primary outcome for the study was the change in average PPM count from baseline (pretaper period) to follow-up (posttaper period) and was assessed using a paired t-test. Secondary outcomes included change in total annualized PPI costs to the organization, proportion of patients who began the taper protocol after primary care provider recommendation, and whether baseline characteristics were predictors of successful response. Change in annualized PPI costs to the organization was calculated by multiplying the average unit cost per pill (determined using a weighted average of the average wholesale price of the individual drugs) by the PPM change seen with the primary outcome and by the number of patients included in the study and expressed over the period of a full year. Logistic regression analysis was used to determine whether baseline variables including alcohol and tobacco use, diagnosis related to PPI use, PPI dose, dosing frequency

  17. 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.

  18. 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

  19. 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.

  20. Proton pump activity is required for active uptake of chloride in isolated amphibian skin exposed to freshwater

    DEFF Research Database (Denmark)

    Jensen, Lars Jørn; Willumsen, Niels J.; Larsen, Erik Hviid

    2002-01-01

    Net proton secretion and unidirectional chloride fluxes were measured in isolated skin of toads (Bufo bufo) and frogs (Rana esculenta) mounted in an Ussing chamber and exposed to a Ringer's solution on the serosal side and a freshwater-like solution (1-3 mM Cl-) on the external side. Active proto...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    STUDY QUESTION: What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)? METHODS: This was a nationwide cohort study based on linked...... 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...

  2. 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.

  3. 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 pylori isolates. OMP and LPZ inhibited 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.

  4. 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.

  5. 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.

  6. A measurement of long-term energy stability of proton beam produced by Pelletron accelerator

    International Nuclear Information System (INIS)

    Takeda, Naoto; Hasegawa, Masataka; Kudo, Katsuhisa; Shimada, Makoto

    1997-01-01

    A 4 MV single-ended Van de Graaff ion accelerator (4UH-HC Pelletron from National Electrostatics Corp., USA) installed in 1982 has been used for various research fields of monoenergetic neutron fluence standards, creation and modification of new materials and material structure diagnostics by using ion beams. The accelerator was equipped with tank liner voltages stabilizer in 1993 in order to improve the terminal voltage stability to 0.01% for the ripple at 3 MV terminal voltage. Recently the power supply for an analyzing magnet located between the accelerator and a neutron producing target was replaced to obtain the better energy stability of 10 -6 . In this study, a long-term stability of proton energy, which is mainly affected by the drift of terminal voltage and the change of proton beam track from the ion source to the target, has been evaluated by measuring the change of neutron yield on the steeply changing lower energy portion of the resonance peak at 2.961 MeV from the Sc(p,n)Ti reaction. The result shows the energy spread (FWHM) to be less than 1.7 keV over 3 hour operation. (author)

  7. 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.

  8. A Genetic Screen for Pathogenicity Genes in the Hemibiotrophic Fungus Colletotrichum higginsianum Identifies the Plasma Membrane Proton Pump Pma2 Required for Host Penetration.

    Directory of Open Access Journals (Sweden)

    Martin Korn

    Full Text Available We used insertional mutagenesis by Agrobacterium tumefaciens mediated transformation (ATMT to isolate pathogenicity mutants of Colletotrichum higginsianum. From a collection of 7200 insertion mutants we isolated 75 mutants with reduced symptoms. 19 of these were affected in host penetration, while 17 were affected in later stages of infection, like switching to necrotrophic growth. For 16 mutants the location of T-DNA insertions could be identified by PCR. A potential plasma membrane H(+-ATPase Pma2 was targeted in five independent insertion mutants. We genetically inactivated the Ku80 component of the non-homologous end-joining pathway in C. higginsianum to establish an efficient gene knockout protocol. Chpma2 deletion mutants generated by homologous recombination in the ΔChku80 background form fully melanized appressoria but entirely fail to penetrate the host tissue and are non-pathogenic. The ChPMA2 gene is induced upon appressoria formation and infection of A. thaliana. Pma2 activity is not important for vegetative growth of saprophytically growing mycelium, since the mutant shows no growth penalty under these conditions. Colletotrichum higginsianum codes for a closely related gene (ChPMA1, which is highly expressed under most growth conditions. ChPMA1 is more similar to the homologous yeast genes for plasma membrane pumps. We propose that expression of a specific proton pump early during infection may be common to many appressoria forming fungal pathogens as we found ChPMA2 orthologs in several plant pathogenic fungi.

  9. Insulin pumps in pediatric routine care improve long-term metabolic control without increasing the risk of hypoglycemia.

    Science.gov (United States)

    Hanas, Ragnar; Adolfsson, Peter

    2006-02-01

    Although continuous subcutaneous insulin infusion (CSII) has been used in pediatric practice for >20 yr, the technique is not widely used in many countries. The aim of this non-randomized population-based study was to evaluate CSII in routine pediatric care. In a 1-yr cross-sectional evaluation, 27/89 patients (30.3%, age 7-21 yr) used pumps (two during the night only), the others 4-6 injections/day. In patients with >2 yr of diabetes, pump users had higher HbA1c (8.9+/-1.0 vs. 8.2+/-1.6%, p=0.04), less insulin/24 h (0.9+/-0.1 vs. 1.0+/-0.2 U/kg, p=0.002), and longer diabetes duration (p=0.02). The higher HbA1c is explained by 67% of pump patients having high HbA1c (>8.5%) as the major indication for CSII. The overall incidence of severe hypoglycemia was 31.5/100 patient years, 40.3 for injection therapy, and 11.1 for pump therapy (p=not significant). The incidence of severe hypoglycemia with unconsciousness was 12.9/100 patient years and with seizures 9.7 for injection therapy, whereas no children on pumps experienced these complications during the cross-sectional study year. We had no admissions for ketoacidosis in either group during this year. The pump patients were followed for 5 yr after pump start. Two stopped using the pump after 2 and 3 yr. For the patients with high HbA1c as indication, mean HbA1c the year before pump was 9.5%. Mean HbA1c during the first year with pump was lowered to 8.9% (p=0.019), the second year 8.6% (p=0.017), the third year 8.6 (p=0.012), the fourth year 8.7 (p=0.062), and the fifth year 8.9% (p=0.28). We found six cases of ketoacidosis corresponding to 4.7/100 patient years. In conclusion, we found a long-term lowering of HbA1c after starting CSII in a pediatric population, decreased frequency of severe hypoglycemia, and a low risk of ketoacidosis.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Optimal short-term operation and sizing of pumped-storage power plants in systems with high penetration of wind energy

    OpenAIRE

    Pérez Díaz, Juan Ignacio; Perea, Alejandro; Wilhelmi Ayza, José-Román

    2010-01-01

    In this paper the short-term optimal operation of an electric system comprising several thermal power plants and one pumped storage plant is studied in several scenarios of power demand and wind penetration in order to draw conclusions about the contribution of the pumped storage plant to system operation costs. A mixed integer linear programming model is used to obtain the optimal hourly thermal, hydro and pumping powers so that the production cost of the entire system is minimized. An aggre...

  16. Proton minibeam radiation therapy spares normal rat brain: Long-Term Clinical, Radiological and Histopathological Analysis

    OpenAIRE

    Prezado, Yolanda; Jouvion, Gregory; Hardy, David; Patriarca, Annalisa; Nauraye, Catherine; Bergs, Judith; González, Wilfredo; Guardiola, Consuelo; Juchaux, Marjorie; Labiod, Dalila; Dendale, Remi; Jourdain, Laurène; Sebrie, Catherine; Pouzoulet, Frederic

    2017-01-01

    Proton minibeam radiation therapy (pMBRT) is a novel strategy for minimizing normal tissue damage resulting from radiotherapy treatments. This strategy partners the inherent advantages of protons for radiotherapy with the gain in normal tissue preservation observed upon irradiation with narrow, spatially fractionated beams. In this study, whole brains (excluding the olfactory bulb) of Fischer 344 rats (n = 16) were irradiated at the Orsay Proton Therapy Center. Half of the animals received st...

  17. 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

  18. 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

  19. 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

  20. 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.

  1. A Water Dimer Shift Activates a Proton Pumping Pathway in the PR → F Transition of ba3 Cytochrome c Oxidase.

    Science.gov (United States)

    Han Du, Wen-Ge; Götz, Andreas W; Noodleman, Louis

    2018-02-05

    Broken-symmetry density functional calculations have been performed on the [Fe a3 4+ ,Cu B 2+ ] state of the dinuclear center (DNC) for the P R → F part of the catalytic cycle of ba 3 cytochrome c oxidase (CcO) from Thermus thermophilus (Tt), using the OLYP-D3-BJ functional. The calculations show that the movement of the H 2 O molecules in the DNC affects the pK a values of the residue side chains of Tyr237 and His376 + , which are crucial for proton transfer/pumping in ba 3 CcO from Tt. The calculated lowest energy structure of the DNC in the [Fe a3 4+ ,Cu B 2+ ] state (state F) is of the form Fe a3 4+ ═O 2- ···Cu B 2+ , in which the H 2 O ligand that resulted from protonation of the OH - ligand in the P R state is dissociated from the Cu B 2+ site. The calculated Fe a3 4+ ═O 2- distance in F (1.68 Å) is 0.03 Å longer than that in P R (1.65 Å), which can explain the different Fe a3 4+ ═O 2- stretching modes in P (804 cm -1 ) and F (785 cm -1 ) identified by resonance Raman experiments. In this F state, the Cu B 2+ ···O 2- (ferryl-oxygen) distance is only around 2.4 Å. Hence, the subsequent O H state [Fe a3 3+ -OH - -Cu B 2+ ] with a μ-hydroxo bridge can be easily formed, as shown by our calculations.

  2. The effectiveness of esomeprazole 40 mg in patients with persistent symptoms of gastro-oesophageal reflux disease following treatment with a full dose proton pump inhibitor

    Science.gov (United States)

    Jones, R; Patrikios, T

    2008-01-01

    Background: Some patients with gastro-oesophageal reflux disease (GORD) remain symptomatic despite proton pump inhibitor (PPI) treatment. There is a need to determine the most appropriate management of these patients. Aims: To assess the effectiveness of esomeprazole 40 mg in GORD symptoms persisting in patients receiving a full daily dose PPI. Methods: In this multi-centre open label study patients who had received full daily dose PPI for 8 weeks, but were still experiencing persistent GORD symptoms, were treated with esomeprazole 40 mg for 8 weeks (n = 99). The primary outcome variable was the change in the frequency of heartburn. Patient-reported outcomes were also assessed using the Reflux Disease Questionnaire (RDQ) and the GORD Impact Scale (GIS). Results: The mean frequency of heartburn was reduced by 78% from 4.4 days a week to 1 day a week at the end of the 8-week treatment period (p esomeprazole (all p esomeprazole 40 mg significantly improved the frequency and severity of all GORD symptoms. PMID:19166433

  3. Efficacy of levofloxacin, amoxicillin and a proton pump inhibitor in the eradication of Helicobacter pylori in Brazilian patients with peptic ulcers.

    Science.gov (United States)

    Silva, Fernando Marcuz; Queiroz, Elaine Cristina Silveira de; Navarro-Rodriguez, Tomás; Barbuti, Ricardo Correa; Mattar, Rejane; Iriya, Kiyoshi; Lee, Jin Hwa; Eisig, Jaime Natan

    2015-05-01

    The eradication of Helicobacter (H.) pylori allows peptic ulcers in patients infected with the bacteria to be cured. Treatment with the classic triple regimen (proton pump inhibitor, amoxicillin and clarithromycin) has shown decreased efficacy due to increased bacterial resistance to clarithromycin. In our country, the eradication rate by intention to treat with this regimen is 83%. In Brazil, a commercially available regimen for bacterial eradication that uses levofloxacin and amoxicillin with lansoprazole is available; however, its efficacy is not known. Considering that such a treatment may be an alternative to the classic regimen, we aimed to verify its efficacy in H. pylori eradication. Patients with peptic ulcer disease infected with H. pylori who had not received prior treatment were treated with the following regimen: 30 mg lansoprazole bid, 1,000 mg amoxicillin bid and 500 mg levofloxacin, once a day for 7 days. A total of 66 patients were evaluated. The patients' mean age was 52 years, and women comprised 55% of the sample. Duodenal ulcers were present in 50% of cases, and gastric ulcers were present in 30%. The eradication rate was 74% per protocol and 73% by intention to treat. Adverse effects were reported by 49 patients (74%) and were mild to moderate, with a prevalence of diarrhea complaints. Triple therapy comprising lansoprazole, amoxicillin and levofloxacin for 7 days for the eradication of H. pylori in Brazilian peptic ulcer patients showed a lower efficacy than that of the classic triple regimen.

  4. Strategies for peptic ulcer healing after 1 week proton pump inhibitor-based triple Helicobacter pylori eradication therapy in Japanese patients: differences of gastric ulcers and duodenal ulcers.

    Science.gov (United States)

    Takeuchi, Toshihisa; Umegaki, Eiji; Takeuchi, Nozomi; Yoda, Yukiko; Kojima, Yuichi; Tokioka, Satoshi; Higuchi, Kazuhide

    2012-11-01

    Helicobacter pylori (H. pylori) eradication therapy alone is insufficient to ensure healing of large ulcers with H. pylori-positive gastric ulcer (GU). The question of what is the optimum antiulcer treatment following H. pylori eradication therapy has not been fully elucidated. Furthermore, the ulcer healing effects of eradication therapy itself with H. pylori-positive duodenal ulcer (DU) have not been investigated. In GU study, the eradication therapy + proton pump inhibitor (PPI) group (group A) were administered eradication therapy followed by 7 weeks of a PPI, and the eradication therapy + gastroprotective drug (GP) group (group B) eradication therapy followed by 7 weeks of a GP. In DU study, the eradication therapy + PPI group (group C) were administered eradication therapy followed by 5 weeks of a PPI, and the eradication therapy only group (group D) was eradication therapy alone. In GU study, healing rates for ulcer of ≥15 mm in diameter were significant greater in the group A. In DU study, high healing rates were seen both the group C and D. In conclusion, a PPI could significantly heal GU than a GP after eradication therapy in GU. Meanwhile, the eradication alone is sufficient for DU.

  5. Efficacy of levofloxacin, amoxicillin and a proton pump inhibitor in the eradication of Helicobacter pylori in Brazilian patients with peptic ulcers

    Directory of Open Access Journals (Sweden)

    Fernando Marcuz Silva

    2015-05-01

    Full Text Available OBJECTIVES: The eradication of Helicobacter (H. pylori allows peptic ulcers in patients infected with the bacteria to be cured. Treatment with the classic triple regimen (proton pump inhibitor, amoxicillin and clarithromycin has shown decreased efficacy due to increased bacterial resistance to clarithromycin. In our country, the eradication rate by intention to treat with this regimen is 83%. In Brazil, a commercially available regimen for bacterial eradication that uses levofloxacin and amoxicillin with lansoprazole is available; however, its efficacy is not known. Considering that such a treatment may be an alternative to the classic regimen, we aimed to verify its efficacy in H. pylori eradication. METHODS: Patients with peptic ulcer disease infected with H. pylori who had not received prior treatment were treated with the following regimen: 30 mg lansoprazole bid, 1,000 mg amoxicillin bid and 500 mg levofloxacin, once a day for 7 days. RESULTS: A total of 66 patients were evaluated. The patients’ mean age was 52 years, and women comprised 55% of the sample. Duodenal ulcers were present in 50% of cases, and gastric ulcers were present in 30%. The eradication rate was 74% per protocol and 73% by intention to treat. Adverse effects were reported by 49 patients (74% and were mild to moderate, with a prevalence of diarrhea complaints. CONCLUSIONS: Triple therapy comprising lansoprazole, amoxicillin and levofloxacin for 7 days for the eradication of H. pylori in Brazilian peptic ulcer patients showed a lower efficacy than that of the classic triple regimen.

  6. 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.

  7. Correlation between the Serum Pepsinogen I Level and the Symptom Degree in Proton Pump Inhibitor-Users Administered with a Probiotic

    Directory of Open Access Journals (Sweden)

    Muneki Igarashi

    2014-06-01

    Full Text Available In patients with functional upper gastrointestinal disorders such as gastroesophageal reflux disease and functional dyspepsia, the presence of symptoms is thought to occur in the absence of any organic diseases and the mechanisms behind this remain unclear. We therefore examined the relationship between stomach-related biomarker levels and symptoms. Twenty-four outpatients who had taken proton-pump inhibitors every day were enrolled in this study. The subjects consumed yogurt containing 109 colony-forming units of Lactobacillus gasseri OLL2716 (LG21 every day for three months. They underwent four clinical examinations in total. Each examination consisted of answering a questionnaire with a frequency scale for the symptoms of GERD (FSSG, and included measurements of the serum gastrin, ghrelin, and pepsinogens I and II levels. As a result, the FSSG score and the PGI value showed a decrease and an increase, respectively, after LG21 treatment when analyzed without age adjustment. A multiple regression analysis with additional adjustments for gender and age revealed a strong association between the PGI value and the FSSG symptom scores. Therefore either the PGI level itself or the factors regulating the PGI level might be involved in the etiology of these symptoms.

  8. 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.

  9. Influence of proton-pump inhibitors on stomach wall uptake of 99mTc-tetrofosmin in cadmium-zinc-telluride SPECT myocardial perfusion imaging.

    Science.gov (United States)

    Mouden, Mohamed; Rijkee, Karlijn S; Schreuder, Nanno; Timmer, Jorik R; Jager, Pieter L

    2015-02-01

    Proton-pump inhibitors (PPIs) induce potentially interfering stomach wall activity in single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) with technetium-99m ((99m)Tc)-sestamibi. However, no data are available for (99m)Tc-tetrofosmin. We assessed the influence of prolonged (>2 weeks) PPI use on the stomach wall uptake of (99m)Tc-tetrofosmin in patients referred for stress MPI with a cadmium-zinc-telluride-based SPECT camera and its relation with dyspepsia symptoms. Consecutive patients (n=127) underwent a 1-day adenosine stress-first SPECT-MPI with (99m)Tc-tetrofosmin, of whom 54 (43%) patients had been on PPIs for more than 2 weeks. Stomach wall activity was identified on stress SPECT using computed tomographic attenuation maps and was scored using a four-point grading scale into clinically relevant (scores 2 or 3) or nonrelevant (scores 0 or 1).Patients on PPIs had stomach wall uptake more frequently as compared with patients not using PPIs (22 vs. 7%, P=0.017). Dyspepsia was similar in both groups. Prolonged use of PPIs is associated with stomach wall uptake of (99m)Tc-tetrofosmin in stress cadmium-zinc-telluride-SPECT images. Gastric symptoms were not associated with stomach wall uptake.

  10. Proton pump inhibitor use and fracture risk - effect modification by histamine H1 receptor blockade. Observational case-control study using National Prescription Data.

    Science.gov (United States)

    Abrahamsen, Bo; Vestergaard, Peter

    2013-11-01

    It remains unknown why proton pump inhibitor (PPI) use may be associated with risk of osteoporotic fractures; evidence of direct effects on calcium absorption or on the osteoclast in humans is weak or absent. However, the ensuing increased gastrin levels may cause histamine production through hypertrophy of gastric enterochromaffin like cells, which could lead to bone loss. We speculated that H1 receptor antagonists (H1RA) used for allergies would then reduce the effect of PPI on bone. We therefore conducted a register-based case-control study comprising 124,655 patients with hospital treated fractures, who were matched 3:1 with non fracture control subjects of the same age and gender. Use of prescription medications was retrieved from the National Prescription Database and data was analyzed using conditional logistic regression analysis. We observed a significant interaction between PPI and H1RA use on fracture risk in general (adjusted OR 0.92, 95% CI 0.87-0.98) though not on hip fracture risk (adjusted OR 0.99, 95% CI 0.85-1.16). There was a significant modification of the interaction by age (peffects of PPI on bone could be driven by in part by increased histamine release as the increased fracture risk can be modified by H1RA. © 2013.

  11. Short term outcome of conventional versus off-pump coronary artery bypass grafting for high-risk patients

    Directory of Open Access Journals (Sweden)

    Ahmed F. Elmahrouk

    2018-03-01

    Full Text Available Background: Off-pump coronary artery bypass grafting (OPCAB, avoiding the use of cardiopulmonary bypass, has attracted the interest of an increasing number of surgeons and patients, and has assumed an increasing role in surgical practice. Whether OPCAB have better outcome in high-risk patients as compared to Conventional coronary artery bypass grafting (C-GABG remains to be confirmed. We describe an analysis of early clinical outcomes of high-risk coronary artery disease (CAD patients, subjected to both techniques. Methods: We studied 450 patients with additive EuroSCORE of ≥5 on admission. Patients were divided into 2 groups; Group A was assigned for patients underwent conventional C-CABG, and Group B for patients underwent OPCAB. Data, including gender, age, demographic variables and postoperative complications were extracted from the medical records. Results: Both groups were matched with regard to age, gender, smoking, Diabetes mellitus, dyslipidemia, renal hemodialysis and the mean Euro-Score. We demonstrated a decrease in the incidence of early postoperative atrial fibrillation and renal failure in the Off-pump group. However, we recorded no statistical difference of neurologic complications, acute myocardial infarction or early mortality between the two groups. Conclusions: We recommend OPCAB in high-risk CAD patients, as this technique may carry potential benefits without compromising their clinical outcomes. Keywords: CABG, Off-pump, High-risk, Short term outcome

  12. Proton minibeam radiation therapy spares normal rat brain: Long-Term Clinical, Radiological and Histopathological Analysis.

    Science.gov (United States)

    Prezado, Yolanda; Jouvion, Gregory; Hardy, David; Patriarca, Annalisa; Nauraye, Catherine; Bergs, Judith; González, Wilfredo; Guardiola, Consuelo; Juchaux, Marjorie; Labiod, Dalila; Dendale, Remi; Jourdain, Laurène; Sebrie, Catherine; Pouzoulet, Frederic

    2017-10-31

    Proton minibeam radiation therapy (pMBRT) is a novel strategy for minimizing normal tissue damage resulting from radiotherapy treatments. This strategy partners the inherent advantages of protons for radiotherapy with the gain in normal tissue preservation observed upon irradiation with narrow, spatially fractionated beams. In this study, whole brains (excluding the olfactory bulb) of Fischer 344 rats (n = 16) were irradiated at the Orsay Proton Therapy Center. Half of the animals received standard proton irradiation, while the other half were irradiated with pMBRT at the same average dose (25 Gy in one fraction). The animals were followed-up for 6 months. A magnetic resonance imaging (MRI) study using a 7-T small-animal MRI scanner was performed along with a histological analysis. Rats treated with conventional proton irradiation exhibited severe moist desquamation, permanent epilation and substantial brain damage. In contrast, rats in the pMBRT group exhibited no skin damage, reversible epilation and significantly reduced brain damage; some brain damage was observed in only one out of the eight irradiated rats. These results demonstrate that pMBRT leads to an increase in normal tissue resistance. This net gain in normal tissue sparing can lead to the efficient treatment of very radio-resistant tumours, which are currently mostly treated palliatively.

  13. 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)

    Parsons, Bryony N; Ijaz, Umer Z; D'Amore, Rosalinda; Burkitt, Michael D; Eccles, Richard; Lenzi, Luca; Duckworth, Carrie A; Moore, Andrew R; Tiszlavicz, Laszlo; Varro, Andrea; Hall, Neil; Pritchard, D Mark

    2017-11-01

    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.

  14. Immediate-type hypersensitivity reactions to proton pump inhibitors: usefulness of skin tests in the diagnosis and assessment of cross-reactivity.

    Science.gov (United States)

    Kepil Özdemir, S; Yılmaz, I; Aydin, Ö; Büyüköztürk, S; Gelincik, A; Demirtürk, M; Erdoğdu, D; Cömert, S; Erdoğan, T; Karakaya, G; Kalyoncu, A F; Oner Erkekol, F; Dursun, A B; Misirligil, Z; Bavbek, S

    2013-08-01

    Data are limited about the value of skin tests in the diagnosis of proton pump inhibitor (PPI)-induced hypersensitivity reactions and the cross-reactivity between PPIs. We aimed to assess the role of skin testing in the diagnosis of PPI-related immediate hypersensitivity reactions and the cross-reactivity patterns among PPIs. The study was designed in a prospective, national, multicentre nature. Sixty-five patients with a suggestive history of a PPI-induced immediate hypersensitivity reaction and 30 control subjects were included. Standardized skin prick and intradermal tests were carried out with a panel of PPIs. Single-blind, placebo-controlled oral provocation tests (OPTs) with the PPIs other than the culprit PPI that displayed negative results in skin tests (n = 61) and diagnostic OPTs with the suspected PPI (n = 12) were performed. The suspected PPIs were lansoprazole (n = 52), esomeprazole (n = 11), pantoprazole (n = 9), rabeprazole (n = 2), and omeprazole (n = 1). The sensitivity, specificity, and negative and positive predictive values of the skin tests with PPIs were 58.8%, 100%, 70.8%, and 100%, respectively. Fifteen of the 31 patients with a hypersensitivity reaction to lansoprazole had a positive OPT or skin test result with at least one of the alternative PPIs (8/52 pantoprazole, 6/52 omeprazole, 5/52 esomeprazole, 3/52 rabeprazole). Considering the high specificity, skin testing seems to be a useful method for the diagnosis of immediate-type hypersensitivity reactions to PPIs and for the evaluation of cross-reactivity among PPIs. However, OPT should be performed in case of negativity on skin tests. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Randomised clinical trial: high-dose vs. standard-dose proton pump inhibitors for the prevention of recurrent haemorrhage after combined endoscopic haemostasis of bleeding peptic ulcers.

    Science.gov (United States)

    Chen, C-C; Lee, J-Y; Fang, Y-J; Hsu, S-J; Han, M-L; Tseng, P-H; Liou, J-M; Hu, F-C; Lin, T-l; Wu, M-S; Wang, H-P; Lin, J-T

    2012-04-01

    The optimal dosage of intravenous proton pump inhibitors (PPIs) for the prevention of peptic ulcer rebleeding remains unclear. To compare the rebleeding rate of high-dose and standard-dose PPI use after endoscopic haemostasis. A total of 201 patients with bleeding ulcers undergoing endoscopic treatment with epinephrine injection and heater probe thermocoagulation were randomised to receive a high-dose regimen (80 mg bolus, followed by pantoprazole 8 mg/h infusion, n = 100) or a standard-dose regimen (pantoprazole 40 mg bolus daily, n = 101). After 72 h, all patients were given 40 mg pantoprazole daily orally for 27 days. There were no statistical differences in mean units of blood transfused, length of hospitalisation ≦5 days, surgical or radiological interventions and mortality within 30 days between two groups. Bleeding recurred within 30 days in six patients [6.2%, 95% confidence interval (CI) 1.3-11.1%] in the high-dose group, as compared to five patients (5.2%, 95% CI 0.6-9.7%) in the standard-dose group (P = 0.77). The stepwise Cox regression analysis showed end-stage renal disease, haematemesis, chronic obstructive pulmonary disease (hazard ratio: 37.15, 10.07, 9.12, 95% CI: 6.76-204.14, 2.07-49.01, 1.66-50.00 respectively) were independent risk factors for rebleeding and Helicobacter pylori infection was associated with lower risk of rebleeding (hazard ratio: 0.20, 95% CI: 0.04-0.94). Following combined endoscopic haemostasis of bleeding ulcers, co-morbidities, haematemesis and H. pylori Status, but not PPI dosage, are associated with rebleeding (http://www.Clinical Trials.gov.ID: NCT00709046). © 2012 Blackwell Publishing Ltd.

  16. Comparing intravenous and oral proton pump inhibitor therapy for bleeding peptic ulcers following endoscopic management: a systematic review and meta-analysis.

    Science.gov (United States)

    Tringali, Alberto; Manta, Raffaele; Sica, Mariano; Bassotti, Gabrio; Marmo, Riccardo; Mutignani, Massimiliano

    2017-08-01

    The efficacy of proton pump inhibitors (PPIs) has been demonstrated for bleeding peptic ulcers but the route of administration remains controversial. Several studies have demonstrated that high-dose oral PPIs are as effective as intravenous PPIs in reducing recurrent bleeding. However, current guidelines recommend intravenous PPIs after endoscopic treatment. Previous data based on numbers that were too small to enable a firm conclusion to be reached suggested that oral and intravenous PPIs had equivalent efficacy. We undertook a meta-analysis to compare oral and intravenous PPIs in patients with bleeding peptic ulcers after endoscopic management. A literature search was undertaken using MEDLINE, EMBASE and the Cochrane Library, between 1990 and February 2016, to identify all randomized controlled trials (RCTs) that assessed the efficacy of PPIs administered by different routes. Nine RCTs, involving 1036 patients, were analysed. Outcomes were: recurrent bleeding, blood transfusion requirement, duration of hospital stay, a need for repeat endoscopy, surgery and 30-day mortality. There were no differences in the rebleeding rates [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.60, 1.46; P = 0.77], need for surgery (OR 0.77, 95% CI 0.25, 2.40; P = 0.65), need for repeat endoscopy (OR 0.69, 95% CI 0.39, 1.21; P = 0.19), need for blood transfusion [(MD) -0.03, 95% CI -0.26, 0.19; P = 0.76], duration of hospital stay (MD -0.61, 95% CI -1.45, 0.23; P = 0.16) or 30-day mortality (OR 0.89, 95% CI 0.27, 2.43; P = 0.84) according to the route of administration. Oral PPIs represent better value for money, with clinical efficacy equivalent to intravenous PPIs. © 2017 The British Pharmacological Society.

  17. Efficacy of Proton Pump Inhibitor Drugs for Inducing Clinical and Histologic Remission in Patients With Symptomatic Esophageal Eosinophilia: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Lucendo, Alfredo J; Arias, Ángel; Molina-Infante, Javier

    2016-01-01

    Proton pump inhibitor (PPI) therapy might lead to clinical and histologic remission in a significant proportion of patients with symptomatic esophageal eosinophilia (>15 eos/high-power field). We aimed to evaluate systematically the efficacy of PPI therapy for these patients. A search in MEDLINE, EMBASE, and SCOPUS databases, and the American Gastroenterological Association Institute, American College of Gastroenterology, and United European Gastroenterology meetings abstract books, was performed. Primary outcomes were clinical response and histologic remission (quality, PPI type, doses and interval dosing, and pH monitoring results. Data were pooled using a random-effects model. Thirty-three studies (11 prospective studies) comprising 619 patients with symptomatic esophageal eosinophilia (188 children and 431 adults) were included. PPI therapy led to a clinical response in 60.8% (95% confidence interval, 48.38%-72.2%; I(2) = 80.2) and histologic remission in 50.5% (95% confidence interval, 42.2%-58.7%; I(2) = 67.5) of patients. No differences were observed regarding the study population (children vs adults), the type of publication, or its quality. PPIs were nonsignificantly more effective in prospective studies (52.6% vs 39.1%) administered twice daily compared with once daily (55.9% vs 49.7%), and with pathologic pH monitoring (65.4% vs 49.3%). A significant publication bias in favor of studies reporting histologic responses to PPIs was observed. PPI therapy induces clinicohistologic remission in half of patients with symptomatic esophageal eosinophilia. This finding should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. A dairy product fermented by lactobacilli cancels the adverse effects of hypochlorhydria induced by a proton pump inhibitor on bone metabolism in growing rats.

    Science.gov (United States)

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

    2011-11-01

    The purpose of the present study is to investigate the effects of hypochlorhydria induced by proton pump inhibitor (PPI) administration and intake of a dairy product fermented by lactobacilli (DFL) on bone metabolism in growing rats. Male rats, aged 3 weeks, were divided into two groups: a control group fed a casein-based diet and a group fed a DFL-based diet. Each group was fed its respective experimental diets for 9 d. At day 5 of the feeding period, each group was divided into two subgroups: one that received a saline injection and one that received a PPI injection. Rats were subcutaneously administered saline or PPI for 5 d. Faecal Ca excretion was determined from day 6 to day 9. At the end of the experiment, plasma and femurs were collected. Administration of PPI significantly decreased bone mineral density (shown by X-ray computerised tomography) and bone strength (shown by a three-point bending test) in the control group. Plasma osteocalcin, type I collagen C-telopeptides, 1,25-dihydroxyvitamin D and parathyroid hormone concentrations were elevated by PPI administration in the control group. Faecal Ca excretion and urinary P excretion in the control group were remarkably increased by PPI administration. On the other hand, these adverse effects of PPI were not observed in the DFL group. These results suggest that hypochlorhydria-induced bone loss may result from high bone turnover induced by secondary hyperparathyroidism due to Ca malabsorption and that DFL intake cancels these adverse effects probably via improving Ca malabsorption in growing rats.

  19. 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.

  20. 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

  1. 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

  2. [Evaluation of pharmacokinetic drug-drug-interactions. Critical considerations of the relevance of pharmacokinetic drug-drug interactions of proton pump inhibitors in self medication].

    Science.gov (United States)

    Petersen, Karl-Uwe

    2011-08-01

    Mechanisms and evaluation of pharmacokinetic drug interactions are discussed in general, including mechanisms beyond the hepatic phase-I reactions, and especially for the example of proton pump inhibitors (PPI), preferentially omeprazole. Particular attention is paid to the use of PPI as self-prescribed drugs. The sequelae of pharmacokinetic drug interactions can be serious. However, only the evidence of clinical consequences will convert such an interaction from a laboratory finding into a possible adverse effect. Without this, interacting drugs can still be co-administered if the specific characteristics of the concerned drugs, quantitative aspects of the interaction, and especially severity and frequency of possible clinical correlates are taken into consideration. It is encouraging that the laboratory findings reported for the PPI--in vitro or ex vivo from volunteer studies--have hardly found equivalents in clinical consequences. As of today, this is also true of the widely discussed interaction with clopidogrel. Regarding the safety of use of PPI as self-prescribed drugs, it also needs to be emphasized that a sizable number of interactions reported for omeprazole and/or pantoprazole were observed at higher dose levels than the 20 mg licensed for self medication. In conjunction with the temporal limitation of PPI self-prescription (14 days), it can be expected that pharmacokinetic drug interactions will generally be no critical factor in the usage of PPI in self-medication. However clinically relevant interactions can occur, e.g. when PPI are combined with extracts from St. John's wort, methotrexat or some inhibitors of HIV-protease with pH-dependent absorption.

  3. Predicting the efficacy of proton pump inhibitors in patients with non-erosive reflux disease before therapy using dual-channel 24-h esophageal pH monitoring.

    Science.gov (United States)

    Shimatani, Tomohiko; Sugimoto, Mitsushige; Nishino, Masafumi; Adachi, Kyoichi; Furuta, Kenji; Ito, Masanori; Kurosawa, Susumu; Manabe, Noriaki; Mannen, Kotaro; Hongo, Michio; Chiba, Tsutomu; Kinoshita, Yoshikazu

    2012-05-01

    We aimed to determine whether reflux- and symptom-related parameters can predict the efficacy of proton pump inhibitors (PPI) in non-erosive reflux disease (NERD). Twenty-seven NERD patients who had experienced heartburn more than once a week within the previous month were enrolled. Intraesophageal pH before therapy was measured simultaneously at 5 and 15 cm above the esophagogastric junction (EGJ) for 24 h. The PPI rabeprazole was administered at a dose of 10 mg once daily for 4 weeks. In the event that heartburn was not relieved, the dose was increased to 10 mg twice daily for an additional 2 weeks, and again to 20 mg twice daily for another 2 weeks. Univariate analysis demonstrated no significant associations between any reflux- or symptom-related parameters at either site and complete heartburn relief after 4 weeks, or cumulative complete heartburn relief after 8 weeks. However, post-hoc analysis demonstrated more satisfactory heartburn relief after 4 weeks in patients with a high symptom index compared with those with a low symptom index, at 5 cm above the EGJ (P = 0.009). Cumulative satisfactory heartburn relief after 8 weeks was also greater in patients with a high total number of acid reflux episodes compared with those with a low total number of episodes, at 15 cm above the EGJ (P = 0.037). Pre-therapeutic pH monitoring in the lower and mid-esophagus is useful for predicting the efficacy of PPI in NERD patients. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  4. Triple therapy with high-dose proton-pump inhibitor, amoxicillin, and doxycycline is useless for Helicobacter pylori eradication: a proof-of-concept study.

    Science.gov (United States)

    Almeida, Nuno; Romãozinho, José M; Donato, Maria M; Luxo, Cristina; Cardoso, Olga; Cipriano, Maria A; Marinho, Carol; Sofia, Carlos

    2014-04-01

    Helicobacter pylori resistance to antibiotics is steadily increasing and multidrug-resistant strains are common and difficult to eliminate, mainly in countries where bismuth, tetracycline, furazolidone, and rifabutin are unavailable. To evaluate the efficacy and safety of a triple therapy with proton-pump inhibitor (PPI), amoxicillin, and doxycycline in patients with multidrug-resistant H. pylori. This prospective study involved 16 patients (13 females; mean age - 50 ± 11.3 years) infected by H. pylori with known resistance to clarithromycin, metronidazole, and levofloxacin, but susceptibility to amoxicillin and tetracycline. All patients were previously submitted to upper endoscopy with gastric biopsies for H. pylori culture and susceptibility testing by Etest. Mutations in 23S rRNA and gyrA genes were determined by real-time PCR. A 10-day eradication regimen with PPI (double-standard dose b.i.d.), amoxicillin (1000 mg b.i.d.), and doxycycline (100 mg b.i.d.) was prescribed after pretreatment with PPI during 3 days. Eradication success was assessed by (13) C-urea breath test 6-10 weeks after treatment. Compliance and adverse events were determined through phone contact immediately after treatment and specific written questionnaires. Only one patient did not complete treatment due to adverse events. Another four patients experienced mild side effects not affecting compliance. The control (13) C-urea breath test was positive in all patients. Per-protocol and intention-to-treat eradication rates were 0%. Although safe, a triple-therapy protocol with high-dose PPI, amoxicillin, and doxycycline is useless for multidrug-resistant H. pylori eradication. © 2014 John Wiley & Sons Ltd.

  5. Improved efficacy of proton pump inhibitor - amoxicillin - clarithromycin triple therapy for Helicobacter pylori eradication in low clarithromycin resistance areas or for tailored therapy.

    Science.gov (United States)

    Prasertpetmanee, Sanchai; Mahachai, Varocha; Vilaichone, Ratha-korn

    2013-08-01

    Standard triple therapy for Helicobacter pylori eradication is no longer effective as an empiric choice in most areas. Even in low clarithromycin resistance areas, results ≥95% are infrequently achieved. This study was designed to search for a version of standard triple therapy for use low prevalence areas or as tailored therapy that is highly effective irrespective of CYP2C19 genotype. Two prospective pilot single center studies were performed in Thailand. H. pylori-infected subjects were randomized to 7- or 14-day regimens using a high-dose proton pump inhibitor (PPI) triple therapy consisting of lansoprazole (60 mg) twice daily, amoxicillin 1 g twice daily, and long-acting clarithromycin MR 1 g once daily. H. pylori was defined as positive H. pylori culture; or two positive tests (rapid urease test and histology); CYP2C19 genotyping was performed. H. pylori eradication was evaluated by (13) C-UBT 4 or more weeks after treatment. Hundred and ten subjects were enrolled (55 each to the 7- and 14-day regimens). Antibiotic susceptibility testing (25 strains) showed 40% metronidazole resistance but no clarithromycin resistance. CYP2C19 genotyping (64 subjects) revealed 56.3% rapid metabolizer, 29.7% intermediate metabolizer, and 14% poor metabolizer. The eradication rate with the 14-day regimen was 100% (95% CI = 93.5-100%) and 92.7% (95% CI = 82-97%) with the 7-day regimen. The difference was related to improved eradication at 14 days in rapid metabolizers (i.e. 100 vs 88.2%). Triple therapy using a 14-day high-dose PPI and long-acting clarithromycin provided an excellent cure rate (100%) regardless of the CYP2C19 genotype. © 2013 John Wiley & Sons Ltd.

  6. Do FDA label changes work? Assessment of the 2010 class label change for proton pump inhibitors using the Sentinel System's analytic tools.

    Science.gov (United States)

    Sobel, Rachel E; Bate, Andrew; Marshall, James; Haynes, Kevin; Selvam, Nandini; Nair, Vinit; Daniel, Gregory; Brown, Jeffrey S; Reynolds, Robert F

    2018-03-01

    To pilot use of the US Food and Drug Administration's (FDA's) Sentinel System data and analytic tools by a non-FDA stakeholder through the Innovation in Medical Evidence Development and Surveillance system of the Reagan Udall Foundation. We evaluated the US FDA 2010 proton pump inhibitor (PPI) class label change that warned of increased risk of bone fracture, to use PPIs for the lowest dose and shortest duration, and to manage bone status for those at risk for osteoporosis. The cohort consisted of adults aged 18 years or older prescribed PPIs without fracture risk factors. We evaluated incident and prevalent uses of the 8 PPIs noted in the label change. Outcomes evaluated before and after label change were PPI dispensing patterns, incident fractures, and osteoporosis screening or interventions. Consistent with FDA use of descriptive tools, we did not include direct comparisons or statistical testing. There were 1 488 869 and 2 224 420 incident PPI users in the before [PRE] and after [POST] periods, respectively. Users with 1 year or more of exposure decreased (8.4% vs 7.5%), as did mean days supplied/user (130.4 to 113.7 d among all users and 830.8 to 645.4 d among users with 1 y or more of exposure). Osteoporosis screening and interventions did not appear to increase, but the proportion of patients with fractures decreased (4.4% vs 3.1%). Prevalent user results were similar. This analysis demonstrated the ability to use Sentinel tools to assess the effectiveness of a label change and accompanying communication at the population level and suggests an influence on subsequent dispensing behavior. Copyright © 2018 John Wiley & Sons, Ltd.

  7. 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.

  8. 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.

  9. Upper GI tract findings in patients with heartburn in whom proton pump inhibitor treatment failed versus those not receiving antireflux treatment.

    Science.gov (United States)

    Poh, Choo Hean; Gasiorowska, Anita; Navarro-Rodriguez, Tomas; Willis, Marcia R; Hargadon, Deborah; Noelck, North; Mohler, Jane; Wendel, Christopher S; Fass, Ronnie

    2010-01-01

    Failure of proton pump inhibitor (PPI) treatment in patients with heartburn is very common. Because endoscopy is easily accessible, it is commonly used as the first evaluative tool in these patients. To compare GERD-related endoscopic and histologic findings in patients with heartburn in whom once-daily PPI therapy failed versus those not receiving antireflux treatment. Cross-sectional study. A Veterans Affairs hospital. Heartburn patients from the GI outpatient clinic. Recording of endoscopic results. Endoscopic findings and association between PPI treatment failure and esophageal mucosal injury by using logistic regression models. A total of 105 subjects (mean age 54.7 +/- 15.7 years; 71 men, 34 women) were enrolled in the PPI treatment failure group and 91 (mean age 53.4 +/- 15.8 years; 68 men, 23 women) were enrolled in the no-treatment group (P = not significant). Anatomic findings during upper endoscopy were significantly more common in the no-treatment group compared with the PPI treatment failure group (55.2% vs 40.7%, respectively; P = .04). GERD-related findings were significantly more common in the no-treatment group compared with the PPI treatment failure group (erosive esophagitis: 30.8% vs 6.7%, respectively; P < .05). Eosinophilic esophagitis was found in only 0.9% of PPI treatment failure patients. PPI treatment failure was associated with a significantly decreased odds ratio of erosive esophagitis compared with no treatment, adjusted for age, sex, and body mass index (adjusted odds ratio 0.11; 95% CI, 0.04-0.30). Heartburn patients in whom once-daily PPI treatment failed demonstrated a paucity of GERD-related findings compared with those receiving no treatment. Eosinophilic esophagitis was uncommon in PPI therapy failure patients. Upper endoscopy seems to have a very low diagnostic yield in this patient population. 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  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. A possible involvement of Nrf2-mediated heme oxygenase-1 up-regulation in protective effect of the proton pump inhibitor pantoprazole against indomethacin-induced gastric damage in rats

    Directory of Open Access Journals (Sweden)

    Lee Ho-Jae

    2012-10-01

    Full Text Available Abstract Background Proton pump is an integral membrane protein that is ubiquitous ATP binding cassette (ABC involved in many transport processes in all living organisms, among which a specialized form of pump, so called p-type proton pump, exists in the parietal cells of stomach. Though proton pump inhibitors (PPIs are frequently prescribed to prevent nonsteroidal anti-inflammatory drugs (NSAIDs-induced gastric damage, the acid suppressive actions do not suffice to explain. Methods In order to document the effects of pantoprazole, one of PPIs, on the NSAIDs-induced gastric damage, in vitro and in vivo studies were performed. Immunocytochemistry, Western blot analysis, electrophoretic mobility shift assay and RT-PCR were conducted to evaluate the induction of heme oxygenase-1 (HO-1 through Nrf2 activation in normal gastric mucosal RGM-1 cells or in vivo stomach tissues from rats treated with indomethacin and/or pantoprazole. Results Pantoprazole activated Nrf2 through inactivation of Keap1, after which the expression of HO-1 was significantly increased in a dose-dependent manner in RGM-1 cells. Increased ARE-DNA binding activity was observed maximally at 1 h with 300 μM of pantoprazole. The expression of HO-1 induced by pantoprazole was significantly associated with the increased in vitro tube formation (P P In vivo model of indomethacin-induced gastric damage could validate in vitro-drawn results that pantoprazole remarkably protected against indomethacin-induced gastric damage, in which zinc protoporphyrin (5 mg/kg, ip significantly abolished the protective efficacy of pantoprazole. Conclusion These results demonstrate that Nrf2-mediated HO-1 induction of PPIs afforded a significant protective effect against NSAIDs-induced gastric damage beyond acid suppressive actions.

  12. Long-term outcome of insulin pump therapy in children with type 1 diabetes assessed in a large population-based case-control study.

    Science.gov (United States)

    Johnson, Stephanie R; Cooper, Matthew N; Jones, Timothy W; Davis, Elizabeth A

    2013-11-01

    We determined the impact of insulin pump therapy on long-term glycaemic control, BMI, rate of severe hypoglycaemia and diabetic ketoacidosis (DKA) in children. Patients on pump therapy at a single paediatric tertiary hospital were matched to patients treated by injections on the basis of age, duration of diabetes and HbA1c at the time of pump start. HbA1c, anthropometric data, episodes of severe hypoglycaemia and rates of hospitalisation for DKA were collected prospectively. A total of 345 patients on pump therapy were matched to controls on injections. The mean age, duration of diabetes at pump start and length of follow-up were 11.4 (± 3.5), 4.1 (± 3.0) and 3.5 (± 2.5) years, respectively. The mean HbA1c reduction in the pump cohort was 0.6% (6.6 mmol/mol). This improved HbA1c remained significant throughout the 7 years of follow-up. Pump therapy reduced severe hypoglycaemia from 14.7 to 7.2 events per 100 patient-years (p pump cohort over the same period from 6.8 to 10.2 events per 100 patient-years. The rate of hospitalisation for DKA was lower in the pump cohort (2.3 vs 4.7 per 100 patient-years, p = 0.003) over the 1,160 patient-years of follow-up. This is the longest and largest study of insulin pump use in children and demonstrates that pump therapy provides a sustained improvement in glycaemic control, and reductions of severe hypoglycaemia and hospitalisation for DKA compared with a matched cohort using injections.

  13. Long-term follow-up of cerebral infarction patients with proton magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Gideon, P; Sperling, B; Arlien-Søborg, P

    1994-01-01

    ) to the chronic stage (> 6 months) with proton magnetic resonance spectroscopy. Cerebral blood flow was measured with single-photon emission-computed tomography with 99mTc-labeled d,l-hexamethylenepropyleneamine oxime as flow tracer. RESULTS: Lactate was found in all patients in the acute stage of stroke. Lactate......BACKGROUND AND PURPOSE: With proton magnetic resonance spectroscopy it is possible to measure the content of various brain metabolites in vivo, including N-acetylaspartate (which may be used as a neuronal marker), creatine, choline, and lactate. The content of these brain metabolites was measured...... serially from the acute stage to the chronic stage of infarction. Regional cerebral blood flow was also measured within the affected areas. These factors were compared with the clinical outcome. METHODS: Six patients with ischemic stroke were examined serially from the acute stage (

  14. 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

  15. Gastrointestinal toxicity among patients taking selective COX-2 inhibitors or conventional NSAIDs, alone or combined with proton pump inhibitors: a case-control study.

    Science.gov (United States)

    Bakhriansyah, Mohammad; Souverein, Patrick C; de Boer, Anthonius; Klungel, Olaf H

    2017-10-01

    To assess the risk of gastrointestinal perforation, ulcers, or bleeding (PUB) associated with the use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) with proton pump inhibitors (PPIs) and selective COX-2 inhibitors, with or without PPIs compared with conventional NSAIDs. A case-control study was performed within conventional NSAIDs and/or selective COX-2 inhibitors users identified from the Dutch PHARMO Record Linkage System in the period 1998-2012. Cases were patients aged ≥18 years with a first hospital admission for PUB. For each case, up to four controls were matched for age and sex at the date a case was hospitalized (index date). Logistic regression analysis was used to calculate odds ratios (ORs). At the index date, 2634 cases and 5074 controls were current users of conventional NSAIDs or selective COX-2 inhibitors. Compared with conventional NSAIDs, selective COX-2 inhibitors with PPIs had the lowest risk of PUB (adjusted OR 0.51, 95% confidence interval [CI]: 0.35-0.73) followed by selective COX-2 inhibitors (adjusted OR 0.66, 95%CI: 0.48-0.89) and conventional NSAIDs with PPIs (adjusted OR 0.79, 95%CI: 0.68-0.92). Compared with conventional NSAIDs, the risk of PUB was lower for those aged ≥75 years taking conventional NSAIDs with PPIs compared with younger patients (adjusted interaction OR 0.79, 95%CI: 0.64-0.99). However, those aged ≥75 years taking selective COX-2 inhibitors, the risk was higher compared with younger patients (adjusted interaction OR 1.22, 95%CI: 1.01-1.47). Selective COX-2 inhibitors with PPIs, selective COX-2 inhibitors, and conventional NSAIDs with PPIs were associated with lower risks of PUB compared with conventional NSAIDs. These effects were modified by age. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

  16. Evaluation of six proton pump inhibitors as inhibitors of various human cytochromes P450: focus on cytochrome P450 2C19.

    Science.gov (United States)

    Zvyaga, Tatyana; Chang, Shu-Ying; Chen, Cliff; Yang, Zheng; Vuppugalla, Ragini; Hurley, Jeremy; Thorndike, Denise; Wagner, Andrew; Chimalakonda, Anjaneya; Rodrigues, A David

    2012-09-01

    Six proton pump inhibitors (PPIs), omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, and rabeprazole, were shown to be weak inhibitors of cytochromes P450 (CYP3A4, -2B6, -2D6, -2C9, -2C8, and -1A2) in human liver microsomes. In most cases, IC₅₀ values were greater than 40 μM, except for dexlansoprazole and lansoprazole with CYP1A2 (IC₅₀ = ∼8 μM) and esomeprazole with CYP2C8 (IC₅₀ = 31 μM). With the exception of CYP2C19 inhibition by omeprazole and esomeprazole (IC₅₀ ratio, 2.5 to 5.9), there was no evidence for a marked time-dependent shift in IC₅₀ (IC₅₀ ratio, ≤ 2) after a 30-min preincubation with NADPH. In the absence of preincubation, lansoprazole (IC₅₀ = 0.73 μM) and esomeprazole (IC₅₀ = 3.7 μM) were the most potent CYP2C19 inhibitors, followed by dexlansoprazole and omeprazole (IC₅₀ = ∼7.0 μM). Rabeprazole and pantoprazole (IC₅₀ = ≥ 25 μM) were the weakest. A similar ranking was obtained with recombinant CYP2C19. Despite the IC₅₀ ranking, after consideration of plasma levels (static and dynamic), protein binding, and metabolism-dependent inhibition, it is concluded that omeprazole and esomeprazole are the most potent CYP2C19 inhibitors. This was confirmed after the incubation of the individual PPIs with human primary hepatocytes (in the presence of human serum) and by monitoring their impact on diazepam N-demethylase activity at a low concentration of diazepam (2 μM). Data described herein are consistent with reports that PPIs are mostly weak inhibitors of cytochromes P450 in vivo. However, two members of the PPI class (esomeprazole and omeprazole) are more likely to serve as clinically relevant inhibitors of CYP2C19.

  17. Indication of acid suppression therapy and predictors for the prophylactic use of proton-pump inhibitors vs. histamine-2 receptor antagonists in a Malaysian tertiary hospital

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    Oh AL

    2015-09-01

    Full Text Available Background: Proton-pump inhibitors (PPI and histamine-2 receptor antagonists (H2RA are common acid suppressants used in gastrointestinal disorders. The trend of usage in Malaysia has changed from predominantly H2RA to PPI from 2007 to 2008, 3.46 versus 2.87 and 2.99 versus 3.24 DDD (Defined Daily Dose/1000 population/day respectively. This raises concerns as PPI overutilization amounts to higher cost expenditure and are associated with various untoward consequences such as Clostridium difficile-associated diarrhea, pneumonia, and osteoporosis. Objectives: To evaluate the indication of acid suppression therapy (AST and to look for predictors associated with the prophylactic use of PPI as compared to H2RA. Methods: Data collection was conducted via a standardized surveillance form over a 2-month period in the general medical wards of Sarawak General Hospital. All patients who received at least one dose of PPI or H2RA in any dosage form were included in the study. Appropriateness of prophylaxis was determined using current available guidelines. Selected risk factors were analysed using simple logistic regression to look for predictors associated with the choice of PPI in prophylactic AST. Results: Out of 212 cases in the present cohort, about three quarters (75.5%, n=160 of acid suppressants were given as prophylaxis. Over half of these did not have appropriate indications for prophylactic AST (58.1%, n=93. Among all cases given prophylactic AST, 75.0% (n=120 of them were given PPI. Renal insufficiency was identified as the only predictor associated with the use of prophylactic PPI in preference to H2RA (OR=2.86, 95%CI 1.21:6.72, p=0.011. Conclusion: Inappropriate prophylactic AST is a major concern and may even be underestimated due to the lack of appropriate guidelines. More data is required to guide the selection between PPI and H2RA, specifically the more cost-effective use of H2RA in patients with lower gastrointestinal risk or in whom PPI has

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

    Science.gov (United States)

    Mody, Reema; Eisenberg, Debra; Hou, Likun; Kamat, Siddhesh; Singer, Joseph; Gerson, Lauren B

    2013-01-01

    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. 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 (HIRD(SM)) 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. 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). Patients receiving twice-daily PPI therapy were likely to have more comorbid conditions and greater health care utilization and overall costs compared with patients using once-daily PPI therapy.

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

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

    2017-12-20

    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 (p<0.001, 2014 vs. 2017; p-for-trend <0.001), while an increasing rate was found in the surgery departments in the same years: 30, 29, 36, 36%, respectively (p<0.001, 2014 vs. 2017; p-for-trend <0.001). The case mix was significantly associated with the probability of new PPI prescriptions in both departments (OR1.35, 95% CI 1.26-1.44 for internal medicine and 1.24, 95% CI 1.19-1.30 for surgery). The introduction 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

  20. The efficacy of second-line anti-Helicobacter pylori therapy using an extended 14-day levofloxacin/amoxicillin/proton-pump inhibitor treatment--a pilot study.

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    Chuah, Seng-Kee; Tai, Wei-Chen; Hsu, Pin-I; Wu, Deng-Chyang; Wu, Keng-Liang; Kuo, Chung-Mou; Chiu, Yi-Chun; Hu, Ming-Luen; Chou, Yeh-Pin; Kuo, Yuan-Hung; Liang, Chih-Ming; Chiu, King-Wah; Hu, Tsung-Hui

    2012-10-01

    Large meta-analyses of second-line Helicobacter pylori eradication with fluoroquinolone triple therapy have shown that neither 7-day nor 10-day therapy provides 90% or better treatment success. Reports describing second-line H. pylori eradication using 14-day fluoroquinolone-containing triple therapy are few. Current study aimed to determine the efficacy of a 14-day levofloxacin/amoxicillin/proton-pump inhibitor regimen as second-line therapy and the clinical factors influencing the outcome. One-hundred and one patients who failed H. pylori eradication using the standard triple therapy for 7 days were randomly assigned to either a levofloxacin/amoxicillin/esomeprazole group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 14 days) or a esomeprazole/metronidazole/bismuth salt/tetracycline group (esomeprazole 40 mg twice daily, metronidazole 250 mg four times daily, tripotassium dicitrate bismuthate 300 mg four times daily, and tetracycline 500 mg four times daily for 14 days). Follow-up to assess treatment response consisted of either endoscopy or a urea breath test, which were carried out 8 weeks later. Eradication rates attained by levofloxacin/amoxicillin/esomeprazole and esomeprazole/metronidazole/bismuth salt/tetracycline treatments in the per-protocol analysis were 44/47 (93.6%; 95% CI = 86-99.8) and 43/47 (91.8%; 95% CI = 83.2-98.5). In the intention-to-treat analysis, these were 43/47 (86.3%; 95% CI = 76.5-96.1) in the LAE group (four lost to follow-up) and 43/50 (86%; 95% CI = 76-96) in the EMBT groups. The observed adverse events were 25.5% and 38.5% among the two groups. There was 100% drug compliance among the levofloxacin/amoxicillin/esomeprazole group. Levofloxacin-resistant strains occurred at a frequency of 32.3%. H. pylori eradication rates for the levofloxacin-susceptible strains and levofloxacin-resistant strains were 92% (11/12) and 33% (1/3) in the per-protocol analysis. A

  1. Systematic review and meta-analysis: triple therapy combining a proton-pump inhibitor, amoxicillin and metronidazole for Helicobacter pylori first-line treatment.

    Science.gov (United States)

    Puig, Ignasi; Baylina, Mireia; Sánchez-Delgado, Jordi; López-Gongora, Sheila; Suarez, David; García-Iglesias, Pilar; Muñoz, Neus; Gisbert, Javier P; Dacoll, Cristina; Cohen, Henry; Calvet, Xavier

    2016-10-01

    Due to clarithromycin resistance, the current efficacy of Helicobacter pylori first-line triple therapies including clarithromycin is low. It seems reasonable to explore alternative clarithromycin-free therapies. The objective of this study was to evaluate the efficacy of triple therapy including a proton-pump inhibitor (PPI), amoxicillin and metronidazole (PAM) as first-line H. pylori therapy by systematic review and meta-analysis. Studies evaluating PAM in adult patients were included. Meta-analyses comparing PAM with other treatments were performed. The primary endpoint was the ITT eradication rate for H. pylori first-line treatment. In addition, sensitivity analyses ascertained the effects of treatment schedule, dosage and duration on cure rates. Ninety-four studies (8061 patients) were included. Meta-analyses comparing PAM versus clarithromycin-including triple therapies showed a significant difference in favour of PPI, amoxicillin and clarithromycin (PAC) (70% versus 77.1%; OR = 0.70, 95% CI = 0.56-0.88) and PPI, metronidazole and clarithromycin (PMC) therapy (66.4% versus 77.7%; OR = 0.55, 95% CI = 0.39-0.76). Sensitivity analyses showed a similar efficacy of PAM versus PAC when drugs were administered for 14 days (80% versus 84%; OR = 0.70, 95% CI = 0.44-1.12). There were not enough studies to perform further comparisons. Number of antibiotic doses (P = 0.012), length of treatment (P < 0.001) and use of high metronidazole doses (P = 0.021) were related to higher cure rates in the sensitivity analysis including observational studies. PAM was less efficacious than clarithromycin-including triple therapies. However, its efficacy was similar to that of PAC when drugs were administered for 14 days, although ITT cure rates did not reach 90%. Use of 14 day, thrice daily and high-metronidazole-dose PAM treatments markedly increased the cure rate. © The Author 2016. Published by Oxford University Press on behalf of the British

  2. Influence of proton pump inhibitors and histamine H2receptor antagonists on serum phosphorus level control by calcium carbonate in patients undergoing hemodialysis: a retrospective medical chart review.

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    Tatsuzawa, Masaomi; Ogawa, Ryuichi; Ohkubo, Atsushi; Shimojima, Kazuyo; Maeda, Kunimi; Echizen, Hirotoshi; Miyazaki, Akihisa

    2016-01-01

    Hyperphosphatemia is one of the common complications in patients undergoing hemodialysis. Although calcium carbonate (CaC) is often used to control serum inorganic phosphorus level in dialysis patients, co-administration of gastric acid reducers (ARs) may interfere with the phosphate binding effect of CaC. We performed a retrospective medical chart review to study whether ARs attenuate the hypophosphatemic effect of CaC in patients undergoing hemodialysis. One hundred and eight chronic hemodialysis patients receiving either CaC alone or CaC concomitant with one of the ARs (proton pump inhibitors and histamine H 2 -receptor antagonists) were retrieved from the medical charts in Juntendo University Nerima Hospital. The patients were subdivided according to the interval between hemodialysis sessions (interdialysis interval of 48 or 72 h). A multivariate analysis was performed to identify clinical covariates associated with the variability of serum inorganic phosphorus levels. The study protocol was approved by the Institutional Review Board before the study was begun. Among patients on hemodialysis with a 72-h interdialysis interval, the magnitude of increase in serum inorganic phosphorus concentration in patients receiving CaC and AR was significantly greater than in those receiving CaC alone. While a similar trend was observed among patients with a 48-h interdialysis interval, the difference did not reach a significant level. A multivariate regression analysis revealed that concomitant administration of ARs with CaC and a longer interdialysis interval (72 h) were significantly and independently associated with the magnitude of increase in serum phosphorus concentration between dialysis sessions. No significant differences in albumin-corrected serum calcium concentrations and incidence of pathological fractures were observed between patients receiving CaC alone and those receiving CaC with ARs. Concomitant use of ARs with CaC may attenuate the hypophosphatemic

  3. Histamine H2-Blocker and Proton Pump Inhibitor Use and the Risk of Pneumonia in Acute Stroke: A Retrospective Analysis on Susceptible Patients.

    Science.gov (United States)

    Arai, Nobuhiko; Nakamizo, Tomoki; Ihara, Hikaru; Koide, Takashi; Nakamura, Akiyoshi; Tabuse, Masanao; Miyazaki, Hiromichi

    2017-01-01

    Although histamine H2-blockers (H2B) and proton pump inhibitors (PPI) are used commonly to prevent gastrointestinal bleeding in acute stroke, they are implicated in the increased risk of pneumonia in other disease populations. In acute stroke, the presence of distinctive risk factors of pneumonia, including dysphagia and impaired consciousness, makes inclusive analysis vulnerable to confounding. Our aim was to assess whether acid-suppressive drugs increase pneumonia in acute stroke in a population controlled for confounding. We analyzed acute stroke patients admitted to a tertiary care hospital. To minimize confounding, we only included subjects who could not feed orally during 14 days of hospitalization. Exposure was defined as H2B or PPI, given in days; the outcome was development of pneumonia within this period. The incidence was calculated from the total number of pneumonias divided by the sum of person-days at risk. We additionally performed multivariate Poisson regression and propensity score analyses, although the restriction largely eliminated the need for multivariate adjustment. A total of 132 pneumonias occurred in 3582 person-days. The incidence was 3.69%/person-day (95% confidence interval (CI); 3.03-4.37%/day). All subjects had dysphagia. Stroke severity and consciousness disturbances were well-balanced between the groups exposed to H2B, PPI, or none. The relative risk (RR) compared with the unexposed was 1.22 in H2B (95%CI; 0.83-1.81) and 2.07 in PPI (95% CI; 1.13-3.62). The RR of PPI compared with H2B was 1.69 (95%CI; 0.95-2.89). In multivariate regression analysis, the RRs of H2B and PPI were 1.24 (95% CI; 0.85-1.81) and 2.00 (95% CI; 1.12-3.57), respectively; in propensity score analyses they were 1.17 (95% CI; 0.89-1.54) and 2.13 (95% CI; 1.60-2.84). The results of this study suggested that prophylactic acid-suppressive therapy with PPI may have to be avoided in acute stroke patients susceptible to pneumonia.

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

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

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    Rok Orel

    2017-06-01

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

  6. 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.

  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. MedTech Mag-Lev, single-use, extracorporeal magnetically levitated centrifugal blood pump for mid-term circulatory support.

    Science.gov (United States)

    Nagaoka, Eiki; Fujiwara, Tatsuki; Kitao, Takashi; Sakota, Daisuke; Shinshi, Tadahiko; Arai, Hirokuni; Takatani, Setsuo

    2013-01-01

    Short- to mid-term extracorporeal ventricular assist devices (VADs) are recommended for critical cardiogenic shock patients. We have designed a preclinical, single-use MedTech Mag-Lev VAD for one-month extracorporeal use. The impeller-rotor of the pump was suspended by a two degree-of-freedom active magnetic bearing in a 300 μm fluid gap, where the computational fluid dynamics analysis predicted a secondary flow of about 400-500 ml/min at a pump speed of 1800-2200 rpm. Three eddy current sensors were employed to implement noise- and drift-free magnetic levitation. The pump components were injection molded using polycarbonate for smooth surfaces as well as improved reproducibility, followed by coating with a biocompatible 2-methacryloyl-oxyethyl phosphorylcholine polymer. Chronic animal experiments were performed in nine calves. Three of the nine calves were excluded from analysis for problems with the circuit. Five of the six (83.3%) completed the 60 day duration of the study, while one prematurely died of massive bleeding due to inflow port detachment. The pump did not stop due to magnetic-levitation malfunction. Neither pump thrombosis nor major organ infarction was observed at autopsy. In comparison to machined surfaces, the injection-molded pump surfaces were thrombus-free after 60 day implantation. This study demonstrates the feasibility of MedTech Mag-Lev VAD for 60 day circulatory support.

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

    NARCIS (Netherlands)

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

    2014-01-01

    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

  14. 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...

  15. Short-term myeloid growth factor mediated expansion of bone marrow haemopoiesis studied by localized magnetic resonance proton spectroscopy

    DEFF Research Database (Denmark)

    Jensen, K E; Hansen, P B; Larsen, V A

    1994-01-01

    spectroscopy (MRS). Six patients were treated with daily subcutaneous injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF, n = 2) or granulocyte-macrophage colony-stimulating factor (rhGM-CSF, n = 4) for 5d before marrow harvest. MRS investigations were performed prior to treatment......Previously we have shown that short-term myeloid growth factor priming of haemopoiesis prior to bone marrow harvest increased the yield of myeloid progenitors in the graft. The present study is intended to investigate the expansion of haemopoiesis by volume selective proton magnetic resonance....../76 x 10(3) (range 28.4-1180.6/23.2-2850.0). MRS detected a significant increase in bone marrow 'relative water content' day 12, 1 week after myeloid growth factor treatment was stopped, from median 30.5% (range 16-45) to 79% (range 56-93). In parallel, haemopoiesis was detected in new areas of femur...

  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. Preclinical study of a novel hydrodynamically levitated centrifugal pump for long-term cardiopulmonary support : In vivo performance during percutaneous cardiopulmonary support.

    Science.gov (United States)

    Tsukiya, Tomonori; Mizuno, Toshihide; Takewa, Yoshiaki; Tatsumi, Eisuke; Taenaka, Yoshiyuki

    2015-12-01

    An extracorporeal centrifugal blood pump with a hydrodynamically levitated impeller was developed for use in a durable extracorporeal membrane oxygenation (ECMO) system. The present study examined the biocompatibility of the blood pump during long-term use by conducting a series of 30-day chronic animal experiments. The ECMO system was used to produce a percutaneous venoarterial bypass between the venae cavae and carotid artery in adult goats. No anticoagulation or antiplatelet therapy was administered during the experiments. Three out of four animals survived for the scheduled 30-day period, and the blood pumps and membrane oxygenators both exhibited sufficient hydrodynamic performance and good antithrombogenicity, while one animal died of massive bleeding from the outflow cannulation site. The animals' plasma free hemoglobin had returned to within the normal range by 1 week after the surgical intervention, and their hemodynamic and biochemistry parameters remained within their normal ranges throughout the experiment. The explanted centrifugal blood pumps did not display any trace of thrombus formation. Based on the biocompatibility demonstrated in this study, the examined centrifugal blood pump, which includes a hydrodynamically levitated impeller, is suitable for use in durable ECMO systems.

  18. Inward H+ pump xenorhodopsin : Mechanism and alternative optogenetic approach

    NARCIS (Netherlands)

    Shevchenko, V.; Mager, T.; Kovalev, K.; Polovinkin, V.; Alekseev, A.; Juettner, J.; Chizhov, I.; Bamann, C.; Vavourakis, C.; Ghai, R.; Gushchin, I.; Borshchevskiy, V.; Rogachev, A.; Melnikov, I.; Popov, A.; Balandin, T.; Rodriguez-Valera, F.; Manstein, D.J.; Bueldt, G.; Bamberg, E.; Gordeliy, V.

    2017-01-01

    Generation of an electrochemical proton gradient is the first step of cell bioenergetics. In prokaryotes, the gradient is created by outward membrane protein proton pumps. Inward plasma membrane native proton pumps are yet unknown. We describe comprehensive functional studies of the representatives

  19. Proton therapy

    Science.gov (United States)

    Proton beam therapy; Cancer - proton therapy; Radiation therapy - proton therapy; Prostate cancer - proton therapy ... that use x-rays to destroy cancer cells, proton therapy uses a beam of special particles called ...

  20. Groundwater sampling at olkiluoto, Eurajoki from the borehole OL-KR6 during a long-term pumping test in 2004

    International Nuclear Information System (INIS)

    Paaso, N.; Hatanpaeae, E.; Ylae-Mella, M.

    2006-09-01

    A long-term pumping test from the borehole OL-KR6 at Olkiluoto was initiated in 2001. Both flow and in situ EC measurements as well as groundwater sampling from specific sections were performed. The aim of this study was to get information on the potential connections via fractures both to the sea and to deep saline groundwater during the long-term pumping of the open borehole. In 2004 four groundwater samples were collected from the borebole OL-KR6 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 from packed-off sections by a membrane pump and two inflatable rubber packers. All groundwater samples taken are of the water type Na-Ca-Cl. They are brackish waters (1000 mg 10000mg/L) and the water type is Na-Cl. This study presents sampling methods and the results of analysis of groundwater samples from the deep borehole OL-KR6. Comparison between the results of the in situ EC measurements and EC results measured during groundwater sampling are presented. This report also contains a short comparison of the results obtained during the long-term pumping test during 2001-2004. Based on the results of this study and on the previous studies, it can be concluded that the pumping of the upper part of the borehole is likely to have caused the changes in salinity at the three sampling sections (except 422-425 m). However, the changes were minor in years 2001-2004. (orig.)

  1. Short-term in vivo performance of the Cleveland clinic PediPump left ventricular assist device.

    Science.gov (United States)

    Fumoto, Hideyuki; Shiose, Akira; Flick, Christine R; Noble, Lawrence D; Dudzinski, David T; Casas, Fernando; Takaseya, Tohru; Arakawa, Yoko; Fukamachi, Kiyotaka; Smith, William A; Duncan, Brian W

    2014-05-01

    The PediPump was implanted in six healthy lambs (mean 25.6 ± 1.4 kg) between the left ventricular apex and the descending aorta to evaluate in vivo performance for up to 30 days. Anticoagulation was achieved by continuous heparin infusion. Three animals were euthanized prematurely, two because of respiratory dysfunction and one because of deteriorating pump performance resulting from thrombus formation inside the pump. Three lambs were electively sacrificed 30 days after implantation; all had stable hemodynamics and minimal hemolysis, as indicated by low plasma free hemoglobin (2.5 ± 3.1 mg/dL). Mean 30-day pump flow was 1.8 ± 0.1 L/min at a pump speed of 12 200 ± 400 rpm. Neither activated clotting time nor activated partial thromboplastin time followed the changes in heparin dose. At necropsy, depositions were observed at the front (n = 1) and rear rotor axial positioning stops (n = 4); improved polishing techniques on the stationary stop surfaces and the addition of a hard-carbon, thin-film coating on the rotating stop of the pumps used for the last two experiments addressed the deposition seen earlier. In conclusion, the PediPump showed excellent hydraulic performance and minimal hemolysis during support for up to 30 days. Depositions observed at the axial positioning stops in earlier experiments were addressed by design and material refinements. We continue to focus on developing effective anticoagulation management in the lamb model as well as on further evaluating and demonstrating pump biocompatibility. Copyright © 2013 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  2. 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

  3. 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.

  4. 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

    -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......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...

  5. Insulin Pumps

    Science.gov (United States)

    ... Size: A A A Listen En Español Insulin Pumps Insulin pumps are small computerized devices that deliver insulin in ... tissue and is taped in place. The insulin pump is not an artificial pancreas (because you still ...

  6. 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 ...

  7. Short-term myeloid growth factor mediated expansion of bone marrow haemopoiesis studied by localized magnetic resonance proton spectroscopy

    DEFF Research Database (Denmark)

    Jensen, K E; Hansen, P B; Larsen, V A

    1994-01-01

    /76 x 10(3) (range 28.4-1180.6/23.2-2850.0). MRS detected a significant increase in bone marrow 'relative water content' day 12, 1 week after myeloid growth factor treatment was stopped, from median 30.5% (range 16-45) to 79% (range 56-93). In parallel, haemopoiesis was detected in new areas of femur......Previously we have shown that short-term myeloid growth factor priming of haemopoiesis prior to bone marrow harvest increased the yield of myeloid progenitors in the graft. The present study is intended to investigate the expansion of haemopoiesis by volume selective proton magnetic resonance......-density cell proliferation rate in marrow samples increased from median 21.9 (range 4.5-31) x 10(3) cpm to 54.7 (range 13.9-94) x 10(3) cpm and the total number of myeloid progenitors enumerated as day 7/14 GM-CFUs per volume aspirated marrow increased from median 11/8 x 10(3) (range 4.0-87.5/2.2-103.0) to 64...

  8. 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

  9. 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

  10. 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

  11. Estimate of the radiation source term for 18F production via thick H218O targets bombarded with 18 MeV protons

    Science.gov (United States)

    Cruzate, Juan Ángel

    2015-12-01

    The positron-emitting radionuclide most important from the point of view of radiation protection is 18F. This isotope is usually produced by bombarding 18O-enriched water with protons. Currently there are few experimental data on the radiation source term generated during these reactions. In addition, presently there is no theoretical estimates of this source term, for use in radiation protection, validated by experimental data. Up till now this term is calculated by using nuclear interactions' simulation codes, such as ALICE91. An estimate of the energy spectra for neutrons and photons, induced by 18 MeV protons on H218O target, have been calculated by using MCNPX code with cross sections from release 0 of ENDF/B VII library for all materials except 18O, for which TENDL-2012 library was used. This estimate was validated against a recent experiment carried out at the Japan Atomic Energy Agency (JAEA). The calculated spectra have generally well reproduced experiments. The results show that the calculated radiation source term may be used to estimate the neutron activation of the accelerator components and the cyclotron building, to calculate the cyclotron shielding, and to carry out radiation protection evaluations in general, for the case of cyclotrons producing 18F by means of the 18O(p,n)18F nuclear reactions, for proton energies up to 18 MeV.

  12. 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.

  13. 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.

  14. Kinetics of the acid pump in the stomach. Proton transport and hydrolysis of ATP and p-nitrophenyl phosphate by the gastric H,K-ATPase

    International Nuclear Information System (INIS)

    Ljungstroem, M.M.; Mardh, S.

    1985-01-01

    Hydrolysis of adenosine 5'-triphosphate (ATP) and p-nitrophenyl phosphate by the hydrogen ion-transporting potassium-stimulated adenosine triphosphatase (H,K-ATPase) was investigated. Hydrolysis of ATP was studied at pH 7.4 in vesicles treated with the ionophore nigericin. The kinetic analysis showed negative cooperativity with one high affinity and one low affinity site for ATP. The rate of hydrolysis decreased at 2000 microM ATP indicating a third site for ATP. When the pH was decreased to 6.5 the experimental results followed Michaelis-Menten enzyme kinetics with one low affinity site. Higher concentrations than 750 microM ATP were inhibitory. Proton transport was measured as accumulation of acridine orange in vesicles equilibrated with 150 mM KCl. The transport at various concentrations of ATP in the pH interval from 6.0 to 8.0 correlated well with the Hill equation with a Hill coefficient between 1.5-1.9. The concentration of ATP resulting in half-maximal transport rate increased from 5 microM at pH 6.0 to 420 microM at pH 8.0. At acidic pH the rate of proton transport decreased at 1000 microM ATP. The K+-stimulated p-nitrophenylphosphatase (pNPPase) activity resulted in a Hill coefficient close to 2 indicating cooperative binding of substrate. These kinetic results are used for a further development of the reaction scheme of the H,K-ATPase

  15. The influence of the biological pump on ocean chemistry: implications for long-term trends in marine redox chemistry, the global carbon cycle, and marine animal ecosystems.

    Science.gov (United States)

    Meyer, K M; Ridgwell, A; Payne, J L

    2016-05-01

    The net export of organic matter from the surface ocean and its respiration at depth create vertical gradients in nutrient and oxygen availability that play a primary role in structuring marine ecosystems. Changes in the properties of this 'biological pump' have been hypothesized to account for important shifts in marine ecosystem structure, including the Cambrian explosion. However, the influence of variation in the behavior of the biological pump on ocean biogeochemistry remains poorly quantified, preventing any detailed exploration of how changes in the biological pump over geological time may have shaped long-term shifts in ocean chemistry, biogeochemical cycling, and ecosystem structure. Here, we use a 3-dimensional Earth system model of intermediate complexity to quantitatively explore the effects of the biological pump on marine chemistry. We find that when respiration of sinking organic matter is efficient, due to slower sinking or higher respiration rates, anoxia tends to be more prevalent and to occur in shallower waters. Consequently, the Phanerozoic trend toward less bottom-water anoxia in continental shelf settings can potentially be explained by a change in the spatial dynamics of nutrient cycling rather than by any change in the ocean phosphate inventory. The model results further suggest that the Phanerozoic decline in the prevalence ocean anoxia is, in part, a consequence of the evolution of larger phytoplankton, many of which produce mineralized tests. We hypothesize that the Phanerozoic trend toward greater animal abundance and metabolic demand was driven more by increased oxygen concentrations in shelf environments than by greater food (nutrient) availability. In fact, a lower-than-modern ocean phosphate inventory in our closed system model is unable to account for the Paleozoic prevalence of bottom-water anoxia. Overall, these model simulations suggest that the changing spatial distribution of photosynthesis and respiration in the oceans has

  16. 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...

  17. Proton transfer in the K-channel analog of B-type Cytochrome c oxidase from Thermus thermophilus.

    Science.gov (United States)

    Woelke, Anna Lena; Wagner, Anke; Galstyan, Gegham; Meyer, Tim; Knapp, Ernst-Walter

    2014-11-04

    A key enzyme in aerobic metabolism is cytochrome c oxidase (CcO), which catalyzes the reduction of molecular oxygen to water in the mitochondrial and bacterial membranes. Substrate electrons and protons are taken up from different sides of the membrane and protons are pumped across the membrane, thereby generating an electrochemical gradient. The well-studied A-type CcO uses two different entry channels for protons: the D-channel for all pumped and two consumed protons, and the K-channel for the other two consumed protons. In contrast, the B-type CcO uses only a single proton input channel for all consumed and pumped protons. It has the same location as the A-type K-channel (and thus is named the K-channel analog) without sharing any significant sequence homology. In this study, we performed molecular-dynamics simulations and electrostatic calculations to characterize the K-channel analog in terms of its energetic requirements and functionalities. The function of Glu-15B as a proton sink at the channel entrance is demonstrated by its rotational movement out of the channel when it is deprotonated and by its high pKA value when it points inside the channel. Tyr-244 in the middle of the channel is identified as the valve that ensures unidirectional proton transfer, as it moves inside the hydrogen-bond gap of the K-channel analog only while being deprotonated. The electrostatic energy landscape was calculated for all proton-transfer steps in the K-channel analog, which functions via proton-hole transfer. Overall, the K-channel analog has a very stable geometry without large energy barriers.

  18. 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.

  19. Clinical Characteristics of Patients with Gastroesophageal Reflux Disease Refractory to Proton Pump Inhibitors and the Effects of Switching to 20 mg Esomeprazole on Reflux Symptoms and Quality of Life.

    Science.gov (United States)

    Takeshima, Fuminao; Hashiguchi, Keiichi; Onitsuka, Yasunori; Tanigawa, Ken; Minami, Hitomi; Matsushima, Kayoko; Akazawa, Yuko; Shiozawa, Ken; Yamaguchi, Naoyuki; Taura, Naota; Ohnita, Ken; Ichikawa, Tatsuki; Isomoto, Hajime; Nakao, Kazuhiko

    2015-12-31

    BACKGROUND Refractory gastroesophageal reflux disease (GERD) may deteriorate patient quality of life (QOL) despite proton pump inhibitor (PPI) therapy. MATERIAL AND METHODS Nineteen Japanese institutions were surveyed to determine the clinical characteristics and QOL of patients with refractory GERD. Those patients treated with a conventional PPI were switched to 20 mg esomeprazole for 4 weeks. Symptoms and QOL were assessed using Global Overall Symptom and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires at baseline and at 2 and/or 4 weeks of esomeprazole treatment. RESULTS Of 120 patients who completed the survey, 58 (48.3%) had refractory GERD. Of these, 69.0% were aged ≥ 65 years, 79.3% were prescribed a PPI at a standard or high dose, and 22.4% were prescribed a PPI together with another drug. After switching to esomeprazole, patients reported significant improvements in heartburn, acid regurgitation, and excessive belching at 2 weeks using a symptom diary, as well as the total score, reflux, abdominal pain, and indigestion, which were assessed using the GSRS at 4 weeks. CONCLUSIONS About half of Japanese patients with GERD may be refractory to conventional PPIs. Their reflux-related symptoms are often severe and may impair QOL. Switching to esomeprazole could be used to improve their symptoms and QOL.

  20. A Real World Report on Intravenous High-Dose and Non-High-Dose Proton-Pump Inhibitors Therapy in Patients with Endoscopically Treated High-Risk Peptic Ulcer Bleeding

    Directory of Open Access Journals (Sweden)

    Lung-Sheng Lu

    2012-01-01

    Full Text Available Background and Study Aims. The optimal dose of intravenous proton-pump inhibitor (PPI therapy for the prevention of peptic ulcer (PU rebleeding remains controversial. This study aimed to understand the real world experiences in prescribing high-dose PPI and non-high-dose PPI for preventing rebleeding after endoscopic treatment of high-risk PU. Patients and Methods. A total of 220 subjects who received high-dose and non-high-dose pantoprazole for confirmed acute PU bleeding that were successfully treated endoscopically were enrolled. They were divided into rebleeding (n=177 and non-rebleeding groups (n=43. Randomized matching of the treatment-control group was performed. Patients were randomly selected for non-high-dose and high-dose PPI groups (n=44 in each group. Results. Univariate analysis showed, significant variables related to rebleeding were female, higher creatinine levels, and higher Rockall scores (≧6. Before case-control matching, the high-dose PPI group had higher creatinine level, higher percentage of shock at presentation, and higher Rockall scores. After randomized treatment-control matching, no statistical differences were observed for rebleeding rates between the high-dose and non-high-dose groups after case-control matching. Conclusion. This study suggests that intravenous high-dose pantoprazole may not be superior to non-high-dose regimen in reducing rebleeding in high-risk peptic ulcer bleeding after successful endoscopic therapy.

  1. 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

  2. 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.

  3. Long-term evaluation of the effect of hypofractionated high-energy proton treatment of benign meningiomas by means of 11C-l-methionine positron emission tomography

    International Nuclear Information System (INIS)

    Ryttlefors, Mats; Latini, Francesco; Gudjonsson, Olafur; Danfors, Torsten; Montelius, Anders; Blomquist, Erik

    2016-01-01

    To determine if 11 C-l-methionine PET is a useful tool in the evaluation of the long-term effect of proton beam treatment in patients with meningioma remnant. Included in the study were 19 patients (4 men, 15 women) with intracranial meningioma remnants who received hypofractionated high-energy proton beam treatment. Patients were examined with 11 C-l-methionine PET and MRI prior to treatment and after 6 months, and 1, 2, 3, 5, 7 and 10 years. Temporal changes in methionine uptake ratio, meningioma volume, meningioma regrowth and clinical symptoms throughout the follow-up period were evaluated. In 17 patients the tumour volume was unchanged throughout the follow-up. The methionine uptake ratio on PET decreased over the years in most patients. In two patients the tumour remnant showed progression on MRI. In these patients, prior to the volume increase on MRI, the methionine uptake ratio increased. One patient experienced transient clinical symptoms and showed radiological evidence of a radiation-induced reaction close to the irradiated field. Proton beam treatment is a safe and effective treatment for achieving long-term growth arrest in meningioma remnants. Follow-up with 11 C-l-methionine PET may be a valuable adjunct to, but not a replacement for, standard radiological follow-up. (orig.)

  4. Using earth-tide induced water pressure changes to measure in situ permeability: A comparison with long-term pumping tests

    Science.gov (United States)

    Allègre, Vincent; Brodsky, Emily E.; Xue, Lian; Nale, Stephanie M.; Parker, Beth L.; Cherry, John A.

    2016-04-01

    Good constraints on hydrogeological properties are an important first step in any quantitative model of groundwater flow. Field estimation of permeability is difficult as it varies over orders of magnitude in natural systems and is scale-dependent. Here we directly compare permeabilities inferred from tidal responses with conventional large-scale, long-term pumping tests at the same site. Tidally induced water pressure changes recorded in wells are used to infer permeability at ten locations in a densely fractured sandstone unit. Each location is either an open-hole well or a port in a multilevel monitoring well. Tidal response is compared at each location to the results of two conventional, long-term and large scale pumping tests performed at the same site. We obtained consistent values between the methods for a range of site-specific permeabilities varying from ˜10-15 m2 to 10-13 m2 for both open wells with large open intervals and multilevel monitoring well. We conclude that the tidal analysis is able to capture passive and accurate estimates of permeability.

  5. 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

  6. 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.

  7. Long-term patency of on- and off-pump coronary artery bypass grafting with bilateral internal thoracic arteries: the significance of late string sign development in the off-pump technique.

    Science.gov (United States)

    Hayashi, Yasunari; Maekawa, Atsuo; Sawaki, Sadanari; Tokoro, Masayoshi; Yanagisawa, Junji; Ozeki, Takahiro; Usui, Akihiko; Ito, Toshiaki

    2017-11-01

    This study aimed to examine the effect of off-pump coronary artery bypass grafting (CABG) in patients who underwent revascularization with bilateral internal thoracic arteries (ITAs). Between January 2000 and December 2014, 499 patients underwent isolated CABG with bilateral ITAs for complete revascularization of the left coronary system at our institution. On-pump CABG was performed in 137 patients, and off-pump CABG was performed in 362 patients. We retrospectively compared the clinical outcomes and patency of the ITAs. The off-pump group showed less respiratory failure and required a shorter postoperative stay than the on-pump group. The survival probability, freedom from cardiac events and early graft patency were similar in both groups. Five-year patency of the ITA anastomosed to the left anterior descending artery was significantly greater in the on-pump group than in the off-pump group (98.8% vs 91.2%, P = 0.010). The incidence of string change in the off-pump group was higher than that in the on-pump group (P = 0.017). There was no significant difference between the groups in the 5-year patency of the ITA anastomosed to the left circumflex artery (on-pump group: 93.8%, off-pump group: 91.8%; P = 0.46). The early graft patency and the late patency of the ITA anastomosed to the left circumflex artery between the groups were similar, implying an equivalent quality of anastomoses. However, the patency of the ITA anastomosed to the left anterior descending artery in the off-pump group showed late deterioration, mainly because of string sign development. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  8. 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

  9. 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

  10. 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

  11. 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...

  12. Centrifugal pumps for rocket engines

    Science.gov (United States)

    Campbell, W. E.; Farquhar, J.

    1974-01-01

    The use of centrifugal pumps for rocket engines is described in terms of general requirements of operational and planned systems. Hydrodynamic and mechanical design considerations and techniques and test procedures are summarized. Some of the pump development experiences, in terms of both problems and solutions, are highlighted.

  13. Ten-Day Quadruple Therapy Comprising Proton Pump Inhibitor, Bismuth, Tetracycline, and Levofloxacin is More Effective than Standard Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori Infection: A Randomized Controlled Trial.

    Science.gov (United States)

    Hsu, Ping-I; Tsai, Feng-Woei; Kao, Sung-Shuo; Hsu, Wen-Hung; Cheng, Jin-Shiung; Peng, Nan-Jing; Tsai, Kuo-Wang; Hu, Huang-Ming; Wang, Yao-Kuang; Chuah, Seng-Kee; Chen, Angela; Wu, Deng-Chyang

    2017-09-01

    Proton pump inhibitor (PPI)-amoxicillin-fluoroquinolone triple therapy is recommended as a second-line treatment of Helicobacter pylori infection in the Maastricht V/Florence Consensus Report. However, the eradication rate of this standard salvage treatment is suboptimal. The objective of this study is to compare the efficacy of esomeprazole-bismuth-tetracycline-levofloxacin therapy (TL quadruple therapy) and esomeprazole-amoxicillin-levofloxacin triple therapy (AL triple therapy) in rescue treatment for H. pylori infection. Consecutive H. pylori-infected subjects after failure of first-line therapies were randomly allocated to receive either TL quadruple therapy (esomeprazole 40 mg b.d., bismuth 120 mg q.d.s., tetracycline 500 mg q.d.s., and levofloxacin 500 mg o.d.) or AL triple therapy (esomeprazole 40 mg b.d., amoxicillin 500 mg q.d.s., and levofloxacin 500 mg o.d.) for 10 days. H. pylori status was assessed 6 weeks after the end of treatment. The study was stopped after an interim analysis. Of 50 patients in the TL quadruple therapy, 49 (98.0%) had successful eradication of H. pylori infection. Cure of H. pylori infection was achieved in 36 of 52 patients (69.2%) receiving AL triple therapy. Intention-to-treat analysis demonstrated that TL quadruple therapy achieved a markedly higher eradication rate than AL triple therapy (difference: 28.8%; 95% confidence interval: 15.7% to 41.9%; Pbismuth quadruple therapy (95.0% vs. 52.6%; P=0.003). Ten-day PPI-bismuth-tetracycline-levofloxacin quadruple therapy is a good option for rescue treatment of H. pylori infection following failure of standard triple or non-bismuth quadruple therapy.

  14. 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...... of membrane proteins: P-type ATPase pumps. This article takes the reader on a tour from Aarhus to Copenhagen, from bacteria to plants and humans, and from ions over protein structures to diseases caused by malfunctioning pump proteins. The magazine Nature once titled work published from PUMPKIN ‘Pumping ions...

  15. Robotic Total Arterial Off-Pump Coronary Artery Bypass Grafting: Seven-Year Single-Center Experience and Long-Term Follow-Up of Graft Patency.

    Science.gov (United States)

    Yang, Ming; Wu, Yang; Wang, Gang; Xiao, Cangsong; Zhang, Huajun; Gao, Changqing

    2015-10-01

    Coronary artery bypass grafting (CABG) is the gold-standard treatment for coronary artery disease, but the long-term benefits of robotic CABG remain unclear. Between January 2007 and November 2014, 240 consecutive patients (187 male and 53 female, average age 59 years) underwent robotic off-pump CABG with the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA) in our center. Totally endoscopic coronary artery bypass (TECAB) (n = 100) or mini-thoracotomy coronary artery bypass (MINICAB) (n = 140) grafting was performed with skeletonized internal mammary arteries (IMA). Patients were followed up and graft patency was assessed every 6 months by coronary angiography or 64-multi-slide computed tomographic angiography. All cases were completed without conversion to median sternotomy or cardiopulmonary bypass. A total of 237 single IMA grafts (98.3%) and 4 bilateral IMA grafts (1.7%) were used. No operative mortality was observed. Hybrid revascularization of non-left anterior descending vessels was performed in 24 patients (10%). No death, stroke, or myocardial infarction occurred in the follow-up of 41.1 ± 12.9 months. All grafts were patent before discharge. The IMA graft patency was 97.1% in TECAB and 96.4 % in MINICAB over 3 years (up to 91 months) postoperatively. Robotic off-pump CABG using IMA grafts is a safe and effective procedure in selected patients. The long-term outcome and patency of IMA grafts are excellent. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  16. 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'.

  17. 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.

  18. 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

  19. 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.

  20. Nuclear-Pumped Lasers. [efficient conversion of energy liberated in nuclear reactions to coherent radiation

    Science.gov (United States)

    1979-01-01

    The state of the art in nuclear pumped lasers is reviewed. Nuclear pumped laser modeling, nuclear volume and foil excitation of laser plasmas, proton beam simulations, nuclear flashlamp excitation, and reactor laser systems studies are covered.

  1. Impact of long-term use of eHealth systems in adolescents with type 1 diabetes treated with sensor-augmented pump therapy.

    Science.gov (United States)

    Schiaffini, R; Tagliente, I; Carducci, C; Ullmann, N; Ciampalini, P; Lorubbio, A; Cappa, M

    2016-07-01

    Telemedicine in diabetes includes telemonitoring and transmission of important data (self monitoring of blood glucose data, insulin therapy, pump setting, etc.) from the patient s home to the diabetic unit, with a real-time health feedback. Moreover, an eHealth approach is thought to facilitate diabetes management and to improve compliance to CSII/SAP treatment in adolescents, but to date, limited literature related to this topic is available and long-term studies are still lacking. The main aim of this study was to compare the long-term effect on glycometabolic control of eHealth intervention and traditional care in T1DM SAP-treated adolescents. In our study we demonstrated a favorable impact of monthly teleassistance on treatment compliance. Adolescents receiving frequent feedback provided by the medicalmultidisciplinary team, due to the telemonitoring, resulted more compliant in self-management of diabetes. In particular, the medical team feedback resulted in interventions on behavioral errors and insulin therapy adjustments, leading to an improved glycometabolic control. © The Author(s) 2015.

  2. 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

  3. Proton pump inhibitors inhibit pancreatic secretion

    DEFF Research Database (Denmark)

    Wang, Jing; Barbuskaite, Dagne; Tozzi, Marco

    2015-01-01

    The mechanism by which pancreas secretes high HCO3- has not been fully resolved. This alkaline secretion, formed in pancreatic ducts, can be achieved by transporting HCO3- from serosa to mucosa or by moving H+ in the opposite direction. The aim of the present study was to determine whether H+/K+-...... it may provide a protective pH buffer zone and K+ recirculation. Furthermore, it seems relevant to re-evaluate whether PPIs should be used in treatment therapies where pancreatic functions are already compromised....

  4. Proton pumps, angiogenesis, and metastatic breast cancer

    Science.gov (United States)

    Rojas, Jose D.; Sanka, Shankar C.; Luo, Defeng; Busch, Christian; Martinez, Gloria M.; Hendrix, Mary J. C.; Martinez-Zaguilan, Raul

    2000-04-01

    We have previously shown the relationship between metastatic potential and plasmalemmal V-H+-ATPase (pmV-ATPase) expression in tumor cells. This led us to hypothesize that pmV-ATPase activity is involved in invasion. Angiogenesis involves invasion of adjacent tissues by microvascular endothelial cells, thus we hypothesized that pmV-ATPases contribute to pHin regulation and invasion in microvascular endothelial cells.

  5. 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

  6. Relating proton pumps with gap junctions: colocalization of ductin, the channel-forming subunit c of V-ATPase, with subunit a and with innexins 2 and 3 during Drosophila oogenesis.

    Science.gov (United States)

    Lautemann, Julia; Bohrmann, Johannes

    2016-07-13

    separately concentrated in presumed gap-junction plaques. Our results support the notion of a large variety of gap junctions existing in the Drosophila ovary. Moreover, since ductin is the channel-forming part of a proton pump and, like the innexins, is able to form junctional as well as non-junctional membrane channels, a plethora of cellular functions could be realized by using these proteins. The distribution and activity patterns of such membrane channels are expected to contribute to developmentally important bioelectric signals.

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

    Science.gov (United States)

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

    2017-01-01

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

  8. SHINE Vacuum Pump Test Verification

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, Gregg A; Peters, Brent

    2013-09-30

    scroll pump will be used to back the booster pump. In this case the ''booster pump'' is an Adixen Molecular Drag Pump (MDP 5011) and the backing pump is an Edwards (nXDS15iC) scroll pump. Various configurations of the two pumps and associated lengths of 3/4 inch tubing (0 feet to 300 feet) were used in combination with hydrogen and nitrogen flow rates ranging from 25-400 standard cubic centimeters per minute (sccm) to determine whether the proposed pump configuration meets the design criteria for SHINE. The results of this study indicate that even under the most severe conditions (300 feet of tubing and 400 sccm flow rate) the Adixen 5011 MDP can serve as a booster pump to transport gases from the accelerator (NDAS) to the TPS. The Target Gas Receiving System pump (Edwards nXDS15iC) located approximately 300 feet from the accelerator can effectively back the Adixen MDP. The molecular drag pump was able to maintain its full rotational speed even when the flow rate was 400 sccm hydrogen or nitrogen and 300 feet of tubing was installed between the drag pump and the Edwards scroll pump. In addition to maintaining adequate rotation, the pressure in the system was maintained below the target pressure of 30 torr for all flow rates, lengths of tubing, and process gases. This configuration is therefore adequate to meet the SHINE design requirements in terms of flow and pressure.

  9. 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.

  10. 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

  11. 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]).…

  12. 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.

  13. Gas-liquid two-phase flow behaviors and performance characteristics of proton exchange membrane fuel cells in a short-term microgravity environment

    Science.gov (United States)

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

    2017-06-01

    In this work, proton exchange membrane fuel cells (PEMFCs) with transparent windows are designed to study the gas-liquid two-phase flow behaviors inside flow channels and the performance of a PEMFC with vertical channels and a PEMFC with horizontal channels in a normal gravity environment and a 3.6 s short-term microgravity environment. Experiments are conducted under high external circuit load and low external circuit load at low temperature where is 35 °C. The results of the present experimental work demonstrate that the performance and the gas-liquid two-phase flow behaviors of the PEMFC with vertical channels exhibits obvious changes when the PEMFCs enter the 3.6 s short-term microgravity environment from the normal gravity environment. Meanwhile, the performance of the PEMFC with vertical channels increases after the PEMFC enters the 3.6 s short-term microgravity environment under high external circuit load, while under low external circuit load, the PEMFC with horizontal channels exhibits better performance in both the normal gravity environment and the 3.6 s short-term microgravity environment.

  14. A Magnetically Coupled Cryogenic Pump

    Science.gov (United States)

    Hatfield, Walter; Jumper, Kevin

    2011-01-01

    the pump, and the pump was successfully operated meeting all expected operating parameters. Unique pump sub-assembly parts were designed and manufactured by the CTL using specialized materials determined to be superior for cryogenic thermal applications under the pump design conditions. This work is a proof-of-concept/proof-of-operation of the pump only. Other known internal design modifications to the pump should be accomplished for the long-term use of the pump. An upscaled version of this pump, which is under development and testing at the CTL, can be used either for current or future vehicle loading or for vehicle replenishment. Scaling of this pump can be easily accomplished.

  15. 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

  16. Long-term use of Proton Pump Inhibitors, Dose-response Relationship, and Associated Risk of Ischemic Stroke and Myocardial Infarction

    DEFF Research Database (Denmark)

    Sehested, Thomas S G; Gerds, Thomas A; Fosbøl, Emil L

    2018-01-01

    Danish individuals with no prior history of MI or stroke, who had an elective upper gastrointestinal endoscopy performed between 1997 and 2012, were identified from nationwide registries. We used multiple Poisson regression to test associations with current PPI use and its dose, and used multiple cause...

  17. 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

  18. 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.

  19. Efficacy of triple therapy with a proton pump inhibitor, levofloxacin, and amoxicillin as first-line treatment to eradicate Helicobacter pylori Eficacia de una triple terapia con un inhibidor de la bomba de protones, levofloxacino y amoxicilina, como primer tratamiento, en la erradicación de Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    M. Castro-Fernández

    2009-06-01

    Full Text Available Background: triple therapy including a proton pump inhibitor, clarithromycin, and amoxicillin (PPI-CA is the first-choice treatment used for H. pylori eradication. The efficacy of this treatment is declining of late, and alternative therapies are currently under evaluation. Objectives: to evaluate the efficacy, safety and compliance of a triple therapy with a PPI, amoxicillin and levofloxacin (PPI-LA - replacing clarithromycin - for the eradication of H. pylori. Methods: the study included 135 patients (65% women, mean age 53 years, with dyspeptic symptoms and H. pylori infection proven by a positive urease rapid test, histological analysis, or C13-urea breath test. Diagnosis: non-investigated dyspepsia 48.9%, functional dyspepsia 36.3%, and ulcerative dyspepsia 14.8%. Treatment was indicated with a proton pump inhibitor at usual doses, amoxicillin 1 g, and levofloxacin 500 mg, administered jointly during breakfast and dinner for 10 days. We studied the performance of this triple therapy and its effects using a questionnaire, and effectiveness by the negativity of the C13-urea breath test after 6-8 weeks after treatment discontinuation. Per protocol, we compared the effectiveness of PPI-LA with a control group of 270 patients treated with PPI-CA for 10 days. Results: 130 patients (96.2% could complete the treatment and follow-up protocol. Effectiveness (intention to treat was 71.8% (97/135 and 74.6% (per protocol (97/130. Sixteen patients (11.8% had well-tolerated adverse effects, except for 5 subjects (3.7% who dropped out. PPI-CA was effective (per protocol in 204 patients out of 270 (75.5% in the control group. Conclusions: triple therapy with a PPI, amoxicillin and levofloxacin for 10 days is a well-tolerated treatment that is easy to comply with; however it has low efficiency - less than 80% - and is not recommended as a first-choice treatment for H. pylori eradication. Similar results were obtained with the classic triple therapy using a

  20. 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.

  1. 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...

  2. Long-Term Efficacy and Safety of Sensor Augmented Insulin Pump Therapy with Low-Glucose Suspend Feature in Patients with Type 1 Diabetes.

    Science.gov (United States)

    Gómez, Ana María; Marín Carrillo, Lisseth Fernanda; Muñoz Velandia, Oscar Mauricio; Rondón Sepúlveda, Martín Alonso; Arévalo Correa, Carol M; Mora Garzón, Edwin; Cuervo Diaz, Maria Camila; Henao Carrillo, Diana Cristina

    2017-02-01

    Literature supports short-term efficacy and safety of Sensor Augmented Insulin Pump (SAP) therapy in patients with type 1 diabetes (T1D). However, no data are available showing long-term outcomes. Our study describes the long-term outcomes of SAP therapy with low-glucose suspend feature (SAP+LGS) in hypoglycemia in a Colombian population with T1D and hypoglycemia. A cohort study was conducted with T1D patients receiving SAP+LGS therapy who initiated this therapy because of hypoglycemia at San Ignacio University Hospital diabetes center in Bogotá, Colombia. Glycated hemoglobin (A1c) was assessed at least every 6 months, severe hypoglycemia (SH) and hypoglycemia unawareness (HU) incidence yearly. Adherence to therapy was also evaluated. One hundred eleven patients were included in the analysis. Total daily insulin dose was reduced during follow-up (mean difference -0.22 U/kg; 95% confidence interval [CI] -0.18 to -0.26; P < 0.001). A1c levels were reduced from a baseline value of 8.8% ± 1.9% to 7.5% ± 1.0% at 5 months (mean difference -1.3%; 95% CI -1.09 to -1.50; P < 0.001) and 7.1% ± 0.8% (mean difference -1.7%; 95% CI -1.59 to -1.90; P < 0.001) at the end of follow-up (47 months on average). The incidence of SH and HU episodes decreased significantly since the first year, and this effect was maintained over time (P < 0.001). SAP+LGS therapy in T1D patients with hypoglycemia led to a significant and sustained decrease in A1c during long periods of follow-up, as well as a significant reduction in SH and HU. Future randomized clinical trials are desired.

  3. 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

  4. Protonated nitrosamide

    DEFF Research Database (Denmark)

    Egsgaard, H.; Carlsen, L.; Øgaard Madsen, J.

    1994-01-01

    The protonated nitrosamide, NH3NO+, has been generated by chemical ionization mass spectrometry. Although a direct search for this species in ammonia flames has proved negative, fast proton transfer to major flame constituents is supported experimentally as well as by MO calculations....

  5. Types of Breast Pumps

    Science.gov (United States)

    ... Devices Consumer Products Breast Pumps Types of Breast Pumps Share Tweet Linkedin Pin it More sharing options ... used for feeding a baby. Types of Breast Pumps There are three basic types of breast pumps: ...

  6. 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.

  7. 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.

  8. Proton Transport

    Science.gov (United States)

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

    2001-01-01

    The transport of protons across membranes is an essential process for both bioenergetics of modern cells and the origins of cellular life. All living systems make use of proton gradients across cell walls to convert environmental energy into a high-energy chemical compound, adenosine triphosphate (ATP), synthesized from adenosine diphosphate. ATP, in turn, is used as a source of energy to drive many cellular reactions. The ubiquity of this process in biology suggests that even the earliest cellular systems were relying on proton gradient for harvesting environmental energy needed to support their survival and growth. In contemporary cells, proton transfer is assisted by large, complex proteins embedded in membranes. The issue addressed in this Study was: how the same process can be accomplished with the aid of similar but much simpler molecules that could have existed in the protobiological milieu? The model system used in the study contained a bilayer membrane made of phospholipid, dimyristoylphosphatidylcholine (DMPC) which is a good model of the biological membranes forming cellular boundaries. Both sides of the bilayer were surrounded by water which simulated the environment inside and outside the cell. Embedded in the membrane was a fragment of the Influenza-A M$_2$ protein and enough sodium counterions to maintain system neutrality. This protein has been shown to exhibit remarkably high rates of proton transport and, therefore, is an excellent model to study the formation of proton gradients across membranes. The Influenza M$_2$ protein is 97 amino acids in length, but a fragment 25 amino acids long. which contains a transmembrane domain of 19 amino acids flanked by three amino acids on each side. is sufficient to transport protons. Four identical protein fragments, each folded into a helix, aggregate to form small channels spanning the membrane. Protons are conducted through a narrow pore in the middle of the channel in response to applied voltage. This

  9. 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.

  10. 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

  11. Molecular mechanisms for generating transmembrane proton gradients

    Science.gov (United States)

    Gunner, M.R.; Amin, Muhamed; Zhu, Xuyu; Lu, Jianxun

    2013-01-01

    Membrane proteins use the energy of light or high energy substrates to build a transmembrane proton gradient through a series of reactions leading to proton release into the lower pH compartment (P-side) and proton uptake from the higher pH compartment (N-side). This review considers how the proton affinity of the substrates, cofactors and amino acids are modified in four proteins to drive proton transfers. Bacterial reaction centers (RCs) and photosystem II (PSII) carry out redox chemistry with the species to be oxidized on the P-side while reduction occurs on the N-side of the membrane. Terminal redox cofactors are used which have pKas that are strongly dependent on their redox state, so that protons are lost on oxidation and gained on reduction. Bacteriorhodopsin is a true proton pump. Light activation triggers trans to cis isomerization of a bound retinal. Strong electrostatic interactions within clusters of amino acids are modified by the conformational changes initiated by retinal motion leading to changes in proton affinity, driving transmembrane proton transfer. Cytochrome c oxidase (CcO) catalyzes the reduction of O2 to water. The protons needed for chemistry are bound from the N-side. The reduction chemistry also drives proton pumping from N- to P-side. Overall, in CcO the uptake of 4 electrons to reduce O2 transports 8 charges across the membrane, with each reduction fully coupled to removal of two protons from the N-side, the delivery of one for chemistry and transport of the other to the P-side. PMID:23507617

  12. 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

  13. 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.

  14. Natural gas vs. heat pumps

    Energy Technology Data Exchange (ETDEWEB)

    Verrips, A.M.; Canney, W.A.

    Spokesmen for gas and electric utilities describe the relative merits of using natural gas and electric heat pumps. Both argue that their product is more economical and operates more efficiently than its competitor. Rising natural gas prices are responsible for making costs more competitive, although rates for both gas and electricity vary by region. The utilities also describe heat pump advantages in terms of installation ease and cost, reliability, maintenance, and thermal comfort. Both provide documentation to support their claims. 2 tables.

  15. Characterizing the proton loading site in cytochrome c oxidase.

    Science.gov (United States)

    Lu, Jianxun; Gunner, M R

    2014-08-26

    Cytochrome c oxidase (CcO) uses the energy released by reduction of O2 to H2O to drive eight charges from the high pH to low pH side of the membrane, increasing the electrochemical gradient. Four electrons and protons are used for chemistry, while four more protons are pumped. Proton pumping requires that residues on a pathway change proton affinity through the reaction cycle to load and then release protons. The protonation states of all residues in CcO are determined in MultiConformational Continuum Electrostatics simulations with the protonation and redox states of heme a, a3, Cu(B), Y288, and E286 used to define the catalytic cycle. One proton is found to be loaded and released from residues identified as the proton loading site (PLS) on the P-side of the protein in each of the four CcO redox states. Thus, the same proton pumping mechanism can be used each time CcO is reduced. Calculations with structures of Rhodobacter sphaeroides, Paracoccus denitrificans, and bovine CcO derived by crystallography and molecular dynamics show the PLS functions similarly in different CcO species. The PLS is a cluster rather than a single residue, as different structures show 1-4 residues load and release protons. However, the proton affinity of the heme a3 propionic acids primarily determines the number of protons loaded into the PLS; if their proton affinity is too low, less than one proton is loaded.

  16. 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

  17. 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

  18. Functional Dynamics and Proton Transfer in Proteins

    Science.gov (United States)

    Boxer, Steven

    2014-03-01

    Internal proton transfer between an enzyme and substrate is a common feature of many enzyme mechanisms. Likewise, internal proton transfer between the chromophore of green fluorescent protein (GFP) and amino acids on the inside of the beta barrel are important both in the ground and excited state. I will discuss an interesting connection between the proton transfer dynamics in GFP and those in an enzyme, ketosteroid isomerase (KSI), bound to substrate analogs. In both cases there is a tug of war between the protein and bound substrate analog or chromophore that depends on their affinities for a proton and which can be tuned either by changing the substrate/chromophore or the protein. This can be observed in the ground state by optical methods (absorption and IR) as well as by nmr, or in the excited state by time-resolved fluorescence or visible pump-IR probe measurements. In both cases the proton dynamics have important functional consequences.

  19. 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, ...

  20. 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

  1. Helium pumping with liquid ring vacuum pump

    International Nuclear Information System (INIS)

    Mathy, C.; Gravil, B.; Sauvigne, G.; Verdier, J.

    1983-09-01

    At first the main principles for operation and building of liquid ring pumps are remembered and an experiment is described which allowed to assess the performance data of such pumps when used to pump helium gas with oil. Although they have been designed to pump air with water the adaptation for helium is rather simple, the input power is slightly higher in the same flow and pressure conditions, but the limit of the succion pressure is lowered [fr

  2. 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.

  3. 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

  4. 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

  5. Polarized proton collider at RHIC

    Energy Technology Data Exchange (ETDEWEB)

    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. E-mail: mackay@bnl.govhttp://www.rhichome.bnl.gov/People/waldowaldo@bnl.gov; 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

    2003-03-01

    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 {radical}s=500 GeV.

  6. 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.

  7. Initiation of insulin pump therapy in children at diagnosis of type 1 diabetes resulted in improved long-term glycemic control.

    Science.gov (United States)

    Lang, Eunice G; King, Bruce R; Miller, Malcolm N; Dunn, Sandra V; Price, Darrell A; Foskett, Deborah C

    2017-02-01

    Insulin pump therapy (IPT) is increasingly used in children and young people with type 1 diabetes. There are limited studies evaluating the optimal time to start IPT. The aim of this study was to determine if early initiation of IPT in children with type 1 diabetes leads to improved glycaemic control and quality of life (QOL) compared with the later introduction of IPT. There were 38 subjects in the early pump group (EPG) (age 12.6 + 4.9 yr, 23 male) and 37 in the later pump group (LPG) (age 13.1 + 4.1 yr, 19 male). Hemoglobin A1c (HbA1c), rate of severe hypoglycemia, and diabetic ketoacidosis (DKA) were collected retrospectively over a 48-month period. Eligible subjects and/or their parents completed both a Paediatric and Paediatric Diabetes-specific Quality of Life Inventory. HbA1c measurements were lower in the EPG (6.8%; 51 mmol/mol) compared to the LPG (7.9%; 63 mmol/mol), across the 48 months of the study (p < 0.0001). There was no significant difference in the rate (per patient years) of severe hypoglycaemia (0.02; 0.07) p = 0.075 between the two groups. There were no episodes of DKA in either group. There was no significant difference in QOL between the groups with both having high satisfaction rates. Initiation of IPT at diagnosis of type 1 diabetes in children resulted in consistently lower HbA1c with no apparent change in hypoglycemia, DKA, or QOL. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. 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;

  9. 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)

  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. 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

  12. Proton radiography to improve proton therapy treatment

    NARCIS (Netherlands)

    Takatsu, J.; van der Graaf, E. R.; van Goethem, Marc-Jan; van Beuzekom, M.; Klaver, T.; Visser, Jan; Brandenburg, S.; Biegun, A. K.

    The quality of cancer treatment with protons critically depends on an accurate prediction of the proton stopping powers for the tissues traversed by the protons. Today, treatment planning in proton radiotherapy is based on stopping power calculations from densities of X-ray Computed Tomography (CT)

  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 MACEs (92.5% vs. 97.3%, P = 0.36 and survival rates free of angina recurrence (80.9% vs. 85.5%, P = 0.48 were similar among individual and sequential venous grafts groups with a mean follow-up of 22.5 months. In the Cox regression analysis, sequential vein bypass grafting was not identified as an independent predictor of both MACEs and angina recurrence. Conclusions: Compared to individual vein bypass grafting, sequential vein bypass grafting was not associated with an increase of either in

  14. Redox-controlled proton gating in bovine cytochrome c oxidase.

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Egawa

    Full Text Available Cytochrome c oxidase is the terminal enzyme in the electron transfer chain of essentially all organisms that utilize oxygen to generate energy. It reduces oxygen to water and harnesses the energy to pump protons across the mitochondrial membrane in eukaryotes and the plasma membrane in prokaryotes. The mechanism by which proton pumping is coupled to the oxygen reduction reaction remains unresolved, owing to the difficulty of visualizing proton movement within the massive membrane-associated protein matrix. Here, with a novel hydrogen/deuterium exchange resonance Raman spectroscopy method, we have identified two critical elements of the proton pump: a proton loading site near the propionate groups of heme a, which is capable of transiently storing protons uploaded from the negative-side of the membrane prior to their release into the positive side of the membrane and a conformational gate that controls proton translocation in response to the change in the redox state of heme a. These findings form the basis for a postulated molecular model describing a detailed mechanism by which unidirectional proton translocation is coupled to electron transfer from heme a to heme a 3, associated with the oxygen chemistry occurring in the heme a 3 site, during enzymatic turnover.

  15. Asymmetric Functional Conversion of Eubacterial Light-driven Ion Pumps*

    Science.gov (United States)

    Inoue, Keiichi; Nomura, Yurika; Kandori, Hideki

    2016-01-01

    In addition to the well-known light-driven outward proton pumps, novel ion-pumping rhodopsins functioning as outward Na+ and inward Cl− pumps have been recently found in eubacteria. They convert light energy into transmembrane electrochemical potential difference, similar to the prototypical archaeal H+ pump bacteriorhodopsin (BR) and Cl− pump halorhodopsin (HR). The H+, Na+, and Cl− pumps possess the conserved respective DTE, NDQ, and NTQ motifs in the helix C, which likely serve as their functional determinants. To verify this hypothesis, we attempted functional interconversion between selected pumps from each category by mutagenesis. Introduction of the proton-pumping motif resulted in successful Na+ → H+ functional conversion. Introduction of the respective characteristic motifs with several additional mutations leads to successful Na+ → Cl− and Cl− → H+ functional conversions, whereas remaining conversions (H+ → Na+, H+ → Cl−, Cl− → Na+) were unsuccessful when mutagenesis of 4–6 residues was used. Phylogenetic analysis suggests that a H+ pump is the common ancestor of all of these rhodopsins, from which Cl− pumps emerged followed by Na+ pumps. We propose that successful functional conversions of these ion pumps are achieved exclusively when mutagenesis reverses the evolutionary amino acid sequence changes. Dependence of the observed functional conversions on the direction of evolution strongly suggests that the essential structural mechanism of an ancestral function is retained even after the gain of a new function during natural evolution, which can be evoked by a few mutations. By contrast, the gain of a new function needs accumulation of multiple mutations, which may not be easily reproduced by limited mutagenesis in vitro. PMID:26929409

  16. Pump element for a tube pump

    DEFF Research Database (Denmark)

    2011-01-01

    The invention relates to a tube pump comprising a tube and a pump element inserted in the tube, where the pump element comprises a rod element and a first and a second non-return valve member positioned a distance apart on the rod element. The valve members are oriented in the same direction...... portion acts to alternately close and open the valve members thereby generating a fluid flow through the tube. The invention further relates to a pump element comprising at least two non-return valve members connected by a rod element, and for insertion in an at least partly flexible tube in such tube...... pump as mentioned above, thereby acting to generate a fluid flow through the tube upon repeated deformation of the tube between the two valve members. The pump element may comprise a connecting part for coupling to another tube and may comprise a sealing part establishing a fluid tight connection...

  17. Pumping mechanisms in sputter-ion pumps low pressure operation

    International Nuclear Information System (INIS)

    Welch, K.M.

    1991-01-01

    It is shown that significant H 2 pumping occurs in the walls of triode pumps. Also, H 2 is pumped in the anode cells of sputter-ion pumps. This pumping occurs in a manner similar to that by which the inert gases are pumped. That is, H 2 is pumped in the walls of the anode cells by high energy neutral burial. Hydrogen in the pump walls and anodes limits the base pressure of the pump

  18. Pumping mechanisms in sputter-ion pumps low pressure operation

    International Nuclear Information System (INIS)

    Welch, K.M.

    1991-01-01

    It is shown that significant H 2 pumping occurs in the walls of triode pumps. Also, H 2 is pumped in the anode cells of sputter-ion pumps. This pumping occurs in a manner similar to that by which the inert gases are pumped. That is, H 2 pumped in the walls of the anode cells by high energy neutral burial. Hydrogen in the pump walls and anodes limits the base pressure of the pump. 13 refs., 5 figs., 1 tab

  19. Pump Early, Pump Often: A Continuous Quality Improvement Project.

    Science.gov (United States)

    Spatz, Diane L; Froh, Elizabeth B; Schwarz, Jessica; Houng, Kathy; Brewster, Isabel; Myers, Carey; Prince, Judy; Olkkola, Michelle

    2015-01-01

    Research demonstrates that although many mothers initiate pumping for their critically ill children, few women are successful at maintaining milk supply throughout their infants' entire hospital stay. At the Garbose Family Special Delivery Unit (SDU) at the Children's Hospital of Philadelphia, we care for mothers who have critically ill infants born with complex cardiac and congenital anomalies. Human milk is viewed as a medical intervention at our institution. Therefore, nurses on the SDU wanted to ensure best practice in terms of pumping initiation. This article describes a continuous quality improvement project that ensured mothers pumped early and often. Childbirth educators can play a key role in preparing mothers who are anticipating an infant who will require hospitalization immediately post-birth.

  20. Adsorption pump for helium pumping out

    International Nuclear Information System (INIS)

    Donde, A.L.; Semenenko, Yu.E.

    1981-01-01

    Adsorption pump with adsorbent cooling by liquid helium is described. Shuttered shield protecting adsorbent against radiation is cooled with evaporating helium passing along the coil positioned on the shield. The pump is also equipped with primed cylindrical shield, cooled with liquid nitrogen. The nitrogen shield has in the lower part the shuttered shield, on the pump casing there is a valve used for pump pre-burning, and valves for connection to recipient as well. Pumping- out rates are presented at different pressures and temperatures of adsorbent. The pumping-out rate according to air at absorbent cooling with liquid nitrogen constituted 5x10 -4 Pa-3000 l/s, at 2x10 -2 Pa-630 l/s. During the absorbent cooling with liquid hydrogen the pumping-out rate according to air was at 4x10 -4 Pa-580 l/s, at 2x10 -3 Pa-680 l/s, according to hydrogen - at 8x10 -5 Pa-2500 l/s, at 5x10 -3 Pa-4200 l/s. During adsorbent cooling with liquid helium the rate of pumping-out according to hydrogen at 3x10 5 Pa-2400% l/s, at 6x10 3 Pa-1200 l/s, and according to helium at 3.5x10 -5 Pa-2800 l/s, at 4x10 -3 Pa-1150 l/s. The limit vacuum is equal to 1x10 -7 Pa. The volume of the vessel with liquid helium is equal to 3.5 l. Helium consumption is 80 cm 3 /h. Consumption of liquid nitrogen from the shield is 400 cm 3 /h. The limit pressure in the pump is obtained after forevacuum pumping-out (adsorbent regeneration) at 300 K temperature. The pump is made of copper. The pump height together with primed tubes is 800 mm diameter-380 mm [ru

  1. Concrete volute pumps: technology review and improvement

    International Nuclear Information System (INIS)

    Prunières, R; Longatte, F; Catelan, F X; Philippot, J M

    2012-01-01

    When pumps need to deliver large water flow rates (typically more than 5 m 3 .s −1 ), concrete volute pumps (CVP) offer an interesting alternative to standard vertical wet-pit pumps. One of the major advantages of CVP is its simplicity in terms of design, manufacturability and maintainability. In addition, CVP geometrical arrangement allows to reach high performances in terms of hydraulic and mechanical behaviour. These advantages can be specifically appreciated when such pumps are used in the energy field for Power Plants which need high flow rate and reliability, and can lead to important financial savings over the Plant lifetime compared to vertical wet-pit pumps. Finally, as CVP was for a long time limited to total head rise lower than 30 mWC, it was established through CFD analysis that the addition of guide vanes between the impeller and the volute allows to achieve higher head rise without risk.

  2. Proton dosimetry intercomparison

    International Nuclear Information System (INIS)

    Vatnitsky, S.; Siebers, J.; Miller, D.; Moyers, M.; Schaefer, M.; Jones, D.; Vynckier, S.; Hayakawa, Y.; Delacroix, S.; Isacsson, U.; Medin, J.; Kacperek, A.; Lomax, A.; Coray, A.; Kluge, H.; Heese, J.; Verhey, L.; Daftari, I.; Gall, K.; Lam, G.; Beck, T.; Hartmann, G.

    1996-01-01

    Background and purpose: Methods for determining absorbed dose in clinical proton beams are based on dosimetry protocols provided by the AAPM and the ECHED. Both groups recommend the use of air-filled ionization chambers calibrated in terms of exposure or air kerma in a 60 Co beam when a calorimeter or Faraday cup dosimeter is not available. The set of input data used in the AAPM and the ECHED protocols, especially proton stopping powers and w-value is different. In order to verify inter-institutional uniformity of proton beam calibration, the AAPM and the ECHED recommend periodic dosimetry intercomparisons. In this paper we report the results of an international proton dosimetry intercomparison which was held at Loma Linda University Medical Center. The goal of the intercomparison was two-fold: first, to estimate the consistency of absorbed dose delivered to patients among the participating facilities, and second, to evaluate the differences in absorbed dose determination due to differences in 60 Co-based ionization chamber calibration protocols. Materials and methods: Thirteen institutions participated in an international proton dosimetry intercomparison. The measurements were performed in a 15-cm square field at a depth of 10 cm in both an unmodulated beam (nominal accelerator energy of 250 MeV) and a 6-cm modulated beam (nominal accelerator energy of 155 MeV), and also in a circular field of diameter 2.6 cm at a depth of 1.14 cm in a beam with 2.4 cm modulation (nominal accelerator energy of 100 MeV). Results: The results of the intercomparison have shown that using ionization chambers with 60 Co calibration factors traceable to standard laboratories, and institution-specific conversion factors and dose protocols, the absorbed dose specified to the patient would fall within 3% of the mean value. A single measurement using an ionization chamber with a proton chamber factor determined with a Faraday cup calibration differed from the mean by 8%. Conclusion: The

  3. Gastrostomy feeding tube - pump - child

    Science.gov (United States)

    ... tube feeding; PEG tube care; Feeding - gastrostomy tube - pump; G-tube - pump; Gastrostomy button - pump; Bard Button - pump; MIC-KEY - pump ... Gather supplies: Feeding pump (electronic or battery powered) Feeding ... pump (includes a feeding bag, drip chamber, roller clamp, ...

  4. Effect of preoperatively continued aspirin use on early and mid-term outcomes in off-pump coronary bypass surgery: a propensity score-matched study of 1418 patients.

    Directory of Open Access Journals (Sweden)

    Fucheng Xiao

    Full Text Available To date, effect of preoperatively continued aspirin administration in off-pump coronary artery bypass grafting (CABG is less known. We aimed to assess the effect of preoperatively continued aspirin use on early and mid-term outcomes in patients receiving off-pump CABG.From October 2009 to September 2013 at the Fuwai Hospital, 709 preoperative aspirin users were matched with unique 709 nonaspirin users using propensity score matching to obtain risk-adjusted outcome comparisons between the two groups. Early outcomes were in-hospital death, stroke, intra- and post-operative blood loss, reoperation for bleeding and blood product transfusion. Major adverse cardiac events (death, myocardial infarction or repeat revascularization, angina recurrence and cardiogenic readmission were considered as mid-term endpoints.There were no significant differences among the groups in baseline characteristics after propensity score matching. The median intraoperative blood loss (600 ml versus 450 ml, P = 0.56, median postoperative blood loss (800 ml versus 790 ml, P = 0.60, blood transfusion requirements (25.1% versus 24.4%, P = 0.76 and composite outcome of in-hospital death, stroke and reoperation for bleeding (2.8% versus 1.6%, P = 0.10 were similar in aspirin and nonaspirin use group. At about 4 years follow-up, no significant difference was observed among the aspirin and nonaspirin use group in major adverse cardiac events free survival estimates (95.7% versus 91.5%, P = 0.23 and freedom from cardiogenic readmission (88.5% versus 85.3%, P = 0.77 whereas the angina recurrence free survival rates was 83.7% and 73.9% in the aspirin and nonaspirin use group respectively (P = 0.02, with odd ratio for preoperative aspirin estimated at 0.71 (95% confidence interval, 0.49-1.04, P = 0.08.Preoperatively continued aspirin use was not associated with increased risk of intra- and post-operative blood loss, blood transfusion requirements and composite outcome of in

  5. When the proton becomes larger

    CERN Document Server

    CERN Bulletin

    2011-01-01

    The TOTEM experiment at the LHC has just confirmed that, at high energy, protons behave as if they were becoming larger. In more technical terms, their total cross-section – a parameter linked to the proton-proton interaction probability – increases with energy. This phenomenon, expected from previous measurements performed at much lower energy, has now been confirmed for the first time at the LHC’s unprecedented energy.   One arm of a TOTEM T2 detector during its installation at interaction point 5. A composite particle like the proton is a complex system that in no way resembles a static Lego construction: sub-components move inside and interactions keep the whole thing together, but in a very dynamic way. This partly explains why even the very common proton can still be hiding secrets about its nature, decades after its discovery. One way of studying the inner properties of protons is to observe how they interact with each other, which, in technical terms, i...

  6. Hemodialysis using a valveless pulsatile blood pump.

    Science.gov (United States)

    Lee, Kyungsoo; Mun, Cho Hae; Lee, Sa Ram; Min, Byoung Goo; Yoo, Kyu Jae; Park, Yong Woo; Won, Yong Soon

    2008-01-01

    Research on pulsatile blood pumps for extracorporeal life support has been widely performed because of the proven advantageous effects of blood pulsation. However, studies on the use of pulsatile blood pumps for hemodialysis are limited, although available evidence demonstrates that pulsatile blood flow has a positive influence on dialysis outcome. Therefore, the authors designed a new pulsatile pump, which is characterized by minimal-occlusion of blood-containing tubing, no requirement for valves, and no blood flow regurgitation. In-vitro hemolysis tests were conducted using fresh bovine blood, and the normalized index of hemolysis was adopted to compare blood traumas induced by the devised pulsatile pump and a conventional roller pump. In addition, experimental hemodialyses with a canine renal failure model were performed using the devised pump. Normalized index of hemolysis levels obtained was much smaller for the devised pulse pump (45 +/- 21 mg/100 L) than for the roller pump (103 +/- 10 mg/100 L), and no technical problems were encountered during dialysis sessions. Blood and dialysate flow rates were maintained at predetermined values and molecular removal was satisfactory. Postdialysis urea and creatinine reduction ratios were 61.8% +/- 10.6% and 57.4% +/- 9.0%, respectively. Pulsatile flow has usually been generated using pulsatile devices containing valves, but the valves cause concern in terms of the clinical applications of these devices. However, the described pulsatile pump does not require valves, and yet no blood flow regurgitation was observed.

  7. Measuring H+ pumping and membrane potential formation in sealed membrane vesicle systems

    DEFF Research Database (Denmark)

    Wielandt, Alex Green; Palmgren, Michael Broberg; Fuglsang, Anja Thoe

    2016-01-01

    is not converted into a product and only moves a few nanometers in space. Here, we describe two methods for the measurement of active proton pumping across lipid bilayers and the concomitant formation of a membrane potential, applying the dyes 9-amino-6-chloro-2-methoxyacridine (ACMA) and oxonol VI. The methods...... are exemplified by assaying transport of the Arabidopsis thaliana plasma membrane H(+)-ATPase (proton pump), which after heterologous expression in Saccharomyces cerevisiae and subsequent purification has been reconstituted in proteoliposomes....

  8. Long-term health economic benefits of sensor-augmented pump therapy vs continuous subcutaneous insulin infusion alone in type 1 diabetes: a U.K. perspective.

    Science.gov (United States)

    Roze, Stéphane; Smith-Palmer, Jayne; Valentine, William J; Cook, Mark; Jethwa, Manisha; de Portu, Simona; Pickup, John C

    2016-01-01

    Continuous subcutaneous insulin infusion (CSII) is an important treatment option for type 1 diabetes patients unable to achieve adequate glycemic control with multiple daily injections (MDI). Combining CSII with continuous glucose monitoring (CGM) in sensor-augmented pump therapy (SAP) with a low glucose-suspend (LGS) feature may further improve glycemic control and reduce the frequency of hypoglycemia. A cost-effectiveness analysis of SAP + LGS vs. CSII plus self-monitoring of blood glucose (SMBG) was performed to determine the health economic benefits of SAP + LGS in type 1 diabetes patients using CSII in the U.K. Cost-effectiveness analysis was performed using the CORE diabetes model. Treatment effects were sourced from the literature, where SAP + LGS was associated with a projected HbA1c reduction of -1.49% vs. -0.62% for CSII, and a reduced frequency of severe hypoglycemia. The time horizon was that of patient lifetimes; future costs and clinical outcomes were discounted at 3.5% and 1.5% per annum, respectively. Projected outcomes showed that SAP + LGS was associated with higher mean quality-adjusted life expectancy (17.9 vs. 14.9 quality-adjusted life years [QALYs], SAP + LGS vs. CSII), and higher life expectancy (23.8 vs. 21.9 years), but higher mean lifetime direct costs (GBP 125,559 vs. GBP 88,991), leading to an incremental cost-effectiveness ratio (ICER) of GBP 12,233 per QALY gained for SAP + LGS vs. CSII. Findings of the base-case analysis remained robust in sensitivity analyses. For UK-based type 1 diabetes patients with poor glycemic control, the use of SAP + LGS is likely to be cost-effective compared with CSII plus SMBG.

  9. Insulin pump (image)

    Science.gov (United States)

    The catheter at the end of the insulin pump is inserted through a needle into the abdominal ... with diabetes. Dosage instructions are entered into the pump's small computer and the appropriate amount of insulin ...

  10. Polarized proton target with horizontal spin orientation

    International Nuclear Information System (INIS)

    Bunyatova, Eh.I.; Kiselev, Yu.F.; Kozlenko, N.G.

    1988-01-01

    Proton target, the polarization vector of which may be arbitrary oriented in horizontal plane relatively to the beam, is developed and tested. 70% value of polarization is obtained. 0.6 K temperature is acquired through 3 He pumping out continuous cycle. 1.2-propylene glycol - Cr(V) was used as working medium. Magnetic system is made in the form of Helmholtz sperconducting coils with working curren close to critical one. Target polarization is measured by NMR technique using original system of proton signal processing

  11. Photovoltaic pump systems

    Science.gov (United States)

    Klockgether, J.; Kiessling, K. P.

    1983-09-01

    Solar pump systems for the irrigation of fields and for water supply in regions with much sunshine are discussed. For surface water and sources with a hoisting depth of 12 m, a system with immersion pumps is used. For deep sources with larger hoisting depths, an underwater motor pump was developed. Both types of pump system meet the requirements of simple installation and manipulation, safe operation, maintenance free, and high efficiency reducing the number of solar cells needed.

  12. Vertical pump assembly

    International Nuclear Information System (INIS)

    Dohnal, M.; Rosel, J.; Skarka, V.

    1988-01-01

    The mounting is described of the drive assembly of a vertical pump for nuclear power plants in areas with seismic risk. The assembly is attached to the building floor using flexible and damping elements. The design allows producing seismically resistant pumps without major design changes in the existing types of vertical pumps. (E.S.). 1 fig

  13. Rapidity spectra in proton-proton and proton-antiproton scattering up to 540 GeV in a dual parton model

    International Nuclear Information System (INIS)

    Aurenche, P.; Bopp, F.W.

    1982-01-01

    Some recent data at the ISR and SPS colliders are discussed in terms of a multi-Pomeron exchange model formulated in the dual parton framework. Charged particle rapidity distributions, energy dependence of the central plateau, ratio of particle densities in proton-proton and antiproton-proton scattering and non diffractive multiplicities are successfully accounted for in the model

  14. Proton imaging apparatus for proton therapy application

    International Nuclear Information System (INIS)

    Sipala, V.; Lo Presti, D.; Brianzi, M.; Civinini, C.; Bruzzi, M.; Scaringella, M.; Talamonti, C.; Bucciolini, M.; Cirrone, G.A.P.; Cuttone, G.; Randazzo, N.; Stancampiano, C.; Tesi, M.

    2011-01-01

    Radiotherapy with protons, due to the physical properties of these particles, offers several advantages for cancer therapy as compared to the traditional radiotherapy and photons. In the clinical use of proton beams, a p CT (Proton Computer Tomography) apparatus can contribute to improve the accuracy of the patient positioning and dose distribution calculation. In this paper a p CT apparatus built by the Prima (Proton Imaging) Italian Collaboration will be presented and the preliminary results will be discussed.

  15. Proton radioactivity from proton-rich nuclei

    International Nuclear Information System (INIS)

    Guzman, F.; Goncalves, M.; Tavares, O.A.P.; Duarte, S.B.; Garcia, F.; Rodriguez, O.

    1999-03-01

    Half-lives for proton emission from proton-rich nuclei have been calculated by using the effective liquid drop model of heavy-particle decay of nuclei. It is shown that this model is able to offer results or spontaneous proton-emission half-life-values in excellent agreement with the existing experimental data. Predictions of half-life-values for other possible proton-emission cases are present for null orbital angular momentum. (author)

  16. Redox-controlled proton gating in bovine cytochrome c oxidase

    Science.gov (United States)

    Rousseau, Denis

    2015-03-01

    Cytochrome c oxidase is the terminal enzyme in the electron transfer chain of essentially all organisms that utilize oxygen to generate energy. It reduces oxygen to water and harnesses the energy to pump protons across the mitochondrial membrane in eukaryotes and the plasma membrane in prokaryotes. The mechanism by which proton pumping is coupled to the oxygen reduction reaction remains unresolved, owing to the difficulty of visualizing proton movement within the massive membrane-associated protein matrix. Here, with a novel hydrogen/deuterium exchange resonance Raman spectroscopy method, we have identified two critical elements of the proton pump: a proton loading site near the propionate groups of heme a, which is capable of transiently storing protons uploaded from the negative-side of the membrane prior to their release into the positive-side of the membrane and a conformational gate that controls proton translocation in response to the change in the redox state of heme a. These findings form the basis for a postulated molecular model describing a detailed mechanism by which unidirectional proton translocation is coupled to electron transfer from heme a to heme a3, associated with oxygen chemistry occurring in the heme a3 site, during enzymatic turnover. Each time heme a undergoes an oxidation-reduction transition a proton is translocated across the membrane accounting for the observation that two protons are translocated during the oxidative phase of the enzymatic cycle and two more are translocated during the reductive phase. This work was done in collaboration with Drs. Tsuyoshi Egawa and Syun-Ru Yeh. This work was supported the National Institutes of Health Grant GM098799 to D.L.R and National Science Foundation Grant NSF 0956358 to S.-R.Y.

  17. Optical pumping and xenon NMR

    International Nuclear Information System (INIS)

    Raftery, M.D.

    1991-11-01

    Nuclear Magnetic Resonance (NMR) spectroscopy of xenon has become an important tool for investigating a wide variety of materials, especially those with high surface area. The sensitivity of its chemical shift to environment, and its chemical inertness and adsorption properties make xenon a particularly useful NMR probe. This work discusses the application of optical pumping to enhance the sensitivity of xenon NMR experiments, thereby allowing them to be used in the study of systems with lower surface area. A novel method of optically-pumping 129 Xe in low magnetic field below an NMR spectrometer and subsequent transfer of the gas to high magnetic field is described. NMR studies of the highly polarized gas adsorbed onto powdered samples with low to moderate surface areas are now possible. For instance, NMR studies of optically-pumped xenon adsorbed onto polyacrylic acid show that xenon has a large interaction with the surface. By modeling the low temperature data in terms of a sticking probability and the gas phase xenon-xenon interaction, the diffusion coefficient for xenon at the surface of the polymer is determined. The sensitivity enhancement afforded by optical pumping also allows the NMR observation of xenon thin films frozen onto the inner surfaces of different sample cells. The geometry of the thin films results in interesting line shapes that are due to the bulk magnetic susceptibility of xenon. Experiments are also described that combine optical pumping with optical detection for high sensitivity in low magnetic field to observe the quadrupoler evolution of 131 Xe spins at the surface of the pumping cells. In cells with macroscopic asymmetry, a residual quadrupolar interaction causes a splitting in the 131 Xe NMR frequencies in bare Pyrex glass cells and cells with added hydrogen

  18. Liquid metal pump

    International Nuclear Information System (INIS)

    Pennell, W.E.

    1981-01-01

    A liquid metal pump comprising a shaft support structure which is isolated from the pump housing for better preservation of alignment of shaft bearings. The shaft carries an impeller and the support structure carries an impeller cage which is slidably disposed in a diffuser so as to allow complete removal of pump internals for inspection and repair. The diffuser is concentrically supported in the pump housing which also takes up all reaction forces generated by the discharge of the liquid metal from the diffuser, with floating seals arranged between impeller cage and the diffuser. The space between the diffuser and the pump housing permits the incoming liquid to essentially surround the diffuser. (author)

  19. Gamma-ray irradiation experiment of magnetically suspended compound molecular pump

    International Nuclear Information System (INIS)

    Wada, Kaoru; Yoshida, Motoo; Nakayasu, Tatsuo; Yamato, Yukio; Ogiwara, Norio; Kinsho, Michikazu

    2004-01-01

    3 GeV-RCS (Rapid Cycling Synchrotron) is constructed in Japan Atomic Energy Research Institute in Proton Accelerator Complex (J-PARC). It will have been composed to the combination magnetic suspension type turbo molecular pump is used at rough pumping and ion pump is used at main pumping in 3 GeV-RCS vacuum pumping system. However, the magnetic suspension type turbo molecular pump uses semiconductor chip for magnetic suspension control inside. This semiconductor chip has problem to use under the radiation and high temperature applications such as accelerator and semiconductor process. The pump used for Gamma-ray irradiation experiment is magnetically suspended compound molecular pump TG1300M is designed without semiconductor chip inside. (author)

  20. Heat pump dryers theory, design and industrial applications

    CERN Document Server

    Alves-Filho, Odilio

    2015-01-01

    Explore the Social, Technological, and Economic Impact of Heat Pump Drying Heat pump drying is a green technology that aligns with current energy, quality, and environmental concerns, and when compared to conventional drying, delivers similar quality at a lower cost. Heat Pump Dryers: Theory, Design and Industrial Applications details the progression of heat pump drying-from pioneering research and demonstration work to an applied technology-and establishes principles and theories that can aid in the successful design and application of heat pump dryers. Based on the author's personal experience, this book compares heat pump dryers and conventional dryers in terms of performance, quality, removal rate, energy utilization, and the environmental effect of both drying processes. It includes detailed descriptions and layouts of heat pump dryers, outlines the principles of operation, and explains the equations, diagrams, and procedures used to form the basis for heat pump dryer dimensioning and design. The author ...